February 22, 2016
Neurocrine Biosciences issued results of the second of two replicate pivotal phase III clinical trials evaluating Elagolix in premenopausal women who suffer pain from endometriosis. The first phase III trial (M12-665) was a 24-week, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of Elagolix in 872 women, age 18 to 49, with moderate-to-severe endometriosis-associated pain. It was conducted at approximately 160 sites in the U.S., Puerto Rico and Canada. The second phase III trial (M12-671) employed the same design as the first phase III pivotal trial, but was multinational and included 815 women with moderate-to-severe endometriosis-associated pain across 226 sites in 13 countries. Trial results show that after six months of continuous treatment, both doses of Elagolix (150mg once daily and 200mg twice daily) met the study’s co-primary endpoints. Elagolix reduced scores of menstrual pain (dysmenorrhea, DYS) and non-menstrual pelvic pain (NMPP) associated with endometriosis, at month three and month six, as measured by the Daily Assessment of Endometriosis Pain scale. The safety profile of Elagolix in this study was consistent with observations from the first phase III pivotal study and prior Elagolix studies. Among the most common treatment-emergent adverse events (TEAEs) were hot flush, headache and nausea. As anticipated by the mechanism of action, some AEs, such as hot flush, other hypoestrogenic TEAEs and changes in bone mineral density (BMD) were dose-dependent. Overall discontinuation rates were similar across treatment groups (25.3%, 21.2% and 19.7% for placebo, 150mg once daily and 200mg twice daily, respectively); discontinuations specifically due to TEAEs were 6.1%, 4.4% and 10% for placebo, 150mg once daily and 200mg twice daily, respectively. AbbVie will complete the clinical database in anticipation of a New Drug Application submission for endometriosis in 2017.
November 23, 2015
AcelRx Pharmaceuticals has released results in a phase III study of Zalviso
(sufentanil sublingual tablet system 15mcg) for the treatment of faster onset of pain relief in obese (BMI 30kg/m2) post-surgical patients. Patients who self-administered Zalviso experienced statistically significantly improved pain relief when compared to self-administered IV morphine as measured by pain intensity difference to baseline (PID). Significant differences in PID were observed as early as 45 minutes after the first dose (p<0.05), a trend that continued until six hours after the initial dose (p<0.001), after which time PID scores equilibrated between the two groups. Results of the subgroup analysis presented by AcelRx also show that obese patients who administered Zalviso experienced statistically fewer adverse events than did those receiving intravenous patient-controlled analgesia morphine. While overall adverse event rates were comparable, incidence rates of anemia, leukocytosis (increase in white blood cells), vomiting, hypoalbuminemia (decrease in albumin levels), hyponatremia (decrease in sodium levels), urinary retention and pruritus (itching) were all significantly lower in the Zalviso arm compared to the morphine arm (p≤0.05).
November 9, 2015
Elite Pharmaceuticals has reported
results of a phase III trial of opioid abuse-deterrent
candidate ELI-200 for the treatment
of moderate to severe pain. It was a
multicenter, randomized, multiple-dose,
double blind, placebo-controlled and parallel
group study. The trial randomized 163
patients. The pivotal trial met its primary
endpoint (p=0.001), demonstrating statistical
significance that the product provided
pain relief following surgery in the treatment
group using ELI-200 compared to the
placebo group. Secondary endpoint results
were consistent with primary findings and
included safety measures. There were no
serious adverse events or deaths related to
ELI-200 reported during the conduct of the
trial. Elite intends to submit an NDA to the
FDA for abuse-deterrent ELI-200 by year-end.
September 14, 2015
Collegium Pharmaceutical reported
results of a phase III trial of Xtampza ER
(oxycodone extended-release capsules)
for moderate-to-severe chronic low back pain.
The multicenter, randomized, double-blind,
enriched enrollment, randomized withdrawal,
placebo-controlled study met its primary
endpoint, which showed a statistically significant
difference in average pain intensity
from Randomization Baseline to week 12
between the Xtampza ER and placebo
groups (p<0.0001). All sensitivity analyses of
the primary endpoint also were statistically
significant. Xtampza ER had an adverse event
profile consistent with other opioids, was
well-tolerated, and no new safety concerns
were identified. The company is seeking FDA
approval for Xtampza ER.
Vernalis released results of a phase II
study of V158866 for neuropathic pain as a
result of spinal cord injury. In the randomized,
double-blind, placebo-controlled, two-period
cross-over study, although dosing of V158866
resulted in elevated endocannabinoid levels,
on an intent-to-treat basis the study failed
to meet its pain reduction primary endpoint.
Treatment with V158866 did show a trend
toward efficacy on a per protocol basis
(p=0.054) and was generally well-tolerated.
July 13, 2015
AcelRx Pharmaceuticals reported
results of a phase III study of Zalviso for the
treatment of moderate-to-severe postoperative
pain in patients following major
joint replacement surgery. The study met
its primary endpoint, demonstrating that
Zalviso was significantly better at managing
pain over 48 hours as measured by Summed
Pain Intensity Difference to Baseline (SPID-
48), than placebo (p<0.001). Zalviso-treated
patients had pain relief scores superior to
placebo-treated patients within 45 minutes
of study initiation. Reports of treatment-related
adverse events were similar between
the two groups, with the exception of
nausea and itching, which were higher in
the Zalviso group. It was noted that fewer
Zalviso patients dropped out of the study
due to inadequate analgesia compared to
placebo (14% v. 48%; p<0.001) and used approximately
half as much rescue morphine
over the duration of the trial (2.3 doses v. 4
doses). As a secondary endpoint, a validated
ease-of-care questionnaire was administered
to patients and healthcare providers.
Both groups gave Zalviso a total overall
rating above four on a scale of zero to five.
Zalviso is currently under review by the FDA.
January 26, 2015
Mesoblast has issued positive results of
a phase II program of MPC-06-ID for the
treatment of chronic low back pain due to
degenerative disc disease. In the randomized,
placebo-controlled trial of 100 patients,
a single injection of Mesoblast’s allogeneic
investigational mesenchymal precursor
cell (MPC) product, MPC-06-ID, was welltolerated.
A single injection of 6 million MPCs
induced substantial and sustained pain relief
over 24 months. At 12 and 24 months, 46%
and 48% of MPC-06-ID-treated patients
achieved minimal or no residual pain (VAS
less than or equal to 20) compared with
13% and 13% of saline treated patients,
p=0.042 and 0.093, respectively. In patients
who received a single injection of six or 18
million MPCs, 44% and 42%, respectively,
achieved the target composite endpoint of
treatment success at both six and 12 months
(50% reduction in pain, 15-point improvement
in function and no further treatment
intervention), compared with 13% of saline
controls (p=0.006 and p=020). In patients
who received six million MPCs and achieved
the target composite endpoint of treatment
success at both six and 12 months, 86%
(11 of 13) maintained treatment success
at 24 months (32% v. 11% saline controls,
p=0.001). The phase III program for this
indication has been initiated.
August 18, 2014
Collegium Pharmaceutical issued results
of a phase III study of Oxycodone DETERx
for the treatment of patients with moderate-to-
severe chronic low back pain. The phase
III study was a multicenter, double-blind,
placebo-controlled study of Oxycodone DETERx
versus placebo in opioid-experienced and
opioid-naïve subjects with moderate-to-severe
chronic low back pain. Patients who achieved a
stable and effective dose of Oxycodone DETERx
during the open-label titration phase were
randomized (n=389) into the 12-week, double-blind
maintenance phase, in which they either
were maintained on their current dose regimen
of Oxycodone DETERx or were tapered to
placebo. The primary efficacy endpoint of the
study was the change in average pain intensity
from baseline to week 12; pain was measured
using an 11-point pain intensity numerical
rating scale (PI-NRS). The study met the primary
efficacy endpoint, showing patients with
chronic low back pain treated with Oxycodone
DETERx experienced a statistically significant
reduction in pain compared with placebo (p<
0.0001). The company is positioned to file an
NDA with the FDA for Oxycodone DETERx by
the end of 2014.
June 16, 2014
OptiNose reported results of a trial
comparing AVP-825 to sumatriptan
tablets for migraine pain during the first
30 minutes after treatment. The multi-center,
randomized, double-blind, double-dummy
crossover, multi-attack study enrolled
275 migraine sufferers and treated a
total of 1,531 acute migraines with either
the only dose of AVP-825 (22mg) plus a
placebo tablet or with a placebo delivered
with an OptiNose Bi-Directional Breath
Powered device, plus a high dose (100mg)
sumatriptan tablet. The trial showed with
AVP-825 treatment, early reduction in pain
was achieved in more headaches than
with oral sumatriptan. The primary endpoint
showed during the first 30 minutes,
headache pain intensity was statistically
significantly lower with AVP-825 treatment
(p<0.0001). In addition, the trial achieved
statistical significance for relevant secondary
measures of Pain Relief and Pain
Freedom as early as 15 minutes and at all of
the following early time points measured
(30, 45, 60, 90) before 120 minutes. Less
than 2% of subjects experienced an adverse
event leading to treatment discontinuation
with use of either medication and there
were no serious adverse events. An NDA for
AVP-825 was filed earlier this year, and the
Prescription Drug User Fee Act (PDUFA) V
goal date is Nov. 26.
March 10, 2014
Sinovac Biotech reported results of phase
III trials of Enterovirus 71 (EV71)vaccine
for the treatment of foot and mouth disease
(HFMD), or herpangina. The phase III clinical
trial on 10,077 healthy infants and young
children in China (six to 35 months of age)
was a randomized, double-blind, placebocontrolled,
multicenter trial method. The subjects were randomly assigned in a 1:1 ratio
to receive two intramuscular doses of either
Sinovac’s EV71 vaccine or placebo, 28 days
apart for 12 months. Clinical results showed
the efficacy of the vaccine was 94.8% among
infants and young children and an anti-EV71
neutralizing antibody titer of 1:16 was associated
with protection against EV71 associated
HFMD or herpangina. Sinovac’s vaccine also
demonstrated a 100% efficacy rate against
EV71-associated hospitalization and against
HFMD with neurologic complications, the
main cause of fatalities. Regulatory approval
November 11, 2013
Cara Therapeutics issued results of a phase II trial of I.V. CR845 for the treatment of acute pain. The randomized, doubleblind, placebo-controlled trial of I.V. CR845 (0.005mg/kg/dose) enrolled 51 women and men undergoing a primary unilateral first-metatarsal bunionectomy surgery in the U.S. Repeat dosing of I.V. CR845 over 48 hours post-surgery provided statistically greater pain reduction than placebo at both the 24- and 48-hour time points following initiation of treatment, as assessed using the FDA recommended endpoint, the Summed Pain Intensity Difference (SPID). The I.V. CR845 treatment arm met the trial’s primary endpoint of a statistically significant reduction in pain intensity, as measured by the SPID score, over the initial 24-hour time period (SPID0-24; p<0.05) compared to placebo. The I.V. CR845 treatment arm also met the secondary endpoint of a statistical reduction in pain intensity over the entire 48-hour dosing period (SPID0-48; p<0.025). In addition, I.V. CR845 treatment resulted in a statistically significant reduction in the incidence of opioid-related adverse events of nausea and vomiting (by 60% and 80%, respectively; p<0.05) compared to placebo during the 48-hour treatment period.
November 4, 2013
AstraZeneca released results of a phase III trial of naloxegol for the treatment of non-cancer pain and opioid-induced constipation (OIC). The study enrolled 844 patients, provided a once-daily 25mg dose of naloxegol and lasted 52 weeks, comparing naloxegol (n=534) to usual care (n=270). Usual care was defined as the investigator’s choice of an existing laxative treatment regimen for OIC. Most naloxegol-emergent gastrointestinal adverse events (AEs) occurred early in treatment and were transient with nine patients (1.6%) discontinuing naloxegol due to abdominal pain. Most common treatment-emergent AEs occurring more often with naloxegol v. usual care were abdominal pain (17.8% v. 3.3%), diarrhoea (12.9% v. 5.9%), nausea (9.4% v. 4.1%), headache (9.0% v. 4.8%) and flatulence (6.9% v. 1.1%). Pain scores and opioid doses were comparable between treatment groups and were stable throughout the study. There were two opioid withdrawal AEs reported in patients taking naloxegol (both were deemed unrelated to treatment with naloxegol).
August 12, 2013
Pharmanest released results of a phase II study of SHACT for the treatment of pain in connection with intrauterine device insertion. SHACT is a product based on a formulation of lidocaine, an anesthetic, and a proprietary application device developed to simplify topical application in the cervix and uterus. The randomized, double-blind trial involving 218 women between ages 18 and 45 showed women receiving SHACT during IUD insertion experienced a more than 30% reduction in pain, measured on a visual analogue scale, compared to patients who received placebo. This effect was statistically significant (p < 0.0001). Patients who received SHACT also experienced less discomfort (p < 0.05) than women who received placebo. Women who received SHACT reported similar adverse events, in terms of type and frequency, as women who received placebo treatment.
July 8, 2013
Nektar Therapeutics issued results from a randomized, double-blind, placebo- and active-controlled, five-way crossover trial of NKTR-181 for the treatment of moderate-to-severe chronic pain. The trial compared three doses of NKTR-181 oral solution (100mg, 200mg, and 400mg) to the effects of 40mg of oxycodone oral solution and placebo. Participants were healthy adults (N=42) who were not currently physically opioid-dependent but had used opioids to attain non-medical effects on at least 10 occasions during the past year and at least once in the 12 weeks before the study. All oral doses of NKTR-181 scored similar to placebo in a Drug Effects Questionnaire (DEQ) assessing the treatment’s effect on how “high” the subject felt (on a scale of 0 to 100). Maximum mean DEQ scores were 14, 14 and 23 for 100mg, 200mg tablet and 400mg, respectively, with p-values < 0.0001 as compared to oxycodone. Placebo achieved a maximum mean score of nine. NKTR-181 is currently being evaluated in phase II development as a twice-daily oral tablet.
April 22, 2013
Iroko Pharmaceuticals issued results from a phase III trial of lower dose submicron indomethacin for the treatment of post surgical acute pain. This multi-center, double-blind, placebo- and active- controlled study enrolled 462 patients with moderate to severe pain following bunionectomy surgery. Subjects received 40mg submicron indomethacin three times daily or twice daily, 20mg submicron indomethacin three times daily, 400mg loading dose of celecoxib plus 200mg twice daily, or placebo. Statistically significant overall decreases in pain intensity were demonstrated for 40mg submicron indomethacin three times daily (509.6, p<0.001), 40mg submicron indomethacin twice daily (328.0, p=0.046), 20mg submicron indomethacin three times daily (380.5, p=0.017), compared with placebo (67.8). Although there was some evidence of analgesia for celecoxib (279.4), it did not achieve statistical significance compared with placebo. Some evidence of pain control was observed as early as 30 minutes in the 40mg submicron indomethacin three times daily (2.9) and 40mg submicron indomethacin twice daily (2.6) groups compared with placebo (0.2). The drug was well tolerated. The most frequent adverse events were similar across treatment groups and included nausea, post-procedural edema, dizziness and headache.
March 18, 2013
AcelRx Pharmaceuticals released results from a phase III trial of sublingual Sufentanil NanoTab PCA System for the treatment of acute post-operative pain. This randomized, double-blind, placebo-controlled study enrolled 178 patients with acute post-operative pain following major open abdominal surgery. Subjects received either sufentanil or placebo for 48 to 72 hours, delivered as needed using the NanoTab PCA System. Results demonstrated patients receiving sufentanil NanoTabs realized a significantly greater SPID-48 (Summed Pain Intensity Difference over 48 hours), 105.6, during the study period than placebo-treated patients, 55.6, (p=0.001). Secondary endpoint data also showed 24 hours and 72 hours after first dose, SPID was significantly greater in the sufentanil-treated patients than in the placebo-treated patients (p<0.001 and p=0.004 respectively). The drug was well tolerated. The most frequent adverse events were comparable between treatment groups and included nausea, fever, vomiting, itching, oxygen saturation decrease and hypertension. Currently, AcelRx Pharmacuticals’ second phase III, double-blind, placebo-controlled study of the Sufentanil NanoTab PCA System is underway. Based on favorable results, AcelRx plans to file a New Drug Application in the third quarter of 2013.
March 11, 2013
AcelRx issued results from a phase III trial of sublingual Sufentanil NanoTab PCA (patient-controlled analgesia) for the treatment of acute post-operative pain. This randomized, double-blind, placebo-controlled trial enrolled 178 adults who were treated for post-operative pain immediately following major abdominal surgery. The subjects were treated for a minimum of 48 hours and up to 72 hours with either sufentanil or placebo. Both treatments were delivered by the each subject, as needed, using the NanoTab System with a 20-minute lock-out period. Both groups could receive up to 2mg morphine intravenously per hour as a rescue medication. The primary endpoint evaluated pain intensity over the 48-hour study period compared to baseline, or Summed Pain Intensity Difference (SPID-48). The sufentanil NanoTabs arm reached a significantly greater SPID-48 during the study period than placebo arm (p=0.001). In addition, 24 hours and 72 hours after first dose, SPID was significantly greater in the sufentanil-treated arm than in the placebo-treated arm (p<0.001 and p=0.004, respectively).
November 28, 2012
AcelRx Pharmaceuticals reported results from a phase III trial of sublingual ARX-01 (Sufentanil NanoTab PCA System) for the treatment of post-operative pain. This randomized, open-label, parallel-group study enrolled 359 patients with acute post-operative pain immediately following major abdominal or orthopedic surgery. Subjects received (15mcg/dose) of the NanoTab System or 1mg/dose of PCA with morphine for a minimum of 48 hours and a maximum of 72 hours. Data demonstrated that the NanoTab System was non-inferior (p<0.001) to IV PCA morphine for the primary endpoint of PGA over the 48-hour study period as determined by the combined percentage of patients with PGA ratings of “good” or “excellent” (78.5% versus 66.1% respectively). In this study, the NanoTab System was found to be statistically superior to IV PCA morphine for the PGA endpoint (p=0.009). This statistically superior PGA was also seen at the 24-hour and 72-hour time points. Additionally, the percentage of patients rating the NanoTab System as “excellent” was higher than those rating IV PCA morphine as excellent (42.9% versus 30.6%, p=0.016). Similar percentages of NanoTab System-treated and IV PCA morphine-treated patients dropped out of the study prematurely due to lack of efficacy (7.3% versus 8.3% respectively) or due to an adverse event (7.9% versus 11.1% respectively). The NanoTab System was well tolerated. AcelRx Pharmaceutical will complete two other phase III trials of the NanoTab System before submitting an NDA to the FDA.
September 10, 2012
NeurogesX reported results from a phase II trial of NGX-1998 for the treatment of postherpetic neuralgia (PHN). This multicenter, placebo-controlled, double-blind study enrolled patients who had experienced pain for at least six months following healing of a herpes zoster lesion and had a Mean Numeric Pain Rating Scale (NPRS) score between 4 and 9, inclusive. Subjects were divided into three arms: NGX-1998 capsaicin 20% solution, NGX-1998 capsaicin 10% solution or placebo. Results indicated that with a single, five-minute treatment with NGX-1998, subjects experienced pain relief for as long as three months. NGX-1998 showed a greater magnitude of response on the pain intensity scale correlating with the concentration of the formulation: 20%>10%>placebo. In addition, it was determined that no topical anesthetic pre-treatment was required for treatment with NGX-1998. The drug was well tolerated. Subjects experienced similar adverse events as those in the placebo arm. Based on these data, NeurogesX plans to enable a phase III trial in neuropathic pain.
August 20, 2012
Eli Lilly released results from a phase III trial of Forteo (teriparatide injection) compared to risedronate for the treatment of back pain. This randomized, double-blind, double-dummy, active-controlled study enrolled 710 postmenopausal women with at least one moderate or severe vertebral fracture thought to be the cause of back pain. Subjects received either Forteo 20mg/day or risedronate 35mg/week for 18 months. From baseline to six months, data showed no difference between Forteo (59.2%) and risedronate (57.4%) on the primary endpoint of at least a 30% reduction in worst back pain, as assessed by a numeric rating scale in each treatment group. However, there were statistically significant differences in favor of Forteo in some exploratory measures, including greater increases in bone mineral density (BMD) and fewer patients with new vertebral fractures. Furthermore, significantly fewer patients treated with Forteo experienced a worsening of average back pain between six and 18 months (23.6% versus 30.6% of risedronate-treated patients; p=0.04). Forteo was well tolerated. The most frequent adverse events were similar between both treatment groups. Eli Lilly did not note its plans for Forteo.
August 13, 2012
Array BioPharma released results from a phase II trial of ARRY-797 for the treatment of moderate to severe chronic knee pain despite the use of non-steroidal anti-inflammatory drugs (NSAIDs). This randomized, placebo-controlled and active controlled study enrolled 157 patients with osteoarthritis. Subjects were divided (1:1:1) to receive ARRY-797, placebo or oxycodone ER while continuing their use of NSAIDs for four weeks. Data showed a statistically significant reduction in pain compared to placebo, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. Patients receiving ARRY-797 experienced a mean reduction in the WOMAC pain subscale score at day 28 vs. baseline that was 0.8 greater than those receiving placebo (2.4 vs. 1.6; one-sided p=0.0247). ARRY-797 was well tolerated. The most frequent adverse events were dizziness, diarrhea and nausea. Array will begin seeking a partner to maximize the value of ARRY-797.
July 2, 2012
Iroko Pharmaceuticals issued results from a phase III trial of diclofenac for the treatment of post-surgery pain. The multi-center, randomized, double-blind, active- and placebo-controlled study enrolled 428 patients. Subjects received diclofenac 18mg or 35mg three times daily, or celecoxib 400mg on day one then 200mg twice a day, or placebo. The trial demonstrated significant improvement in pain relief as measured by the combined differences in pain intensity measured at intervals over 48 hours using a visual analog scale (VASSPID 48) in patients with acute pain. Pain relief scores were 524 for submicron particle diclofenac 35mg, 393 for 18mg, 390 for celecoxib and 0 for placebo. Subjects receiving submicron particle diclofenac capsules 35mg achieved pain relief (P=0.009) during the first four hours after initiating oral treatment (TOTPAR-4). The most frequent adverse events, comparable across treatment groups, were post-procedural swelling, nausea and headache. Based on these data, Iroko will pursue diclogenac as a low-dose alternative to NSAIDs.
October 26, 2009
Pacira released positive results from a phase III trial of Exparal (DepoBupivacaine) for the reduction of pain following bunionectomy. This US-based, randomized, double-blind, parallel-group, placebo controlled study enrolled 193 subjects undergoing first metatarsal osteotomy (bunionectomy). The subjects received a single administration of Exparel or placebo following surgery and evaluated for analgesic effect. The primary endpoint, reduction in area under the curve analysis (AUC) of the numeric rating scale scores, was reached with statistical significance in the subjects receiving Exparel compared to placebo over the first 24 hours following surgery (p≡0.0005). This difference continued to be statistically significant through 36 hours. The study also met secondary endpoints with statistical significance favoring Exparel for the percentage of subjects who were pain free through 8 hours and at 48 hours; the percentage of subjects who received no rescue medication through 24 hours; and the total amount of rescue required by 24 hours. Exparel was well tolerated, with the incidence of adverse events similar to placebo.
March 23, 2009
Durect reported positive results from a phase IIb trial of Transdur-sufentanil, a transdermal patch formulation of the opioid sufentanil. This open label, two-stage study enrolled 74 opioid-experienced subjects with non-malignant moderate to severe chronic pain. The study was designed to explore the conversion schedule for transitioning this population from current oral and transdermal opioid therapies to Transdur-Sufentanil. Following a baseline screening, the subjects were randomized into multiple titration regimens. After achieving an endpoint of adequate, stable pain control and an acceptable safety profile on Transdur-Sufentanil, they entered a 28-day continuous treatment maintenance period. This was followed by a seven day follow-up period to ensure that an adequate pain control regimen was re-established. Of the 74 initially enrolled subjects, 36 successfully entered the maintenance period. Two acceptable dose titration intervals achieved the desired analgesic effect and side-effect profile. The mean pain score during the maintenance period was 3.88 (on a ratings scale for pain intensity, with 0 being no pain) representing a reduction of approximately 19% from the mean baseline pain score of 4.78. Treatment was safe and well tolerated.