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

Sponsor

Alexion Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03108274

Collaborator

Achillion, a wholly owned subsidiary of Alexion (Industry)

Enrollment

Location

Arms

1.9

Actual Duration (Months)

18.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Danicopan Drug: Midazolam Drug: Fexofenadine Drug: Mycophenolate Mofetil	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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.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.

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Apr 18, 2017

Actual Primary Completion Date :

Jun 2, 2017

Actual Study Completion Date :

Jun 16, 2017

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

Parts 1-3: Participants Experiencing Treatment-emergent Adverse Events [7 (±1) days following the last dose in Period 2]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.