PMID- 18348746
OWN - NLM
STAT- MEDLINE
DCOM- 20080613
LR  - 20190911
IS  - 1473-4877 (Electronic)
IS  - 0300-7995 (Linking)
VI  - 24
IP  - 4
DP  - 2008 Apr
TI  - Bioequivalence of recombinant human FSH and recombinant human LH in a fixed 2:1 
      combination: two phase I, randomised, crossover studies.
PG  - 1199-208
AB  - OBJECTIVES: To assess bioequivalence of recombinant human follicle stimulating 
      hormone (r-hFSH, follitropin alfa) and recombinant human luteinising hormone 
      (r-hLH, lutropin alfa) in a fixed 2:1 combination (Pergoveris) compared with 
      injection of each of the hormones separately. RESEARCH DESIGN AND METHODS: Two, 
      two-way crossover, phase I studies in healthy female volunteers after 
      gonadotrophin-releasing hormone agonist down-regulation. Volunteers were 
      randomised to the order in which they received subcutaneous injections. In the 
      r-hFSH study, volunteers received one injection of r-hFSH (300 IU) and one of 
      r-hFSH (300 IU)/r-hLH (150 IU) > or = 7 days apart; in the r-hLH study they 
      received r-hLH (450 IU) and r-hFSH (900 IU)/r-hLH (450 IU) > 21 days apart. MAIN 
      OUTCOME MEASURES: The serum concentration-time profiles of FSH in the r-hFSH 
      study and LH in the r-hLH study from zero to the last measurable concentration 
      (AUC(0-last)) and the peak FSH/LH serum concentrations (C(max)) were assessed by 
      non-compartmental analysis. The pre-defined range for bioequivalence was 0.8-1.25 
      for 90% confidence intervals (CI) of the ratio (fixed combination/single 
      gonadotrophin) of the mean for each pharmacokinetic parameter. RESULTS: 
      Bioequivalence criteria were met for the r-hFSH study (n = 34) for C(max) (ratio 
      of means 1.0024, 90% confidence interval (CI) 0.9611-1.0454) and AUC(0-last) 
      (ratio of means 1.0167, 90% CI 0.9933-1.0407), and for the r-hLH study (n = 63) 
      for C(max) (ratio of means 0.9687, 90% CI 0.9194-1.0207) and AUC(0-last) (ratio 
      of means 0.9753, 90% CI 0.8990-1.0581). In the r-hFSH study, 20 adverse events 
      (AEs) were reported after injection of r-hFSH and 20 after r-hLH/r-hFSH. In the 
      r-hLH study, 179 AEs were reported after injection of r-hLH and 193 after the 
      fixed-dose combination. Across both studies, headache was the most commonly 
      reported AE. No serious AEs occurred. CONCLUSIONS: These studies demonstrated 
      bioequivalence between r-hFSH and r-hLH administered alone or in fixed 2:1 
      combination. The 2:1 combination of follitropin alfa and lutropin alfa allows 
      administration of both recombinant gonadotrophins in a single injection.
FAU - Picard, M
AU  - Picard M
AD  - Merck Serono International SA, Geneva, Switzerland.
FAU - Rossier, C
AU  - Rossier C
FAU - Papasouliotis, O
AU  - Papasouliotis O
FAU - Lugan, I
AU  - Lugan I
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20080317
PL  - England
TA  - Curr Med Res Opin
JT  - Current medical research and opinion
JID - 0351014
RN  - 0 (Follicle Stimulating Hormone, Human)
RN  - 0 (Recombinant Proteins)
RN  - 9002-67-9 (Luteinizing Hormone)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Follicle Stimulating Hormone, Human/administration & 
      dosage/*pharmacokinetics/therapeutic use
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Luteinizing Hormone/administration & dosage/*pharmacokinetics/therapeutic use
MH  - Recombinant Proteins/*pharmacokinetics
MH  - Therapeutic Equivalency
EDAT- 2008/03/20 09:00
MHDA- 2008/06/14 09:00
CRDT- 2008/03/20 09:00
PHST- 2008/03/20 09:00 [pubmed]
PHST- 2008/06/14 09:00 [medline]
PHST- 2008/03/20 09:00 [entrez]
AID - 4409 [pii]
AID - 10.1185/030079908x291949 [doi]
PST - ppublish
SO  - Curr Med Res Opin. 2008 Apr;24(4):1199-208. doi: 10.1185/030079908x291949. Epub 
      2008 Mar 17.