A Pilot Study Comparing Megestrol Acetate Concentrated Suspension (MA-CS) to Megestrol Acetate Oral Suspension (MA-OS) on Weight Gain and Body Composition in Patients with HIV-Associated Unintended Weight Loss (UWL).

BACKGROUND: MA-CS is a new NanoCrystal^® technology formulation of megestrol acetate that is bioavailable in the fasted state, which may provide benefit in the treatment of UWL in HIV patients.

METHODS: 63 patients with HIV-associated UWL (weight loss to 90% of the lower limit of ideal body weight) were recruited from South Africa, India and the US and then randomized to receive MA-CS (575 mg/5 mL) or MA-OS (800 mg/20 mL) once-daily for 12 weeks in a randomized, open-labeled, multi-center, pilot proof-of-principle study (sample size determined empirically). Patients had weight, body composition (bioimpedance analysis - BIA), and anthropometric measurements obtained at baseline and weekly thereafter, except BIA which was measured at 6 and 12 weeks. Weight changes were compared using the Wilcoxon Rank Sum test.

RESULTS: The demographics were comparable between the two groups. The mean weight change from baseline to Week 12 for MA-CS was 5.4 kg (55.6 kg to 61 kg, 10% of baseline body weight). The mean weight change from baseline to Week 12 for MA-OS was 3.5 kg (54.4 kg to 57.9 kg, 6% of baseline body weight). Differences from baseline, in the mean changes in weight, were observed as early as Day 3 (p=0.024) for MA-CS, however no increase was noted until the second week for MA-OS. Similar between group differences were noted consistently at the weekly assessment intervals until week 12 (p= 0.024). Of these weight changes, lean body mass accounted for ~40% of the increase in both treatment groups (MA-CS was ~5% greater than MA-OS). Of the anthropometric measures, the mean triceps skin fold increased by ~36% at Week 12, relative to baseline, in both MA-CS and MA-OS treatment groups. Other anthropometric changes were all smaller (less than 7%) and comparable between treatments. The types and incidence rates of adverse events were similar between MA-CS and MA-OS.

CONCLUSIONS: Both products were successful at increasing body weight. There was a greater and more rapid mean change from baseline in the weight gain for MA-CS than MA-OS. The observed weight changes reflected increases in both lean body mass and body fat. MA-CS had a greater change in lean body mass. This trial supports the principle that improved bioavailability of megestrol acetate in the fasted state with MA-CS may be associated with faster time to onset of changes in body weight.