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

Study Overview
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Brief Summary
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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.

Official Title
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An Open, Randomized, Two-way Cross-over Phase I Study to Compare the Bioavailability, Safety and Tolerability of Single s.c. Doses of 300 IU XM17 With 300 IU Gonal-f® in 36 Healthy, Down-regulated Young Women

Conditions
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Bioequivalence

Intervention / Treatment
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* Drug: XM17
* Drug: Gonal-f®
* Drug: Zoladex®


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XM17<br>XM17 will be administered by 1 mL syringes in graduated steps of 0.01 mL. | Drug: XM17<br>* 300 IU corresponds to an injection volume of 0.5 mL.<br>|
| Experimental: Gonal-f®<br>Gonal-f® will be provided in pens with integrated vials of 0.5 mL | Drug: Gonal-f®<br>* 300 IU corresponds to an injection volume of 0.5 mL.<br>* Other names: follitropin alfa;|
| Active Comparator: Zoladex®<br>Zoladex® 3.6 mg will be administered by subcutaneous injection | Drug: Zoladex®<br>* 3.6 mg<br>* Other names: goserelin acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of single dose pharmacokinetics (Cmax) | XM17 and Gonal-f® tested statistically for bioequivalence. | 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 | 
| Comparison of single dose pharmacokinetics (AUC0-t) | XM17 and Gonal-f® tested statistically for bioequivalence. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics AUC0-∞ | Area under the XM17 / Gonal-f® concentration time curve from time 0 extrapolated to infinity | 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 | 
| Pharmacokinetics AUC0-168h | Area under the XM17 / Gonal-f® concentration time curve from time 0 to 168 h | 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 | 
| Pharmacokinetics Cmax,obs | Maximum XM17 / Gonal-f® concentration determined during the interval of sample taking | 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 | 
| Pharmacokinetics Tmax | Time to maximum XM17 / Gonal-f® concentration | 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 | 
| Pharmacokinetics λZ | Apparent terminal elimination rate constant. | 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 | 
| Pharmacokinetics t1/2 | Apparent terminal elimination half life. | 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 | 
| Pharmacokinetics CL/F | Serum clearance after dosing | 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 | 
| Pharmacokinetics Vz/F | Volume of Distribution during the terminal phase after extravascular administration | 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 | 
| Percentage of participants with adverse events |  | Signing of informed consent to final data collection (27 days) |