The Safety and Pharmacokinetics of Primapur and Gonal-f
Condition: Area Under Curve; Pharmacokinetics; Absorption
Intervention: Follitropin alfa (Primapur); Follitropin alfa (Gonal-F)
Intervention description: During the crossover pharmacokinetic phase, after 42 days of combined oral contraceptive (ethinylestradiol and drospirenone) administration subjects with endogenous level of follicle stimulating hormone (FSH) less than 5 IU/l were randomly assigned to receive one of the following treatment sequences:
Sequence A: Single subcutaneous injection of 300 IU Primapur on study day 1, after 10 days of wash out a single subcutaneous injection of 300 IU Gonal-F.
Sequence B: Single subcutaneous injection of 300 IU US Gonal-F on study day 1, after 10 days of wash out a single subcutaneous injection of 300 IU Primapur.; During the crossover pharmacokinetic phase, after 42 days of combined oral contraceptive (ethinylestradiol and drospirenone) administration subjects with endogenous level of follicle stimulating hormone (FSH) less than 5 IU/l were randomly assigned to receive one of the following treatment sequences:
Sequence A: Single subcutaneous injection of 300 IU Primapur on study day 1, after 10 days of wash out a single subcutaneous injection of 300 IU Gonal-F.
Sequence B: Single subcutaneous injection of 300 IU US Gonal-F on study day 1, after 10 days of wash out a single subcutaneous injection of 300 IU Primapur.
Intervention MeSH terms: Follicle Stimulating Hormone
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: follitropin alfa; follicle stimulating hormone; hormones, hormone substitutes, and hormone antagonists; physiological effects of drugs; biosimilar; bioequivalence

Summary:

      The purpose of the current phase I study was to establish bioequivalence, safety, and
      tolerance of single 300 IU subcutaneous dose of follitropin alfa biosimilar (Primapur) in
      comparison to that of reference follitropin alfa preparation (Gonal-F) in healthy young
      female volunteers.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy female volunteers aged 18 to 40 years.

          2. Body mass index (BMI) of 18.5 to 30.0 kg/m2.

          3. Subjects who have used oral contraceptives for at least 2 menstrual cycles before
             study entry.

          4. Regular menstruation cycle (24 to 35 days) before initiation of oral contraception.

          5. Presence of both ovaries.

          6. Subjects who are negative for drugs of abuse and alcohol tests at screening.

          7. Subjects who are healthy as validated by pre study medical history, physical
             examination.

          8. Subjects with acceptable clinical laboratory test results.

          9. A signed informed consent form that confirms in writing the volunteer's consent to
             participate in this clinical study and the volunteer's willingness to comply with all
             physician recommendations and protocol limitations for the time of participation in
             the clinical study.

         10. Ability to comply with the requirements of the protocol.

         11. Participants in the study, as well as their sexual partners, are knowledgeable and
             willing to voluntarily, starting from the week before being included in the study and
             up to 4 weeks after the last dose of the study drug, and in addition to the
             contraceptive used, use at least 1 barrier contraceptive method or spermicide.

        Exclusion Criteria:

          1. Hypersensitivity to follitropin alpha, combined oral contraceptive (ethinylestradiol
             and drospirenone) or excipients.

          2. Allergy, angioedema (hereditary or idiopathic) in history.

          3. Previous history of ovarian hyperstimulation syndrome (OHSS).

          4. Inability to establish a venous catheter for blood sampling.

          5. Presence of polycystic ovaries (PCO) and ovarian cysts.

          6. Neoplasia and a history of malignant disease.

          7. Deep vein thrombosis, pulmonary embolism.

          8. Subjects with impaired thyroid function.

          9. Regular usage or administration of any drugs, including non-prescription drugs,
             vitamins, homeopathic remedies and dietary supplements, less than 2 weeks before the
             study (with the exception of contraceptive pills).

         10. Admission less than 2 months before the start of the study of drugs that have a
             pronounced effect on hemodynamics, liver function, and medication contained follicle
             stimulating hormone (FSH), luteinizing hormone (LH), chorionic gonadotropin (hCG),
             clomiphene, gonadotropin-releasing hormone (GnRH) analogues.

         11. Cardiovascular, bronchopulmonary, nervous, endocrine systems, gastrointestinal tract,
             liver, kidney, hematopoietic, immune systems, mental diseases.

         12. Acute infectious diseases less than 4 weeks before the start of the study.

         13. Systolic pressure less than 100 mm or above 130 mm Hg; diastolic pressure less than 70
             mm or above 90 mm Hg; heart rate less than 60 or more than 80 beats/min.

         14. Blood donation less than 3 months before the start of the study.

         15. Participation in clinical studies of drugs less than 3 months before the start of the
             present study.

         16. More than 5 alcohol units per week (1 unit is equal to 50 ml of a strong alcoholic
             drink, 200 ml of dry wine or 500 ml of beer) or anamnestic information about
             alcoholism, drug addiction, drug abuse.

         17. Smoking more than 5 cigarettes/day.

         18. Narcomania, alcoholism.

         19. Presence of pregnancy.

         20. Lactating.

         21. Any reason that, in the opinion of the investigator, could interfere with safety of
             the subject or interfere with the objectives of the study.

         22. Subjects with a lactose intolerance, lactase deficiency or glucose-galactose
             malabsorption.