A Study of the Cardiac Effects of Danicopan in Healthy Adults

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Danicopan; Drug: Moxifloxacin-matching Placebo; Drug: Danicopan-matching placebo; Drug: Moxifloxacin

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 Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm (ABC); 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; Danicopan tablets administered as a single oral dose.; Other Names: ALXN2040; ACH-0144471 (formerly); ACH-4471; ACH4471; 4471; Drug: Moxifloxacin-matching Placebo; Moxifloxacin-matching placebo was administered as a single oral dose.
Placebo Comparator: Control Arm (EFG and IJK); 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; Moxifloxacin-matching placebo was administered as a single oral dose.; Drug: Danicopan-matching placebo; Danicopan-matching placebo was administered as a single oral dose.; Drug: Moxifloxacin; Moxifloxacin 400 mg was administered as a single tablet oral dose.; Other Names: Avelox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)]

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals
• Collaborators: Achillion, a wholly owned subsidiary of Alexion

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2018
• Primary Completion (Actual): October 12, 2018
• Study Completion (Actual): October 12, 2018

Study Registration Dates

• First Submitted: August 16, 2021
• First Submitted That Met QC Criteria: August 16, 2021
• First Posted (Actual): August 23, 2021

Study Record Updates

• Last Update Posted (Actual): August 23, 2021
• Last Update Submitted That Met QC Criteria: August 16, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Electrocardiogram; Danicopan; ALXN2040; ACH-0144471; QT Interval; Concentration-QT
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination
• Other Study ID Numbers: ACH471-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No