Effect on body weight and safety of RC-1291, a novel, orally available ghrelin mimetic and growth hormone secretagogue: Results of a phase I, randomized, placebo-controlled, multiple-dose study in healthy volunteers

Purpose. RC-1291is a novel, oral ghrelin mimetic and growth hormone (GH) secretagogue being developed to increase appetite and lean muscle mass in patients with cancer-associated anorexia/cachexia. This randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation phase I study in healthy volunteers evaluated RC1291 once daily (qd) and twice daily ( bid) for effect on body weight and safety. Methods. The study was conducted with three sequential groups of volunteers. Panel A subjects ( n = 8) received placebo or RC-1291, 25 mg qd, for 5 days. Panel B subjects received RC-1291, 25 mg bid or 50 mg qd, for 6 days then crossed over to the other dosage for 5 days ( n = 12); three subjects received placebo for all 11 doses to maintain double-blinding. Panel C subjects ( n = 9) received placebo or RC-1291, 75 mg qd, for 6 days. Results. Subjects who received RC-1291, 50 or 75 mg, had significant dose-related weight gain after 6 days versus placebo, with the greatest increases seen with daily dosing. The mean increase in weight from baseline after 50 mg qd was 1.25 +/- 0.725 kg ( p =.0022 versus placebo), and after 75 mg qd it was 1.16 +/- 0.651 kg ( p =.0022 versus placebo). One subject in the 50 mg qd group had moderate transient elevation in aspartate aminotransferase and alanine aminotransferase levels. No other laboratory or clinical adverse events of consequence were reported. Conclusions. Results indicate that RC-1291 produces dose-related increases in body weight with no dose-limiting adverse effects, and may be an effective treatment for anorexia/cachexia.