PMID- 26621118
OWN - NLM
STAT- MEDLINE
DCOM- 20161020
LR  - 20240324
IS  - 1477-7827 (Electronic)
IS  - 1477-7827 (Linking)
VI  - 13
DP  - 2015 Dec 1
TI  - Phase I, two-way, crossover study to demonstrate bioequivalence and to compare 
      safety and tolerability of single-dose XM17 vs Gonal-f(R) in healthy women after 
      follicle-stimulating hormone downregulation.
PG  - 130
LID - 10.1186/s12958-015-0124-y [doi]
LID - 130
AB  - 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((R))) 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((R)) 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((R)) 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-infinity and t1/2 were also ~1, and no difference in tmax was detected. 
      Both XM17 and Gonal-f((R)) 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(R) was statistically demonstrated. XM17 was well tolerated both 
      systemically and locally. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02592031 ; 
      date of registration: 28 October, 2015.
FAU - Lammerich, Andreas
AU  - Lammerich A
AD  - Merckle GmbH, Member of the Teva Group, Graf-Arco-Str. 3, 89079, Ulm, Germany. 
      andreas.lammerich@ratiopharm.de.
FAU - Mueller, Arnd
AU  - Mueller A
AD  - Merckle GmbH, Member of the Teva Group, Graf-Arco-Str. 3, 89079, Ulm, Germany. 
      Arnd.Mueller@ratiopharm.de.
FAU - Bias, Peter
AU  - Bias P
AD  - Merckle GmbH, Member of the Teva Group, Graf-Arco-Str. 3, 89079, Ulm, Germany. 
      Peter.Bias@ratiopharm.de.
LA  - eng
SI  - ClinicalTrials.gov/NCT02592031
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20151201
PL  - England
TA  - Reprod Biol Endocrinol
JT  - Reproductive biology and endocrinology : RB&E
JID - 101153627
RN  - 0 (Follicle Stimulating Hormone, Human)
RN  - 0 (Recombinant Proteins)
RN  - 0 (follitropin alfa)
RN  - 0F65R8P09N (Goserelin)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cross-Over Studies
MH  - Female
MH  - Follicle Stimulating Hormone, Human/adverse 
      effects/*pharmacokinetics/pharmacology
MH  - Gonadotropin-Releasing Hormone/agonists
MH  - Goserelin/pharmacology
MH  - Humans
MH  - Recombinant Proteins/adverse effects/pharmacokinetics/pharmacology
MH  - Therapeutic Equivalency
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC4665917
EDAT- 2015/12/02 06:00
MHDA- 2016/10/21 06:00
PMCR- 2015/12/01
CRDT- 2015/12/02 06:00
PHST- 2015/07/08 00:00 [received]
PHST- 2015/08/20 00:00 [accepted]
PHST- 2015/12/02 06:00 [entrez]
PHST- 2015/12/02 06:00 [pubmed]
PHST- 2016/10/21 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - 10.1186/s12958-015-0124-y [pii]
AID - 124 [pii]
AID - 10.1186/s12958-015-0124-y [doi]
PST - epublish
SO  - Reprod Biol Endocrinol. 2015 Dec 1;13:130. doi: 10.1186/s12958-015-0124-y.