title: Randomized, active-controlled, comparative phase 3 efficacy and safety equivalence trial of Ovaleap® (recombinant human follicle-stimulating hormone) in infertile women using assisted reproduction technology (ART).
abstract: BACKGROUND
  Pharmacokinetic studies with XM17 (Ovaleap®), a recombinant human follicle-stimulating hormone (r-hFSH, follitropin alfa), have demonstrated good safety and tolerability in healthy women whose endogenous FSH levels were down-regulated with a long agonist protocol. In these studies, Ovaleap® pharmacokinetics were dose-proportional and bioequivalent to the reference follitropin alfa product (Gonal-f®). The objective of the present study is to determine whether Ovaleap® is equivalent to Gonal-f® with respect to the number of oocytes retrieved in infertile but ovulatory women undergoing assisted reproductive technology (ART) therapy.
  
  
  METHODS
  This multinational, multicenter, randomized (1:1), active-controlled, assessor-blind, comparative study included infertile normally gonadotrophic women 18 to 37 years old with a body mass index of 18 to 29 kg/m(2) and regular menstrual cycles of 21 to 35 days undergoing ART therapy. During a 5-day fixed-dose phase, women received 150 IU/day of Ovaleap® (n = 153) or Gonal-f® (n = 146), followed by an up to 15-day dose-adaptation phase during which doses could be adjusted every 3 to 5 days, up to a maximum of 450 IU/day. Ovaleap® was to be deemed equivalent to Gonal-f® if the two-sided 0.95 confidence interval (CI) for the difference in the number of oocytes retrieved fell within the equivalence range of ±3 oocytes.
  
  
  RESULTS
  Similar numbers of oocytes were retrieved in the 2 treatment groups. The mean ± SD number of oocytes retrieved was 12.2 ± 6.7 in the Ovaleap® group and 12.1 ± 6.7 in the Gonal-f® group (intent-to-treat [ITT] population). Regression analysis estimated a mean difference of 0.03 oocytes between the treatment groups (95 % CI: -0.76-0.82), which was well within the prespecified equivalence range of ±3 oocytes. Ovaleap® and Gonal-f® showed favorable and comparable safety profiles, with no unexpected safety findings.
  
  
  CONCLUSIONS
  Ovaleap® has shown the same efficacy and safety as Gonal-f® for stimulation of follicular development in infertile women (up to 37 years of age) who are undergoing ART therapy.
  
  
  BACKGROUND
  EudraCT: 2009-017674-20. Current controlled trials: ISRCTN74772901 . Date of trial registration: 19 March 2010.
authors.affiliation: Department of Gynecological Endocrinology and Reproductive Medicine, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany. thomas_strowitzki@med.uni-heidelberg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Strowitzki
authors.affiliation: Centre for Reproductive Medicine, Cryobank, 15879, Bialystok, Poland. kuczynski@umb.edu.pl.|Department of Gynaecology and Gynaecological Oncology, Medical University, 15089, Bialystok, Poland. kuczynski@umb.edu.pl.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kuczynski
authors.affiliation: Merckle GmbH, A Member of The Teva Group, 89079, Ulm, Germany. Arnd.Mueller@ratiopharm.de.
authors.forename: Arnd
authors.initials: A
authors.lastname: Mueller
authors.affiliation: Merckle GmbH, A Member of The Teva Group, 89079, Ulm, Germany. Peter.Bias@ratiopharm.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Bias
mesh_terms: D000328:Adult; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D054315:Oocyte Retrieval; D009865:Oocytes / Q000187:drug effects; D010062:Ovulation Induction / Q000379:methods*; D017060:Patient Satisfaction; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012044:Regression Analysis; D016037:Single-Blind Method
chemical_list: D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; C571801:follitropin alfa