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

A Three-Part Phase 1 Study to Determine the Potential Drug Interaction Between ACH-0144471 and Midazolam, Fexofenadine and Mycophenolate Mofetil in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Danicopan; Drug: Midazolam; Drug: Fexofenadine; Drug: Mycophenolate Mofetil

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1: Danicopan and Midazolam; 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; Oral tablet.; Other Names: ALXN2040; ACH-0144471 (formerly); Drug: Midazolam; Oral syrup.; Other Names: Midazolam HCl
EXPERIMENTAL: Part 2: Danicopan and Fexofenadine; 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; Oral tablet.; Other Names: ALXN2040; ACH-0144471 (formerly); Drug: Fexofenadine; Oral tablet.
EXPERIMENTAL: Part 3: Danicopan and MMF; 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; Oral tablet.; Other Names: ALXN2040; ACH-0144471 (formerly); Drug: Mycophenolate Mofetil; Oral tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
Parts 1-3: Participants Experiencing Treatment-emergent Adverse Events	7 (±1) days following the last dose in Period 2

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals
• Collaborators: Achillion, a wholly owned subsidiary of Alexion

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 18, 2017
• Primary Completion (ACTUAL): June 2, 2017
• Study Completion (ACTUAL): June 16, 2017

Study Registration Dates

• First Submitted: March 28, 2017
• First Submitted That Met QC Criteria: April 5, 2017
• First Posted (ACTUAL): April 11, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 24, 2021
• Last Update Submitted That Met QC Criteria: June 21, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Mycophenolate Mofetil; Midazolam; Danicopan; ALXN2040; ACH-0144471; Factor D Inhibitor; Drug Interaction; Fexofenadine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Antineoplastic Agents; Anti-Bacterial Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Antibiotics, Antineoplastic; Anti-Allergic Agents; Antitubercular Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antibiotics, Antitubercular; Histamine H1 Antagonists, Non-Sedating; Midazolam; Mycophenolic Acid; Fexofenadine
• Other Study ID Numbers: ACH471-010; U1111-1193-2774 (OTHER: Universal Trial Number (UTN))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes