A Study of the Cardiac Effects of Danicopan in Healthy Adults

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Danicopan; Drug: Moxifloxacin-matching Placebo; Drug: Danicopan-matching placebo; Drug: Moxifloxacin

• Registration Number: NCT05016206
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary

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

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.

Study Timeline

• Study Start: 2018-07-26
• Primary Completion: 2018-10-12
• Study Completion: 2018-10-12
• Status Verified: 2021-08
• Study First Submitted: 2021-08-16
• Study First Submitted QC: 2021-08-16
• Last Update Submitted: 2021-08-16
• Study First Posted: 2021-08-23
• Last Update Posted: 2021-08-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm (ABC)	Moxifloxacin-matching Placebo	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.
Control Arm (EFG and IJK)	Moxifloxacin-matching Placebo	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.
Control Arm (EFG and IJK)	Danicopan-matching placebo	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.
Treatment Arm (ABC)	Danicopan	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.
Control Arm (EFG and IJK)	Moxifloxacin	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.

Primary Outcome Measures

Name	Time	Method
Placebo-corrected Change From Baseline In QTc Intervals (ddQTc) For Danicopan	Pre-dose through 24 hours post-dose

Secondary Outcome Measures

Name	Time	Method
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
Number Of Participants Experiencing Treatment-emergent Adverse Events	Day 1 (postdose) through follow-up visit (14 [+/- 2] days after last study drug administration)]
Change From Baseline In Heart Rate (HR) 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
Change From Baseline In Pulse Rate (PR) For 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
Change From Baseline In QT Interval For Danicopan	Pre-dose through 24 hours post-dose

Trial Locations

Locations (1)

Clinical Trial Site; 🇺🇸 Tempe, Arizona, United States