A Study of the Cardiac Effects of ALXN2050 in Healthy Adults

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: ALXN2050; Drug: ALXN2050-matching Placebo; Drug: Moxifloxacin-matching Placebo; Drug: Moxifloxacin

• Registration Number: NCT04660890
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

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.

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 Timeline

• Study First Submitted: 2020-11-12
• Study First Submitted QC: 2020-12-03
• Study First Posted: 2020-12-09
• Study Start: 2020-12-12
• Primary Completion: 2021-03-16
• Study Completion: 2021-03-16
• Status Verified: 2021-11
• Last Update Submitted: 2021-12-09
• Last Update Posted: 2021-12-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

1. 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.
2. No clinically significant history or presence of ECG abnormalities at screening.
3. Female participants must be of non-childbearing potential and need not employ a method of contraception.
4. Non-sterile male participants must agree to abstinence or use a highly effective method of contraception.

Exclusion Criteria

1. Clinically significant laboratory abnormalities.
2. 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.
3. 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.
4. History or presence of clinically significant seizures, head injury, or head trauma.
5. History of procedures that could alter absorption or excretion of orally administered drugs.
6. History of meningococcal infection, or a first-degree relative with a history of meningococcal infection.
7. History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs.
8. 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.
9. 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.
10. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm (ABC)	ALXN2050	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.
Treatment Arm (ABC)	Moxifloxacin-matching Placebo	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.
Control Arm (DEF)	ALXN2050-matching Placebo	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.
Control Arm (DEF)	Moxifloxacin-matching Placebo	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.
Control Arm (GHI)	ALXN2050-matching Placebo	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.
Control Arm (GHI)	Moxifloxacin-matching Placebo	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.
Control Arm (DEF)	Moxifloxacin	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.
Control Arm (GHI)	Moxifloxacin	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Maximum Observed Plasma Concentration Following Multiple Dosing (Cmax,ss) For ALXN2050	Up to 24 hours postdose
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.
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
ddQTc For Moxifloxacin	Pre-dose through 24 hours post-dose	Twelve-lead ECGs will be extracted from continuous (Holter) recordings.
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)

Trial Locations

Locations (1)

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