A day after it reported losing $16.1 million in the third quarter, San Diego-based Arena Pharmaceuticals Inc. (Nasdaq: ARNA, News) on Tuesday announced data from its positive Phase 2a clinical trial studying APD356 in 352 obese patients.
The results were presented by Steven Smith, M.D., principal investigator and associate professor of the Pennington Biomedical Research Center, at the 2005 annual meeting of the North American Association for the Study of Obesity.
Over the 28-day treatment period in the trial, there was a highly statistically significant (p=0.0002) mean placebo adjusted weight loss of approximately 1 kilogram in patients taking the 15 mg dose of APD356. APD356 was generally well tolerated at all doses investigated in the trial, the company said.
APD356 is a selective agonist of 5-HT2C serotonin receptors, which are located in the hypothalamus, an area of the brain known to play an important role in regulating food intake and metabolism.
The primary efficacy endpoint of the Phase 2a study was a reduction in weight in patients completing the 28-day treatment period. Compared to placebo, treatment with APD356 was associated with a highly statistically significant (p=0.0002) mean weight loss of 1.3 kilograms in the 15 mg group versus 0.4 kilograms in the placebo group. No statistically significant weight loss was observed in the 1 mg or 5 mg groups, according to Arena.
Average weight loss using an intent-to-treat analysis yields a similar statistically significant (p=0.0003) result, with patients taking the 15 mg dose of APD356 losing 1.2 kilograms versus 0.4 kilograms for the placebo group. Weight loss was progressive from week to week under both the complete and intent-to-treat analysis. The weight loss data reported today at NAASO is consistent with the top-line data previously reported by Arena.
APD356 was generally well tolerated at all doses investigated in the trial. Adverse events occurring in greater than 5 percent in any group were headache, nausea, diarrhea, cough and nasopharyngitis, according to the company.
An assessment of Day 29 and Day 90 echocardiograms indicates no apparent APD356 effect on heart valves or pulmonary artery pressure in the Phase 2a clinical trial.
There were no statistically significant changes in the secondary efficacy endpoints of waist circumference and waist-hip circumference ratio, Arena announced. Total cholesterol, HDL, and triglyceride levels, which were not an endpoint in the Phase 2a trial, were slightly reduced in the 15 mg group compared to placebo at Day 29.
This Phase 2 clinical trial of APD356 was a randomized, double-blinded, multiple-dose study examining 352 obese volunteers at 24 clinical sites in the United States. The trial was to enroll otherwise healthy male and female patients with a body mass index of between 30 and 45. Patients were randomized into four groups to compare doses of 1, 5 and 15 mg of APD356 versus placebo. The trial evaluated safety and weight loss after oral administration of APD356 once daily for 28 days.
The trial protocol provided that patients should maintain their normal diet and level of activity, but required that patients abstain from consuming alcohol. In addition to standard safety evaluations, patients were assessed by echocardiogram upon enrollment, and were scheduled for follow-up echocardiograms at 29 and 90 days after receiving their first dose, the company said in a statement.
Arena's shares rose 13 cents to $9.98 a share in midday trading.