NCT07215806已完成1 期
A Phase I, Open-Label, Multiple-Dose Study of the Effect of Evobrutinib on the Pharmacokinetics of a Combined Oral Contraceptive in Healthy Female Participants
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany1 个研究点 分布在 1 个国家目标入组 20 人开始时间: 2022年8月24日最近更新:
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Ethinyl Estradiol and Norethisterone
研究概览
简要总结
The purpose of this study was to assess the effect of M2951 on the pharmacokinetics (PK) of a combined oral contraceptive [Ethinyl estradiol/Norethisterone (EE/NET)] in healthy female participants.
- Study Duration: up to 46 days
- Treatment Duration: Days 4 to 17 (14 days treatment with M2951); Days 1 and 15 (2 days treatment with Combined Oral Contraceptive [COC])
- Visit Frequency: Participants were resident in the Clinical Research Unit from Day -1 to Day 18.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 68 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Participants are overtly healthy as determined by medical evaluation, including no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion
- •Participants have a body weight within 50.0 and 100.0 kilograms (kg) (inclusive) and body mass index within the range 19.0 and 30.0 kilograms per square meter (kg/m^2) (inclusive)
- •Participants are nonsmokers for at least 6 months preceding Screening
- •Female participants who are not a Woman of Childbearing Potential (WOCBP)
- •Other protocol defined inclusion criteria could apply
排除标准
- •Participants with history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, as determined by medical evaluation
- •Participants with diagnosis of hemochromatosis, Wilson´s disease, alpha 1 antitrypsin deficiency, or any other chronic liver disease including Gilbert's disease will be excluded from the study
- •Participants with prior history of splenectomy or any clinically relevant surgery within 3 months prior to Screening
- •Participants with history of any malignancy
- •Participants with history of chronic or recurrent acute infection or any bacterial, viral, parasitic, or fungal infections within 30 days prior to Screening and at any time between Screening and admission, or hospitalization due to infection within 6 months prior to Screening
- •Participants with history of shingles within 12 months prior to Screening
- •Administration of live vaccines or live-attenuated virus vaccines within 3 months prior to Screening. Administration of other types of vaccines [e.g., Severe acute respiratory syndrome coronavirus 2 (SARSCoV2) vaccines] is allowed until 4 weeks before admission to CRU, thereafter it is prohibited until the end of the study
- •Note: In case of clinical symptoms, the participant should be symptom-free for at least 1 week prior to admission to Clinical Research Unit (CRU)
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
COC + Evobrutinib
Experimental
Participants received combined oral contraceptive (COC) [0.03 milligrams (mg) of Ethinyl Estradiol (EE)], 0.5 mg of Norethisterone (NET)] orally on Day 1 and 15 in combination with Evobruitnib at a dose of 45 mg orally twice daily on Days 4 to 17.
干预措施: Evobruitnib (Drug)
COC + Evobrutinib
Experimental
Participants received combined oral contraceptive (COC) [0.03 milligrams (mg) of Ethinyl Estradiol (EE)], 0.5 mg of Norethisterone (NET)] orally on Day 1 and 15 in combination with Evobruitnib at a dose of 45 mg orally twice daily on Days 4 to 17.
干预措施: Combined oral contraceptive [ethinyl estradiol/ norethisterone (EE/NET)] (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Ethinyl Estradiol and Norethisterone
时间窗: Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.
Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethisterone
时间窗: Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18
Cmax was obtained directly from the concentration versus time curve.
次要结局
- Change From Baseline in Chemistry Parameters: Sodium, Potassium, Calcium, Glucose, Chloride and Triglycerides at Day 18(Baseline, Day 18)
- Change From Baseline in Chemistry Parameters: Total Protein at Day 18(Baseline, Day 18)
- Change From Baseline in Chemistry Parameters: C Reactive Protein at Day 18(Baseline, Day 18)
- Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure at Day 18(Baseline, Day 18)
- Change From Baseline in Vital Signs: Pulse Rate at Day 18(Baseline, Day 18)
- Change From Baseline in Vital Signs: Respiratory Rate at Day 18(Baseline, Day 18)
- Change From Baseline in Vital Signs: Temperature at Day 18(Baseline, Day 18)
- Change From Baseline in Electrocardiograms (ECGs) Parameter: Heart Rate at Day 18(Baseline, Day 18)
- Change From Baseline in Electrocardiograms (ECGs) Parameter: RR Duration, QT Duration, QTcF Duration, PR Duration, QRS Duration at Day 18(Baseline, Day 18)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethisterone(Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18)
- Terminal Half Life (T1/2) of Ethinyl Estradiol and Norethisterone(Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18)
- Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Ethinyl Estradiol and Norethisterone(Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18)
- Number of Participants With Treatment- Emergent Adverse Events (TEAEs) by Severity(Up to 46 days)
- Change From Baseline in Hematology Parameter: Hemoglobin at Day 18(Baseline, Day 18)
- Change From Baseline in Hematology Parameter: Erythrocytes at Day 18(Baseline, Day 18)
- Change From Baseline in Hematology Parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes and Lymphocytes at Day 18(Baseline, Day 18)
- Apparent Total Body Clearance (CL/f) of Ethinyl Estradiol and Norethisterone(Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18)
- Change From Baseline in Hematology Parameters: Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes at Day 18(Baseline, Day 18)
- Change From Baseline in Coagulation Parameter: Activated Partial Thromboplastin Time at Day 18(Baseline, Day 18)
- Apparent Volume of Distribution During Terminal Phase (VZ/f) of Ethinyl Estradiol and Norethisterone(Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18)
- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin at Day 18(Baseline, Day 18)
- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume at Day 18(Baseline, Day 18)
- Change From Baseline in Coagulation Parameter: Prothrombin Intl. Normalized Ratio at Day 18(Baseline, Day 18)
- Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate at Day 18(Baseline, Day 18)
- Number of Participants With Treatment- Emergent Adverse Events (TEAEs)(Up to 46 days)
- Change From Baseline in Chemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Day 18(Baseline, Day 18)
研究者
研究点 (1)
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