Clinical trial NCT03735030: Comparative Bioavailability Study of Human Chorionic Gonadotropin (hCG)-IBSA Versus a Marketed hCG Formulation
Official title: Comparative Bioavailability Study of Choriomon® (IBSA) Versus a Marketed hCG Formulation, Following Subcutaneous Administration in Healthy Women. Single-dose, Open-label, Randomized, Two-period, Two-way Cross-over, Bioavailability Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Infertility
Lead sponsor: IBSA Institut Biochimique SA
Sponsor class: INDUSTRY
First posted: 2018-11-08
Enrollment: 26
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: In the present study, the rate and extent of hCG absorption will be compared between the two treatments in healthy women aged 20 to 45 years.


Eligibility criteria: Inclusion Criteria:

1. Informed consent: signed written informed consent before inclusion in the study;
2. Sex and Age: healthy pre-menopausal women, 20-45 years old inclusive;
3. Body Mass Index: 18.5-30 kg/m2 inclusive;
4. Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 50-90 bpm, measured after 5 min at rest in the sitting position;
5. Hormonal oral contraceptives: Combined oral contraceptive pill for at least 2 months before the screening visit;
6. Menstrual cycle: history of a normal menstrual cycle before combined oral contraceptive pill use;
7. hCG: endogenous hCG levels \<1.2 IU/L at screening and Day -1, Period 1;
8. Pituitary down-regulation: Luteinizing hormone (LH) \<5 IU/L; Follicle stimulating hormone (FSH) \<4 IU/L at Day -1, Period 1;
9. Papanicolaou smear (PAP) test: negative or not clinically significant PAP test results within 12 months before the screening visit or at screening;
10. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study;
11. Additional contraception: study participants with an active sexual life must be using one additional contraceptive method, as follows:

    1. A male sexual partner who agrees to use a male condom with spermicide
    2. A sterile sexual partner.

Exclusion Criteria:

1. Contraindications: any contraindications to combined oral contraceptive pill or gonadotropins;
2. Electrocardiogram 12-leads (supine position): clinically significant abnormalities;
3. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study;
4. Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness;
5. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study;
6. Diseases: relevant history of cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, immunological, dermatological, endocrine, genitourinary (e.g. polycystic ovary disease, ovarian cysts, primary ovarian failure, early menopause or abnormal bleeding of undetermined origin), malignant neoplasia, neurological or psychiatric diseases that could interfere with the aim of the study;
7. Medications: treatment with gonadotropin preparations within 6 months prior to screening; other medications, including over the counter medications and herbal remedies, for 2 weeks before the start of the study;
8. Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study;
9. Blood donation: blood donations for 3 months before this study;
10. Drug, alcohol, caffeine, tobacco: history of drug, alcohol (\>1 drink/day defined according to the United Stated Department of Agriculture (USDA) Dietary Guidelines 2015-2020; 17), caffeine (\>5 cups coffee/tea/day) or tobacco abuse (≥10 cigarettes/day);
11. Drug test: positive result at the drug test at screening or day -1, Period 1;
12. Alcohol test: positive alcohol breath test on day -1;
13. Diet: abnormal diets (\<1600 or \>3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians;
14. Pregnancy: positive or missing pregnancy test at screening or at day -1 of each period; pregnant or lactating women.

Primary outcomes:
measure: Rate of absorption (Cmax)
timeFrame: 192 hours post dose
measure: Extent of absorption (AUC0-t), Area under the concentration-time curve
timeFrame: 192 hours post dose
Secondary outcomes:
measure: t1/2: Half-life
timeFrame: 192 hours post dose
measure: Tmax: Time to achieve Cmax
timeFrame: 192 hours post dose
measure: AUC0-∞: Area under the concentration-time curve extrapolated to infinity
timeFrame: 192 hours post dose
measure: Frel : Relative bioavailability
timeFrame: 192 hours post dose
measure: Treatment emergent adverse events (TEAEs)
timeFrame: through study completion up to 46 days.
Other outcomes:
Locations:
city: Arzo
country: Switzerland
facility: CROSS Research SA
state: Ticino
Study officials:
References:
citation: Radicioni M, Leuratti C, Cometti B. Randomized Pharmacokinetic Study of a Highly Purified Human Chorionic Gonadotropin and of a Recombinant Human Chorionic Gonadotropin Following Single Subcutaneous Administration in Healthy Women. Clin Drug Investig. 2022 Mar;42(3):199-206. doi: 10.1007/s40261-022-01118-w. Epub 2022 Feb 9.