Anxiety Disorders

October 17, 2016

Bionomics issued results of a single-center, double-blinded, placebo and lorazepam-controlled, four-way, cross-over, phase II clinical trial of BNC210 conducted in 24 patients with untreated generalized anxiety disorder (GAD). The objective of the study was to evaluate the capacity of BNC210 to engage brain systems relevant to anxiety while resting and in response to anxiety-related tasks. The co-primary endpoints were a change in cerebral perfusion measured by arterial spin labelling and a change in task-related brain activity, specifically in the amygdala as measured by functional Magnetic Resonance Imaging (fMRI) during the Emotional Faces Task (EFT). The results of the study show that BNC210 induced statistically significant changes in cerebral perfusion (300mg BNC210, p<0.05) and also significantly reduced amygdala activation in response to fearful faces during the EFT (300mg BNC210, p<0.05). In comparison, lorazepam exerted a modest suppressive effect on amygdala activation during performance of the EFT (1.5mg lorazepam, p=0.069). A secondary endpoint of the trial was to determine the effect of BNC210 on defensive behaviour using the Joystick Operated Runway Task (JORT) which uses a force-sensing interface to obtain an objective measure of the intensity of threat avoidance motivation. BNC210 administration was associated with a significant decrease in the intensity of threat avoidance behaviour (300mg BNC210, p=0.007; 2,000mg BNC210, p=0.033). BNC210 outperformed lorazepam in this regard (1.5mg lorazepam, p=0.165).

January 14, 2008

Addex issued negative results from a phase IIa trial of ADX10059 for the treatment of acute anticipatory anxiety. This double-blind, placebo-controlled trial enrolled fifty subjects in the United Kingdom. All subjects were undergoing a routine dental procedure and presented with moderately severe anxiety. The subjects received a single 250 mg dose of ADX10059 or placebo sixty minutes prior to the procedure. The primary endpoint was a reduction on the Visual Analog Scale of anxiety (VAS anxiety) sixty minutes after dosing (immediately prior to the start of the dental procedure). Anxiety was measured at specific time points before, during and after the procedure. The results did not show a statistical difference between ADX10059 and placebo (mean VAS 4.81 cm compared to 4.67 cm, respectively). Based on the results, Addex did not announce plans to move forward with ADX10059 for this indication.

March 19, 2007

CeNeRx issued positive results from a phase I trial of Tyrima for thetreatment of depression and anxiety. This single-dose, placebo-controlled trialenrolled 41 subjects who received Tyrima in doses escalating from 5 mg to 120mg. Treatment was safe and well tolerated up to the highest dose. Thepharmacokinetic profile was positive, showing that Tyrima reached high plasmaconcentrations that increased linearly with dose and the half-life shouldfavorability towards once or twice daily dosing. Based on the results, CeNeRxplans to move forward with multiple dose trials.

October 2, 2006

Epix announced negative results from a phase III trial of PRX-00023 for the treatment of generalized anxiety disorder. This double-blind, placebo-controlled, multi-center trial enrolled 310 subjects in the US who were randomized equally into one of two arms: placebo or treatment with PRX-00023. They were administered a dose of 40 mg once daily for three days followed by 80 mg once daily for the remainder of the study. Treatment failed to demonstrate a statistically significant improvement over placebo in the primary endpoint, change from baseline in Hamilton Rating Scale for Anxiety (HAM-A). The secondary endpoint, statistically significant improvement from baseline in the Montgomery Asberg Depression Rating Scale (MADRS) compared to placebo, was met. Based on the data Epix plans to refocus the development efforts of PRX-00023 towards the treatment of depression.

August 22, 2005

Predix reported positive results of a phase II trial of PRX-00023, their investigational 5-HT1A agonist, for the treatment of generalized anxiety disorder (GAD). Results demonstrated a positive overall safety profile, with no serious adverse events or drug related adverse events leading to discontinuation. The most common overall adverse event was flu-like symptoms. Secondary efficacy data produced preliminary improvements on the HAM-A, CGI-Global Improvement, and Hospital Anxiety and Depression diagnostic scales. This open-label, multi-center study enrolled 20 patients with moderate-to-severe GAD, who received sequential ascending dose regimens of the drug after a 1 week placebo run-in: subjects received 40 mg once daily for 4 days, then 80 mg once daily for 10 days, then 120 mg once daily for 14 days.

May 2, 2005

Ceregene reported the results of a phase I trial of human nerve growth factor (NGF), delivered via NGF-expressing modified fibroblast implantation into the forebrain, for the treatment of Alzheimer's disease. Results from the study indicated that the treatment was well tolerated, with no long term adverse events reported. Serial PET scanning yielded significant increases in cortical 18-fluorodeoxyglucose uptake following treatment (p<0.05), and evaluation of the Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive subcomponent suggested mitigation of rate of cognitive decline. Autopsy results from one patient suggested robust neuronal growth following treatment. This unblended study performed NGF fibroblast implantation on 6 patients with mild Alzheimer's disease, who were followed for indications of safety and efficacy for 22 months.

Neurochem has reported positive interim results of a phase III trial of Alzhemed, their investigational amyloid beta fibrillogenesis inhibitor for the treatment of Alzheimer's disease (AD). Preliminary safety 12-week results from the first 562 patients enrolled yielded no indication of serious adverse events or tolerability concerns, and prompted the trial's Independent Safety Review Board to recommend that the study continue without modification. This multicenter, randomized, double-blind, placebo- controlled, three-armed, parallel-design study has enrolled 950 patients with AD across 68 sites in North America, who were to receive treatment for 18 months. The company announced plans to initiate a phase III trial of Alzhemed in Europe in the fall of 2005.

Neurologix presented positive interim results of a phase I trial of GAD (glutamic acid decarboxylase) gene therapy for the treatment of Parkinson's disease at the 73rd annual meeting of the American Association of Neurological Surgeons in New Orleans. Preliminary data from the first 4-patient dosing cohort in the ongoing study have met their primary safety endpoints, with no serious adverse events or tolerability concerns raised. This open-label dose- escalation study enrolled 12 patients with advanced Parkinson's disease at the The New York Presbyterian Hospital/Weill Medical College of Cornell University. Subjects were randomized to receive one of three single doses of the therapy delivered via stereotactic neurosurgically- implanted microcatheter. The company announced plans to initiate efficacy evaluation of the drug in the near future, based upon the positive safety profile presented in this study.

NovaDel has issued positive results of a pilot study of a lingual spray formulation of the approved anxiolytic alprazolam, marketed by Pfizer as Xanax. Pharmacokinetic data indicated that the lingual spray produced a more rapid rate of absorption than the approved formulation, with a time to therapeutic plasma concentration of 15 minutes, versus 35 minutes for the oral tablet. Further, the drug showed higher percentage of maximum concentration (Cmax) at earlier time- points, including a statistically significant results at 12 minutes: 38.5% for the spray vs. 18.8% for the tablet (p<0.05). Preliminary efficacy was also demonstrated, with all lingual spray groups self-rating higher on relaxation and drowsiness parameters at 30 minutes. This open- label study enrolled 9 healthy volunteers, who each received 3 ascending doses of the lingual spray (0.25mg, 0.75mg, and 1mg) and 3 doses (0.5 mg) of the oral tablets. NovaDel announced plans to meet with the FDA to discuss a broader clinical development program for the drug.

September 20, 2004

Acadia Pharmaceuticals has reported the results of a phase II study of their investigational drug ACP-103, in mitigating side effects caused by antipsychotic therapy. Data indicated that the drug met its primary endpoint, with a significant reduction in observed symptoms of haloperidol-induced akathisia (motor disturbance), and a significant reduction in the elevated serum prolactin levels (hyperprolactinemia) caused by haloperidol; hyperprolactinemia can cause sexual and menstrual disturbance, increase risk of osteoporosis, and promote mammary tissue formation in men. The double-blind, placebo-controlled study enrolled 18 healthy volunteers in Sweden, who received either a single high dose or lower daily dose regimen of ACP-103 following a single dose of haloperidol. Acadia announced plans to replicate this phase II protocol with other antipsychotics.<

Predix Pharmaceuticals announced positive results of two pilot studies of PRX-00023, their serotonin-1A (5HT1A) receptor agonist for the treatment of anxiety and depression. Both studies found that the drug was safe, and very well tolerated. Pharmacokinetic and pharmacodynamic analyses indicated that trial doses of the drug produced noteworthy increases in 5HT1A-receptor activation surrogates, and demonstrated an elimination half-life consistent with once-daily dosing. The first study was a phase I investigation enrolling healthy male volunteers, who received single doses of 10-60 mg; the second study was a phase I b investigation enrolling healthy male and female volunteers, who received once-daily 10-60 mg. doses of the drug for 28 days. Both studies were designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics or PRX-00023 treatment. Predix announced that phase II trials, as well as INDs for two additional drugs based upon the same platform, were planned for the next 8 months.

August 11, 2003

Acadia Pharmaceuticals reported positive results from a phase I trial investigating ACP-103, a 5-HT2A inverse agonist for the treatment of various neuropsychiatric conditions. Results demonstrated that ACP-103 was safe and well tolerated with dose proportional pharmacokinetics and a long half-life. Data also demonstrated that ACP-103 was well tolerated with no changes in cardiovascular and neurological function and no serious adverse events. The randomized, double blind, placebo-controlled, dose-escalation study enrolled 49 subjects and used both single-dose and multiple-dose regimens. The single-dose study evaluated five doses ranging from 20 to 300 mg and the multiple dose-escalation study evaluated oral doses of 50, 100, and 150 mg given once-daily for 14-days.

March 10, 2003

Biovail reported negative results from a phase III trial investigating once daily Buspirone for the treatment of generalized anxiety disorder. The primary endpoint, change from baseline to final visit using the Hamilton Anxiety Rating Scale, did not achieve statistical significance compared to placebo. All secondary variables favored active drug, but were not statistically significantly different compared to placebo. Based on these results Biovail plans to discontinue development of this product. Buspirone is currently marketed in the U.S. by Bristol Myers Squibb and is only available in an immediate release, three times per day dosage format.

November 25, 2002

DOV Pharmaceuticals reported positive results from a phase II trial investigating ocinaplon for the treatment of generalized anxiety disorder. The study, a double blind, placebo-controlled trial with 117 male and female GAD subjects, produced statistically significant reductions in anxiety as compared to placebo. The study used the Hamilton Anxiety Rating Scale (HAM-A) as a primary endpoint measure and the Patient Self-Rating Scale (PSR) and the Clinical Global Impression Scale (CGI) as secondary measures. Prior to treatment, the average HAM-A scores for subjects were approximated at 32, indicative of a high degree of anxiety. After two weeks of drug administration, data showed a statistically significant decrease in HAM-A scores compared to placebo. Statistically significant declines in the PSR and the CGI were also observed.

June 10, 2002

Study results indicate that Pfizer's Zoloft (sertraline HCl) is more effective than placebo in reducing fear, anxiety and avoidance behavior in subjects with social phobia. The double-blind, placebo-controlled, multicenter trial included 415 outpatients with a primary diagnosis of generalized social anxiety disorder. Subjects were randomized to receive either a flexible dose of Zoloft (50-200mg) or placebo for 12 weeks. The Liebowitz Social Anxiety Scale (LSAS) Total Score mean change was -35.0 for subjects treated with Zoloft, compared to -21.4 for placebo-treated subjects. Additionally, 55.6% of Zoloft-treated subjects who completed 12 weeks of treatment had Clinical Global Impression-Improvement (CGI-I) ratings less than or equal to two, compared to 29.5% of subjects in the placebo group.

April 8, 2002

NeuroSearch and the Spanish pharmaceutical company Grupo Ferrer have decided to discontinue the development of NS2710 for the treatment of anxiety. While NS2710 has demonstrated improvement of anxiety disorders, some subjects experienced skin rashes with treatment. Grupo Ferrer conducted a clinical safety study to address this issue; results of the placebo-controlled trial showed a significantly larger prevalence of skin rashes in the group treated with NS2710. After an overall evaluation, the companies have decided not to pursue further development.