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

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

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

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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