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Schizophrenia and Schizoaffective Disorders
January 19, 2015
Alkermes reported results of a 12-week,
randomized, multi-center, double-blind,
active-controlled, dose-ranging stage
of a phase II study of ALKS 383 for the
treatment for schizophrenia. The study
enrolled 209 subjects. Following a one-week
oral lead-in of olanzapine, patients
were randomly assigned to treatment with
olanzapine or one of three different doses
of ALKS 3831 (olanzapine + 5mg, 10mg
or 20mg samidorphan) for a period of 12
weeks. Data from the 300-patient study
showed ALKS 3831 achieved the study’s
primary efficacy endpoint, demonstrating
equivalence to olanzapine in reduction from
baseline in Positive and Negative Syndrome
Scale (PANSS) total scores at week 12. ALKS
3831 also met the principal pre-specified
secondary endpoint of the study, demonstrating
a 37% lower mean weight gain
compared to olanzapine at week 12 in
the full study population (p=0.006), and a
51% lower mean weight gain compared to
olanzapine at week 12 in a pre-specified
subset of patients who gained weight in
the one-week olanzapine lead-in (p<0.001).
ALKS 3831 was generally well-tolerated in
the study. The most common adverse events
in the ALKS 3831 treatment groups relative
to olanzapine were somnolence, sedation
and dizziness. In the full study population,
treatment with ALKS 3831 demonstrated a
37% lower mean weight gain from baseline,
compared to olanzapine alone (p=0.006). In
the early weight gain population, treatment
with ALKS 3831 demonstrated a 51% lower
mean weight gain from baseline, compared
to olanzapine alone (p<0.001). Across the
full study population, the risk of weight gain
of at least 10% of baseline body weight with
olanzapine was 2.7 times that of ALKS 3831
((95% CI 1.1 – 6.7), p=0.023). In the early
weight gain population, the risk of weight
gain of at least 10% of baseline body weight
with olanzapine was 4.1 times that of ALKS
3831 ((95% CI 1.4 – 12.3), p=0.008). Based
on the positive results from this phase II
study, Alkermes plans to request an end-ofphase
II meeting with the FDA and advance
ALKS 3831 into a pivotal development
program in 2015.
June 30, 2014
Alkermes released results of a phase III trial of aripiprazole lauroxil for schizophrenia. The randomized, multi-center, double-blind, placebo-controlled study enrolled 623 subjects experiencing acute exacerbation of schizophrenia. Patients were randomized to receive once-monthly intramuscular injections of aripiprazole lauroxil 441mg, aripiprazole lauroxil 882mg or a matching placebo injection of either high volume or low volume for 12 weeks. Patients randomized to the two aripiprazole lauroxil treatment groups received oral aripiprazole for those initial three weeks, while patients randomized to the placebo group received matching oral placebo for three weeks. Patients treated once-monthly with either 441mg or 882mg of aripiprazole lauroxil demonstrated statistically and clinically significant placebo-
adjusted mean reductions from baseline in PANSS total scores (-10.9 points). Overall, 64% of patients who received aripiprazole lauroxil completed the study, compared to 46% of patients who received placebo. Alkermes intends to submit an NDA to the FDA in the third quarter.
May 19, 2014
Janssen Pharmaceuticals has reported
results of a relapse prevention study
of INVEGA SUSTENNA (paliperidone
palmitate) for schizoaffective disorder.
The 15-month, randomized, double-blind,
placebo (PBO)-controlled, international
study evaluated 334 adults (INVEGA
SUSTENNA n=164; PBO n=170) who met the
DSM-IV diagnosis of schizoaffective disorder
experiencing an acute exacerbation of
psychotic symptoms with prominent mood
symptoms. Individuals were first stabilized
with INVEGA SUSTENNA (78-234mg)
either as monotherapy or an adjunct to
antidepressants or mood stabilizers during
a 13-week, open-label, flexible-dose, lead-in
period and then continued into a 12-week,
open-label, fixed-dose stabilization period.
Stable patients were randomized to
treatment once every four weeks or placebo
and evaluated until relapse, discontinuation
or completion of the 15-month relapse
prevention period. INVEGA SUSTENNA
significantly delayed time to relapse
compared to placebo (P<0.001). A higher
percentage of patients relapsed in the
placebo group (57 patients, 33.5%) than in
the INVEGA SUSTENNA arm (25 patients,
15.2%) with the risk of relapse being 2.49-
fold higher in the placebo group (HR 2.49;
95% CI: 1.55-3.99; P<0.001). A decrease in
the risk of relapse occurred regardless of
whether INVEGA SUSTENNA was taken alone
or with another medication in a subgroup
analysis. The risk of relapse was 3.38 times
higher in the placebo group when INVEGA
SUSTENNA was taken alone (HR 3.38; 95%
CI: 1.57-7.28; P = 0.002). The risk of relapse
was 2.03 times higher in the placebo group
when INVEGA SUSTENNA was taken in
combination with antidepressants or mood
stabilizers treatment (HR 2.03; 95% CI:
1.11-3.68; P = 0.021). The risk in the placebo
group was 2.93 times higher for relapse due
to any mood symptom (95% CI: 1.70, 5.04;
p<0.001); 3.62 times higher for relapse due
to manic symptoms (95% CI: 1.32, 9.89;
p=0.012); 3.12 times higher for relapse due
to depressive symptoms (95% CI: 1.39, 6.98;
p=0.006); 1.93 times higher for relapse due
to mixed symptoms (95% CI: 0.65, 5.78;
p=0.238); and 2.82 times higher for relapse
due to psychotic symptoms (95% CI: 1.70,
4.67; p<0.001). The company will file an
sNDA in May.
April 14, 2014
Alkermes released results of a phase III, randomized,
multicenter, double-blind, placebo-controlled
study of aripiprazole lauroxil in
patients experiencing acute exacerbation of
schizophrenia. A total of 623 patients were
randomized to receive once-monthly intramuscular
injections of aripiprazole lauroxil 441mg,
aripiprazole lauroxil 882mg or placebo for 12
weeks. Patients treated once monthly with
aripiprazole lauroxil demonstrated statistically
significant reductions from baseline in
Positive and Negative Syndrome Scale (PANSS)
total scores at week 12, compared to placebo
(p<0.001 aripiprazole lauroxil 441mg, p<0.001
aripiprazole lauroxil 882mg), which was the
prespecified primary endpoint in the study. The
study also met the prespecified key secondary
endpoint of improvement on the Clinical
Global Impression-Improvement scale (CGI-I)
versus placebo at week 12 (p<0.001). Aripiprazole
lauroxil was generally well-tolerated in the
phase III study, and the safety profile of aripiprazole
lauroxil was similar to that reported with
oral aripiprazole. The most common adverse
events in the study were insomnia, akathisia
and headache. Based on the positive results
from this study, Alkermes plans to submit a
NDA to the FDA in the third quarter.
February 24, 2014
Omeros released positive results of a phase
IIa trial of OMS824, a phosphodiesterase 10
(PDE10) inhibitor, when administered alone
and concomitantly with approved antipsychotic
agents in patients with schizophrenia. In
this phase IIa randomized, double-blind, placebo-
controlled trial, OMS824 was administered
at two dose levels for two weeks to psychiatrically
stable patients whose antipsychotic medications
were temporarily discontinued or who
continued their usual antipsychotic regimen.
The trial enrolled 33 patients, and the results
showed that OMS824 was well-tolerated, with
mild or moderate adverse events that were
self-limited and resolved during the treatment
period. The tolerability and pharmacokinetics
of OMS824 were not affected by concomitant
antipsychotic medications, allowing the drug
to be developed as both a monotherapy and
as adjunctive therapy in combination with
currently approved antipsychotics. The plasma
concentrations of OMS824 in the high-dose
cohort were similar to levels that corresponded
to greater than 60% target occupancy of
PDE10 in a phase I positron emission tomography
(PET) trial. Omeros expects to initiate further
phase II and III trials in this indication and
to begin enrollment this quarter in a phase
II clinical trial evaluating OMS824 in patients
with Huntington’s disease.
January 20, 2014
Neurocrine Biosciences issued results of a
phase IIb study of NBI-98854. The randomized,
parallel, double-blind, placebo-controlled,
dose-titration trial utilized the
capsule formulation in moderate to severe
tardive dyskinesia patients with an underlying
mood disorder, schizophrenia or
schizoaffective disorder, or a gastrointestinal
disorder with exposure to metoclopramide.
This 100-subject study assessed once-daily
NBI-98854 over a six-week placebo-controlled
dosing period. The dosing regimen
began with a once-daily dose of 25mg for
the initial two weeks before patients were
titrated to a once-daily 50mg dose, or continued
on the once-daily 25mg dose for the
following two-week period. At the completion
of the second two weeks of treatment,
patients were eligible to be titrated to a
once-daily 75mg, 50mg or 25mg dose for
the final two weeks of treatment. At week 6,
the Abnormal Involuntary Movement Scale
(AIMS) scores were reduced by 2.6 points
in the NBI-98854 intention-to-treat (ITT)
group compared to a reduction of 0.2 points
in the placebo arm (p<0.001). Additionally,
the responder rate (>= 50% improvement
from baseline) was 49% in the NBI-98854
ITT group compared to 18% in placebo
(p=0.002). In the per-protocol (PP) group
AIMS scores were reduced by 3.3 points for
those subjects taking NBI-98854 (p<0.001),
with a corresponding responder rate of 59%
April 8, 2013
Omeros reported results from a phase I trial of OMS824 for Huntington’s disease, schizophrenia and other central nervous system disorders. This randomized, double-blind, single- and multiple-dose escalation study enrolled 64 male patients. Subjects received a single dose of OMS824, daily doses of OMS824 for seven to 10 days. Results showed the pharmacokinetic parameters (Cmax and AUC) increased linearly with the dose and OMS824 had a long half-life that is consistent with once daily. OMS824 was detected in the cerebrospinal fluid at the expected concentration relative to that in the blood. The drug concentration in the cerebrospinal fluid is predicted to achieve near-complete inhibition of the PDE10 target in the brain. OMS824 was well tolerated. The only apparent drug-related adverse event was mild somnolence at the highest dose evaluated. No subject had extrapyramidal symptoms (involuntary muscle movements), which are associated with marketed antipsychotic medications and have been seen with other companies’ PDE10 inhibitors at levels of approximately 50% engagement of the PDE10 enzyme in the brain. Based on these data, Omeros is advancing OMS824 toward a phase II clinical program.
March 5, 2012
Forest Labs and Gedeon Richter released results from two phase III trials of cariprazine for the treatment of acute exacerbation of schizophrenia. The primary endpoint for both double-blind, placebo controlled, parallel-group trials was the change from baseline to week six in the Positive And Negative Syndrome Scale (PANSS) total score for the individual cariprazine treatment groups compared to placebo. Fixed dose study: this study enrolled 617 adults who were randomized to 3 mg/d or 6 mg/d cariprazine, 10 mg/d aripiprazole or placebo given once daily for six weeks. Statistically significant improvement in PANSS total score was observed in each of the cariprazine dose groups compared to the placebo group (3 mg/day: -6.0, p≡0.0044 and 6 mg/day: -8.8, p<0.0001). The change from baseline in PANSS total score was statistically significant at every time point starting at week one for the cariprazine 6 mg/d group and week three onwards for the cariprazine 3 mg/d group. Fixed-flexible dose study: this study enrolled 446 adults who were randomized to 3-6 mg/d cariprazine, 6-9 mg/d cariprazine, or placebo given once daily for six weeks. Statistically significant improvement in PANSS total score was observed in each of the cariprazine dose groups compared to the placebo group (3-6 mg/day: -6.8, p≡0.0029 and 6-9 mg/day: -9.9, p< 0.0001). The change from baseline was statistically significant at every time point starting at week one for the cariprazine 6-9 mg/d group and week two onward for the cariprazine 3-6 mg/d group. Cariprazine was generally well tolerated; the most common adverse events were akathisia, insomnia, and headache.
July 11, 2011
Alkermes issued results from a phase I trial of ALKS9070 for schizophrenia. This randomized, multicenter, double-blind, placebo-controlled, 20-week study enrolled 32 subjects with chronic, stable schizophrenia. The subjects received a single administration of three ascending doses of ALKS 9070. Dose proportionality was achieved across all three dose levels and the pharmacokinetic profile supports once-monthly dosing. ALKS 9070 was generally well tolerated at all three dose levels and there were no serious adverse events related to study drug.
January 24, 2011
Targacept issued positive results from a phase II trial of TC-5619 for cognitive dysfunction in schizophrenia. This double blind, placebo controlled trial enrolled 185 subjects across the U.S. and India. The subjects received either TC-5619 (1mg daily for the first four weeks, 5mg daily dose for the next four weeks and 25mg daily dose for the last four weeks) or placebo, together with continued treatment of an approved antipsychotic, for 12 weeks. The primary endpoint was the change from baseline on the Groton Maze Learning item of the CogState Schizophrenia Test Battery (GMLT). The GMLT results met the pre-defined criteria, as well as at two of the trials three measurement dates, at 4 weeks and at 12 weeks. Positive results were also observed for several secondary efficacy outcome measures, including Scale for Assessment of Negative Symptoms, Clinical Global Impression Global Improvement, and Subject Global Impression Cognition scale.
August 2, 2010
Intra-Cellular Therapies released positive results from a phase Ib/II trial of ITI-007 for schizophrenia. This randomized, double-blind, placebo-controlled, multiple ascending dose study enrolled 45 subjects with stable schizophrenia. The subjects were withdrawn from their previous antipsychotic medications and were randomized to receive placebo or ITI-007 at doses up to and including 140 mg once daily for five days. The trial met its primary endpoint demonstrating that ITI-007 was safe and well-tolerated up to the highest tested dose. Treatment with ITI-007 also showed clinical signs consistent with antipsychotic and antidepressant efficacy, including a reduction in the total Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia.
November 2, 2009
Forest Labs and Gedeon Richter announced positive top-line results from a phase IIb trial of cariprazine for the treatment of acute exacerbation of schizophrenia. This placebo- and active-controlled, fixed dose study enrolled 732 subjects. Following a washout period of no antipsychotic therapy for up to seven days, subjects were randomized to one of the following treatment arms: 1.5 mg/d cariprazine, 3.0 mg/d cariprazine, 4.5 mg/d cariprazine, 4 mg/d risperidone or placebo given daily for six weeks followed by an additional two week safety follow-up period, where no drug was administered. The primary endpoint was the change from baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) total score for the individual cariprazine fixed dose treatment groups compared to placebo. Statistically significant improvement was observed for the comparison of each cariprazine dose group relative to the placebo treatment group (change of -7.5, -8.9, and -10.4 points for the 1.5, 3.0, and 4.5 mg/day dose groups, respectively; p < 0.001). Statistically significant improvements were also seen in the secondary endpoint, the change from baseline to Week 6 in the Clinical Global Impression-Severity Score.
September 7, 2009
Dainippon Sumitomo Pharma reported positive results a phase III trial of lurasidone for the treatment of schizophrenia. The international, randomized, placebo- and active-controlled trial, PEARL-2, enrolled 478 subjects with acute schizophrenic psychosis. The subjects received lurasidone 40 or 120 mg/day, olanzapine 15 mg/day or placebo for six weeks. The primary endpoint was change in total Positive and Negative Syndrome Scale (PANSS) score from baseline to the treatment period. Lurasidone 40 and 120 mg, taken once-daily, demonstrated significantly greater improvement versus placebo. PANSS score changes from baseline for lurasidone 40 and 120 mg/day versus placebo were -25.7 and -23.6 versus -16.0, respectively. A total of 53% of subjects on lurasidone 40 mg/day and 47% of patients on lurasidone 120 mg/day demonstrated a 30% or more improvement on the PANSS total score from baseline versus 38% on placebo. The key secondary endpoint, change from baseline on the Clinical Global Impressions Severity scale (CGI-S), was also reached. The CGI-S score changes from baseline in the lurasidone 40 and 120 mg/day versus placebo were -1.5 and -1.4 versus -1.1, respectively, at study endpoint.
June 1, 2009
Dainippon Sumitomo issued positive results from a phase III trial of lurasidone for the treatment of schizophrenia. This six-week, double-blind, randomized, placebo-controlled trial, PEARL 1 (Program to Evaluate the Antipsychotic Response to Lurasidone), enrolled 500 subjects with acute schizophrenia across several international sites. The subjects received lurasidone 40 mg, 80 mg and 120 mg once daily or placebo over six weeks. The primary endpoint was change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score over the six-week study duration for each lurasidone dose group versus placebo. A key secondary endpoint was the change from baseline in Clinical Global Impressions Severity scale (CGI-S) over the six-week study period. Both the primary and secondary endpoint revealed lurasidone 80 mg/day to be significantly more effective than placebo by week six. The 40 mg/day and 120 mg/day doses did not differ from placebo. Lurasidones effect on weight was similar to placebo (median change 0.3 kg for overall lurasidone group vs. 0 kg for placebo) as was its effect on lipid and glucose measures. Lurasidone was also well tolerated.
September 8, 2008
Alexza reported positive results from a phase III trial of AZ-004 for the treatment of acute agitation in schizophrenia. This in-clinic, multi-center, randomized, double-blind, placebo-controlled study enrolled 344 subjects in the US. The subjects received AZ-004 at two dose levels, 5 mg and 10 mg; they were eligible to receive up to 3 doses of study drug in a 24-hour period, depending on their clinical status. The primary endpoint was the change from baseline in the PANSS (Positive and Negative Symptom Scale) Excited Component score, measured at two hours after the first dose. Both doses of AZ-004 reached the primary endpoint with statistical significance over placebo. The PANSS baseline scores were 17.6, 17.8 and 17.4 in the AZ-004 10 mg, 5 mg and placebo arms, respectively. At two hours post-dose the PANSS score was 9.0 in the AZ-004 10 mg arm (p< 0.0001) and 9.8 in the AZ-004 5 mg arm (p= 0.0004) versus 11.8 for placebo. The key secondary endpoint was the Clinical Global Impression-Improvement (CGI-I) score, also measured at two hours after the first dose. Both doses also reached this endpoint with statistical significance over placebo. The CGI-I scores were 2.1 in the AZ-004 10 mg arm (p < 0.0001) and 2.3 in the AZ-004 5 mg arm (p= 0.0015) versus 2.8 in the placebo arm. Based on the results, Alexza plans to continue with the development of AZ-004 with an expected NDA filing date in early 2010.
June 30, 2008
Eli Lilly issued positive results from two clinical trials of olanzapine long acting injection (LAI) for the treatment of schizophrenia. The first is a maintenance study and the second is an ongoing extension study. The 24-week double-blind maintenance study (HGKA) enrolled 1,065 adult outpatient subjects with schizophrenia who had been previously stabilized on open-label oral olanzapin. The subjects were randomized to one of three therapeutic dosing regimens of olanzapine LAI (150 mg every two weeks, 405 mg every four weeks, or 300 mg every two weeks), or to a low reference dose of olanzapine LAI (45 mg every four weeks), or remained on oral olanzapine. At the three higher doses, olanzapine LAI showed maintenance of treatment effect for schizophrenia for up to 24 weeks. The subjects remained free of relapse, as assessed by the Brief Psychiatric Rating Scale (BPRS), at a rate of 95% with 300 mg/two weeks, 90% with 405 mg/four weeks, and 84% with 150 mg/two weeks of olanzapine LAI. In the oral olanzapine arm 93% of the subjects remained free of relapse. The 405 mg/four weeks and the pooled two-week dosing regimens showed non-inferiority when compared to oral olanzapine as well as to each other. All three higher olanzapine LAI doses had longer time to symptom exacerbation than the reference dose (p<.01). The most commonly reported adverse event was injection site reaction. Two subjects experienced and recovered fully from Post-Injection Delirium/Sedation Syndrome (PDSS). The ongoing open-label extension trial (HGKB) enrolled 931 subjects who had participated in one of three randomized, controlled studies of olanzapine LAI. Treatment response was measured by the Clinical Global Impression Severity of Illness (CGI-S) scale. Baseline-to-endpoint mean change on the CGI-S was -0.16, from a baseline of 2.92. At 160 weeks, the discontinuation rate was 39.6 percent. The mean weight change of study subjects was an increase of 1.4 kilograms; 28.1% experienced an increase of 7% or more. The percentage of subjects with a fasting glucose increase from normal to high at any time was 4.7%, with a random total cholesterol increase from normal to high at any time was 5.2% and the percentage with a random triglycerides increase from normal to high at any time was 11.9%. At the time of this interim analysis, 23 PDSS events were reported. At this time, regulatory reviews of olanzapine LAI are ongoing in the European Union, Canada, Australia and United States.
June 23, 2008
Acadia issued negative results from a phase IIb trial of ACP-104 for the treatment of schizophrenia. This multi-center, double-blind, placebo-controlled study enrolled 247 subjects with schizophrenia who were experiencing an acute psychotic episode. The subjects were randomized to one of three study arms: ACP-104 (100 mg or 200 mg, twice daily) or placebo for six weeks. The primary endpoint was antipsychotic efficacy as measured by the mean change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score for ACP-104 versus placebo. Secondary endpoints included the PANSS subscales and the Clinical Global Impression Severity scale. The study did not meet the primary or secondary endpoints, as neither dose of ACP-104 demonstrated improved efficacy as compared to placebo. Acadia plans to fully analyze the data in order to determine a future course of action.
February 11, 2008
BioLine RX reported positive results from a phase IIa trial of BL-1020 for the treatment of schizophrenia. This open label, 6-week study enrolled 36 treatment refractory and hospitalized subjects. The subjects were started on 32mg (20mg free base) of BL-1020 and received increasing dosages over the first 7 days in order to reach the maximum dose of 64 mg (40mg free base). The primary endpoints were reached in the BL-1020 arm, with significant improvements from baseline in the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression of Severity and Improvement (CGI-S, CGI-I). There was a statistically significant improvement on the PANSS total (baseline=84.9; day 42=63.8), and the positive (baseline=22.3; day 42=15.1) negative (baseline=20.9; day 42=16.6) and general psychopathology subscales (baseline=42.4; day 42=32.1) (p less than 0.001). In addition, more than 80% of the subjects treated with BL-1020 showed a clinically significant improvement as reflected by the CGI-S and CGI-I. Treatment was well tolerated, with no unexpected adverse events. Based on the results, BioLine RX is planning to commence a phase IIb trial during the second quarter of 2008.
Neuro-Hitech released mixed results from the double blind portion of a phase II trial of Huperzine A for the treatment of Alzheimers disease. This multi-center, randomized, double-blind, placebo-controlled trial enrolled two hundred subjects with mid-to-moderate Alzheimers disease. The subjects were administered either 200 or 400 micrograms of Huperzine A or placebo, orally twice a day for sixteen weeks. Approximately half the subjects received concomitant treatment with Namenda, an approved treatment for Alzheimers. The primary endpoint was the mean change on AD Assessment Scale- Cognitive (ADAS-Cog) scores after sixteen weeks. Results showed that there was no statistical difference in the mean ADAS-Cog scores for the Huperzine A 200 micrograms arm compared to placebo (p=0.81). However, the higher dose tested, 400 micrograms, showed cognitive enhancement on the ADAS-Cog versus placebo; the maximum cognitive improvement was observed at week eleven of treatment (p=0.001). Over sixteen weeks the Huperzine A 400 micrograms arm improved cognition compared to placebo (p=0.03) and there was a trend to cognitive improvement over placebo at week 16 (p=0.069). There was no statistical difference between placebo and either 200 or 400 micrograms of Huperzine A in any of the secondary endpoints, including clinical global impression of change (ADCS-CGIC) and the Neuropsychiatric Inventory (NPI). Treatment was safe and well tolerated, with an adverse event profile similar to placebo. Neuro-Hitech plans to move forward with the development of Huperzine A.
Penwest issued mixed results from a phase IIa trial of nalbuphine ER for the treatment of moderate chronic pain. This randomized, double-blind, placebo controlled study enrolled one hundred and thirty eight subjects with chronic pain secondary to osteoarthritis of the knee or hip. The subjects received the lowest dose of nalbuphine ER for week one, increased to a mid-dose level for week two, and increased to the highest dose studied for week three. The primary endpoint was the Sum of Pain Intensity Differences between baseline and day twenty one. Nalbuphine ER did not meet this endpoint, which was possibly due to patient dropouts in the first week of dosing. The drug did, however, achieve a number of the secondary endpoints compared to placebo, including statistical significance in the Global Assessment of Pain Control (p=0.006) and the Integrated Assessment of Pain Intensity and Rescue Medication Use (p=0.009). Nalbuphine ER was well tolerated, with no reports of drug related serious adverse events. Based on the results, a phase IIb trial is planned for later in 2008.
January 7, 2008
Schering Plough announced positive results from a clinical trial of asenapine for the treatment of schizophrenia. This trial enrolled four hundred and forty-eight adult subjects who received asenapine 5 mg twice daily, asenapine 10 mg twice daily, haloperidol 4 mg twice daily or placebo, for six weeks. The primary endpoint was the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to day forty-two. The PANSS score was significantly better for the asenapine 5 mg, 10 mg and haloperidol arms versus placebo (-21.3, - 19.4, -20.0 and -14.6, respectively). Statistical significance was reached in a key secondary endpoint, PANSS positive subscale score, in the asenapine 5 mg, 10 mg and haloperidol arms versus placebo (-7.5, -6.9 and -7.3 vs. -5.0, respectively). In addition, significant changes were seen in the PANSS negative subscale score for the asenapine 5 mg, 10 mg and haloperidol arms (-4.5, -4.3 and -4.2 vs. -3.0, respectively) and on the PANSS general psychopathology subscale score (-9.6, -8.5 and -8.6 vs. -6.8, respectively). Significantly more subjects in both asenapine 5 mg and 10 mg, and haloperidol demonstrated reductions in PANSS total score of greater than or equal to 30% versus placebo (55%, 49% and 43% versus 33%, respectively). Changes on the Clinical Global Impression-Severity of Illness (CGI-S) scale for asenapine 5 mg and 10 mg, and haloperidol were higher than for placebo (-1.2 , -1.1 and -1.2 vs. -0.8, respectively). Treatment was generally safe and well tolerated. An NDA is currently under review by the FDA.
Vanda presented positive results from a phase III trial of iloperidone for the treatment of schizophrenia. This randomized, double-blind, placebo-controlled, multi-center, four-week inpatient study enrolled six hundred four subjects. Following fixed-dose titration, the subjects were randomized to receive iloperidone at 24 mg/day, ziprasidone at 160 mg/day, or placebo. The subjects treated with iloperidone had significantly greater improvements in Positive and Negative Syndrome Scale-Total (PANSS-T) scores than those on placebo and had PANSS-T improvement comparable to ziprasidone. Iloperidone was also associated with a favorable profile on the Extrapyramidal Symptoms Rating Scale (ESRS) versus placebo. In addition, iloperidone had a similar akathisia profile to placebo, while ziprasidone was associated with a 26% rate of worsening of akathisia compared to placebo on the Barnes Akathisia Scale (BAS). An NDA is currently under review by the FDA.
Wyeth announced results from two phase III trials of Prisitq for the treatment of depression. These identical multicenter, randomized, double-blind, placebo-controlled, eight-week studies enrolled four hundred and eighty-three adult subjects outside of the United States and four hundred and forty-seven subjects in the United States. Subjects in both trials received Prisitq at fixed doses of 50 mg/day and 100 mg/day. For the 100 mg/day group, the dose was increased from 50 mg/day to 100 mg/day on the eighth day of the study. The 50 mg/day dose of desvenlafaxine was associated with a significant reduction in the symptoms of Major Depressive Disorder as measured by the Hamilton Depression Scale (HAM-D17) scores over eight weeks compared with placebo (ex-US: p=0.002, 50 mg = -13.2, placebo = -10.7; U.S.: p=0.018, 50 mg = -11.5, placebo = -9.5). While the 100 mg/day dose showed a statistically significant improvement in the international study versus placebo (p<0.001, 100 mg = -13.7), this dose did not statistically separate from placebo in the U.S. study (p=0.065, 100 mg = -11.0). An NDA is currently under review by the FDA.
November 5, 2007
BioLineRx released positive interim results from an ongoing phase IIa trial of BL-1020 for the treatment of schizophrenia. This open-label, six-week study enrolled subjects who were hospitalized for treatment resistant schizophrenia. Data are from the first twenty treated subjects. Efficacy was measured by the improvements on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) scores. BL-1020 reduced the PANSS total score by 26.1 points, from the baseline score of 85.6 to the Day forty-two score of 58.2 (p less than 0.001). The PANSS negative score was significantly improved by 7.1 points, from the baseline score of 20.5 to the Day forty-two score of 13.4 (p less than 0.001). In addition, CGI results showed that 92.35% of subjects improved by at least one category the end of the treatment period. Treatment was well tolerated, with all side effects minimal to mild in nature. Based on these positive results, BioLineRx plans to continue with the study as it was designed.
October 22, 2007
Forest Labs and Gedeon Richter announced positive preliminary results from a phase IIb trial of RGH-188 for the treatment of schizophrenia. This randomized, double-blind, three-arm placebo-controlled study enrolled 389 subjects with schizophrenia in the US. Following a 7 day wash-out period, the subjects were randomized to one of three treatment groups to receive placebo, RGH-188 low dose (1.5- 4.5 mg/day) or RGH-188 high dose (6-12 mg/day). All subjects started with one capsule and were titrated up to the maximum dose according to response and tolerability based on investigator's judgment. The double-blind phase lasted 6 weeks and was followed by a 4 week safety assessment phase. The primary endpoint was change from baseline to Week 6 on the Positive and Negative Syndrome Scale (PANSS). The RGH-188 low dose arm demonstrated a nominally statistically significant (not adjusted for multiple comparisons) therapeutic effect compared to placebo and a numerical improvement compared to placebo in the high dose arm that did not reach nominal statistical significance. Treatment was well tolerated with adverse events comparable between all arms. Based on the results the companied plan to move forward with the development of RGH-188.
September 24, 2007
Nabi issued positive nine-month data from a phase IIb trial of NicVAX for the treatment of nicotine addiction and relapse. This double-blind, placebo-controlled, dose-ranging trial enrolled 301 heavy smokers who received placebo or two doses of NicVAX (200 mcg and 400 mcg per injection) and two different regimens of administration. The primary endpoint was eight weeks of continuous abstinence between weeks 19-26. At nine months, the continuous abstinence rate in the NicVAX 400 mcg arm was 18% versus 4% for placebo (p=0.0047) and in the NicVAX 200 mcg arm was 14% versus 4% for placebo (p=0.027). The most effective schedule was determined to be five injections over six months and the most effective dose was determined to be 400 mcg. In addition, there was no compensatory smoking or increase in withdrawal symptoms. Treatment continued to be well tolerated over nine months, with a safety and tolerability profile comparable to placebo. Based on the results, Nabi plans to continue with the development of NicVAX.
TorreyPines reported positive results from a phase I trial of NGX267 for the treatment of cognitive impairment associated with schizophrenia (CIAS). This double-blind, placebo-controlled study enrolled 60 healthy males in Belgium. The subjects were placed in sequential dosing cohorts to receive a single, oral dose of either 10, 20, 30 or 35 mg of NGX267 once daily for four consecutive days. The primary endpoint of safety was achieved. Treatment was well tolerated at doses up to and including 30 mg. A secondary endpoint was to obtain quantitative measures of salivary flow, taken prior to and at multiple points post-dosing. Results showed increases in peak and total salivary flow for NGX267 arms in comparison to placebo. These effects increased with dose and maintained over the four day treatment period. These subject peak increases in salivary flow correlated with peak plasma levels of NGX267. Based on the results, TorreyPines plans to initiate a phase II dose-ranging trial in the first half of 2008.
September 10, 2007
Clinical Data reported positive results from a phase III trial of Vilazodone for the treatment of depression. This randomized, double-blind, placebo-controlled study enrolled 410 adult subjects with major depressive disorder. The trial achieved the primary endpoint of mean change from baseline in the Montgomery-Asberg Depression Rating Scale total score compared to placebo (p=.001). A key secondary endpoint, mean change from baseline on the Hamilton Depression Rating Scale versus placebo, was also reached (p=.022). Based on the results Clinical Data plans to meet with the FDA to discuss any additional NDA filing requirements.
Eli Lilly issued positive results from a phase II trial of LY2140023 for the treatment of psychosis and schizophrenia. This randomized, double-blind, placebo-controlled clinical trial enrolled 196 subjects with schizophrenia. Following a period of gradual removal of pre-trial antipsychotic medications, the subjects were assigned to LY2140023 (40 mg twice daily), olanzapine (15 mg daily) or placebo for four weeks. The trial was designed to determine the superiority of LY2140023 versus placebo; olanzapine was used as an active control. In the 118 subjects who completed treatment the primary endpoint was achieved. A statistically significant improvement in PANSS (Positive and Negative Syndrome Scale) total score over placebo was seen in both the LY2140023 and olanzapine groups (-20.8, P < 0.001; -26.7, P < 0.001; respectively). After four weeks of treatment, both the LY2140023 group and the olanzapine group demonstrated significantly greater response rates compared to the placebo group (32.0%, P < 0.001; 41.2%, P < 0.001 and 3.2%, respectively). In addition, a mean 0.51-kg weight reduction from baseline was observed in the LY2140023 arm. Treatment with LY2140023 was shown to be safe and well tolerated, with all reported adverse events mild to moderate in nature. Based on the results Eli Lilly plans to continue with the development of LY2140023.
June 4, 2007
Novartis and Vanda reported positive results from a phase III trial of iloperidone for the treatment of akathisia in schizophrenia. This randomized, double-blind, placebo controlled trial enrolled 706 subjects who were placed into one of four treatment groups: iloperidone 12.16 mg/d or 20.24 mg/d, risperidone 6.8 mg/d or placebo for 6 weeks. Changes in akathisia were measured weekly by the Barnes Akathisia Scale (BAS) and the Extrapyramidal Symptom Rating Scale (ESRS) from baseline to the six-week end point. Both iloperodone groups had fewer subjects whose total akathisia score worsened (12%, p=0.04; 8%, p=0.004, respectively), compared to placebo and risperidone (20%, p=1.00). In addition, anticholinergic medication was needed for extrapyramidal symptoms in 5% and 7% of the two iloperidone dose groups respectively, compared with 22% for risperidone and 7% for placebo. Based on the results, the companies plan to file a NDA in Q4 of 2007.
April 2, 2007
Alexza reported positive results from a phase IIa trial of AZ-004for the treatment of acute agitation in schizophrenia. This randomized,double-blind, placebo-controlled trial enrolled 120 subjects who received asingle dose of AZ-004 (5 mg or 10 mg) or placebo. The primary endpoint was thechange in the PANSS (Positive and Negative Symptom Scale) Excited Component(PEC) score at the 2-hour post-dose time point. The primary endpoint was met inthe 10 mg dose group, with statistically significant results compared toplacebo (p=0.0005). Statistical significance was also seen in the 10 mg groupin terms of rapid onset of effect and on the Behavioral Activity Rating Scale(BARS). The 5 mg dose of AZ-004 did not reach statistical significance. Basedon the results, Alexza plans to move forward with the development of AZ-004.
March 26, 2007
AstraZeneca issued positive results from two phase III trials of Seroquel SR for the treatment of schizophrenia. The first was a randomized, double-blind trial and enrolled 588 subjects who received Seroquel SR (400, 600 or 800 mg/day) or placebo for six weeks. By the end of treatment, significant improvements in the PANNS scores from baseline were observed for all treatment groups. Reductions of 24.8 (p=0.03), 30.9 (p>0.001), and 31.3 (p>0.001) points were seen with 400, 600, and 800 mg doses, respectively, compared with a reduction of 18.8 points for placebo. The second trial was a double-blind placebo controlled study and enrolled 197 subjects who received Seroquel SR at a mean dose of 669 mg/day, or placebo. This trial was designed to evaluate the time to first psychiatric relapse. When compared to placebo, Seroquel SR showed a reduced risk of relapse of 87% (p>0.0001) as well as a longer time to relapse. AstraZeneca filed a NDA with the FDA for Seroquel SR in July of 2006.
Corcept released negative results from a phase III trial of Corlux for the treatment of major depressive disorder. This randomized, double-blind, placebo-controlled trial enrolled 443 subjects in the US and Europe. Subjects received Corlux (300 mg, 600 mg and 1200 mg) or placebo, once daily for seven days. Subjects were off any antidepressant/antipsychotic medication for at least one week before the treatment period. Concomitant antidepressant therapy started on day 1 and lasted through day 56. The primary endpoint was responder analysis, the proportion of subjects with at least a 50% improvement in the Brief Psychiatric Rating Scale Positive Symptom Subscale (BPRS PSS) at day 7 and day 56. Statistical significance was not reached in the primary endpoint. However there was a significant correlation between plasma levels and clinical outcome achieved during treatment. Based on the combination of this and two other phase III results, Corcept plans to initiate a new phase III trial later in 2007.
February 19, 2007
BioLine issued positive results from a phase I trial of BL-1020 for the treatment of schizophrenia. This randomized, double blind, placebo-controlled, dose-escalation trial enrolled 48 healthy male subjects who were placed into 6 dose cohorts at a ratio of 6:2 (BL-1020:placebo). In each cohort, subjects received a single dose of BL-1020 or matching placebo (4, 8, 16, 24, 32 or 40 mg). Treatment was safe and well tolerated at single doses up to 40 mg, with no drug related adverse events. The pharmacokinetic profiles of BL-1020 were linear across the range of doses studied, as assessed by the dose-dependent elevation of serum prolactin levels. In addition, BL-1020 showed evidence of protection against extrapyramidal symptoms and enhanced the neurotransmitter gamma aminobutyric acid (GABA). Based on the results, BioLine plans to initiate phase II trials later in 2007.
September 25, 2006
Johnson & Johnson and Jenssen released positive results from a phase III trial of paliperidone ER for the treatment of schizophrenia- related insomnia. This multi-center, double-blind, randomized, placebo- controlled trial enrolled 36 subjects who received 9 mg of paliperidone ER or placebo, every morning for two weeks. The most commonly reported adverse effects were mild and included involuntary movements and headaches. Efficacy data revealed that those subjects in the treatment arm achieved a mean reduction of over half an hour in the time required to first fall asleep and a reduction of more than 40 minutes in the time required to remain asleep, compared to placebo. Treated subjects also had enhanced sleep duration and continuity, with the treated subjects increasing their time in stage two sleep by 51 minutes. In addition, time spent in rapid eye movement (REM) increased by 18 minutes for the treated arm versus placebo. Johnson & Johnson submitted a NDA to the FDA for paliperidone ER in the treatment of schizophrenia in November of 2005. The drug is currently in phase III trials for the treatment of bipolar disorder.
July 17, 2006
Johnson & Johnson issued positive results of a phase III trial of paliperidone ER, for the treatment of schizophrenia, at the Biennial Congress of the Collegium Internationale Neuro-Psychopharmacologicum (CINP). This randomized, double-blind, placebo-controlled, parallel-group study enrolled 207 patients, who received flexible daily doses of the drug (3 mg-15 mg) or placebo following a 6 week disease stabilization phase. The drug demonstrated significant efficacy in preventing disease recurrence, with 22% of subjects experiencing symptom recurrence for the drug, vs. 52% for placebo. Additional measures of disease severity also supported the drug’s efficacy, with superior performance vs. placebo on PANSS total score and factor scores, PSP, CGI-S, SQLS, and Sleep VAS diagnostics.
April 24, 2006
Acadia issued positive results of a proof-of-concept trial of ACP-103, for the treatment of sleep disturbances related to Parkinson's disease and schizophrenia. This double-blind, placebo-controlled study enrolled 45 healthy adult volunteers (age 40-64), who were randomized to receive one of four doses of the drug (1 mg, 2.5 mg, 5 mg, or 20 mg) or placebo every morning for 14 consecutive days. Trial data indicated that the two higher doses of the drug significantly increased slow wave (Stage 3/4) sleep from baseline compared to placebo, both at day 1 (5 mg: +37.3 min, 20 mg: +46.0 min, vs. placebo: -11.2 min; p<0.001) and at day 13 (+41.9 min, +39.0 min, respectively, vs. -3.1 min; p<0.001). Increases in total slow-wave sleep time were seen to be dose dependent across all groups. Secondary measures also yielded positive efficacy trends, including decreases in number of awakenings (p=0.04) and time awake after sleep onset (p=0.09).
January 2, 2006
Durect Corporation has reported positive results of a phase II trial of their TRANSDUR sufentanil patch, for the treatment of chronic pain. Preliminary data met all primary endpoints, including pharmacokinetic measures of dose-proportional absorption rates and steady state plasma levels, and a positive overall safety and tolerability profile. Efficacy data yielded comparable levels of pain for the drug and treatment with Duragesic, an approved sufentanil patch. This open-label study enrolled 13 patients across 2 sites (1 in the US, 1 in Europe), who were transitioned from approved treatment with Duragesic to TRANSDUR sufentanil for 4 weeks.
Saegis Pharmaceuticals issued positive results of a phase IIa trial of SGS518, for the treatment of cognitive impairment associated with schizophrenia (CIAS), at the American College of Neuropsychopharmacology Annual Meeting. Trial data indicated a dose-proportional pharmacokinetic profile, with steady-state plasma concentrations reached within 3 days. No dose-limiting toxicities or serious toxicities were observed. Preliminary evidence of efficacy was also noted, with statistically significant improvements vs. baseline in Brief Assessment of Cognition in Schizophrenia score, compared to no improvement for placebo. This placebo-controlled, blinded study enrolled 20 schizophrenic patients at the Claghorn-Lesem Clinic in Houston. Subjects were randomized to one of two dose-escalating cohorts (60 mg/180mg or 120 mg/240 mg; 8 active:2 placebo) for 14 days.
April 18, 2005
Neuro3d has announced positive results of a pair of phase II trial of their investigational antipsychotic ocaperidone, for the treatment of schizophrenia. Data from both studies yielded strong evidence of efficacy, with significant improvement in all primary efficacy measures, including both positive (e.g. hallucinations) and negative (e.g. social withdrawal, emotional flatness) symptom severity scores on the PANSS, BPRS and CGI diagnostic scales, vs. placebo. The drug also demonstrated non-inferiority of efficacy vs. an approved antipsychotic, and significant relative superiority in reducing drug-induced weight gain. The first trial, a double-blind, placebo-controlled safety and efficacy study, randomized 127 patients to receive dose ranging regimens of ocaperidone (0.1 mg-0.6 mg) or placebo daily for 8 weeks. The second was an active-controlled approved-therapy comparison study which enrolled 105 subjects, who received ocaperidone or an approved atypical antipsychotic for the treatment daily for 12 weeks. The company announced that these data would form the basis of phase III trials in the near future.
April 4, 2005
Saegis Pharmaceuticals reported positive results from a phase I trial investigating SGS518, a selective antagonist of the 5-HT6 serotonin receptor for the treatment of Cognitive Impairment Associated with Schizophrenia (CIAS). The drug is thought to enhance brain chemical transmission. Clinical results found the drug to be safe and well tolerated. The placebo-controlled, blinded study enrolled healthy subjects who were dosed in two cohorts: a single-dose, dose-ranging arm, followed by a multi-dose arm. The study’s primary objective was to evaluate the safety, tolerability and pharmacokinetics of SGS518. Saegis is developing SGS518 in partnership with Eli Lilly.
February 14, 2005
Axonyx announced top-line results of their first phase III trial of phenserine, their acetylcholinesterase inhibitor under investigation for the treatment of mild-to-moderate Alzheimer’s disease (AD). Trial data indicated that the neither trial dose of the drug met the primary endpoint, improvement in score on the ADAS-cog and CIBIC diagnostic scales, vs. placebo after 26 weeks of treatment. Non-significant trends towards improvement were noted in both metrics at both dose regimens, and no serious safety or tolerability concerns were raised. This double-blind, placebo-controlled study enrolled 384 subjects across 16 sites in Spain, the United Kingdom, Croatia, and Austria. Subjects were randomized to receive one of two doses of phenserine (10mg or 15mg) or placebo twice daily for 6 months. Axonyx announced that the planned interim analysis of their ongoing phase II b trials of the drug, investigating phenserine’s ability to lower levels of beta-amyloid precursor protein and beta-amyloid in the plasma and cerebrospinal fluid (CSF), would not be affected by these results.
Cephalon has reported positive combined results from four phase III trials of Nuvigil (armodafinil) for the treatment of excessive sleepiness associated with narcolepsy (1 study), shift work sleep disorder (1 study) or obstructive sleep apnea/hypopnea syndrome (2 studies). Compiled data demonstrated significant efficacy in improving measures of objective sleep latency, including the Maintenance of Wakefulness Test and the Multiple Sleep Latency Test, and in the physician rating of Clinical Global Impression-Change, vs. placebo (p<0.05). The drug was also shown to promote wakefulness late in the day when administered in the morning, confirming a long duration of action. All 4 trials were 12-week, double-blind, randomized, placebo-controlled studies, which enrolled a combined total of roughly 1,000 patients. Subjects received one of two doses of the drug (150 or 250 mg) or placebo once daily. Cephalon announced that these results were in line with their intention to submit and NDA for the drug before the end of Q1 2005.
Repligen announced preliminary results of a phase II trial of secretin, for the treatment of refractory schizophrenia. Data from the study yielded no significant improvements in symptom severity scores on either the Clinical Global Impression (CGI) or the Positive And Negative Syndrome Scale (PANSS), which were assessed at baseline and 6 times during the study. Responders on the CGI scale were noted in both the low dose (n=3, 20% response rate) and high dose (n=4, 29% response rate) secretin group and in the placebo group (n=2, 13% response rate), but the difference between these rates was also non-significant, possibly due to the small cohort size. A non-significant trend towards improvement was seen in a sub-section analysis of the PANSS dysphoric mood scale (anxiety, tension, etc.) in the secretin group (p=0.06), and several clinical investigators were reported to have noted transient changes in the social interaction at the time of the treatment, though these responses were not quantified. This double-blind trial enrolled 44 subjects, who received one of two doses of secretin (2 CU/kg, n=15; or 5 CU/kg, n=14) or placebo (n=15) in 4 intravenous doses over 2 weeks. The company announced that they were preparing a follow-up study to statistically measure the transient changes in mood noted by investigators.
December 15, 2003
Janssen Pharmaceuticals reported positive results from a phase IV trial investigating Risperdal Consta, a long-acting formulation for the treatment of schizophrenia. Results showed that 49% of subjects taking Risperdal Consta experienced significant clinical improvement. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS). Data showed that PANSS scores improved across all doses, with greater improvements in the 25 and 50 mg groups. The most common side effects were anxiety, insomnia, psychosis and depression. The 12-month, open-label, multi-center trial enrolled 615 symptomatically stable subjects with a diagnosis of schizophrenia, conducted in Europe and Canada.
April 7, 2003
Eli Lilly reported positive results from a phase IV trial investigating Zyprexa (olanzapine) versus Geodon (ziprasidone) for the treatment of schizophrenia. Results showed that subjects treated with Zyprexa achieved significantly better improvement in schizophrenic symptoms, including delusions and hallucinations. Data also showed that significantly more Zyprexa subjects completed the study compared to Geodon subjects (59.6% vs. 42.4%). In addition, Zyprexa subjects were significantly more likely to maintain their response throughout the 28 week study than subjects taking Geodon (81.6% vs. 62.8%). Subjects receiving Geodon reported some adverse events more frequently than those receiving Zyprexa including aggravated psychosis (4.4 % vs. 1.4 %), insomnia (22.1 % vs. 6.9 %) and vomiting (9.2 % vs. 4.0 %). The study enrolled 548 subjects with DSM-IV-defined schizophrenia.
October 21, 2002
Positive Phase IV trial results were reported for Seroquel, a drug designed by AstraZeneca for the treatment of schizophrenia. Seroquel, which was previously approved in 1997, was investigated further as an alternative treatment for patients on other antipsychotic medications. This was a 12-week, international, multi-center, open-label study and was noncomparative. The trial examined the effects of switching to Seroquel in subjects who showed an inadequate response to previous antipsychotic treatment or who experienced severe side effects with those treatments. Results suggested that patients might benefit from switching to Seroquel if they experience an undesirable response from another antipsychotic treatment.