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Lack of a Pharmacokinetic Interaction Between SYM-1219 Granules Containing 2 Grams of Secnidazole and a Combined Oral Contraceptive in a Phase 1, Randomized, Open-Label Study in Healthy Female Volunteers

Abstract

Introduction

Bacterial vaginosis (BV) is a serious infection that is the most common vaginal infection in women of childbearing potential. SYM-1219 is a novel, granule formulation containing 2 g of secnidazole that is being developed as a single, oral dose to treat women with BV. Because many of the women diagnosed with BV use hormonal contraception, the effect of SYM-1219 on the pharmacokinetics (PK) of commonly prescribed oral contraceptive drugs, ethinyl estradiol (EE2), and norethindrone (NET) was evaluated.

Methods

This two-period, randomized, open-label study examined effects in 54 healthy female subjects. During the first period of the study, each subject received EE2 0.035-mg/NET 1-mg tablets. During the second period of the study, subjects were randomized to receive either EE2 0.035-mg/NET 1-mg tablets with concomitant 2-g SYM-1219 or 2-g SYM-1219 followed by EE2 0.035-mg/NET 1-mg tablets 1 day later. The PK of EE2 and NET were analyzed for 24 h following administration.

Results

Coadministration of SYM-1219 and EE2/NET, either on the same day or 1 day apart, had no clinically relevant effects on the bioavailability of EE2 or NET. The combined use of SYM-1219 with EE2/NET was well tolerated. Taken together, these results indicate that contraceptive efficacy should be maintained during coadministration of SYM-1219 and EE2/NET.

Conclusion

SYM-1219 is a valuable single-dose treatment option for women with BV that will not interfere with combined oral contraceptive methods.

Funding

Symbiomix Therapeutics.

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Acknowledgments

Sponsorship and article processing charges for this study were funded by Symbiomix Therapeutics. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. The authors would like to thank Chantelle Rein-Smith, Ph.D., of Whitsell Innovations, Inc. for aid in manuscript preparation (funded by Symbiomix Therapeutics) and Sara Obregon for timeline, contract, and vendor management for this project. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.

Disclosures

Helen Pentikis is a paid consultant to Symbiomix Therapeutics. Carol Braun is a paid consultant to Symbiomix Therapeutics. Nikki Adetoro is an employee of Symbiomix Therapeutics.

Compliance with Ethics Guidelines

All study procedures were approved by an independent investigational review board (IRB) (Chesapeake IRB, Columbia, MD, USA). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. All subjects provided written informed consent for participation prior to undergoing any study procedures.

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Correspondence to Helen S. Pentikis.

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Pentikis, H.S., Adetoro, N. & Braun, C.J. Lack of a Pharmacokinetic Interaction Between SYM-1219 Granules Containing 2 Grams of Secnidazole and a Combined Oral Contraceptive in a Phase 1, Randomized, Open-Label Study in Healthy Female Volunteers. Adv Ther 33, 2229–2241 (2016). https://doi.org/10.1007/s12325-016-0411-9

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Keywords

  • Bacterial vaginosis
  • Clinical trial
  • Infectious diseases
  • Oral contraceptives
  • Pharmacokinetics
  • Secnidazole