Bioequivalence
Conditions
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.
Interventions
DRUGXM17
300 IU corresponds to an injection volume of 0.5 mL.
DRUGGonal-f®
300 IU corresponds to an injection volume of 0.5 mL.
DRUGZoladex®
3.6 mg
Sponsors
Merckle GmbH
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 39 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Cmax,obs | 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 | Maximum XM17 / Gonal-f® concentration determined during the interval of sample taking |
| Pharmacokinetics Tmax | 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 | Time to maximum XM17 / Gonal-f® concentration |
| Pharmacokinetics λZ | 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 | Apparent terminal elimination rate constant. |
| 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 CL/F | 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 | Serum clearance after dosing |
| Pharmacokinetics Vz/F | 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 | Volume of Distribution during the terminal phase after extravascular administration |
| Percentage of participants with adverse events | Signing of informed consent to final data collection (27 days) | — |
| Pharmacokinetics t1/2 | 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 | Apparent terminal elimination half life. |
| Pharmacokinetics AUC0-168h | 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 to 168 h |
Outcome results
None listed