A Phase 1, Open Label, Randomized, 2-sequence, 2-period, Cross-over, Single Center Study to Assess the Bioequivalence of Follitropin Alfa Solution for Injection in Prefilled Pen (Test) and Follitropin Alfa Powder and Diluent for Solution for Injection in Vial (Reference) in Healthy Downregulated Male Participants
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 55
- Locations
- 1
- Primary Endpoint
- Baseline Adjusted Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Sampling Time After Administration (AUC0-t, adj) of Follitropin Alfa
Study Overview
Brief Summary
The purpose of this study is to assess the bioequivalence of Test and Reference in healthy downregulated male participants. This is a 2-sequence, 2-period study using the following treatment sequences across Study Periods 1 and 2. At the end of the first Downregulation period (DR1), eligible participants will be randomly assigned to 1 of the 2 treatment sequences:
Sequence 1: Test - Reference Sequence 2: Reference - Test Where, Test = follitropin alfa (solution for injection in prefilled pen), and Reference = follitropin alfa (powder and diluent for solution for injection in vial).
The total duration of the study will be up to approximately 9 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Are overtly healthy, as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring
- •Have a normal baseline testosterone level
- •Have a body weight of more than equal to 60 kilograms and Body Mass Index within the range 18 to 30 kilograms per meter square
- •Other protocol defined inclusion criteria could apply
Exclusion Criteria
- •Any condition, that, in the Investigator's opinion, constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation.
- •Participants using the following within 28 days prior to start of study intervention:
- •Drugs or herbal formulations known to increase testosterone levels (e.g. topical testosterone, sildenafil, fluoxymesterone, herbal remedies containing ginseng)
- •Medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes (e.g. antiarrhythmic, antipsychotics, antidepressants, macrolide and quinine antimicrobials, azole antifungals).
- •History of clinically relevant cardiovascular events
- •History of tumors of the pituitary gland or hypothalamus
- •Other protocol defined exclusion criteria could apply
Arms & Interventions
Sequence 1
Participants will receive Test follitropin alfa in Period 1 followed by Reference follitropin alfa in Period 2.
Intervention: Zoladex (Drug)
Sequence 2
Participants will receive reference follitropin alfa in Period 1 followed by test follitropin alfa in Period 2.
Intervention: Zoladex (Drug)
Sequence 1
Participants will receive Test follitropin alfa in Period 1 followed by Reference follitropin alfa in Period 2.
Intervention: Test: Follitropin alfa (Combination Product)
Sequence 1
Participants will receive Test follitropin alfa in Period 1 followed by Reference follitropin alfa in Period 2.
Intervention: Reference: Follitropin alfa (Drug)
Sequence 2
Participants will receive reference follitropin alfa in Period 1 followed by test follitropin alfa in Period 2.
Intervention: Test: Follitropin alfa (Combination Product)
Sequence 2
Participants will receive reference follitropin alfa in Period 1 followed by test follitropin alfa in Period 2.
Intervention: Reference: Follitropin alfa (Drug)
Outcomes
Primary Outcomes
Baseline Adjusted Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Sampling Time After Administration (AUC0-t, adj) of Follitropin Alfa
Time Frame: Predose at -45, - 30, -15 minutes, and at 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, (Day 1), 24 and 36 hour (h) (Day 2), 48 h (Day 3), 72 h (Day 4), 96 h (Day 5), 120 h (Day 6), 168 h (Day 8) and 216h (Day 10) after Test/Reference administration
Baseline Adjusted Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC0-inf,adj) of Follitropin Alfa
Time Frame: Predose at -45, - 30, -15 minutes, and at 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, (Day 1), 24 and 36 hour (h) (Day 2), 48 h (Day 3), 72 h (Day 4), 96 h (Day 5), 120 h (Day 6), 168 h (Day 8) and 216h(Day 10) after Test/Reference administration
Baseline Adjusted Maximum Observed Serum Concentration (Cmax,adj) of Follitropin Alfa
Time Frame: Predose at -45, - 30, -15 minutes, and at 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, (Day 1), 24 and 36 hour (h) (Day 2), 48 h (Day 3), 72 h (Day 4), 96 h (Day 5), 120 h (Day 6), 168 h (Day 8) and 216h(Day 10) after Test/Reference administration
Secondary Outcomes
- Occurrence of Abnormalities (Grade >=3) in Laboratory Test Values(Up to Day 37)
- Occurrence of Abnormalities (Grade >=3) in Vital Signs(Up to Day 37)
- Occurrence of Clinically Significantly Abnormal Electrocardiograms (ECGs)(Up to Day 37)
- Number of Participants With Local Tolerability/Injection Site Reactions (ISRs)(Up to Day 37)
- Number of Participants with Treatment-Emergent Adverse Events (TEAEs)(Up to Day 37)
- Number of Participants with Treatment-Emergent Adverse Events (TEAEs) by Severity(Up to Day 37)
- Pharmacokinetic (PK) Plasma Concentrations of Follitropin Alfa(Predose at -45, - 30, -15 minutes, and at 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, (Day 1), 24 and 36 hour (h) (Day 2), 48 h (Day 3), 72 h (Day 4), 96 h (Day 5), 120 h (Day 6), 168 h (Day 8) and 216h(Day 10) after Test/Reference administration)
- Number of Participants With Positive Anti-Drug Antibody (ADA) of Follitropin Alfa(Predose: Day 1 (Period 1), Day 28 (Period 2), Day 37 (End of Treatment). ADA positive participants followed until end of study(earliest of ADA negative(baseline) or loss to follow-up (upto 40 months))