A Phase I, Monocenter, Randomized, Placebo and Comparator Controlled, Single Blind, Rising Dose, Clinical Study to Determine Single Dose Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Four Doses of FSH-GEX™ According to Adaptive Design (25, 75, 150 and 300 IU) Administered Subcutaneously in Healthy Pituitary-suppressed Female Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- to assess the safety and (local) tolerability of FSH-GEX™ following single rising dose administration by subcutaneous injection
研究概览
简要总结
The aim of the current study was the pharmacokinetic and pharmacodynamic characterization of a single dose administration of four doses of FSH-GEX™ in healthy pituitary-suppressed female volunteers, in comparison with two marketed comparator products.
详细描述
Healthy pituitary-suppressed female subjects received FSH-GEX™ (25, 75, 150 and 300 IU) in three of four possible ascending doses or one dose of two comparators (Bravelle® and Gonal-f®) and placebo in random order. The study consisted of three separate treatment periods. During each treatment period the subject received one single dose via a subcutaneous injection in the lower abdominal wall.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
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
- •Female subjects from 18-40 years of age.
- •Subjects must be in good health.
- •Subjects must be willing to use additional non-hormonal contraception
- •Subjects must have used a combined oral contraceptive (COC) for at least one cycle.
- •Vital signs which are within the following ranges at baseline measurements: systolic blood pressure of 90-140 mmHg, diastolic blood pressure of 50-90 mmHg and pulse rate of 40 - 100 bpm.
- •Subjects must have a body weight of minimally 50.0 kg with a BMI between 18.0 and 29.0 kg/m^2 at baseline measurements.
- •Able to provide written informed consent prior to study participation.
- •Able to communicate well with the investigator and to understand and comply with the requirements of the study.
排除标准
- •Smokers of more than 10 cigarettes per day.
- •Average daily intake of more than 3 units of alcohol per day or an average weekly intake of more than 21 units alcohol.
- •Use of any prescription drug or ove the counter medication from screening until the end-of-study visit, without prior approval of the investigator.
- •Any drugs thay may reduce the effectiveness of COC from screening until the end-of-study visit.
- •Any follicle-stimulating hormone (FSH) preparation within 90 days prior to screening.
- •Administration of any investigational product or use of any investigational device within 30 days prior to screening.
- •Donation or loss of 500 mL or more blood within 90 days prior to first FSH-GEX™ dosing.
- •History of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
- •History of allergies for drugs, seafood, nuts, eggs, wasp-stings; history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to any of the study drugs.
- •Any surgical or medical condition which might alter the absorption, distribution, metabolism, or excretion of drugs or which may jeopardize the subject in case of participation in the study.
- •History or presence of any malignancy.
- •Determined or suspected pregnancy.
- •Breast feeding women.
- •History of (or current) endocrine abnormalities.
- •Contraindication for the use of oral contraceptives.
- •Contraindication for the use of follitropin alfa, FSH or any of the excipients (hypersensitivity to follitropin alfa, FSH or any of the excipients; tumors of the hypothalamus or the pituitary gland; ovarian enlargement or cyst not due to polycystic ovarian disease; gynecological bleeding of unknown origin; ovarian, uterine, or mammary carcinoma).
- •Porphyria or family history of porphyria.
- •History of ovarian surgery.
- •Any ovarian or abdominal abnormality that would interfere with adequate ultrasound investigation.
- •An abnormal cervical smear.
- •History or presence of an immune-compromising disease, or a positive human immunodeficiency virus (HIV) test result in the past or at the screening visit.
- •History of Hepatitis B or C, or a positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result at the screening visit.
- •History of drug or alcohol abuse within the 12 months prior to the screening visit or evidence of such abuse.
- •Planned surgery or hospitalization during the period of the study.
- •Concurrent participation or participation within 30 days before screening in another clinical trial, or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study.
- •Injection of one or more doses of any depot contraceptive drug /drug combination or hormonal implants <= 10 months prior to screening.
研究组 & 干预措施
FSH-GEX 150 IU
150 IU single dose
干预措施: FSH-GEX™ (Drug)
FSH-GEX 300 IU
300 IU single dose
干预措施: FSH-GEX™ (Drug)
FSH-GEX 25 IU
25 IU single dose
干预措施: FSH-GEX™ (Drug)
FSH-GEX 75 IU
75 IU single dose
干预措施: FSH-GEX™ (Drug)
Gonal-f
150 IU single dose
干预措施: Gonal-f (Drug)
Bravelle
150 IU single dose
干预措施: Bravelle (Drug)
Placebo
single dose
干预措施: Placebo (Drug)
结局指标
主要结局
to assess the safety and (local) tolerability of FSH-GEX™ following single rising dose administration by subcutaneous injection
时间窗: up to 87 days
frequency of dose related adverse events, measurement of vital signs, body measurements, transvaginal ultrasound, ECG and laboratory values in comparison to placebo and the two comparators with marketing authorization
to determine FSH pharmacokinetic parameters of FSH-GEX™ following single dose administration by subcutaneous injection (part 1)
时间窗: before FSH/Placebo administration until 240 hours thereafter
Peak plasma concentration (Cmax)
to determine FSH pharmacokinetic parameters of FSH-GEX™ following single dose administration by subcutaneous injection (part 2)
时间窗: before FSH/Placebo administration until 240 hours thereafter
Area under the plasma concentration versus time curve (AUC)
次要结局
- to assess the pharmacodynamic effect of FSH-GEX™ following single rising dose administration by subcutaneous injection (part 1)(before FSH/Placebo administration until 240 hours thereafter)
- to assess the pharmacodynamic effect of FSH-GEX™ following single rising dose administration by subcutaneous injection (part 2)(up to a maximum of 87 days)