A Phase I, Open-label, Randomized, Three-period, Crossover, Single-center Trial to Assess the Bioequivalence of the Co-administration of 900 IU of Follitropin Alfa (Gonal-f) and 450 IU of Lutropin Alfa (Luveris) Versus the Fixed Combination of 900 IU Follitropin Alfa and 450 IU Lutropin Alfa in Pergoveris, Administered SC as Liquid and FD Formulation, in Pituitary Suppressed Healthy Premenopausal Female Chinese Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
The main purpose of this study is to assess the bioequivalence (BE) of the fixed combination of follitropin alfa and lutropin alfa in Pergoveris freeze-dried (FD) (Test 1) or in Pergoveris Liquid (Test 2) versus the co-administration of Gonal-f and Luveris (Reference), administered subcutaneously (SC) in pituitary suppressed, healthy premenopausal Chinese female participants, at the doses of 900 international unit (IU) of follitropin alfa and 450 IU lutropin alfa.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Participants who are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and ECG, blood pressure (systolic and diastolic) and pulse rate
- •Participants who have a negative serum pregnancy test before starting Marvelon and on the days before the Pergoveris or Gonal-f/Luveris dose
- •Participants who are taking an oral contraceptive pill (OCP) for at least 1 month prior to Screening and are willing to take the combined oral contraceptive pill (COCP) during the study and to recommence taking their own OCP from Day 55 after the first Pergoveris or Gonal-f/Luveris dosing
- •Participants with normal baseline follicle stimulating hormone (FSH) (< 12 IU/L) and estradiol (E2) levels [<= 100 picograms per millilitre (pg/mL)] and showing follicle size <= 11 millimeter (mm)
- •Participants who had a normal Thinprep cytologic test (TCT) within the last 1 year before Screening (timeframe to be adjusted based on local routine clinical care). If not performed in routine clinical care, participant must be willing to undergo a cervical smear at Screening
- •Participants who have a body weight within >= 45 kilogram (kg) and body mass index within the range 18.5 to 29.9 kilogram per meter square (kg/m^2) (inclusive)
- •Other protocol defined inclusion criteria could apply
排除标准
- •Participants with 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 with clinically significant abnormalities of the genital organs as determined by gynecological examination and Trans Vaginal Ultrasound Scan (TVUS) and based on the Investigator's judgment (example., ovarian tumors, non-functional ovarian cysts, endometrial hyperplasia)
- •Participants with polycystic ovaries as defined by at least 1 of the following 2 criteria fulfilled: More than 12 follicles < 10 mm mean diameter in either ovary or at least one ovary of > 10 mL volume
- •Participants with ovarian follicle-like structures larger than 11 mm (at Screening)
- •Participants with positive result for syphilis, human immunodeficiency virus, hepatitis B surface antigen or hepatitis C Virus
- •Participants using drugs that may reduce the effectiveness of COCP (e.g., phenytoin, barbiturates, primidone, carbamazapine, oxcarbazepine, topiramate, felbamate,rifampicin, nelfinavir, ritonavir, griseofulvin, oral ketoconazole, and herbal remedies containing Hypericum perforatum [St. John's Wort])
- •Participation in any clinical study within 3 months or 5 half-lives, whichever is longer, prior to Screening or during participation Unsuccessful downregulation, demonstrated by serum luteinising hormone (LH) or FSH levels > 2.0 IU/L or E2 levels > 100 pg/mL the day before Pergoveris or Gonal-f/Luveris administration, or showing follicle size > 11 mm
- •Participants vaccinated with any Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov-2) vaccine within 4 weeks before administration of study intervention (Marvelon)
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Sequence 1: First Reference, Then Test 1, Then Test 2
Participants will receive single dose of Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 1 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 2 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Pergoveris FD (Drug)
Sequence 1: First Reference, Then Test 1, Then Test 2
Participants will receive single dose of Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 1 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 2 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Pergoveris Liquid (Drug)
Sequence 1: First Reference, Then Test 1, Then Test 2
Participants will receive single dose of Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 1 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 2 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Gonal-f (Drug)
Sequence 1: First Reference, Then Test 1, Then Test 2
Participants will receive single dose of Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 1 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 2 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Luveris (Drug)
Sequence 2: First Test 1, Then Test 2, Then Reference
Participants will receive single dose of Test 1 drug (Pergoveris FD) on Day 1 in investigation period 1 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 2 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Pergoveris FD (Drug)
Sequence 2: First Test 1, Then Test 2, Then Reference
Participants will receive single dose of Test 1 drug (Pergoveris FD) on Day 1 in investigation period 1 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 2 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Pergoveris Liquid (Drug)
Sequence 2: First Test 1, Then Test 2, Then Reference
Participants will receive single dose of Test 1 drug (Pergoveris FD) on Day 1 in investigation period 1 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 2 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Gonal-f (Drug)
Sequence 2: First Test 1, Then Test 2, Then Reference
Participants will receive single dose of Test 1 drug (Pergoveris FD) on Day 1 in investigation period 1 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 2 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Luveris (Drug)
Sequence 3: First Test 2, Then Reference, Then Test 1
Participants will receive single dose of Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 1 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 2 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Pergoveris FD (Drug)
Sequence 3: First Test 2, Then Reference, Then Test 1
Participants will receive single dose of Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 1 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 2 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Pergoveris Liquid (Drug)
Sequence 3: First Test 2, Then Reference, Then Test 1
Participants will receive single dose of Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 1 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 2 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Gonal-f (Drug)
Sequence 3: First Test 2, Then Reference, Then Test 1
Participants will receive single dose of Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 1 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 2 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Luveris (Drug)
Sequence 4: First Reference, Then Test 2, Then Test 1
Participants will receive single dose of Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 1 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 2 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Pergoveris FD (Drug)
Sequence 4: First Reference, Then Test 2, Then Test 1
Participants will receive single dose of Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 1 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 2 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Pergoveris Liquid (Drug)
Sequence 4: First Reference, Then Test 2, Then Test 1
Participants will receive single dose of Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 1 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 2 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Gonal-f (Drug)
Sequence 4: First Reference, Then Test 2, Then Test 1
Participants will receive single dose of Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 1 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 2 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Luveris (Drug)
Sequence 5: First Test 1, Then Reference, Then Test 2
Participants will receive single dose of Test 1 drug (Pergoveris FD) on Day 1 in investigation period 1 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 2 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Pergoveris FD (Drug)
Sequence 5: First Test 1, Then Reference, Then Test 2
Participants will receive single dose of Test 1 drug (Pergoveris FD) on Day 1 in investigation period 1 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 2 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Pergoveris Liquid (Drug)
Sequence 5: First Test 1, Then Reference, Then Test 2
Participants will receive single dose of Test 1 drug (Pergoveris FD) on Day 1 in investigation period 1 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 2 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Gonal-f (Drug)
Sequence 5: First Test 1, Then Reference, Then Test 2
Participants will receive single dose of Test 1 drug (Pergoveris FD) on Day 1 in investigation period 1 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 2 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Luveris (Drug)
Sequence 6: First Test 2, Then Test 1, Then Reference
Participants will receive single dose of Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 1 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 2 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Pergoveris FD (Drug)
Sequence 6: First Test 2, Then Test 1, Then Reference
Participants will receive single dose of Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 1 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 2 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Pergoveris Liquid (Drug)
Sequence 6: First Test 2, Then Test 1, Then Reference
Participants will receive single dose of Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 1 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 2 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Gonal-f (Drug)
Sequence 6: First Test 2, Then Test 1, Then Reference
Participants will receive single dose of Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 1 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 2 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.
干预措施: Luveris (Drug)
结局指标
主要结局
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
时间窗: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Baseline Adjusted Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Sampling Time After Administration (AUC0-t, adj) of Lutropin Alfa
时间窗: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Baseline Adjusted Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC0-inf,adj) of Follitropin Alfa
时间窗: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Baseline Adjusted Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC0-inf,adj) of Lutropin Alfa
时间窗: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Baseline Adjusted Maximum Observed Serum Concentration (Cmax,adj) of Follitropin Alfa
时间窗: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Baseline Adjusted Maximum Observed Serum Concentration (Cmax,adj) of Lutropin Alfa
时间窗: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
次要结局
- Number of Participants with Clinically Significant Changes From Baseline in Laboratory Parameters(Baseline up to Day 55)
- Number of Participants with Clinically Significant Changes From Baseline in Vital Signs(Baseline up to Day 55)
- Number of Participants with Clinically Significant Changes From Baseline in Electrocardiogram (ECGs) Findings(Baseline up to Day 55)
- Number of Participants with Treatment Emergent Adverse Events (TEAEs)(Baseline up to Day 55)
- Absolute Value and Change From Baseline in Serum Estradiol Levels(Baseline, Day 14 and 39)
- Change From Baseline in Follicle Size Assessed by Trans Vaginal Ultrasound Scan(Baseline, Day 8, 14, 22, 39 and 55)
- Change From Baseline in Follicle Number Assessed by Trans Vaginal Ultrasound Scan(Baseline, Day 8, 14, 22, 39 and 55)
- Number of Participants With Local Tolerability/Injection Site Reactions (ISRs)(At 5 minutes and 1, 2, 4, 6, 12 and 24 hours post-dose)
- Time to Reach the Maximum Observed Serum Concentration (Tmax) of Follitropin Alfa and Lutropin Alfa(Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period)
- Apparent Terminal Half-Life (T1/2) of Follitropin Alfa and Lutropin Alfa(Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period)
- Apparent Terminal Elimination Rate Constant (Lambda z) of Follitropin Alfa and Lutropin Alfa(Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period)