A Three-Part Phase 1 Study to Evaluate the Potential Drug-Drug Interactions Between Vemircopan and Rosuvastatin, Metformin, Levonorgestrel-Ethinyl Estradiol-Containing Oral Contraceptives, and Carbamazepine in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Part 1: Cmax of Rosuvastatin
研究概览
简要总结
This study will investigate the potential drug interactions between vemircopan and metformin, rosuvastatin, levonorgestrel/ ethinyl estradiol (LNG/EE)-containing oral contraceptive(s) (OCs), and carbamazepine in healthy participants.
详细描述
This a 3-part drug-drug interaction (DDI) study. Part 1 - Potential Drug-drug Interaction Between Vemircopan, Metformin, and Rosuvastatin, Part 2 - Potential Drug-drug Interaction Between Vemircopan and LNG/EE-Containing OCs (Female Participants Only) Part 3 - Potential Drug-drug Interaction Between Vemircopan and Carbamazepine
All the 3 parts of the study includes:
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Screening Period: 27 days (Day -28 through Day -2)
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Two Treatment Periods:
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Part 1: Treatment Period 1 (Day -1 through Day 8) and Treatment Period 2 (Day 1 through Day 12)
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Part 2: Treatment Period 1 (Day -1 through Day 7) and Treatment Period 2 (Day 1 through Day 10)
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Part 3: Treatment Period 1 (Day -1 through Day 4) and Treatment Period 2 (Day 1 through Day 22)
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Follow-up/Early Discontinuation Visit: 7 (± 2) days following the last dose of study intervention
Up to 20 participants will be enrolled per study part. Participants will be enrolled in only one study part and will not be allowed to participate in more than 1 study part.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants who are medically healthy with no clinically significant or relevant abnormalities as determined by medical history, physical or neurological examination, vital signs, 12-lead ECG, screening clinical laboratory profiles (hematology, biochemistry, coagulation, and urinalysis), as deemed by the Investigator or designee.
- •Body weight of at minimum 50 kg and body mass index (BMI) within the range 18 to 32 kg/m^2 (inclusive) at the Screening.
- •Male and female participants should adhere to the protocol defined contraceptive methods.
排除标准
- •History or presence of medical (eg, cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, neurological or other disorders) or psychiatric conditions or diseases.
- •History of clinically significant hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.
- •History of drug or alcohol abuse within 2 years prior to first dosing
- •Current tobacco users or smokers (defined as any tobacco or nicotine-containing product use within 3 months prior to first dosing).
- •Donation of whole blood from 3 months prior to first dose administration, or of plasma from 30 days before first dose administration.
- •Female participants who have a positive pregnancy test at Screening or Day -1, or who are lactating.
- •Positive drugs of abuse, cotinine, or alcohol screen at Screening or Day -1.
研究组 & 干预措施
Part 1: Vemircopan, Metformin and Rosuvastatin
Participants will receive Vemircopan, Metformin and Rosuvastatin in a fixed sequence over 2 periods.
Period 1 (8 days): Participants will receive a single dose of metformin on day 1 and a single dose of rosuvastatin on day 4.
Period 2 (12 days): Participants will receive vemircopan twice daily from day 1 to day 11. On day 5, participants will receive metformin co-administered with vemircopan. On day 8, participants will receive rosuvastatin co-administered with vemircopan.
There will be a washout period of at least 4 days between the dose of rosuvastatin in Period 1 and the first dose of vemircopan in Period 2.
干预措施: Vemircopan (Drug)
Part 1: Vemircopan, Metformin and Rosuvastatin
Participants will receive Vemircopan, Metformin and Rosuvastatin in a fixed sequence over 2 periods.
Period 1 (8 days): Participants will receive a single dose of metformin on day 1 and a single dose of rosuvastatin on day 4.
Period 2 (12 days): Participants will receive vemircopan twice daily from day 1 to day 11. On day 5, participants will receive metformin co-administered with vemircopan. On day 8, participants will receive rosuvastatin co-administered with vemircopan.
There will be a washout period of at least 4 days between the dose of rosuvastatin in Period 1 and the first dose of vemircopan in Period 2.
干预措施: Rosuvastatin (Drug)
Part 1: Vemircopan, Metformin and Rosuvastatin
Participants will receive Vemircopan, Metformin and Rosuvastatin in a fixed sequence over 2 periods.
Period 1 (8 days): Participants will receive a single dose of metformin on day 1 and a single dose of rosuvastatin on day 4.
Period 2 (12 days): Participants will receive vemircopan twice daily from day 1 to day 11. On day 5, participants will receive metformin co-administered with vemircopan. On day 8, participants will receive rosuvastatin co-administered with vemircopan.
There will be a washout period of at least 4 days between the dose of rosuvastatin in Period 1 and the first dose of vemircopan in Period 2.
干预措施: Metformin (Drug)
Part 2: Vemircopan and LNG/EE-Containing OCs
Participants will receive Vemircopan and LNG/EE-Containing OCs in a fixed sequence over 2 periods.
Period 1 (7 days): Participants will receive a single dose of OC, consisting of LNG and EE on day 1.
Period 2 (10 days): Participants will receive multiple doses of vemircopan from day 1 to day 9. On day 5, participants will receive a single dose of OC co-administered with vemircopan.
There will be a washout period of at least 7 days between the dose of OC in Period 1 and the first dose of vemircopan in Period 2.
干预措施: Vemircopan (Drug)
Part 2: Vemircopan and LNG/EE-Containing OCs
Participants will receive Vemircopan and LNG/EE-Containing OCs in a fixed sequence over 2 periods.
Period 1 (7 days): Participants will receive a single dose of OC, consisting of LNG and EE on day 1.
Period 2 (10 days): Participants will receive multiple doses of vemircopan from day 1 to day 9. On day 5, participants will receive a single dose of OC co-administered with vemircopan.
There will be a washout period of at least 7 days between the dose of OC in Period 1 and the first dose of vemircopan in Period 2.
干预措施: Levonorgestrel / Ethinyl Estradiol (Drug)
Part 3: Vemircopan and Carbamazepine
Participants will receive Vemircopan and Carbemazepine in a fixed sequence over 2 periods.
Period 1 (4 days): Participants will receive a single oral dose of vemircopan on day 1.
Period 2 (22 days): Participants will receive carbemazepine twice daily from day 1 to day 21. On day 19, participants will receive a single oral dose of vemircopan co-administered with carbamazepine.
There will be a washout period of at least 4 days between the dose of vemircopan in Period 1 and the first dose of carbamazepine in Period 2.
干预措施: Vemircopan (Drug)
Part 3: Vemircopan and Carbamazepine
Participants will receive Vemircopan and Carbemazepine in a fixed sequence over 2 periods.
Period 1 (4 days): Participants will receive a single oral dose of vemircopan on day 1.
Period 2 (22 days): Participants will receive carbemazepine twice daily from day 1 to day 21. On day 19, participants will receive a single oral dose of vemircopan co-administered with carbamazepine.
There will be a washout period of at least 4 days between the dose of vemircopan in Period 1 and the first dose of carbamazepine in Period 2.
干预措施: Carbamazepine (Drug)
结局指标
主要结局
Part 1: Cmax of Rosuvastatin
时间窗: Up to 96 hours post-dose
Cmax for single-dose rosuvastatin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of rosuvastatin.
Part 1: Maximum observed plasma (peak) concentration (Cmax) of Metformin
时间窗: Up to 48 hours post-dose
Cmax for single-dose metformin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of metformin.
Part 1: AUC from time zero to the last quantifiable concentration (AUCt) of Metformin
时间窗: Up to 48 hours post-dose
AUCt for single-dose metformin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of metformin.
Part 2: Cmax of EE
时间窗: Up to 120 hours post-dose
Cmax for single-dose EE without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of EE.
Part 2: AUC∞ of EE
时间窗: Up to 120 hours post-dose
Cmax for single-dose EE without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of EE.
Part 2: AUCt of EE
时间窗: Up to 120 hours post-dose
AUCt for single-dose EE without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of EE.
Part 3: AUC∞ of Vemircopan
时间窗: Up to 72 hours post-dose
Cmax for single-dose vemircopan without and with co-administration with carbamazepine will be assessed to determine the effect of multiple doses of carbamazepine on the single-dose PK of vemircopan.
Part 1: AUC from time zero extrapolated to infinity (AUC∞) of Metformin
时间窗: Up to 48 hours post-dose
Cmax for single-dose metformin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of metformin.
Part 1: AUC∞ of Rosuvastatin
时间窗: Up to 96 hours post-dose
Cmax for single-dose rosuvastatin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of rosuvastatin.
Part 2: AUCt of LNG
时间窗: Up to 120 hours post-dose
AUCt for single-dose LNG without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of LNG.
Part 3: AUCt of Vemircopan
时间窗: Up to 72 hours post-dose
AUCt for single-dose vemircopan without and with co-administration with carbamazepine will be assessed to determine the effect of multiple doses of carbamazepine on the single-dose PK of vemircopan.
Part 1: AUCt of Rosuvastatin
时间窗: Up to 96 hours post-dose
AUCt for single-dose rosuvastatin without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of rosuvastatin.
Part 2: Cmax of LNG
时间窗: Up to 120 hours post-dose
Cmax for single-dose LNG without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of LNG.
Part 2: AUC∞ of LNG
时间窗: Up to 120 hours post-dose
Cmax for single-dose LNG without and with co-administration with vemircopan will be assessed to determine the effect of multiple doses of vemircopan on the single-dose PK of LNG.
Part 3: Cmax of Vemircopan
时间窗: Up to 72 hours post-dose
Cmax for single-dose vemircopan without and with co-administration with carbamazepine will be assessed to determine the effect of multiple doses of carbamazepine on the single-dose PK of vemircopan.
次要结局
- Part 1: Time corresponding to the occurrence of Cmax (tmax) of Metformin(Up to 48 hours post-dose)
- Part 1: CL/F of Rosuvastatin(Up to 96 hours post-dose)
- Part 3: Number of participants with Treatment Emergent Adverse Events(From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 63 days))
- Part 1: Apparent terminal elimination half-life (t½) of Metformin(Up to 48 hours post-dose)
- Part 2: Number of participants with Treatment Emergent Adverse Events(From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 54 days))
- Part 1: AUC during a dosing interval at steady state (AUCtau) of Vemircopan(Period 2: Days 4, 5 and 8)
- Part 1: Number of participants with Treatment Emergent Adverse Events(From Screening (Day -28 to Day -2) up to follow-up Visit or early discontinuation visit (approximately 57 days))
- Part 1: t½ of Rosuvastatin(Up to 96 hours post-dose)
- Part 1: λz of Rosuvastatin(Up to 96 hours post-dose)
- Part 1: Terminal elimination rate constant (λz) of Metformin(Up to 48 hours post-dose)
- Part 1: Volume of distribution (apparent) following extravascular administration (Vd/F) of Metformin(Up to 48 hours post-dose)
- Part 1: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Metformin(Up to 48 hours post-dose)
- Part 1: tmax of Rosuvastatin(Up to 96 hours post-dose)
- Part 1: Predose concentration prior to morning dose (Ctrough) of Vemircopan(Period 2: Days 3, 4, 5 and 8)
- Part 2: λz of LNG(Up to 120 hours post-dose)
- Part 2: Vd/F of LNG(Up to 120 hours post-dose)
- Part 2: CL/F of LNG(Up to 120 hours post-dose)
- Part 2: tmax of EE(Up to 120 hours post-dose)
- Part 2: λz of EE(Up to 120 hours post-dose)
- Part 2: Vd/F of EE(Up to 120 hours post-dose)
- Part 1: Vd/F of Rosuvastatin(Up to 96 hours post-dose)
- Part 1: Cmax of Vemircopan(Period 2: Days 4, 5 and 8)
- Part 1: tmax of Vemircopan(Period 2: Days 4, 5 and 8)
- Part 2: t½ of LNG(Up to 120 hours post-dose)
- Part 2: tmax of LNG(Up to 120 hours post-dose)
- Part 2: t½ of EE(Up to 120 hours post-dose)
- Part 2: AUCtau of Vemircopan(Period 2: Days 4, and 5)
- Part 3: tmax of Vemircopan(Up to 72 hours post-dose)
- Part 2: CL/F of EE(Up to 120 hours post-dose)
- Part 2: Cmax of Vemircopan(Period 2: Days 4, and 5)
- Part 3: λz of Vemircopan(Up to 72 hours post-dose)
- Part 3: Cmax of Carbamazepine(Period 2: Days 4, 18 and 19)
- Part 3: AUCtau of Carbamazepine(Period 2: Days 4, 18 and 19)
- Part 2: tmax of Vemircopan(Period 2: Days 4, and 5)
- Part 2: Ctrough of Vemircopan(Period 2: Days 3, 4, and 5)
- Part 3: t½ of Vemircopan(Up to 72 hours post-dose)
- Part 3: Vd/F of Vemircopan(Up to 72 hours post-dose)
- Part 3: CL/F of Vemircopan(Up to 96 hours post-dose)
- Part 3: tmax of Carbamazepine(Period 2: Days 4, 18 and 19)
- Part 3: Ctrough of Carbamazepine(Period 2: Days 18 and 19)