A Study of the Drug Interactions Between Danicopan and Cyclosporine, Tacrolimus, Antacids, and Omeprazole in Healthy Adults

Study Overview
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Brief Summary
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This was a 3-part study with each part being an open-label, fixed-sequence, 2-period study in healthy adult participants.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Danicopan
* Drug: Cyclosporine
* Drug: Tacrolimus
* Drug: Calcium Carbonate
* Drug: Aluminum/Magnesium Hydroxide/Simethicone
* Drug: Omeprazole


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 1. Key Exclusion Criteria: 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 1. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This was a 3-part study, each part is a fixed-sequence with 2 periods.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Danicopan plus Cyclosporine<br>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. | Drug: Danicopan<br>* Oral tablet.<br>* Other names: 4471;Drug: Cyclosporine<br>* Oral capsule.<br>* Other names: Neoral;|
| Experimental: Part 2: Danicopan plus Tacrolimus<br>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. | Drug: Danicopan<br>* Oral tablet.<br>* Other names: 4471;Drug: Tacrolimus<br>* Oral capsule.<br>* Other names: Prograf;|
| Experimental: Part 3: Danicopan plus Antacids and Omeprazole<br>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. | Drug: Danicopan<br>* Oral tablet.<br>* Other names: 4471;Drug: Calcium Carbonate<br>* Chewable tablet.<br>* Other names: Antacid;Drug: Aluminum/Magnesium Hydroxide/Simethicone<br>* Chewable tablet.<br>* Other names: Gelusil;Drug: Omeprazole<br>* Oral, delayed-release capsule.<br>* Other names: Prilosec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Cyclosporine Maximum Observed Concentration (Cmax) Following Single-dose Cyclosporine Alone Versus In The Presence Of Steady-state Danicopan |  | Up to 72 hours postdose | 
| Part 1: Cyclosporine Time To Reach The Maximum Observed Concentration (Tmax) Following Single-dose Cyclosporine Alone Versus In The Presence Of Steady-state Danicopan |  | 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 |  | Up to 72 hours postdose | 
| Part 2: Tacrolimus Cmax Following Single-dose Tacrolimus Alone Versus In The Presence Of Steady-state Danicopan |  | Up to 144 hours postdose | 
| Part 2: Tacrolimus Tmax Following Single-dose Tacrolimus Alone Versus In The Presence Of Steady-state Danicopan |  | Up to 144 hours postdose | 
| Part 2: Tacrolimus AUC0-inf Following Single-dose Tacrolimus Alone Versus In The Presence Of Steady-state Danicopan |  | Up to 144 hours postdose | 
| Part 3: Steady-state Omeprazole Cmax Following Multiple-dose Omeprazole Alone Versus In The Presence Of Steady-state Danicopan |  | Up to 24 hours postdose | 
| Part 3: Steady-state Omeprazole Tmax Following Multiple-dose Omeprazole Alone Versus In The Presence Of Steady-state Danicopan |  | 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 |  | Up to 24 hours postdose | 
| Part 3: Steady-state Danicopan Cmax Alone Versus In The Presence Of Multiple-dose Omeprazole |  | Up to 8 hours postdose | 
| Part 3: Steady-state Danicopan Tmax Alone Versus In The Presence Of Multiple-dose Omeprazole |  | 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 |  | 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 |  | 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 |  | 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 |  | Up to 8 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Of Participants Experiencing Treatment-emergent Adverse Events |  | Day 1 through up to Day 31 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Danicopan, ALXN2040, ACH-0144471, Drug Interaction, Cyclosporine, Tacrolimus, Antacids, Omeprazole