Clinical trial NCT05016206: A Study of the Cardiac Effects of Danicopan in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Danicopan
ALXN2040
ACH-0144471
Electrocardiogram
QT Interval
Concentration-QT
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Achillion, a wholly owned subsidiary of Alexion
First posted: 2021-08-23
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This was a double-dummy, placebo- and positive-controlled study.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Placebo-corrected Change From Baseline In QTc Intervals (ddQTc) For Danicopan
timeFrame: Pre-dose through 24 hours post-dose
Secondary outcomes:
measure: Change From Baseline In Heart Rate (HR) For Danicopan
timeFrame: Pre-dose through 24 hours post-dose
measure: Change From Baseline In QT Interval For Danicopan
timeFrame: Pre-dose through 24 hours post-dose
measure: Change From Baseline In Pulse Rate (PR) For Danicopan
timeFrame: Pre-dose through 24 hours post-dose
measure: Change From Baseline In RR Interval For Danicopan
timeFrame: Pre-dose through 24 hours post-dose
measure: Change From Baseline In QRS Interval For Danicopan
timeFrame: Pre-dose through 24 hours post-dose
measure: ddQTcF Of Moxifloxacin
timeFrame: Pre-dose through 24 hours post-dose
measure: Treatment-emergent T-wave Morphology Abnormalities And Pathologic U-waves
timeFrame: Pre-dose through 24 hours post-dose
measure: Area Under The Plasma Concentration Versus Time Curve From Time 0 To 24 Hours Post-dose (AUC0-24) Of Danicopan
timeFrame: Pre-dose through 24 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) Of Danicopan
timeFrame: Pre-dose through 24 hours post-dose
measure: Time To Reach The Maximum Observed Plasma Concentration (Tmax) Of Danicopan
timeFrame: Pre-dose through 24 hours post-dose
measure: Number Of Participants Experiencing Treatment-emergent Adverse Events
timeFrame: Day 1 (postdose) through follow-up visit (14 [+/- 2] days after last study drug administration)]
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Clinical Trial Site
state: Arizona
Study officials:
References: