A preliminary analysis of the study results demonstrated that it is safe and well-tolerated at the doses examined, and produced a statistically significant reduction in plasma triglyceride levels, as described more fully below.
This double-blind, placebo-controlled Phase Ib study enrolled 46 male and female volunteers. Following a one-week placebo run-in, subjects received either escalating daily doses of 50mg, 100mg and 150mg of DOV 21,947 (31 subjects) or placebo (15 subjects), for a total of eight weeks. Those subjects with detectable blood levels of DOV 21,947 or its principal metabolite during at least three of four bimonthly visits (approximately 70% of the drug-treated subjects) were classified as drug compliant.
At the end of this eight-week study, the mean difference in body weight change from baseline between the drug-compliant and placebo groups was 4.6 pounds (p<0.006). Furthermore, following a one-week wash-out period, this highly significant difference in body weight change between the groups was reduced by almost 50%, indicating a reversible, drug-related effect. Statistical results similar to those for the body weight reduction were obtained for the body mass index. The mean difference in body mass index change from baseline between the drug-compliant and placebo groups was 0.75kg/m2 (p<0.005), with a reversible drug-related effect at the end of the one-week wash-out period. Dr Phil Skolnick, president and CEO of DOV, said: "There is a significant co-morbidity of obesity with major depressive disorder that can be exacerbated by the weight gain produced by many antidepressants. We believe a product that could not only manage depression but also impact weight gain would represent a significant advantage over currently marketed antidepressants."