A Study Comparing MENOPUR in a Pen Formulation With a Powder and Solvent Formulation in Healthy Women

Study Overview
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Brief Summary
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MENOPUR is a human menotrophin product, with a combination of human follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity. Human chorionic gonadotrophin (hCG) is the major contributor to the LH activity in the product. MENOPUR is approved in more than 130 countries for a variety of strengths and indications. In China, MENOPUR, 75 IU is approved for controlled ovarian hyperstimulation in relation to assisted reproductive technology (ART). The current trial is intended for supporting marketing authorization approval of a new formulation of MENOPUR in China. MENOPUR is currently available in China as a powder and solvent for solution for injection, containing 75 IU of FSH and 75 IU of LH activity. A new liquid formulation is developed by Ferring Pharmaceuticals for administration with a disposable pre-filled injection pen, containing 600 IU of FSH and 600 IU of LH activity. MENOPUR solution for injection in pre-filled pen, 600 IU/0.96 mL is the test product and MENOPUR powder and solvent for solution for injection, 75 IU is the reference product in this trial.

Official Title
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An Open-label, Randomised, 2-way Crossover, Single-dose, Bioequivalence Trial Comparing MENOPUR Solution for Injection in Pre-filled Pen and MENOPUR Powder and Solvent for Solution for Injection, After Subcutaneous Administration in Healthy Women

Conditions
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Infertility, Female

Intervention / Treatment
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* Drug: A MENOPUR solution for injection in pre-filled pen, 600 IU/0.96 mL
* Drug: A MENOPUR powder including solvent for solution for injection, 75 IU


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Chinese women between the ages of 21 to 40 years at the time of signing the informed consent form Non-users or users of the combined oral contraceptive (COC) pill who describe experiencing menstrual cycles of 24 to 35 days in duration (both inclusive) Healthy according to medical history, physical and gynecological examinations, vital signs, 12-lead electrocardiogram, and laboratory tests in blood and urine Serum FSH levels ≤5 IU/L and estradiol levels ≤50 pg/mL on Day -3 and Day -1 in TP1 Key Exclusion Criteria: Any finding at the gynecological examination, transvaginal ultrasound or by cervical smear that is considered medically important A history of medical problems that could affect the functioning of the reproductive organs (ovaries and womb) A history of any medical problems that may prevent use of the combined hormonal contraceptive pill

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 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: MENOPUR pen<br> | Drug: A MENOPUR solution for injection in pre-filled pen, 600 IU/0.96 mL<br>* Single dose cross-over bioequivalence trial<br>* Other names: Highly purified menotropin;|
| Active Comparator: MENOPUR powder<br> | Drug: A MENOPUR powder including solvent for solution for injection, 75 IU<br>* Single dose cross-over bioequivalence trial<br>* Other names: Highly purified menotropin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameter of FSH: AUCt | AUCt is defined as area under the concentration-time curve from dosing to the last time point when the baseline adjusted concentration is above zero. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before investigational medicinal product [IMP] administration), and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 168 and 216 hours after administration | 
| Pharmacokinetic parameter of FSH: Cmax | Cmax is defined as baseline adjusted maximum observed concentration. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before IMP administration), and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 168 and 216 hours after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameter of FSH: AUCinf | AUCinf is defined as area under concentration-time curve from dosing to infinity using baseline adjusted concentrations. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before IMP administration), and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 168 and 216 hours after administration | 
| Pharmacokinetic parameter of FSH: Tmax | Tmax is defined as time of maximum observed concentration. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before IMP administration), and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 168 and 216 hours after administration | 
| Pharmacokinetic parameter of FSH: CL/F | CL/F is defined as apparent systemic clearance. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before IMP administration), and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 168 and 216 hours after administration | 
| Pharmacokinetic parameter of FSH: Vz/F | Vz/F is defined as apparent volume of distribution during terminal phase. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before IMP administration), and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 168 and 216 hours after administration | 
| Pharmacokinetic parameter of FSH: λz | λz is defined as first-order rate constant associated with the terminal (log-linear) portion of the concentration-time curve. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before IMP administration), and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 168 and 216 hours after administration | 
| Pharmacokinetic parameter of FSH: t½ | t½ is defined as terminal half-life. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before IMP administration), and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 168 and 216 hours after administration | 
| Pharmacokinetic parameter of human chorionic gonadotrophin (hCG): AUCt | AUCt is defined as area under the concentration-time curve from dosing to the last time point when the baseline adjusted concentration is above zero. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before IMP administration), and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 168 and 216 hours after administration | 
| Pharmacokinetic parameter of hCG: AUCinf | AUCinf is defined as area under concentration-time curve from dosing to infinity using baseline adjusted concentrations. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before IMP administration), and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 168 and 216 hours after administration | 
| Pharmacokinetic parameter of hCG: Cmax | Cmax is defined as baseline adjusted maximum observed concentration. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before IMP administration), and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 168 and 216 hours after administration | 
| Pharmacokinetic parameter of LH: AUCt | AUCt is defined as area under the concentration-time curve from dosing to the last time point when the baseline adjusted concentration is above zero. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before IMP administration), and 4, 8, 12, 24 and 48 hours after administration | 
| Pharmacokinetic parameter of LH: Cmax | Cmax is defined as baseline adjusted maximum observed concentration. | At -1, -0.5 hours pre-dose, and immediately pre-dose (within 10 min before IMP administration), and 4, 8, 12, 24 and 48 hours after administration | 
| Frequency of adverse events (AEs) stratified by intensity | The frequency of subjects with total AEs and AEs by categories of intensity (mild, moderate, severe) are presented. An AE was any untoward medical occurrence in a subject participating in clinical trial. The intensity of AE was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activities); moderate = disruption of usual activities (disturbing); or severe = inability to work or perform usual activities (unacceptable). | From signing of the informed consent up to the end-of-trial (11 to 18 days after the last IMP administration) | 
| Frequency of injection site reactions stratified by intensity | The presence of injection site reactions (redness, pain, itching, swelling and bruising) immediately, 0.5 hours and 24 hours after the injection are presented. The injection site reactions were assessed as none, mild, moderate and severe. The number of injection site reactions (mild, moderate or severe) based on all assessments performed is presented. | Immediately after administration, and at 0.5 and 24 hours after administration on Day 1 and Day 2 of Treatment period 1 (TP1) and Time period 2 (TP2) | 
| Change from baseline of vital signs (systolic and diastolic blood pressure) | Vital signs comprising systolic and diastolic blood pressure will be presented. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of vital sign (pulse) | Vital sign comprising pulse will be presented. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of vital sign (body temperature) | Vital sign comprising body temperature will be presented. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of 12-lead electrocardiogram (ECG): Heart rate | Change from baseline for 12-lead ECG (heart rate) parameter will be reported. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of 12-lead ECG: PR interval | Change from baseline for 12-lead ECG (PR interval) parameter will be reported. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of 12-lead ECG: RR interval | Change from baseline for 12-lead ECG (RR interval) parameter will be reported. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of 12-lead ECG: QRS interval | Change from baseline for 12-lead ECG (QRS interval) parameter will be reported. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of 12-lead ECG: QT interval | Change from baseline for 12-lead ECG (QT interval) parameter will be reported. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of 12-lead ECG: QTc interval | Change from baseline for 12-lead ECG (QTc interval) parameter will be reported. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of 12-lead ECG: QRS axis | Change from baseline for 12-lead ECG (QRS axis) parameter will be reported. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Blood samples were collected for the analysis of clinical chemistry parameters including: Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase, and Gamma glutamyl transferase. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Albumin | Blood samples were collected for the analysis of clinical chemistry parameter including: Albumin. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Glucose | Blood samples were collected for the analysis of clinical chemistry parameter including: Glucose. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Calcium | Blood samples were collected for the analysis of clinical chemistry parameter including: Calcium. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Chloride | Blood samples were collected for the analysis of clinical chemistry parameter including: Chloride. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Cholesterol | Blood samples were collected for the analysis of clinical chemistry parameter including: Cholesterol. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Phosphate | Blood samples were collected for the analysis of clinical chemistry parameter including: Phosphate. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Potassium | Blood samples were collected for the analysis of clinical chemistry parameter including: Potassium. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Sodium | Blood samples were collected for the analysis of clinical chemistry parameter including: Sodium. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Urea (blood urea nitrogen) | Blood samples were collected for the analysis of clinical chemistry parameter including: Urea (blood urea nitrogen). | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: C-reactive protein | Blood samples were collected for the analysis of clinical chemistry parameter including: C-reactive protein. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Creatinine, Total bilirubin | Blood samples were collected for the analysis of clinical chemistry parameters including: Creatinine, Total bilirubin. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Thyroid stimulating hormone | Blood samples were collected for the analysis of clinical chemistry parameter including: Thyroid stimulating hormone. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Free triiodothyronine | Blood samples were collected for the analysis of clinical chemistry parameter including: Free triiodothyronine. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Free thyroxine | Blood samples were collected for the analysis of clinical chemistry parameter including: Free thyroxine. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: FSH | Blood samples were collected for the analysis of clinical chemistry parameter including: FSH. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of clinical chemistry: Estradiol | Blood samples were collected for the analysis of clinical chemistry parameter including: Estradiol. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of haematology parameter: Haematocrit | Blood samples were collected for the analysis of haematology parameter including: Haematocrit. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of haematology parameter: Haemoglobin | Blood samples were collected for the analysis of haematology parameter including: Haemoglobin. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of haematology parameter: Mean cellular volume | Blood samples were collected for the analysis of haematology parameter including: Mean cellular volume. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of haematology parameter: Mean corpuscular haemoglobin content | Blood samples were collected for the analysis of haematology parameter including: Mean corpuscular haemoglobin content. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of haematology parameter: Mean corpuscular haemoglobin concentration | Blood samples were collected for the analysis of haematology parameter including: Mean corpuscular haemoglobin concentration. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of haematology parameter: Red blood cell (RBC) count | Blood samples were collected for the analysis of haematology parameter including: RBC count. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of haematology parameter: Platelet count | Blood samples were collected for the analysis of haematology parameter including: Platelet count. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of haematology parameter: Reticulocytes | Blood samples were collected for the analysis of haematology parameter including: Reticulocytes. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of haematology parameter: White blood cell count | Blood samples were collected for the analysis of haematology parameter including: White blood cell count. | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of urinalysis parameter: Protein |  | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of urinalysis parameter: Glucose |  | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of urinalysis parameter: Bilirubin |  | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of urinalysis parameter: pH and Specific Gravity |  | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of urinalysis parameter: Nitrite |  | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of urinalysis parameter: Ketone |  | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of urinalysis parameter: Urobilinogen |  | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of urinalysis parameter: Blood |  | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) | 
| Change from baseline of urinalysis parameter: Leukocytes |  | On Day -1 in TP1 and TP2, and at the follow-up (end-of-trial, 11 to 18 days after the last IMP administration) visit. Baseline is defined as pre-administration (Day -1) |