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Study to Compare the Bioavailability, Safety and Tolerability of XM17 in Healthy, Down Regulated Young Women

Phase 1
Completed
Conditions
Bioequivalence
Interventions
Registration Number
NCT02592031
Lead Sponsor
Merckle GmbH
Brief Summary

Aim of this study is to demonstrate the bioequivalence of single subcutaneous doses of XM17 and Gonal-f® in a confirmatory design. Furthermore, safety and tolerability will be assessed in human healthy female subjects. Only female subjects will be included in the study to reach the objectives of the study.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
49
Inclusion Criteria
  • Having signed written informed consent
  • Healthy female subjects of any racial origin
  • 18-39 years at the time of screening
  • Body mass index (BMI) between 18-29 kg/m2 and a body weight of ≥ 50 kg
  • Use of oral contraceptives for contraceptive purposes only and not for regularization of menstrual cycle, for at least 3 months
  • Normal uterus and two functioning ovaries
  • Agrees to use an adequate method of contraception during the study
  • Non-smoking or moderate smokers of < 10 cigarettes a day
Exclusion Criteria
  • Pregnancy
  • Polycystic ovary syndrome, impaired ovarian function, severe endometriosis class III or IV, submucosal myoma uteri
  • History of endocrine abnormalities with treatment within the last six months.
  • Contraindications for the use of gonadotropins and goserelin
  • Breast-feeding or being within a period of 2 months after delivery or abortion.
  • Use of an injectable hormonal contraceptive within a period of 6 months prior to screening
  • Treatment in the previous three months with any drug known to have a well-defined potential for toxicity to a major organ

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
XM17XM17XM17 will be administered by 1 mL syringes in graduated steps of 0.01 mL.
Gonal-f®Gonal-f®Gonal-f® will be provided in pens with integrated vials of 0.5 mL
Zoladex®Zoladex®Zoladex® 3.6 mg will be administered by subcutaneous injection
Primary Outcome Measures
NameTimeMethod
Comparison of single dose pharmacokinetics (Cmax)Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

XM17 and Gonal-f® tested statistically for bioequivalence.

Comparison of single dose pharmacokinetics (AUC0-t)Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

XM17 and Gonal-f® tested statistically for bioequivalence.

Secondary Outcome Measures
NameTimeMethod
Pharmacokinetics AUC0-168hPre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Area under the XM17 / Gonal-f® concentration time curve from time 0 to 168 h

Pharmacokinetics AUC0-∞Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Area under the XM17 / Gonal-f® concentration time curve from time 0 extrapolated to infinity

Pharmacokinetics λZPre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Apparent terminal elimination rate constant.

Pharmacokinetics Cmax,obsPre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Maximum XM17 / Gonal-f® concentration determined during the interval of sample taking

Pharmacokinetics TmaxPre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Time to maximum XM17 / Gonal-f® concentration

Pharmacokinetics t1/2Pre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Apparent terminal elimination half life.

Pharmacokinetics CL/FPre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Serum clearance after dosing

Pharmacokinetics Vz/FPre-dose at -10 min, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Volume of Distribution during the terminal phase after extravascular administration

Percentage of participants with adverse eventsSigning of informed consent to final data collection (27 days)
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