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

NCT05109390 | Completed Phase 1 FDA Drug

• 1 other identifier: ACH471-014
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

Danicopan; ALXN2040; ACH-0144471; Drug Interaction; Cyclosporine; Tacrolimus; Antacids; Omeprazole

Outcome Measures

Primary Outcomes (15)

• 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 Outcomes (1)

• Number Of Participants Experiencing Treatment-emergent Adverse Events

  Day 1 through up to Day 31

Study Arms (3)

Part 1: Danicopan plus Cyclosporine

EXPERIMENTAL

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; Drug: Cyclosporine

Part 2: Danicopan plus Tacrolimus

EXPERIMENTAL

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; Drug: Tacrolimus

Part 3: Danicopan plus Antacids and Omeprazole

EXPERIMENTAL

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; Drug: Calcium Carbonate; Drug: Aluminum/Magnesium Hydroxide/Simethicone; Drug: Omeprazole

Interventions

Danicopan DRUG

Oral tablet.

Also known as: ALXN2040, ACH-0144471 (formerly), ACH-4471, ACH4471, 4471

Part 1: Danicopan plus Cyclosporine; Part 2: Danicopan plus Tacrolimus; Part 3: Danicopan plus Antacids and Omeprazole

Cyclosporine DRUG

Oral capsule.

Also known as: Neoral

Part 1: Danicopan plus Cyclosporine

Tacrolimus DRUG

Oral capsule.

Also known as: Prograf

Part 2: Danicopan plus Tacrolimus

Calcium Carbonate DRUG

Chewable tablet.

Also known as: Antacid

Part 3: Danicopan plus Antacids and Omeprazole

Aluminum/Magnesium Hydroxide/Simethicone DRUG

Chewable tablet.

Also known as: Antacid, Gelusil

Part 3: Danicopan plus Antacids and Omeprazole

Omeprazole DRUG

Oral, delayed-release capsule.

Also known as: Prilosec

Part 3: Danicopan plus Antacids and Omeprazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead
• Achillion, a wholly owned subsidiary of Alexion: collaborator

Study Sites (1)

Clinical Trial Site

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

danicopan; rhoA GTP-Binding Protein; Cyclosporine; Tacrolimus; Calcium Carbonate; Antacids; aluminum hydroxide, magnesium hydroxide, simethicone drug combination; Gelusil; Omeprazole

Intervention Hierarchy (Ancestors)

rho GTP-Binding Proteins; Monomeric GTP-Binding Proteins; GTP-Binding Proteins; GTP Phosphohydrolases; Acid Anhydride Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Intracellular Signaling Peptides and Proteins; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Macrolides; Lactones; Organic Chemicals; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Gastrointestinal Agents; Therapeutic Uses; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This was a 3-part study, each part is a fixed-sequence with 2 periods.

Study Record Dates

• First Submitted: September 9, 2021
• First Posted: November 5, 2021
• Study Start: July 27, 2018
• Primary Completion: October 17, 2018
• Study Completion: October 17, 2018
• Last Updated: November 5, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)