A Study of the Cardiac Effects of Danicopan in Healthy Adults

Study Overview
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Brief Summary
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This was a randomized, double-blind, double-dummy, placebo- and positive-controlled, 2-arm (Treatment Arm and Control Arm), parallel study to evaluate the effect of ACH-0144471 (danicopan) on the QT interval in healthy adult participants.

Detailed Description
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Participants randomized to the Treatment Arm received all 3 doses of danicopan in a single ascending fashion over 3 periods (Treatment Sequence ABC). A single oral dose of danicopan was administered with a moxifloxacin-matching placebo on Day 1 of each period. Participants randomized to the Control Arm were further randomized to receive 1 of 2 treatment sequences (Treatment Sequences EFG or IJK). A single oral dose of danicopan-matching placebo was administered with moxifloxacin or with moxifloxacin-matching placebo, as per the assigned randomization scheme, on Day 1 of each period.

Official Title
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A Single Ascending Dose, Randomized, Double-Blind, Double-Dummy, Placebo- and Positive Controlled Study to Evaluate the Effect of ACH-0144471 on the QT Interval in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Danicopan
* Drug: Moxifloxacin-matching Placebo
* Drug: Danicopan-matching placebo
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Body mass index in the range of 18.0 to 32.0 kilograms (kg)/meter squared, inclusive, with a minimum body weight of 50 kg at screening. Female participants must have been of nonchildbearing potential. Nonsterile male participants must have agreed to abstinence or used a highly effective method of contraception. No clinically significant history or presence of electrocardiogram findings at screening and check-in. Key Exclusion Criteria: Evidence of any clinically significant deviation from normal in clinical laboratory evaluations. History of any medical or psychiatric condition or disease that might limit the participant's ability to complete or participate in this clinical study, confound the results of the study, or pose an additional risk to the participant by their participation in the study. History or presence of drug or alcohol abuse within 2 years prior to first dosing; current tobacco/nicotine user or a positive cotinine test at screening; positive for alcohol and/or drugs-of-abuse screen at screening or first check-in. Any previous procedure that could alter absorption or excretion of orally administered drugs. A history of significant multiple and/or severe allergies or had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs. Body temperature ≥ 38°Celsius on Day -2 or Day 1 prior to first dosing; history of febrile illness, or other evidence of infection, within 14 days prior to first dosing. Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives (if known) or 30 days before first dosing, whichever was longer. Donation of whole blood from 3 months before first dosing, or of plasma from 30 days before first dosing; received blood products within 6 months before first dosing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This was a double-dummy, placebo- and positive-controlled study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm (ABC)<br>Treatment Sequence ABC - Participants received all 3 doses of danicopan in ascending fashion over 3 periods: Treatment A (Period 1): Danicopan 400 milligrams (mg) and moxifloxacin-matching placebo. Treatment B (Period 2): Danicopan 800 mg and moxifloxacin-matching placebo. Treatment C (Period 3): Danicopan 1200 mg and moxifloxacin-matching placebo. | Drug: Danicopan<br>* Danicopan tablets administered as a single oral dose.<br>* Other names: 4471;Drug: Moxifloxacin-matching Placebo<br>* Moxifloxacin-matching placebo was administered as a single oral dose.<br>|
| Placebo Comparator: Control Arm (EFG and IJK)<br>Participants received 1 of 2 treatment sequences (Treatment Sequence EFG or Treatment Sequence IJK) over 3 periods: Treatment E (Period 1): Danicopan-matching placebo (400 mg) and moxifloxacin-matching placebo. Treatment F (Period 2): Danicopan-matching placebo (800 mg) and moxifloxacin 400 mg. Treatment G (Period 3): Danicopan-matching placebo (1200 mg) and moxifloxacin-matching placebo. Treatment I (Period 1): Danicopan-matching placebo (400 mg) and moxifloxacin 400 mg. Treatment J (Period 2): Danicopan-matching placebo (800 mg) and moxifloxacin-matching placebo. Treatment K (Period 3): Danicopan-matching placebo (1200 mg) and moxifloxacin 400 mg. | Drug: Moxifloxacin-matching Placebo<br>* Moxifloxacin-matching placebo was administered as a single oral dose.<br>Drug: Danicopan-matching placebo<br>* Danicopan-matching placebo was administered as a single oral dose.<br>Drug: Moxifloxacin<br>* Moxifloxacin 400 mg was administered as a single tablet oral dose.<br>* Other names: Avelox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Placebo-corrected Change From Baseline In QTc Intervals (ddQTc) For Danicopan |  | Pre-dose through 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline In Heart Rate (HR) For Danicopan |  | Pre-dose through 24 hours post-dose | 
| Change From Baseline In QT Interval For Danicopan |  | Pre-dose through 24 hours post-dose | 
| Change From Baseline In Pulse Rate (PR) For Danicopan |  | Pre-dose through 24 hours post-dose | 
| Change From Baseline In RR Interval For Danicopan |  | Pre-dose through 24 hours post-dose | 
| Change From Baseline In QRS Interval For Danicopan |  | Pre-dose through 24 hours post-dose | 
| ddQTcF Of Moxifloxacin |  | Pre-dose through 24 hours post-dose | 
| Treatment-emergent T-wave Morphology Abnormalities And Pathologic U-waves |  | Pre-dose through 24 hours post-dose | 
| Area Under The Plasma Concentration Versus Time Curve From Time 0 To 24 Hours Post-dose (AUC0-24) Of Danicopan |  | Pre-dose through 24 hours post-dose | 
| Maximum Observed Plasma Concentration (Cmax) Of Danicopan |  | Pre-dose through 24 hours post-dose | 
| Time To Reach The Maximum Observed Plasma Concentration (Tmax) Of Danicopan |  | Pre-dose through 24 hours post-dose | 
| Number Of Participants Experiencing Treatment-emergent Adverse Events |  | Day 1 (postdose) through follow-up visit (14 [+/- 2] days after last study drug administration)] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Danicopan, ALXN2040, ACH-0144471, Electrocardiogram, QT Interval, Concentration-QT