Alkermes, Inc. announced preliminary results from its Phase III study of Vivitrex (naltrexone for injectable suspension) in a total of 624 male and female patients with alcohol dependence. Patients received psychosocial therapy and once-monthly injections of Vivitrex 380 mg, Vivitrex 190 mg, or placebo for a six- month period. The primary endpoint of the study was the rate of heavy drinking over the period. In the overall study population, patients treated with Vivitrex 380 mg experienced approximately a 25per cent reduction in the rate of heavy drinking relative to placebo, which was statistically significant (p<0.03).
Gender played a dominant role in the study results. Two thirds of the patients enrolled in the study were male, which is representative of the alcohol dependent population. Male patients treated with Vivitrex 380 mg showed approximately a 48per cent reduction in the rate of heavy drinking relative to placebo, which was highly statistically significant (p<0.0001). Female patients treated with Vivitrex 380 mg showed no significant difference from placebo.
In the overall study population, patients treated with Vivitrex 190 mg experienced approximately a 17per cent reduction in the rate of heavy drinking relative to placebo with a trend toward statistical significance (p<0.10). Again, gender played a dominant role in the study results at the 190 mg dose. Male patients treated with Vivitrex 190 mg showed approximately a 25per cent reduction in the rate of heavy drinking relative to placebo, which was statistically significant (p<0.03), suggesting a clear dose response relationship in the male treatment groups in this study. Female patients treated with Vivitrex 190 mg showed no significant difference from placebo.
The study was prospectively designed to control for gender differences and other key factors that were believed to be predictive of drinking behaviour. The study subjects were randomized and balanced across each of the 24 treatment centres and within treatment groups with respect to key factors, including gender. The reduction in the rate of heavy drinking observed in the overall treatment group (males and females combined) does not appear to be representative of the average treatment effect across all patients in the study because the entire effect was observed in the male treatment group.
“These data show that the long-acting formulation of Vivitrex results in meaningful clinical benefit for male alcohol-dependent patients and can significantly advance the practice of treating alcoholism,” said James Garbutt, MD, professor of Psychiatry at University of North Carolina at Chapel Hill and a lead investigator for the Vivitrex Phase III trial. “As one of the largest studies ever conducted for alcohol pharmacotherapy, this landmark Phase III trial shows that treatment with Vivitrex resulted in a reduction in heavy drinking events and highlights the role that drug therapy can play in helping patients break the cycle of alcoholism.”
“Based on the results of this successful study, Alkermes intends to move forward with our extensive development plans for Vivitrex,” said Richard Pops, CEO of Alkermes. “These Phase III results represent an important milestone in reaching our ultimate goal of developing Vivitrex into an innovative product that offers the potential to improve outcomes for alcohol-dependent patients. We look forward to sharing these data with the US FDA as we proceed on our path towards submission of a New Drug Application.”
“The data from this Phase III trial with Vivitrex indicates a potentially significant development in treating people with alcohol problems,” said Richard Rosenthal, MD, immediate past president of the American Academy of Addiction Psychiatry (AAAP). Kathleen Brady, MD, PhD, president of AAAP adds, “A new contribution to our tools to treat the major public health problem of alcohol abuse and dependence is welcome.”
The Phase III clinical trial, a randomized, placebo-controlled, double-blind study, was designed to evaluate the safety and efficacy of Vivitrex in alcohol-dependent patients during a six-month period. The primary endpoint was the event rate of heavy drinking over the six-month period. A heavy drinking event is defined as five or more drinks per day for a man and four or more drinks per day for a woman. The multi-centre study enrolled 624 patients, and randomized patients to receive, in addition to psychosocial therapy, Vivitrex 190 mg, Vivitrex 380 mg, or placebo. Vivitrex was administered by injection in a clinical setting once per month for six months. At designated intervals during the study, patients returned to the clinic for study evaluations and psychosocial therapy. Following the six-month treatment period, patients were eligible to enter an extension study designed to collect long-term safety data for an additional 12 months.