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

Alexion Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Cyclosporine; Drug: Omeprazole; Drug: Aluminum/Magnesium Hydroxide/Simethicone; Drug: Danicopan; Drug: Tacrolimus; Drug: Calcium Carbonate

Study type: Interventional

Funder types: Industry

Identifiers

NCT05109390

ACH471-014

Details and patient eligibility

About

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

Enrollment: 72 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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72 participants in 3 patient groups

Part 1: Danicopan plus Cyclosporine

Experimental group

Description:

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.

Treatment:

Drug: Danicopan

Drug: Cyclosporine

Part 2: Danicopan plus Tacrolimus

Experimental group

Description:

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.

Treatment:

Drug: Tacrolimus

Drug: Danicopan

Part 3: Danicopan plus Antacids and Omeprazole

Experimental group

Description:

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.

Treatment:

Drug: Calcium Carbonate

Drug: Danicopan

Drug: Omeprazole

Drug: Aluminum/Magnesium Hydroxide/Simethicone