A Study of the Cardiac Effects of ALXN2050 in Healthy Adults

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ALXN2050; Drug: Moxifloxacin-matching Placebo; Drug: ALXN2050-matching Placebo; Drug: Moxifloxacin

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 Type: Interventional
• Enrollment (Actual): 39
• 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

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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: Moxifloxacin-matching Placebo; Moxifloxacin-matching placebo will be administered as a single oral dose.; 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.
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: Moxifloxacin-matching Placebo; Moxifloxacin-matching placebo will be administered as a single oral dose.; 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline PR Interval (dPR) For ALXN2050	Twelve-lead ECGs will be extracted from continuous (Holter) recordings.	Pre-dose through 24 hours post-dose
ddQTc For Moxifloxacin	Twelve-lead ECGs will be extracted from continuous (Holter) recordings.	Pre-dose through 24 hours post-dose
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)

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals
• Collaborators: Celerion

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2020
• Primary Completion (Actual): March 16, 2021
• Study Completion (Actual): March 16, 2021

Study Registration Dates

• First Submitted: November 12, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): December 29, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Electrocardiogram; Factor D Inhibitor; QT Interval; Concentration-QT; ALXN2050
• 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: ALXN2050-HV-107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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