A Drug Interaction Study Between Danicopan and Midazolam, Fexofenadine, and Mycophenolate Mofetil in Healthy Participants

NCT03108274 | Completed Phase 1 FDA Drug

• 2 other identifiers: ACH471-010U1111-1193-2774
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to determine the potential drug interaction between danicopan (ACH-0144471) and midazolam, fexofenadine, and mycophenolate mofetil. This was a 3-part study, with each part being an open-label, fixed-sequence, 2-treatment study in healthy adult participants.

Conditions

Healthy

Keywords

Danicopan; ALXN2040; ACH-0144471; Midazolam; Fexofenadine; Mycophenolate Mofetil; Drug Interaction; Pharmacokinetics; Factor D Inhibitor; Safety

Outcome Measures

Primary Outcomes (12)

• Part 1: Midazolam Area Under The Plasma Concentration-time Curve From Time 0 To The Time Of The Last Observed Non-zero Concentration (AUC0-t) Following Single-dose Midazolam Alone Versus In The Presence of Steady-state Danicopan

  Up to 24 hours postdose

• Part 1: Midazolam Area Under The Plasma Concentration-time Curve From Time 0 Extrapolated To Infinity (AUC0-inf) Following Single-dose Midazolam Alone Versus In The Presence of Steady-state Danicopan

  Up to 24 hours postdose

• Part 1: Midazolam Maximum Observed Plasma Concentration (Cmax) Following Single-dose Midazolam Alone Versus In The Presence of Steady-state Danicopan

  Up to 24 hours postdose

• Part 1: Midazolam Time To Reach Maximum Observed Plasma Concentration (Tmax) Following Single-dose Midazolam Alone Versus In The Presence of Steady-state Danicopan

  Up to 24 hours postdose

• Part 2: Fexofenadine AUC0-t Following Single-dose Fexofenadine Alone Versus In The Presence of Steady-state Danicopan

  Up to 72 hours postdose

• Part 2: Fexofenadine AUC0-inf Following Single-dose Fexofenadine Alone Versus In The Presence of Steady-state Danicopan

  Up to 72 hours postdose

• Part 2: Fexofenadine Cmax Following Single-dose Fexofenadine Alone Versus In The Presence of Steady-state Danicopan

  Up to 72 hours postdose

• Part 2: Fexofenadine Tmax Following Single-dose Fexofenadine Alone Versus In The Presence of Steady-state Danicopan

  Up to 72 hours postdose

• Part 3: Mycophenolic Acid (MPA) and Mycophenolic Acid Glucuronide (MPAG) AUC0-t Following Single-dose Mycophenolate Mofetil (MMF) Alone Versus In The Presence of Steady-state Danicopan

  Up to 72 hours postdose

• Part 3: MPA and MPAG AUC0-inf Following Single-dose MMF Alone Versus In The Presence of Steady-state Danicopan

  Up to 72 hours postdose

• Part 3: MPA and MPAG Cmax Following Single-dose MMF Alone Versus In The Presence of Steady-state Danicopan

  Up to 72 hours postdose

• Part 3: MPA and MPAG Tmax Following Single-dose MMF Alone Versus In The Presence of Steady-state Danicopan

  Up to 72 hours postdose

Secondary Outcomes (1)

• Parts 1-3: Participants Experiencing Treatment-emergent Adverse Events

  7 (±1) days following the last dose in Period 2

Study Arms (3)

Part 1: Danicopan and Midazolam

EXPERIMENTAL

Period 1: Participants received a single dose of midazolam. Period 2: Participants received multiple doses of danicopan, in addition to coadministration with a single dose of midazolam. Scheduled pharmacokinetics (PK) blood samples were collected, with a washout period of at least 3 days between the dose in Period 1 and the first dose in Period 2.

Drug: Danicopan; Drug: Midazolam

Part 2: Danicopan and Fexofenadine

EXPERIMENTAL

Period 1: Participants received a single dose of fexofenadine. Period 2: Participants received multiple doses of danicopan, in addition to coadministration with a single dose of fexofenadine. Scheduled PK blood samples were collected, with a washout period of at least 3 days between the dose in Period 1 and the first dose in Period 2.

Drug: Danicopan; Drug: Fexofenadine

Part 3: Danicopan and MMF

EXPERIMENTAL

Period 1: Participants received a single dose of MMF. Period 2: Participants received multiple doses of danicopan, in addition to coadministration with a single dose of MMF. Scheduled PK blood samples were collected, with a washout period of at least 3 days between the dose in Period 1 and the first dose in Period 2.

Drug: Danicopan; Drug: Mycophenolate Mofetil

Interventions

Danicopan DRUG

Oral tablet.

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

Part 1: Danicopan and Midazolam; Part 2: Danicopan and Fexofenadine; Part 3: Danicopan and MMF

Midazolam DRUG

Oral syrup.

Also known as: Midazolam HCl

Part 1: Danicopan and Midazolam

Fexofenadine DRUG

Oral tablet.

Part 2: Danicopan and Fexofenadine

Mycophenolate Mofetil DRUG

Oral tablet.

Part 3: Danicopan and MMF

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy was defined as having no clinically relevant abnormalities identified by a detailed medical history, physical examination, blood pressure and heart rate measurements, 12-lead electrocardiogram, and clinical laboratory tests.
• Body mass index of 18.5 to 32 kilograms (kg)/square meter with a minimum body weight of 50 kg.

You may not qualify if:

• Mentally or legally incapacitated or significant emotional problems.
• Any condition that might interfere with drug absorption.
• History of sensitivity to study medication or other drug allergies.
• Body temperature greater than or equal to 38°Celsius on Day -1 or Day 1 predose; history of febrile illness within 14 days of the first dose.
• Positive urine drug test; current tobacco/nicotine users and smokers; consumption of alcohol within 72 hours of study drug administration.
• Participated in another clinical study within 28 days prior to the first dose.
• Significant laboratory abnormalities.
• Blood donation of more than 500 milliliters within 3 months of the first dose; received a blood transfusion or blood products within 6 months to the first dose.

Sponsors & Collaborators

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

Study Sites (1)

Clinical Trial Site

Auckland, New Zealand

Location

MeSH Terms

Interventions

danicopan; rhoA GTP-Binding Protein; Midazolam; fexofenadine; Mycophenolic Acid

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; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

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: Part 1, Part 2, and Part 3 could be conducted concurrently or separately, and the order of the parts could be determined according to the needs of the program.

Study Record Dates

• First Submitted: March 28, 2017
• First Posted: April 11, 2017
• Study Start: April 18, 2017
• Primary Completion: June 2, 2017
• Study Completion: June 16, 2017
• Last Updated: June 24, 2021

Record last verified: 2021-06

Locations

NZ (1)