Clinical trial NCT04902131: A Study Comparing MENOPUR in a Pen Formulation With a Powder and Solvent Formulation in Healthy Women
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Infertility, Female
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-05-26
Enrollment: 95
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetic parameter of FSH: AUCt
timeFrame: 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
measure: Pharmacokinetic parameter of FSH: Cmax
timeFrame: 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 outcomes:
measure: Pharmacokinetic parameter of FSH: AUCinf
timeFrame: 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
measure: Pharmacokinetic parameter of FSH: Tmax
timeFrame: 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
measure: Pharmacokinetic parameter of FSH: CL/F
timeFrame: 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
measure: Pharmacokinetic parameter of FSH: Vz/F
timeFrame: 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
measure: Pharmacokinetic parameter of FSH: λz
timeFrame: 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
measure: Pharmacokinetic parameter of FSH: t½
timeFrame: 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
measure: Pharmacokinetic parameter of human chorionic gonadotrophin (hCG): AUCt
timeFrame: 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
measure: Pharmacokinetic parameter of hCG: AUCinf
timeFrame: 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
measure: Pharmacokinetic parameter of hCG: Cmax
timeFrame: 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
measure: Pharmacokinetic parameter of LH: AUCt
timeFrame: 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
measure: Pharmacokinetic parameter of LH: Cmax
timeFrame: 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
measure: Frequency of adverse events (AEs) stratified by intensity
timeFrame: From signing of the informed consent up to the end-of-trial (11 to 18 days after the last IMP administration)
measure: Frequency of injection site reactions stratified by intensity
timeFrame: 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)
measure: Change from baseline of vital signs (systolic and diastolic blood pressure)
timeFrame: 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)
measure: Change from baseline of vital sign (pulse)
timeFrame: 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)
measure: Change from baseline of vital sign (body temperature)
timeFrame: 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)
measure: Change from baseline of 12-lead electrocardiogram (ECG): Heart rate
timeFrame: 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)
measure: Change from baseline of 12-lead ECG: PR interval
timeFrame: 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)
measure: Change from baseline of 12-lead ECG: RR interval
timeFrame: 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)
measure: Change from baseline of 12-lead ECG: QRS interval
timeFrame: 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)
measure: Change from baseline of 12-lead ECG: QT interval
timeFrame: 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)
measure: Change from baseline of 12-lead ECG: QTc interval
timeFrame: 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)
measure: Change from baseline of 12-lead ECG: QRS axis
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Albumin
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Glucose
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Calcium
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Chloride
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Cholesterol
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Phosphate
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Potassium
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Sodium
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Urea (blood urea nitrogen)
timeFrame: 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)
measure: Change from baseline of clinical chemistry: C-reactive protein
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Creatinine, Total bilirubin
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Thyroid stimulating hormone
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Free triiodothyronine
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Free thyroxine
timeFrame: 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)
measure: Change from baseline of clinical chemistry: FSH
timeFrame: 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)
measure: Change from baseline of clinical chemistry: Estradiol
timeFrame: 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)
measure: Change from baseline of haematology parameter: Haematocrit
timeFrame: 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)
measure: Change from baseline of haematology parameter: Haemoglobin
timeFrame: 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)
measure: Change from baseline of haematology parameter: Mean cellular volume
timeFrame: 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)
measure: Change from baseline of haematology parameter: Mean corpuscular haemoglobin content
timeFrame: 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)
measure: Change from baseline of haematology parameter: Mean corpuscular haemoglobin concentration
timeFrame: 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)
measure: Change from baseline of haematology parameter: Red blood cell (RBC) count
timeFrame: 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)
measure: Change from baseline of haematology parameter: Platelet count
timeFrame: 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)
measure: Change from baseline of haematology parameter: Reticulocytes
timeFrame: 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)
measure: Change from baseline of haematology parameter: White blood cell count
timeFrame: 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)
measure: Change from baseline of urinalysis parameter: Protein
timeFrame: 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)
measure: Change from baseline of urinalysis parameter: Glucose
timeFrame: 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)
measure: Change from baseline of urinalysis parameter: Bilirubin
timeFrame: 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)
measure: Change from baseline of urinalysis parameter: pH and Specific Gravity
timeFrame: 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)
measure: Change from baseline of urinalysis parameter: Nitrite
timeFrame: 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)
measure: Change from baseline of urinalysis parameter: Ketone
timeFrame: 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)
measure: Change from baseline of urinalysis parameter: Urobilinogen
timeFrame: 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)
measure: Change from baseline of urinalysis parameter: Blood
timeFrame: 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)
measure: Change from baseline of urinalysis parameter: Leukocytes
timeFrame: 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)
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Ferring investigational site
state: Gaoxin District
city: Nanjing
country: China
facility: Ferring investigational site
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References: