Original Article Phase I and Phase II clinical trials of androst-5-ene-3β,7β,17β-triol
Dwight R. Stickney, Clarence N. Ahlem, Elizabeth Morgan, Christopher L. Reading, Nanette Onizuka, James M. Frincke
Harbor Biosciences, Inc., 9171 Towne Centre Drive, Suite 180, San Diego, CA 92122, USA.
Received February 14, 2011; Accepted March 28, 2011; Epub April, 2011; Published April 15, 2011
Abstract: The immune regulating DHEA metabolite, androst-5-ene-3β,7β,17β-triol (βAET), was evaluated for safety, cholesterol lowering, and vaccine enhancement in phase I and phase II clinical trials. Safety and pharmacokinetics were evaluated in one study of normal subjects that received βAET or placebo transmucosally (buccal tablets) for 4 days. In a second study βAET was given by daily subcutaneous injection for 3 days. βAET was subsequently evaluated in placebo-controlled trials for cholesterol lowering in hyperlipidemic subjects and for vaccine potentiation of hepatitis B surface antigen (HBsAg) in elderly subjects. Adverse events were primarily associated with injection site reactions. Pharmacokinetics indicated that βAET was rapidly cleared after either route of administration in both normal and elderly subjects. Plasma βAET concentrations typically declined below the limit of detection within a few hours of administration. βAET pharmacokinetics was similar in males and females and in normal and elderly subjects. βAET significantly lowered cholesterol in normal adult, but not in elderly or hyperlipidemic subjects. HBsAg titers were not increased in elderly βAET treated subjects relative to placebo. Conclusions: Short-term administration of βAET is safe in humans. βAET has a cholesterol lowering effect in healthy humans, but not hyperlipidemics. Exogenous βAET appeared to be rapidly metabolized, which may be consequential to the lack of pharmacological activity. A longer duration of treatment with higher doses or chemical derivatives that are resistant to metabolic inactivation are likely necessary to treat human disease. The utility of βAET in humans may be limited to maintenance of homeostasis in healthy adults. (AJTR1103004).