Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03108274




Registration number
NCT03108274
Ethics application status
Date submitted
28/03/2017
Date registered
11/04/2017
Date last updated
24/06/2021

Titles & IDs
Public title
A Drug Interaction Study Between Danicopan and Midazolam, Fexofenadine, and Mycophenolate Mofetil in Healthy Participants
Scientific 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
Secondary ID [1] 0 0
U1111-1193-2774
Secondary ID [2] 0 0
ACH471-010
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Danicopan
Treatment: Drugs - Midazolam
Treatment: Drugs - Fexofenadine
Treatment: Drugs - Mycophenolate Mofetil

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.

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.

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.


Treatment: Drugs: Danicopan
Oral tablet.

Treatment: Drugs: Midazolam
Oral syrup.

Treatment: Drugs: Fexofenadine
Oral tablet.

Treatment: Drugs: Mycophenolate Mofetil
Oral tablet.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Up to 24 hours postdose
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
Up to 24 hours postdose
Primary outcome [3] 0 0
Part 1: Midazolam Maximum Observed Plasma Concentration (Cmax) Following Single-dose Midazolam Alone Versus In The Presence of Steady-state Danicopan
Timepoint [3] 0 0
Up to 24 hours postdose
Primary outcome [4] 0 0
Part 1: Midazolam Time To Reach Maximum Observed Plasma Concentration (Tmax) Following Single-dose Midazolam Alone Versus In The Presence of Steady-state Danicopan
Timepoint [4] 0 0
Up to 24 hours postdose
Primary outcome [5] 0 0
Part 2: Fexofenadine AUC0-t Following Single-dose Fexofenadine Alone Versus In The Presence of Steady-state Danicopan
Timepoint [5] 0 0
Up to 72 hours postdose
Primary outcome [6] 0 0
Part 2: Fexofenadine AUC0-inf Following Single-dose Fexofenadine Alone Versus In The Presence of Steady-state Danicopan
Timepoint [6] 0 0
Up to 72 hours postdose
Primary outcome [7] 0 0
Part 2: Fexofenadine Cmax Following Single-dose Fexofenadine Alone Versus In The Presence of Steady-state Danicopan
Timepoint [7] 0 0
Up to 72 hours postdose
Primary outcome [8] 0 0
Part 2: Fexofenadine Tmax Following Single-dose Fexofenadine Alone Versus In The Presence of Steady-state Danicopan
Timepoint [8] 0 0
Up to 72 hours postdose
Primary outcome [9] 0 0
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
Timepoint [9] 0 0
Up to 72 hours postdose
Primary outcome [10] 0 0
Part 3: MPA and MPAG AUC0-inf Following Single-dose MMF Alone Versus In The Presence of Steady-state Danicopan
Timepoint [10] 0 0
Up to 72 hours postdose
Primary outcome [11] 0 0
Part 3: MPA and MPAG Cmax Following Single-dose MMF Alone Versus In The Presence of Steady-state Danicopan
Timepoint [11] 0 0
Up to 72 hours postdose
Primary outcome [12] 0 0
Part 3: MPA and MPAG Tmax Following Single-dose MMF Alone Versus In The Presence of Steady-state Danicopan
Timepoint [12] 0 0
Up to 72 hours postdose
Secondary outcome [1] 0 0
Parts 1-3: Participants Experiencing Treatment-emergent Adverse Events
Timepoint [1] 0 0
7 (±1) days following the last dose in Period 2

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
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 design
Purpose of the study
Basic Science
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/04/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/06/2017
Sample size
Target
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alexion Pharmaceuticals, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Achillion, a wholly owned subsidiary of Alexion
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03108274
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03108274