Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health

Moré MI, Kenley D · Journal of Endocrinology and Metabolism

No mutagenic or clastogenic activity, and no toxicological finding at chronic oral doses up to 100 mg/kg a day in rats or 50 mg/kg a day in monkeys, which the authors give as the no-observed-adverse-effect levels. In pigs the intravenous half-life was about 3 minutes with the peptide almost cleared from plasma by 12 minutes, and oral dosing produced slower entry with the same amino-terminal degradation fragments; the authors estimate 40 percent oral availability from rat radiolabel distribution, with label concentrating in pancreas, pineal, thyroid, liver and kidney cortex and excluded from the central nervous system. The paper also states that weight loss seen in the sponsor's earlier trials was not seen in the last trial, which added diet and exercise, and that the efficacy manuscript was in preparation.

Population

Sponsor-commissioned non-clinical studies from 1999 to 2006: bacterial and Chinese hamster ovary genotoxicity assays, a four-week intravenous rat study with a bone-marrow micronucleus test, six-month oral rat and nine-month oral cynomolgus monkey toxicology, radiolabel distribution in rats, and pharmacokinetics in six pigs

Intervention

AOD9604 intravenously at 0.1 to 10 mg/kg a day in rats, orally by gavage in rats and monkeys, and 400 µg/kg intravenously or 2 mg/kg orally in pigs

Comparator

Vehicle

Limitations

Every study was commissioned and funded by Metabolic Pharmaceuticals, whose chief executive is a co-author and holds stock in its parent company; the first author is a consultant to the sponsor. The studies are summarised from contract-laboratory reports rather than reported in full, the weight-loss efficacy data the paper refers to have never appeared in a peer-reviewed journal, and nothing here concerns a joint.