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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2015

Open Access 01-12-2015 | Research

Phase I, two-way, crossover study to demonstrate bioequivalence and to compare safety and tolerability of single-dose XM17 vs Gonal-f® in healthy women after follicle-stimulating hormone downregulation

Authors: Andreas Lammerich, Arnd Mueller, Peter Bias

Published in: Reproductive Biology and Endocrinology | Issue 1/2015

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Abstract

Background

XM17 is a recombinant human follicle-stimulating hormone (rhFSH) intended mainly for use in controlled ovarian hyperstimulation and the treatment of anovulation. The purpose of the current study was to establish bioequivalence, safety and tolerability of single 300-IU subcutaneous (sc) doses of XM17 to that of the reference follitropin alfa (Gonal-f®) in healthy young women.

Methods

This open-label, Phase I, single-dose, single-center, two-way crossover study was conducted from February to May 2009. Thirty-six women aged 18–39 years were included, with a study duration of ~27 days per participant. After endogenous FSH downregulation with goserelin (3.6 mg) on study Day 0, XM17 and Gonal-f® were administered on Days 11 and 19 in random sequence. Frequent serum samples were drawn for standard pharmacokinetics until 168 h postdosing. Laboratory values, adverse events (AEs) and local tolerability were assessed throughout the study period. Primary endpoints included Cmax and AUC0-t. Secondary endpoints included additional pharmacokinetic (PK) parameters, safety and tolerability.

Results

Ratios of XM17 to Gonal-f® for Cmax and AUC0-t equaled 1.017 (90 % confidence interval [CI]: 0.958, 1.080) and 1.028 (90 % CI: 0.931, 1.134), respectively, with the CIs contained within the predefined interval (0.8, 1.25). Ratios for AUC0-168h, AUC0-∞ and t1/2 were also ~1, and no difference in tmax was detected. Both XM17 and Gonal-f® were well tolerated, with no detectable anti-FSH antibodies, serious AEs or AEs leading to discontinuation or dose reduction.

Conclusions

PK bioequivalence of single 300-IU sc doses of XM17 to the reference product Gonal-f® was statistically demonstrated. XM17 was well tolerated both systemically and locally.

Trial registration

ClinicalTrials.gov: NCT02592031; date of registration: 28 October, 2015.
Literature
1.
Daya S. Follicle-stimulating hormone in clinical practice: an update. Treat Endocrinol. 2004;3:161–71.CrossRefPubMed
2.
3.
Pouwer AW, Farquhar C, Kremer JAM. Long-acting FSH versus daily FSH for women undergoing assisted reproduction. Cochrane Database Syst Rev. 2012;6:CD009577.PubMed
4.
5.
Weise M, Bielsky MC, De Smet K, Ehmann F, Ekman N, Narayanan G, et al. Biosimilars-why terminology matters. Nat Biotechnol. 2011;29:690–3.CrossRefPubMed
6.
7.
8.
Lammerich A, Bias P, Gertz B. Phase 1 safety, tolerability, and pharmacokinetic study of single ascending doses of XM17 (recombinant human follicle-stimulating hormone) in downregulated healthy women. Int J Womens Health. 2015;7:707–16.PubMedCentralCrossRefPubMed
9.
World Medical Association. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. Ferney-Voltaire, France, World Medical Association, Inc. 2012.
10.
11.
le Cotonnec JY, Porchet HC, Beltrami V, Khan A, Toon S, Rowland M. Clinical pharmacology of recombinant human follicle-stimulating hormone (FSH). I. Comparative pharmacokinetics with urinary human FSH. Fertil Steril. 1994;61:669–78.PubMed
12.
Matta WHM, Shaw RW, Burford GD. Endocrinologic and clinical evaluation following a single administration of a gonadotrophin-releasing hormone agonist (Zoladex), in a depot formulation, to premenopausal women. Fertil Steril. 1988;49:163–5.PubMed
13.
Gonal-f [summary of product characteristics]. London: European Medicines Agency; 2010.
Metadata
Title
Phase I, two-way, crossover study to demonstrate bioequivalence and to compare safety and tolerability of single-dose XM17 vs Gonal-f® in healthy women after follicle-stimulating hormone downregulation
Authors
Andreas Lammerich
Arnd Mueller
Peter Bias
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2015
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-015-0124-y

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