A Study of the Cardiac Effects of ALXN2050 in Healthy Adults

Sponsor

Alexion Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT04660890

Collaborator

Celerion (Industry)

Enrollment

Location

Arms

3.1

Actual Duration (Months)

12.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, double-dummy, placebo- and positive-controlled parallel study to evaluate the effect of ALXN2050 on the QT interval in healthy adult participants.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: ALXN2050 Drug: ALXN2050-matching Placebo Drug: Moxifloxacin Drug: Moxifloxacin-matching Placebo	Phase 1

Detailed Description

Participants randomized to the treatment arm will receive ALXN2050 in a multiple-ascending doses fashion over 3 periods (treatment sequence ABC). Participants randomized to the control arms will be further randomized to 1 of 2 treatment sequences (treatment sequence DEF or GHI) to receive placebo or active control over 3 periods.

Study Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

A Multiple-Ascending-Dose, Randomized, Double-Blind, Double-Dummy, Placebo- and Positive-Controlled Study to Evaluate the Effect of ALXN2050 on the QT Interval in Healthy Adult Participants

Actual Study Start Date :

Dec 12, 2020

Actual Primary Completion Date :

Mar 16, 2021

Actual Study Completion Date :

Mar 16, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm (ABC) Treatment Sequence ABC - Participants will receive all 3 doses of ALXN2050 in a multiple-ascending fashion over 3 periods: Treatment A (Period 1): ALXN2050 Dose 120 milligrams (mg) and moxifloxacin-matching placebo. Treatment B (Period 2): ALXN2050 Dose 240 mg and moxifloxacin-matching placebo. Treatment C (Period 3): ALXN2050 Dose 360 mg and moxifloxacin-matching placebo.	Drug: ALXN2050 ALXN2050 will be administered orally twice daily as powder-in-capsule. Other Names: ACH-0145228 (formerly) Drug: Moxifloxacin-matching Placebo Moxifloxacin-matching placebo will be administered as a single oral dose.
Placebo Comparator: Control Arm (DEF) Treatment Sequence DEF - Participants will receive ALXN2050-matching placebo over 3 periods: Treatment D (Period 1): 120 mg ALXN2050-matching placebo and moxifloxacin-matching placebo. Treatment E (Period 2): 240 mg ALXN2050-matching placebo and moxifloxacin. Treatment F (Period 3): 360 mg ALXN2050-matching placebo and moxifloxacin-matching placebo.	Drug: ALXN2050-matching Placebo ALXN2050-matching placebo will be administered orally twice daily as placebo powder-in-capsule. Drug: Moxifloxacin Moxifloxacin will be administered as a single oral dose. Drug: Moxifloxacin-matching Placebo Moxifloxacin-matching placebo will be administered as a single oral dose.
Placebo Comparator: Control Arm (GHI) Treatment Sequence GHI - Participants will receive ALXN2050-matching placebo over 3 periods: Treatment G (Period 1): 120 mg ALXN2050-matching placebo and moxifloxacin. Treatment H (Period 2): 240 mg ALXN2050-matching placebo and moxifloxacin-matching placebo. Treatment I (Period 3): 360 mg ALXN2050-matching placebo and moxifloxacin.	Drug: ALXN2050-matching Placebo ALXN2050-matching placebo will be administered orally twice daily as placebo powder-in-capsule. Drug: Moxifloxacin Moxifloxacin will be administered as a single oral dose. Drug: Moxifloxacin-matching Placebo Moxifloxacin-matching placebo will be administered as a single oral dose.

Arm

Intervention/Treatment

Experimental: Treatment Arm (ABC)

Treatment Sequence ABC - Participants will receive all 3 doses of ALXN2050 in a multiple-ascending fashion over 3 periods: Treatment A (Period 1): ALXN2050 Dose 120 milligrams (mg) and moxifloxacin-matching placebo. Treatment B (Period 2): ALXN2050 Dose 240 mg and moxifloxacin-matching placebo. Treatment C (Period 3): ALXN2050 Dose 360 mg and moxifloxacin-matching placebo.

Drug: ALXN2050

ALXN2050 will be administered orally twice daily as powder-in-capsule.

Other Names:

ACH-0145228 (formerly)

Drug: Moxifloxacin-matching Placebo

Moxifloxacin-matching placebo will be administered as a single oral dose.

Placebo Comparator: Control Arm (DEF)

Treatment Sequence DEF - Participants will receive ALXN2050-matching placebo over 3 periods: Treatment D (Period 1): 120 mg ALXN2050-matching placebo and moxifloxacin-matching placebo. Treatment E (Period 2): 240 mg ALXN2050-matching placebo and moxifloxacin. Treatment F (Period 3): 360 mg ALXN2050-matching placebo and moxifloxacin-matching placebo.

Drug: ALXN2050-matching Placebo

ALXN2050-matching placebo will be administered orally twice daily as placebo powder-in-capsule.

Drug: Moxifloxacin

Moxifloxacin will be administered as a single oral dose.

Drug: Moxifloxacin-matching Placebo

Moxifloxacin-matching placebo will be administered as a single oral dose.

Placebo Comparator: Control Arm (GHI)

Treatment Sequence GHI - Participants will receive ALXN2050-matching placebo over 3 periods: Treatment G (Period 1): 120 mg ALXN2050-matching placebo and moxifloxacin. Treatment H (Period 2): 240 mg ALXN2050-matching placebo and moxifloxacin-matching placebo. Treatment I (Period 3): 360 mg ALXN2050-matching placebo and moxifloxacin.

Drug: ALXN2050-matching Placebo

ALXN2050-matching placebo will be administered orally twice daily as placebo powder-in-capsule.

Drug: Moxifloxacin

Moxifloxacin will be administered as a single oral dose.

Drug: Moxifloxacin-matching Placebo

Moxifloxacin-matching placebo will be administered as a single oral dose.

Outcome Measures

Primary Outcome Measures

Placebo-corrected Change From Baseline QTc Intervals (ddQTc) For ALXN2050 [Pre-dose through 24 hours post-dose]
Twelve-lead electrocardiograms (ECGs) will be extracted from continuous (Holter) recordings.

Secondary Outcome Measures

Change From Baseline PR Interval (dPR) For ALXN2050 [Pre-dose through 24 hours post-dose]
Twelve-lead ECGs will be extracted from continuous (Holter) recordings.
ddQTc For Moxifloxacin [Pre-dose through 24 hours post-dose]
Twelve-lead ECGs will be extracted from continuous (Holter) recordings.
Area Under The Plasma Concentration-time Curve During A Dosing Interval (tau) At Steady-state (AUCtau) For ALXN2050 [Pre-dose through 24 hours post-dose]
Maximum Observed Plasma Concentration Following Multiple Dosing (Cmax,ss) For ALXN2050 [Up to 24 hours postdose]
Time To Maximum Observed Plasma Concentration Following Multiple Dosing (Tmax,ss) For ALXN2050 [Pre-dose through 24 hours post-dose]
Incidence Of Treatment-emergent Adverse Events [Day 1 (postdose) through follow-up (7 [+/- 2] days after last study drug administration)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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 50.0 kg at screening.
No clinically significant history or presence of ECG abnormalities at screening.
Female participants must be of non-childbearing potential and need not employ a method of contraception.
Non-sterile male participants must agree to abstinence or use a highly effective method of contraception.

Exclusion Criteria:

Clinically significant laboratory abnormalities.
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 previous 2 years, current tobacco and/or nicotine user, or positive alcohol and/or drug screen at screening or Day -1 of Period 1.
History or presence of clinically significant seizures, head injury, or head trauma.
History of procedures that could alter absorption or excretion of orally administered drugs.
History of meningococcal infection, or a first-degree relative with a history of meningococcal infection.
History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs.
Body temperature ≥ 38.0°Celsius at screening or prior to first dosing in Period 1 or history of febrile illness, or other evidence of infection, within 14 days prior to (first) dosing.
Donation of whole blood from 3 months prior to first dosing, or of plasma from 30 days before first dosing, or receipt of blood products within 6 months 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 is longer.