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

November 3, 2021 updated by: Alexion Pharmaceuticals

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

72

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tempe, Arizona, United States, 85283
        • Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Danicopan
Oral tablet.
Other Names:
  • ALXN2040
  • ACH-0144471 (formerly)
  • ACH-4471
  • ACH4471
  • 4471
Drug: Cyclosporine
Oral capsule.
Other Names:
  • Neoral
Experimental: 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.
Drug: Danicopan
Oral tablet.
Other Names:
  • ALXN2040
  • ACH-0144471 (formerly)
  • ACH-4471
  • ACH4471
  • 4471
Drug: Tacrolimus
Oral capsule.
Other Names:
  • Prograf
Experimental: 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.
Drug: Danicopan
Oral tablet.
Other Names:
  • ALXN2040
  • ACH-0144471 (formerly)
  • ACH-4471
  • ACH4471
  • 4471
Drug: Calcium Carbonate
Chewable tablet.
Other Names:
  • Antacid
Drug: Aluminum/Magnesium Hydroxide/Simethicone
Chewable tablet.
Other Names:
  • Antacid
  • Gelusil
Drug: Omeprazole
Oral, delayed-release capsule.
Other Names:
  • Prilosec

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion Pharmaceuticals

Collaborators

Achillion, a wholly owned subsidiary of Alexion

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 27, 2018

Primary Completion (Actual)

October 17, 2018

Study Completion (Actual)

October 17, 2018

Study Registration Dates

First Submitted

September 9, 2021

First Submitted That Met QC Criteria

November 3, 2021

First Posted (Actual)

November 5, 2021

Study Record Updates

Last Update Posted (Actual)

November 5, 2021

Last Update Submitted That Met QC Criteria

November 3, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACH471-014

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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