Source: Kardiologiia  |  Posted 7 years ago

By M. M. Pennell

NEW ORLEANS, LA -- March 10, 2004 -- Positive results from 2 phase III studies of an investigational drug in a new class called selective CB 1 blockers suggest that rimonabant is an effective treatment for smoking cessation, weight loss, and metabolic syndrome risk factors.

The results from the STudies with Rimonabant And Tobacco Use (STRATUS-US) and the Rimonabant In Obesity (RIO-Lipids) study were presented here on March 9th during a late-breaking clinical trials session at the American College of Cardiology 53rd Annual Scientific Sessions.

Jean-Pierre Despr?s, PhD, Division of Kinesiology, Faculty of Medicine, Laval University, Ste-Foy, Quebec, Canada, and Robert Anthenelli, MD, Associate Professor of Psychiatry, University of Cincinnati College of Medicine, and Cincinnati VA Medical Center, Cincinnati, Ohio, presented results.

Dr. Anthenelli, who reported the STRATUS-US results, said rimonabant has the potential to be the first drug to treat the 2 major risk factors for heart disease -- smoking and obesity.

The study involved 11 clinical trial sites in the United States, where 787 smokers were recruited. The researchers randomized 262 patients to 5 mg rimonabant, 261 patients to 20 mg, and 264 to placebo. The average age of smokers was 42 and most had smoked about a pack a day for 11 to 24 years, said Dr. Anthenelli. The study lasted 10 weeks and the subjects were permitted to smoke during the first 2 weeks, but were asked to abstain after that.

Subjects who were completely smoke-free during the last 4 weeks of the study, as verified by blood cotinine levels and by carbon monoxide levels in the breath, were considered treatment successes.

About one quarter of the 20 mg rimonabant cohort kicked the smoking habit in 10 weeks, which was "about twice the quit rate seen in the placebo arm," said Dr. Anthenelli. This quit rate is slightly better than current smoking cessation aids such as nicotine gum or transdermal nicotine replacement.

"These smokers quit without gaining weigh, and some even lost weight," Dr. Anthenelli also said. Smokers in the 20 mg of rimonabant cohort who were of normal weight at baseline gained no weight, while normal weight smokers taking placebo gained about 2 lbs (0.9 kg).

Overweight and obese smokers in the 20 mg of rimonabant group lost 1 lb (0.45 kg) compared to an increase of 1 lb and 3 lbs (1.35 kg), respectively, in overweight and obese smokers given placebo. "And they lost weight without changing diet or increasing exercise," said Dr. Anthenelli.

Dr. Despr?s, who reported the RIO-Lipids results, and colleagues evaluated 1,036 subjects with dyslipidemia and a body mass index of 27 to 40. Patients received 5 mg or 20 mg of rimonabant or placebo. While no specific diet was required, patients were told to reduce caloric intake by 600 calories a day and were given nutritional guidance, Dr. Despr?s said. All patients were treated for 1 year.

More than 70% of patients in the 20 mg group lost 5% of total body weight and 44% lost more than 10% of total body weight during treatment, and the weight loss occurred where it was most needed -- right around the middle with waist size dropping by 3.4 inches, said Dr. Despr?s.

Additionally, there was a 23% increase in levels of high-density lipoprotein, a 15% decrease in triglyceride levels, a 27% reduction in C-reactive protein levels and a favorable change in cholesterol composition with a decrease in the proportion of small, dense low-density lipoprotein particles.

At the beginning of the study more than half of patients had the metabolic syndrome, Dr. Despr?s said. By the end of treatment, the rate among patients taking rimonabant 20 mg was cut in half.

"We have many drugs that treat high blood pressure or elevated cholesterol but this is the first drug with the potential to treat metabolic syndrome," Dr. Despr?s said

Rimonabant is made by Sanofi-Synthelabo, which funded the study.

[Late breaking clinical trials II. Session 409]