A Drug Interaction Study of Danicopan

NCT04709094 | Completed Phase 1 FDA Drug

• 2 other identifiers: ACH471-017CA27858
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This was a 3-part study (Part 1, Part 2, Part 3) with each part being an open-label, fixed sequence, 2-period study in healthy adult participants.

Conditions

Healthy

Keywords

Factor D Inhibitor; Complement; Danicopan; Oral Contraceptive; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (9)

• Part 1: Area Under The Concentration Versus Time Curve From Time 0 Extrapolated To Infinity (AUC0-inf) Of Single-dose Warfarin Under Multiple Doses Of Danicopan

  Up to 168 hours postdose

• Part 1: Maximum Observed Concentration (Cmax) Of Single-dose Warfarin Under Multiple Doses Of Danicopan

  Up to 168 hours postdose

• Part 1: Time To Maximum Observed Concentration (Tmax) Of Single-dose Warfarin Under Multiple Doses Of Danicopan

  Up to 168 hours postdose

• Part 2: AUC0-inf Of Single-dose Bupropion Under Multiple Doses Of Danicopan

  Up to 96 hours postdose

• Part 2: Cmax Of Single-dose Bupropion Under Multiple Doses Of Danicopan

  Up to 96 hours postdose

• Part 2: Tmax Of Single-dose Bupropion Under Multiple Doses Of Danicopan

  Up to 96 hours postdose

• Part 3: AUC0-inf Of Single-dose EE/NET Under Multiple Doses Of Danicopan

  Up to 96 hours postdose

• Part 3: Cmax Of Single-dose EE/NET Under Multiple Doses Of Danicopan

  Up to 96 hours postdose

• Part 3: Tmax Of Single-dose EE/NET Under Multiple Doses Of Danicopan

  Up to 96 hours postdose

Secondary Outcomes (4)

• Part 1: International Normalized Ratio (INR) Of Single-dose Warfarin Under Multiple Doses Of Danicopan

  Up to 168 hours postdose

• Part 1: Number Of Participants With Treatment-emergent Adverse Events (TEAEs) After Multiple Doses Of Danicopan Coadministered With A Single Dose Of Warfarin

  Day 1 (postdose) through follow-up (14 [+/- 2] days after last study drug administration)

• Part 2: Number Of Participants With TEAEs After Multiple Doses Of Danicopan Coadministered With A Single Dose Of Bupropion

  Day 1 (postdose) through follow-up (14 [+/- 2] days after last study drug administration)

• Part 3: Number Of Participants With TEAEs After Multiple Doses Of Danicopan Coadministered With A Single Dose Of EE/NET

  Day 1 (postdose) through follow-up (14 [+/- 2] days after last study drug administration)

Study Arms (3)

Part 1: Danicopan and Warfarin

EXPERIMENTAL

Period 1: Participants received a single dose of warfarin. Period 2: Participants received danicopan three times daily, in addition to coadministration with a single dose of warfarin. Scheduled pharmacokinetics (PK) and pharmacodynamics samples were collected, with a washout period of at least 14 days between the dose of warfarin in Period 1 and the first dose of danicopan in Period 2.

Drug: Danicopan; Drug: Warfarin

Part 2: Danicopan and Bupropion

EXPERIMENTAL

Period 1: Participants received a single dose of bupropion. Period 2: Participants received danicopan three times daily, in addition to coadministration with a single dose of bupropion. Scheduled PK samples were collected, with a washout period of at least 7 days between the dose of bupropion in Period 1 and the first dose of danicopan in Period 2.

Drug: Danicopan; Drug: Bupropion

Part 3: Danicopan and EE/NET

EXPERIMENTAL

Period 1: Participants received a single dose of EE/NET. Period 2: Participants received danicopan three times daily, in addition to coadministration with a single dose of EE/NET. Scheduled PK samples were collected, with a washout period of at least 7 days between the dose of EE/NET in Period 1 and the first dose of danicopan in Period 2.

Drug: Danicopan; Drug: Ethinyl Estradiol/Norethindrone

Interventions

Danicopan DRUG

Danicopan was dosed as 2 x 100 milligram (mg) tablets.

Also known as: ACH-0144471, ALXN2040

Part 1: Danicopan and Warfarin; Part 2: Danicopan and Bupropion; Part 3: Danicopan and EE/NET

Warfarin DRUG

Warfarin was dosed as 2 x 10 mg and 1 x 5 mg warfarin sodium tablets (Coumadin or generic equivalent).

Also known as: Coumadin

Part 1: Danicopan and Warfarin

Bupropion DRUG

Bupropion was dosed as Wellbutrin (or generic equivalent) as 1 x 100 mg tablet.

Also known as: Bupropion HCl, Wellbutrin

Part 2: Danicopan and Bupropion

Ethinyl Estradiol/Norethindrone DRUG

EE/NET (0.035 mg/1 mg) was dosed as Ortho-Novum-1/35 (or generic equivalent) fixed-dose combination tablets.

Also known as: Ortho-Novum

Part 3: Danicopan and EE/NET

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Parts 1 and 2: adult males or females between 18 and 55 years of age, inclusive, at screening. Part 3: adult females between 18 and 65 years of age, inclusive, at screening.
• 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.
• No clinically significant history or presence of electrocardiogram abnormalities at screening.
• Non-sterile male participants must agree to abstinence or use a highly effective method of contraception.
• Female participants must be of non-childbearing potential and need not employ a method of contraception.
• Part 1 only: Participant has a negative fecal occult blood test at screening.

You may not qualify if:

• Clinically significant laboratory abnormalities.
• History of any medical or psychiatric condition or disease that might limit 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 previous 2 years, current tobacco/nicotine user, or positive for alcohol and/or drug screen at screening or Day -1 of Period 1.
• History or presence of clinically significant seizures, head injury, or head trauma.
• History of procedures that could alter absorption or excretion of orally administered drugs.
• History of meningococcal infection, or a first-degree relative with a history of meningococcal infection.
• A history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs.
• Body temperature ≥ 38.0°Celsius at screening or prior to first dosing in Period 1 or history of febrile illness, or other evidence of infection, within 14 days prior to first dosing.
• Donation of whole blood from 3 months prior to first dosing, or of plasma from 30 days before first dosing, or receipt of blood products within 6 months 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 is longer.
• Part 1 Only:
• History or presence of any of the following, with clinical significance:
• bleeding disorder(s), including relevant familial history;
• anemia (for example, history of temporary anemia during pregnancy is acceptable);
• thromboembolic disease;

Sponsors & Collaborators

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

Study Sites (1)

Clinical Study Site

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

danicopan; Warfarin; Bupropion; ovcon 35; Norinyl

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Propiophenones; Ketones; Organic Chemicals

Study Design

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

Model Details: Part 1, Part 2, and Part 3 could be conducted concurrently or separately.

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: January 14, 2021
• Study Start: July 28, 2019
• Primary Completion: October 14, 2019
• Study Completion: April 17, 2020
• Last Updated: January 14, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)