An Open-label, Two-way Cross-over Study to Determine the Effect of Multiple Doses of Valproic Acid on the Pharmacokinetics and Safety of a Single Oral Dose of Estetrol/Drospirenone in Healthy Female Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Estetra
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Maximum concentration (Cmax) of E4
研究概览
简要总结
The present study is designed to determine the effect of valproic acid (VAL), a UGT2B7 inhibiting drug, on the pharmacokinetics (PK) of estetrol (E4)
详细描述
In the present study, E4/DRSP will be administered alone (Treatment A) and in combination with VAL (Treatment B) following two sequences A-B or B-A.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy premenopausal, aged 18-45 years (inclusive) at the time of signing informed consent.
- •For subjects who are sexually active and are of childbearing potential: willing to use a highly effective non-hormonal method of contraception from screening until the follow-up assessment, such as (but not limited to): non-hormonal intra-uterine device (copper IUD), bilateral tubal occlusion, vasectomised partner, or sexual abstinence in a heterosexual relationship; this is acceptable when it is in line with the subject's preferred and usual lifestyle. If a subject is usually not sexually active but becomes active, they, with their partner, must comply with the contraceptive requirements as stated earlier.
- •Body weight ≥45 kg, and a body mass index between 18.0 and 30.0 kg/m² (inclusive).
- •Negative serum pregnancy test at screening and a negative urine pregnancy test at Day -1.
排除标准
- •The use of:
- •any prescription drugs, including oral or vaginal hormonal contraceptives, from 28 days prior to first dose administration until study completion;
- •any herbal medication or dietary supplements acting on cytochrome P450 3A4 (CYP3A4) functions (i.e., St John's Wort), from 28 days prior to first dose administration until study completion;
- •any over-the-counter medication (including paracetamol or dietary supplements (including vitamins and herbal products ), from 14 days prior to first dose administration until study completion. Limited use (i.e., up to 1200 mg/day) of ibuprofen is allowed;
- •any depot progestogen preparations or an injectable hormonal method of contraception, from 6 months prior to the first dose administration until study completion.
- •History of hypersensitivity, serious adverse reaction, or existing contraindication to E4, DRSP or VAL, or excipients.
研究组 & 干预措施
E4/DRSP (Treatment A) - E4/DRSP + VAL (Treatment B)
Sequence A-B: A single oral dose of E4 combined with DRSP (Treatment A) will be administered during the Period 1. After a washout, subjects will enter into the Period 2. They will receive the Treatment B which consists in multiple oral doses of VAL for 12 consecutive days and one single oral dose of E4/DRSP on Day 5 of the VAL administration.
干预措施: E4/DRSP (Drug)
E4/DRSP (Treatment A) - E4/DRSP + VAL (Treatment B)
Sequence A-B: A single oral dose of E4 combined with DRSP (Treatment A) will be administered during the Period 1. After a washout, subjects will enter into the Period 2. They will receive the Treatment B which consists in multiple oral doses of VAL for 12 consecutive days and one single oral dose of E4/DRSP on Day 5 of the VAL administration.
干预措施: VAL (Drug)
E4/DRSP + VAL (Treatment B) - E4/DRSP (Treatment A)
Sequence B-A: During Period 1, subjects will receive the Treatment B (multiple oral doses of VAL for 12 consecutive days and one single oral dose of E4/DRSP on Day 5 of the VAL administration) . After a washout, subjects will enter into the Period 2 and receive the Treatment A (a single oral dose of E4 combined with DRSP).
干预措施: E4/DRSP (Drug)
E4/DRSP + VAL (Treatment B) - E4/DRSP (Treatment A)
Sequence B-A: During Period 1, subjects will receive the Treatment B (multiple oral doses of VAL for 12 consecutive days and one single oral dose of E4/DRSP on Day 5 of the VAL administration) . After a washout, subjects will enter into the Period 2 and receive the Treatment A (a single oral dose of E4 combined with DRSP).
干预措施: VAL (Drug)
结局指标
主要结局
Maximum concentration (Cmax) of E4
时间窗: 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
PK sampling
Area under the plasma concentration versus time curve from time 0 to the last determined concentration (AUC0-tdlc) of E4
时间窗: 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
PK sampling
Area under the plasma concentration versus time curve from time 0 to infiny (AUC0-inf) of E4
时间窗: 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
PK sampling
次要结局
- Number of subjects with adverse events as a measure of safety and tolerability(The total study duration (between 50 and 86 days))
- Cmax of DRSP(0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A)
- Cmax of E4-glucuronide metabolites(0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A)
- AUC0-tdlc of DRSP(0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A)
- AUC0-tdlc of E4-glucuronide metabolites(0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A)
- AUC0-inf of DRSP(0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A)
- AUC0-inf of E4-glucuronide metabolites(0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A)