Evaluation of bioequivalence of five 0.1 mg dutasteride capsules compared to one 0.5 mg dutasteride capsule: a randomized study in healthy male volunteers

Abstract

Objective:

To evaluate the bioequivalence of five 0.1 mg dutasteride capsules to one 0.5 mg dutasteride capsule in healthy adult male subjects under fasting conditions.

Methods:

This was a single-center, open-label, randomized, single dose, two-way cross-over study (ClinicalTrials.gov identifier NCT01929330). Thirty-six healthy male subjects aged 18–65 years received 5 × 0.1 mg dutasteride softgel capsules and 1 × 0.5 mg dutasteride softgel capsule in a randomized order, with a minimum washout of 28 days between each drug administration. Serial blood samples were collected for the measurement of serum dutasteride concentrations by a validated HPLC-MS/MS method. Dutasteride pharmacokinetic parameters were calculated using non-compartmental analysis. Maximum concentration (Cmax) and area under the concentration-time curve to the last quantifiable concentration (AUC[0–t]) were compared between treatments. Safety and tolerability were monitored throughout the study.

Results:

Five 0.1 mg dutasteride capsules were demonstrated to be bioequivalent to 1 × 0.5 mg dutasteride capsule, as the 90% confidence intervals for Cmax and AUC were within the accepted bioequivalence range of 0.80–1.25. The geometric least squares means ratios and associated 90% confidence intervals for 5 × 0.1 mg capsules vs 1 × 0.5 mg capsule were 1.01 (0.97–1.05) for Cmax and 0.91 (0.84–1.00) for AUC(0–t). Adverse events (AEs) were reported for 42% (15/36) and 36% (12/33) of subjects in the 5 × 0.1 mg and 1 × 0.5 mg dosing sessions, respectively. The most frequent AE for both treatments was headache. No subject had a serious AE.

Conclusions:

Five 0.1 mg dutasteride capsules were shown to be bioequivalent to one 0.5 mg dutasteride capsule in healthy adult male subjects under fasted conditions, suggesting that the two dose strengths can be interchanged. Both treatments were generally well tolerated in healthy male subjects.

Key words::

• Dutasteride
• Pharmacokinetics
• Bioequivalence
• Clinical trial
• Male

Transparency

Declaration of funding

GlaxoSmithKline sponsored the study and provided funding for the study and for the development and publishing of the present manuscript.

Declaration of financial/other relationships

All authors are employees of GlaxoSmithKline. MJF, DAC, NS, CLB, and OB have stock/stock options in the company.

Acknowledgments

The authors thank study volunteers for their participation and the staff at GlaxoSmithKline Medicines Research Unit, Australia for support in conducting the study. Writing assistance was provided by Julie Taylor of Peak Biomedical Ltd, paid for and on behalf of GlaxoSmithKline.