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Pharmacokinetic Bioequivalence Studies of a Fixed-Dose Combination of Tamsulosin and Dutasteride in Healthy Volunteers

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Abstract

Background and Objectives

The combination of dutasteride and tamsulosin may be more effective for the treatment of symptomatic benign prostatic hyperplasia than either treatment alone. We report the results of three pharmacokinetics and tolerability studies, which used a dutasteride/tamsulosin HCl (0.5 mg/0.2 mg) fixed-dose combination (FDC) capsules containing a small dutasteride soft gelatin capsule (smaller than commercial Avodart™) and modified-release tamsulosin pellets that have different amounts of enteric coating. These studies compared the test products to commercial Avodart™ (dutasteride 0.5 mg) and two different commercial tamsulosin HCl 0.2 mg products, Harnal™ Capsules or Harnal-D™ Tablets, which are reportedly bioequivalent to each other.

Methods

All three studies were randomized single-dose studies in healthy male adults.

Study 1 [N = 86 (NCT01254071)] was a two-period crossover study of a dutasteride/tamsulosin HCl FDC versus coadministered Avodart™ and Harnal-D™ Tablets. The pharmacokinetics of both dutasteride and tamsulosin were studied.

Study 2 [N = 27 (NCT01471678)] was a four-period crossover study of dutasteride/tamsulosin HCl FDC formulations versus Avodart™ and Harnal™ Capsules or Harnal-D™ Tablets. Only the pharmacokinetics of tamsulosin were studied.

Study 3 [N = 40 (NCT01495026)] was a two-period study of dutasteride/tamsulosin HCl FDC formulations versus coadministered Avodart™ and Harnal-D™ Tablets. In this study, only the pharmacokinetics of tamsulosin were studied.

Study 2 assessed fed-state pharmacokinetics. Studies 1 and 3 assessed fed- and fasted-state pharmacokinetics.

Results

All dutasteride/tamsulosin HCl FDC formulations and coadministered treatments were well-tolerated. In Study 1, the FDC dutasteride was bioequivalent to Avodart™ coadministered with tamsulosin under fed and fasted conditions. In Study 1, the FDC tamsulosin had a slower release than commercial Harnal-D™ Tablets coadministered with dutasteride (fed and fasted state). In Study 2, the FDC tamsulosin containing 15 % by weight enteric-coated tamsulosin pellets was bioequivalent to Harnal™ Capsules coadministered with dutasteride in the fed state. In Study 3, the FDC containing 15 % by weight enteric-coated tamsulosin pellets combined with uncoated tamsulosin pellets (coated:uncoated = 10:90) were bioequivalent to Harnal-D™ Tablets coadministered with dutasteride in the fasted state but not the fed state.

Conclusions

The FDC formulations were well-tolerated and some FDC formulations were comparable with concomitant administration of commercially available dutasteride and tamsulosin.

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Acknowledgments

The conduct and data analysis of the studies presented here were funded by GlaxoSmithKline. Editorial assistance in the preparation of the manuscript was provided by David Griffiths and Sarah White of FWG Scientific Communications, which was funded by GlaxoSmithKline.

Disclosures

Michael J. Fossler, David A. Collins, Meg M. Thompson, Antonio Nino, Joseph J. Bianco, and Dushen Chetty are all employees of GlaxoSmithKline. Michael J. Fossler, David A. Collins, Meg M. Thompson, Antonio Nino, and Dushen Chetty all own stock/stock options in GlaxoSmithKline.

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Authors and Affiliations

  1. GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA, 19406, USA

    Michael J. Fossler & Antonio Nino

  2. GlaxoSmithKline, Research Triangle Park, NC, USA

    David A. Collins & Meg M. Thompson

  3. GlaxoSmithKline R&D, Melbourne, VIC, Australia

    Joseph J. Bianco

  4. GlaxoSmithKline, Singapore, Singapore

    Dushen Chetty

Authors
  1. Michael J. Fossler
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  2. David A. Collins
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  3. Meg M. Thompson
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  4. Antonio Nino
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  5. Joseph J. Bianco
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  6. Dushen Chetty
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Corresponding author

Correspondence to Michael J. Fossler.

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Fossler, M.J., Collins, D.A., Thompson, M.M. et al. Pharmacokinetic Bioequivalence Studies of a Fixed-Dose Combination of Tamsulosin and Dutasteride in Healthy Volunteers. Clin Drug Investig 34, 335–349 (2014). https://doi.org/10.1007/s40261-014-0179-0

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