A Three-Part Phase 1 Study to Evaluate the Potential Drug Interaction Between ACH-0144471 and Cyclosporine, Tacrolimus, Antacids, and Omeprazole in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Part 1: Cyclosporine Time To Reach The Maximum Observed Concentration (Tmax) Following Single-dose Cyclosporine Alone Versus In The Presence Of Steady-state Danicopan
研究概览
简要总结
This was a 3-part study with each part being an open-label, fixed-sequence, 2-period study in healthy adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Body mass index in the range of 18.0 to 32.0 kilograms (kg)/meter squared, inclusive, with a minimum body weight of 50.0 kg at Screening.
- •Female participants must have been of non-childbearing potential and not needing to employ a method of contraception.
- •Non-sterile male participants must have agreed to abstinence or used a highly effective method of contraception.
- •No clinically significant history or presence of electrocardiogram findings at Screening and Day -1 of Period
排除标准
- •Evidence of any clinically significant deviation from normal in clinical laboratory evaluations.
- •History of any medical or psychiatric condition or disease that might have limited the participant's ability to complete or participate in this clinical study, confound the results of the study, or pose an additional risk to the participant by their participation in the study.
- •History or presence of drug or alcohol abuse within 2 years prior to first dosing; current tobacco/nicotine users and smokers; positive drugs-of-abuse and/or alcohol screen at Screening or Day -1 of Period
- •Any previous procedure that could have altered absorption or excretion of orally administered drugs.
- •A history of significant multiple and/or severe allergies or had had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs.
- •Body temperature ≥ 38°Celsius at Screening, on Day -1, or Day 1 prior to first dosing; history of febrile illness, or other evidence of infection, within 14 days prior to first dosing.
- •Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives (if known) or 30 days before first dosing, whichever was longer.
- •Donation of whole blood from 3 months prior to first dosing, or of plasma from 30 days before first dosing; receipt of blood products within 6 months prior to first dosing.
- •Part 3 Only: Genotyped as poor metabolizer of cytochrome P450 2C19.
研究组 & 干预措施
Part 1: Danicopan plus Cyclosporine
Participants (N=14) received danicopan and cyclosporine in a fixed sequence over 2 periods:
Treatment A (Period 1): 300 milligrams (mg) cyclosporine administered on Day 1.
Treatment B (Period 2): 200 mg danicopan administered 3 times daily (TID) on Days 1-7 with 300 mg cyclosporine coadministered on Day 5.
There was a washout period of 3 days between the dose of cyclosporine in Period 1 and the first dose of danicopan in Period 2.
干预措施: Danicopan (Drug)
Part 1: Danicopan plus Cyclosporine
Participants (N=14) received danicopan and cyclosporine in a fixed sequence over 2 periods:
Treatment A (Period 1): 300 milligrams (mg) cyclosporine administered on Day 1.
Treatment B (Period 2): 200 mg danicopan administered 3 times daily (TID) on Days 1-7 with 300 mg cyclosporine coadministered on Day 5.
There was a washout period of 3 days between the dose of cyclosporine in Period 1 and the first dose of danicopan in Period 2.
干预措施: Cyclosporine (Drug)
Part 2: Danicopan plus Tacrolimus
Participants (N=28) received danicopan and tacrolimus in a fixed sequence over 2 periods:
Treatment C (Period 1): 2 mg tacrolimus administered on Day 1.
Treatment D (Period 2): 200 mg danicopan administered TID on Days 1-10 with 2 mg tacrolimus coadministered on Day 5.
There was a washout period of 7 days between the dose of tacrolimus in Period 1 and the first dose of danicopan in Period 2.
干预措施: Danicopan (Drug)
Part 2: Danicopan plus Tacrolimus
Participants (N=28) received danicopan and tacrolimus in a fixed sequence over 2 periods:
Treatment C (Period 1): 2 mg tacrolimus administered on Day 1.
Treatment D (Period 2): 200 mg danicopan administered TID on Days 1-10 with 2 mg tacrolimus coadministered on Day 5.
There was a washout period of 7 days between the dose of tacrolimus in Period 1 and the first dose of danicopan in Period 2.
干预措施: Tacrolimus (Drug)
Part 3: Danicopan plus Antacids and Omeprazole
Participants (N=30) received danicopan, calcium carbonate, aluminum/magnesium hydroxide/simethicone, and omeprazole in fixed sequences over 2 periods:
Treatment E1 (Period 1): 200 mg danicopan administered TID on Days 1-4. Treatment E2 (Period 1): 200 mg danicopan coadministered with 1 gram calcium carbonate on Day 5.
Treatment F1 (Period 1): 200 mg danicopan administered TID on Days 1-4. Treatment F2 (Period 1): 200 mg danicopan coadministered with 200 mg aluminum hydroxide/200 magnesium hydroxide/25 mg simethicone on Day 5.
Note: Participants were randomized in a 1:1 ratio to receive either Treatment E2 or F2 coadministered with danicopan on Day 5.
Treatment G1 (Period 2): 40 mg omeprazole administered once daily (QD) on Days 1-4.
Treatment G2 (Period 2): 40 mg omeprazole administered QD with 200 mg danicopan administered orally TID on Days 5-8.
There was a washout period of 2 days between the last dose of danicopan in Period 1 and the first dose of omeprazole in Period 2.
干预措施: Danicopan (Drug)
Part 3: Danicopan plus Antacids and Omeprazole
Participants (N=30) received danicopan, calcium carbonate, aluminum/magnesium hydroxide/simethicone, and omeprazole in fixed sequences over 2 periods:
Treatment E1 (Period 1): 200 mg danicopan administered TID on Days 1-4. Treatment E2 (Period 1): 200 mg danicopan coadministered with 1 gram calcium carbonate on Day 5.
Treatment F1 (Period 1): 200 mg danicopan administered TID on Days 1-4. Treatment F2 (Period 1): 200 mg danicopan coadministered with 200 mg aluminum hydroxide/200 magnesium hydroxide/25 mg simethicone on Day 5.
Note: Participants were randomized in a 1:1 ratio to receive either Treatment E2 or F2 coadministered with danicopan on Day 5.
Treatment G1 (Period 2): 40 mg omeprazole administered once daily (QD) on Days 1-4.
Treatment G2 (Period 2): 40 mg omeprazole administered QD with 200 mg danicopan administered orally TID on Days 5-8.
There was a washout period of 2 days between the last dose of danicopan in Period 1 and the first dose of omeprazole in Period 2.
干预措施: Calcium Carbonate (Drug)
Part 3: Danicopan plus Antacids and Omeprazole
Participants (N=30) received danicopan, calcium carbonate, aluminum/magnesium hydroxide/simethicone, and omeprazole in fixed sequences over 2 periods:
Treatment E1 (Period 1): 200 mg danicopan administered TID on Days 1-4. Treatment E2 (Period 1): 200 mg danicopan coadministered with 1 gram calcium carbonate on Day 5.
Treatment F1 (Period 1): 200 mg danicopan administered TID on Days 1-4. Treatment F2 (Period 1): 200 mg danicopan coadministered with 200 mg aluminum hydroxide/200 magnesium hydroxide/25 mg simethicone on Day 5.
Note: Participants were randomized in a 1:1 ratio to receive either Treatment E2 or F2 coadministered with danicopan on Day 5.
Treatment G1 (Period 2): 40 mg omeprazole administered once daily (QD) on Days 1-4.
Treatment G2 (Period 2): 40 mg omeprazole administered QD with 200 mg danicopan administered orally TID on Days 5-8.
There was a washout period of 2 days between the last dose of danicopan in Period 1 and the first dose of omeprazole in Period 2.
干预措施: Aluminum/Magnesium Hydroxide/Simethicone (Drug)
Part 3: Danicopan plus Antacids and Omeprazole
Participants (N=30) received danicopan, calcium carbonate, aluminum/magnesium hydroxide/simethicone, and omeprazole in fixed sequences over 2 periods:
Treatment E1 (Period 1): 200 mg danicopan administered TID on Days 1-4. Treatment E2 (Period 1): 200 mg danicopan coadministered with 1 gram calcium carbonate on Day 5.
Treatment F1 (Period 1): 200 mg danicopan administered TID on Days 1-4. Treatment F2 (Period 1): 200 mg danicopan coadministered with 200 mg aluminum hydroxide/200 magnesium hydroxide/25 mg simethicone on Day 5.
Note: Participants were randomized in a 1:1 ratio to receive either Treatment E2 or F2 coadministered with danicopan on Day 5.
Treatment G1 (Period 2): 40 mg omeprazole administered once daily (QD) on Days 1-4.
Treatment G2 (Period 2): 40 mg omeprazole administered QD with 200 mg danicopan administered orally TID on Days 5-8.
There was a washout period of 2 days between the last dose of danicopan in Period 1 and the first dose of omeprazole in Period 2.
干预措施: Omeprazole (Drug)
结局指标
主要结局
Part 1: Cyclosporine Time To Reach The Maximum Observed Concentration (Tmax) Following Single-dose Cyclosporine Alone Versus In The Presence Of Steady-state Danicopan
时间窗: Up to 72 hours postdose
Part 2: Tacrolimus Cmax Following Single-dose Tacrolimus Alone Versus In The Presence Of Steady-state Danicopan
时间窗: Up to 144 hours postdose
Part 2: Tacrolimus Tmax Following Single-dose Tacrolimus Alone Versus In The Presence Of Steady-state Danicopan
时间窗: Up to 144 hours postdose
Part 3: Steady-state Danicopan Cmax Alone Versus In The Presence Of Multiple-dose Omeprazole
时间窗: Up to 8 hours postdose
Part 3: Steady-state Danicopan Tmax Alone Versus In The Presence Of Multiple-dose Omeprazole
时间窗: Up to 8 hours postdose
Part 3: Steady-state Danicopan Area Under The Concentration-time Curve From Time 0 To The 8-hour Time Point (AUC0-8) Alone Versus In The Presence Of Multiple-dose Omeprazole
时间窗: Up to 8 hours postdose
Part 3: Steady-state Danicopan Cmax Alone Versus In The Presence Of Single-dose Calcium Carbonate Or Aluminum/Magnesium Hydroxide/Simethicone
时间窗: Up to 8 hours postdose
Part 3: Steady-state Danicopan Tmax Alone Versus In The Presence Of Single-dose Calcium Carbonate Or Aluminum/Magnesium Hydroxide/Simethicone
时间窗: Up to 8 hours postdose
Part 3: Steady-state Danicopan AUC0-8 Alone Versus In The Presence Of Single-dose Calcium Carbonate Or Aluminum/Magnesium Hydroxide/Simethicone
时间窗: Up to 8 hours postdose
Part 1: Cyclosporine Maximum Observed Concentration (Cmax) Following Single-dose Cyclosporine Alone Versus In The Presence Of Steady-state Danicopan
时间窗: Up to 72 hours postdose
Part 1: Cyclosporine Area Under The Concentration-time Curve From Time 0 Extrapolated To Infinity (AUC0-inf) Following Single-dose Cyclosporine Alone Versus In The Presence Of Steady-state Danicopan
时间窗: Up to 72 hours postdose
Part 2: Tacrolimus AUC0-inf Following Single-dose Tacrolimus Alone Versus In The Presence Of Steady-state Danicopan
时间窗: Up to 144 hours postdose
Part 3: Steady-state Omeprazole Cmax Following Multiple-dose Omeprazole Alone Versus In The Presence Of Steady-state Danicopan
时间窗: Up to 24 hours postdose
Part 3: Steady-state Omeprazole Tmax Following Multiple-dose Omeprazole Alone Versus In The Presence Of Steady-state Danicopan
时间窗: Up to 24 hours postdose
Part 3: Steady-state Omeprazole Area Under The Concentration-time Curve From Time 0 To The 24-hour Time Point (AUC0-24) Following Multiple-dose Omeprazole Alone Versus In The Presence Of Steady-state Danicopan
时间窗: Up to 24 hours postdose
次要结局
- Number Of Participants Experiencing Treatment-emergent Adverse Events(Day 1 through up to Day 31)