Healthy
Conditions
Keywords
Danicopan, ALXN2040, ACH-0144471, Electrocardiogram, QT Interval, Concentration-QT
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.
Interventions
DRUGDanicopan
Danicopan tablets administered as a single oral dose.
Moxifloxacin-matching placebo was administered as a single oral dose.
DRUGDanicopan-matching placebo
Danicopan-matching placebo was administered as a single oral dose.
DRUGMoxifloxacin
Moxifloxacin 400 mg was administered as a single tablet oral dose.
Sponsors
Achillion, a wholly owned subsidiary of Alexion
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This was a double-dummy, placebo- and positive-controlled study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Placebo-corrected Change From Baseline In QTc Intervals (ddQTc) For Danicopan | Pre-dose through 24 hours post-dose |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Change From Baseline In Heart Rate (HR) For Danicopan | 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)] |
| Treatment-emergent T-wave Morphology Abnormalities And Pathologic U-waves | Pre-dose through 24 hours post-dose |
Countries
United States
Outcome results
None listed