Clinical trial NCT04150861: Rekovelle PK Trial in Chinese Women
Official title: An Open-label Trial Investigating the Pharmacokinetics of FE 999049 Given as a Single Subcutaneous Dose in Gonadotropin Down-regulated Healthy Chinese Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Infertility
Keywords: In vitro fertilisation
Controlled ovarian stimulation
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-11-05
Enrollment: 24
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Serum Concentration-time Curve From Dosing to Infinity (AUC)
timeFrame: 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
measure: Area Under the Serum Concentration-time Curve From Dosing up to Time t (AUCt)
timeFrame: 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
measure: Maximum Serum Concentration Observed (Cmax)
timeFrame: 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
measure: Time of Maximum Observed Serum Concentration (Tmax)
timeFrame: 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
measure: Apparent Total Systemic Clearance (CL/F)
timeFrame: 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
measure: Apparent Volume of Distribution Associated With the Terminal Phase (VZ/F)
timeFrame: 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
measure: Terminal Elimination Half-life (t½)
timeFrame: 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 outcomes:
measure: Number of Participants With Clinically Significant Abnormal Changes in Electrocardiogram (ECG)
timeFrame: At screening, on Day -1, at 12, 24, 48 hours postdose, and at the follow-up visit (Day 11)
measure: Number of Participants With Clinically Significant Abnormal Changes in Vital Signs
timeFrame: At screening, on Day -1, at 12, 24, 48 hours postdose, and at the follow-up visit (Day 11)
measure: Number of Participants With Clinically Significant Abnormal Findings in Laboratory Parameters
timeFrame: At screening, on Day -1 and Day 3, and at the follow-up visit (Day 11)
measure: Number of Participants With Adverse Events (AEs) and Type of AEs
timeFrame: From signed informed consent until the end-of-trial visit (Day 28)
measure: Frequency of Injection Site Reactions
timeFrame: Immediately, 30 minutes, and 24 hours after administration
measure: Number of Participants With Treatment-induced Anti-follicle-stimulating Hormone (Anti-FSH) Antibodies
timeFrame: On Day 1 predose, Day 7, and Day 28
Other outcomes:
Locations:
city: Nanjing
country: China
facility: First Hospital Affiliated to Nanjing Medical University Jiangsu Province Hospital
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References:
citation: Shao F, Jiang Y, Ding S, Larsson P, Pinton P, Jonker DM. Pharmacokinetics and Safety of Follitropin Delta in Gonadotropin Down-Regulated Healthy Chinese Women. Clin Drug Investig. 2023 Jan;43(1):37-44. doi: 10.1007/s40261-022-01232-9. Epub 2022 Dec 7.