Rekovelle PK Trial in Chinese Women

Study Overview
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Brief Summary
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FE 999049 is a gonadotropin preparation containing recombinant human follicle stimulating hormone (rhFSH) under development by Ferring Pharmaceuticals. It is intended for controlled ovarian stimulation for the development of multiple follicles in women undergoing assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycle. In previous trials the exposure to and dose proportionality of FE 999049 in a clinically relevant dose range in Caucasian and Japanese healthy women have been shown to be very similar. This is a trial in healthy Chinese women investigating the pharmacokinetics, safety, and tolerability of a single subcutaneous dose of FE 999049.

Official Title
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An Open-label Trial Investigating the Pharmacokinetics of FE 999049 Given as a Single Subcutaneous Dose in Gonadotropin Down-regulated Healthy Chinese Women

Conditions
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Infertility

Intervention / Treatment
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* Drug: Follitropin Delta


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female of Chinese origin, with two ethnic Chinese parents and four ethnic Chinese grandparents 21-40 years of age (both inclusive) Willing to stop using combined oral contraceptives (COC) in relation to the first DECAPEPTYL Depot administration on Day -28 Agrees to use a double barrier method of contraception between Day -63 and Day 28, if not abstinent. A double barrier method of contraception should also be used after Day 28 until menses resumes or until another contraceptive method has been established Normal menstrual cycles with a range of 24-35 days in the absence of oral contraceptives Serum FSH less than equal to (≤)5 IU/L on Day -3 and Day -1 Body mass index (BMI) of 18.5 -25 kg/m^2 (both inclusive) Negative serology for human immunodeficiency virus (HIV) antibody, hepatitis B (surface antigen), hepatitis C antibody, and syphilis bacteria Healthy according to medical history, physical examination, gynaecological examination, ECG, blood pressure, and laboratory profile of blood and urine Negative urine drug screen and alcohol breath test at screening and on Day -1 Non-smoker or light smoker (≤ 5 cigarettes/day) for at least 6 months prior to trial Exclusion Criteria: Presence or a history of clinically significant diseases of the renal, hepatic, gastrointestinal, cardiovascular, or musculoskeletal systems, or presence or history of clinically significant reproductive, psychiatric, immunological, endocrine or metabolic diseases Cancer within the last 5 years except for adequately managed basal cell carcinoma and squamous cell carcinoma of the skin Pregnancy or breastfeeding Current or a history of endocrine abnormalities such as hyperprolactinaemia, polycystic ovary syndrome or other ovarian dysfunction, tumours of the pituitary gland or hypothalamus, thyroid or adrenal disease Clinically significant findings on the trans-vaginal ultrasound, cytology, gynaecological or breast examination at screening or on Day -1 including ovarian cysts or tumours of the ovaries or uterus Contraindications for the use of gonadotropins and gonadotropin-releasing hormone (GnRH) agonists Previously treated with gonadotropins within the last 6 months prior to screening History within the last two years or current abuse of alcohol or drugs Presence or history of severe allergy or anaphylactic reactions Intake of prescribed medication, over-the-counter (OTC) medication, or herbal medicines, with the exceptions of COC, cromoglycate, and paracetamol according to the labelling, within 2 weeks or 5 half-lives of the drug, whichever is longer, prior to first dose of DECAPEPTYL Depot. Topical treatments of bacterial or fungal infection are allowed if stopped before first dose of IMP Intake of any non-registered investigational drug within the last 12 weeks preceding screening, or longer if judged by the investigator to possibly influence the outcome of the current trial High daily consumption of caffeine-containing beverages (e.g. more than five cups of coffee or equivalent) with a risk of withdrawal symptoms arising during the trial that may confound the safety evaluation Blood donation or major blood loss (greater than equal to [≥]500 mL) within the last 8 weeks, or plasma donation with the last 4 weeks preceding the first day of IMP dosing Current non-smokers or light smoker with a history of long-term, heavy smoking (>10 pack-years) Previously dosed in this trial Mental incapacity or language barrier precluding adequate understanding or co-operation Considered by the investigator to be unsuitable to participate in the trial for any other reason

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Follitropin delta 12 μg<br>Participants received single subcutaneous abdominal injection of Follitropin delta 12 μg on Day 1. | Drug: Follitropin Delta<br>* Solution for Injection, subcutaneous administration<br>* Other names: FE 999049;|
| Experimental: Follitropin delta 18 μg<br>Participants received single subcutaneous abdominal injection of Follitropin delta 18 μg on Day 1. | Drug: Follitropin Delta<br>* Solution for Injection, subcutaneous administration<br>* Other names: FE 999049;|
| Experimental: Follitropin delta 24 μg<br>Participants received single subcutaneous abdominal injection of Follitropin delta 24 μg on Day 1. | Drug: Follitropin Delta<br>* Solution for Injection, subcutaneous administration<br>* Other names: FE 999049;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Serum Concentration-time Curve From Dosing to Infinity (AUC) | Area under the concentration-time curve from dosing to infinity. | At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose | 
| Area Under the Serum Concentration-time Curve From Dosing up to Time t (AUCt) | AUCt is defined as the area under the serum concentration-time curve from dosing up to time t, where t is the last time point at which the concentration is above the lower limit of quantification. | At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose | 
| Maximum Serum Concentration Observed (Cmax) | Maximum concentration observed in serum. | At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose | 
| Time of Maximum Observed Serum Concentration (Tmax) | Time of maximum observed concentration in serum. | At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose | 
| Apparent Total Systemic Clearance (CL/F) |  | At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose | 
| Apparent Volume of Distribution Associated With the Terminal Phase (VZ/F) |  | At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose | 
| Terminal Elimination Half-life (t½) |  | At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Significant Abnormal Changes in Electrocardiogram (ECG) | Number of participants with clinically significant abnormal changes in ECG are presented. | At screening, on Day -1, at 12, 24, 48 hours postdose, and at the follow-up visit (Day 11) | 
| Number of Participants With Clinically Significant Abnormal Changes in Vital Signs | Number of participants with clinically significant abnormal changes in vital signs (systemic blood pressures, heart rate and body temperature) are presented. | At screening, on Day -1, at 12, 24, 48 hours postdose, and at the follow-up visit (Day 11) | 
| Number of Participants With Clinically Significant Abnormal Findings in Laboratory Parameters | Number of participants with clinically significant abnormal findings in laboratory parameters (clinical chemistry, haematology, urinalysis) are presented. | At screening, on Day -1 and Day 3, and at the follow-up visit (Day 11) | 
| Number of Participants With Adverse Events (AEs) and Type of AEs | An AE is any untoward medical occurrence in a participant participating in a clinical trial. Number of participants with any AE (serious or non-serious) and type of AEs ( mild, moderate, severe) are presented. | From signed informed consent until the end-of-trial visit (Day 28) | 
| Frequency of Injection Site Reactions | The injection site reactions (redness, pain, itching, swelling, and bruising) will be assessed by the investigator after injection, 30 minutes, and 24 hours after administration of the IMP. Each injection site reaction will be assessed as none, mild, moderate, or severe. | Immediately, 30 minutes, and 24 hours after administration | 
| Number of Participants With Treatment-induced Anti-follicle-stimulating Hormone (Anti-FSH) Antibodies |  | On Day 1 predose, Day 7, and Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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In vitro fertilisation, Controlled ovarian stimulation