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

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Danicopan
* Drug: Midazolam
* Drug: Fexofenadine
* Drug: Mycophenolate Mofetil


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Danicopan and Midazolam<br>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<br>* Oral tablet.<br>* Other names: ACH-0144471 (formerly);Drug: Midazolam<br>* Oral syrup.<br>* Other names: Midazolam HCl;|
| Experimental: Part 2: Danicopan and Fexofenadine<br>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<br>* Oral tablet.<br>* Other names: ACH-0144471 (formerly);Drug: Fexofenadine<br>* Oral tablet.<br>|
| Experimental: Part 3: Danicopan and MMF<br>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<br>* Oral tablet.<br>* Other names: ACH-0144471 (formerly);Drug: Mycophenolate Mofetil<br>* Oral tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Danicopan, ALXN2040, ACH-0144471, Midazolam, Fexofenadine, Mycophenolate Mofetil, Drug Interaction, Pharmacokinetics, Factor D Inhibitor, Safety