A Study of the Cardiac Effects of ALXN1840 in Healthy Adults

Sponsor

Alexion Pharmaceuticals (Industry)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04560816

Collaborator

PPD (Industry), ERT: Clinical Trial Technology Solutions (Other)

Enrollment

Location

Arms

7.2

Anticipated Duration (Months)

7.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the effect of a supratherapeutic dose of ALXN1840 on the heart rate (HR)-corrected QT interval (QTc) in healthy adult participants. Moxifloxacin will be used as the active control.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: ALXN1840 Drug: Placebo Drug: Moxifloxacin	Phase 1

Detailed Description

This is a randomized, 3-treatment, 3-period, 6-sequence, crossover, placebo- and active-controlled, double-blind for ALXN1840, open-label for moxifloxacin, in healthy adult participants. Participants will be domiciled in the clinic for 7 days during Treatment Period 1 and for 6 days during Treatment Period 2 and 3. A single oral dose of each treatment (ALXN1840, matching ALXN1840 placebo, or moxifloxacin) will be administered on Day 1 of each period following an overnight fast of at least 10 hours. There will be a minimum 14-day washout between study intervention administrations for each treatment period. Cardiodynamic, pharmacokinetic, and safety assessments will be performed at certain times during the study. An end-of-study visit will occur 14 days (±2 days) after the last dose.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

54 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

This will be a 3-treatment, 3-period, 6-sequence, crossover study in healthy adults.This will be a 3-treatment, 3-period, 6-sequence, crossover study in healthy adults.

Masking:

Double (Participant, Care Provider)

Masking Description:

This study will employ a double-blind study design. The ALXN1840 and matching placebo will be identical in appearance and will be administered in a double-blind manner. Moxifloxacin will not be blinded.

Primary Purpose:

Treatment

Official Title:

A Randomized, Three-Treatment, Three-Period, Six-Sequence, Crossover, Placebo- and Active-Controlled, Double-Blind for ALXN1840 (Open-Label for Moxifloxacin) Thorough QT/QTc (TQT) Study to Evaluate the Effect of ALXN1840 on Cardiac Repolarization in Healthy Adult Participants

Actual Study Start Date :

Jul 24, 2020

Anticipated Primary Completion Date :

Mar 1, 2021

Anticipated Study Completion Date :

Mar 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Sequence 1 On Day 1 of each period, participants will receive a single dose of the following study interventions: Period 1: ALXN1840. Period 2: Placebo-matching ALXN1840. Period 3: Moxifloxacin.	Drug: ALXN1840 ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose). Other Names: WTX101 Bis-choline tetrathiomolybdate Tiomolibdate choline Drug: Placebo Placebo will be administered orally. Other Names: Placebo-matching ALXN1840 Drug: Moxifloxacin Moxifloxacin (400 milligrams) will be administered orally.
Experimental: Treatment Sequence 2 On Day 1 of each period, participants will receive a single dose of the following study interventions: Period 1: ALXN1840. Period 2: Moxifloxacin. Period 3: Placebo-matching ALXN1840.	Drug: ALXN1840 ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose). Other Names: WTX101 Bis-choline tetrathiomolybdate Tiomolibdate choline Drug: Placebo Placebo will be administered orally. Other Names: Placebo-matching ALXN1840 Drug: Moxifloxacin Moxifloxacin (400 milligrams) will be administered orally.
Experimental: Treatment Sequence 3 On Day 1 of each period, participants will receive a single dose of the following study interventions: Period 1: Placebo-matching ALXN1840. Period 2: ALXN1840. Period 3: Moxifloxacin.	Drug: ALXN1840 ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose). Other Names: WTX101 Bis-choline tetrathiomolybdate Tiomolibdate choline Drug: Placebo Placebo will be administered orally. Other Names: Placebo-matching ALXN1840 Drug: Moxifloxacin Moxifloxacin (400 milligrams) will be administered orally.
Experimental: Treatment Sequence 4 On Day 1 of each period, participants will receive a single dose of the following study interventions: Period 1: Placebo-matching ALXN1840. Period 2: Moxifloxacin. Period 3: ALXN1840.	Drug: ALXN1840 ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose). Other Names: WTX101 Bis-choline tetrathiomolybdate Tiomolibdate choline Drug: Placebo Placebo will be administered orally. Other Names: Placebo-matching ALXN1840 Drug: Moxifloxacin Moxifloxacin (400 milligrams) will be administered orally.
Experimental: Treatment Sequence 5 On Day 1 of each period, participants will receive a single dose of the following study interventions: Period 1: Moxifloxacin. Period 2: ALXN1840. Period 3: Placebo-matching ALXN1840.	Drug: ALXN1840 ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose). Other Names: WTX101 Bis-choline tetrathiomolybdate Tiomolibdate choline Drug: Placebo Placebo will be administered orally. Other Names: Placebo-matching ALXN1840 Drug: Moxifloxacin Moxifloxacin (400 milligrams) will be administered orally.
Experimental: Treatment Sequence 6 On Day 1 of each period, participants will receive a single dose of the following study interventions: Period 1: Moxifloxacin. Period 2: Placebo-matching ALXN1840. Period 3: ALXN1840.	Drug: ALXN1840 ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose). Other Names: WTX101 Bis-choline tetrathiomolybdate Tiomolibdate choline Drug: Placebo Placebo will be administered orally. Other Names: Placebo-matching ALXN1840 Drug: Moxifloxacin Moxifloxacin (400 milligrams) will be administered orally.

Outcome Measures

Primary Outcome Measures

Placebo-corrected Change From Baseline QTc For ALXN1840 Using The By-time Point Analysis [Pre-dose through 24 hours post-dose]
Twelve-lead electrocardiograms (ECGs) will be extracted from approximately 25-hour continuous (Holter) recordings on Day -1 of Treatment Period 1 and Days 1 and 2 in each treatment period.

Secondary Outcome Measures

Change From Baseline ΔΔQTcF For Moxifloxacin Using The By-time Point Analysis [Pre-dose through 24 hours post-dose]
Twelve-lead ECGs will be extracted from approximately 25-hour continuous (Holter) recordings on Day -1 of Treatment Period 1 and Days 1 and 2 in each treatment period.
Change From Baseline Heart Rate (ΔHR) For ALXN1840 [Baseline, 24 hours postdose]
Twelve-lead ECGs will be extracted from approximately 25-hour continuous (Holter) recordings on Day -1 of Treatment Period 1 and Days 1 and 2 in each treatment period.
Change From Baseline PR Interval (ΔPR) For ALXN1840 [Baseline, 24 hours postdose]
Twelve-lead ECGs will be extracted from approximately 25-hour continuous (Holter) recordings on Day -1 of Treatment Period 1 and Days 1 and 2 in each treatment period.
Change From Baseline QRS Interval (ΔQRS) For ALXN1840 [Baseline, 24 hours postdose]
Twelve-lead ECGs will be extracted from approximately 25-hour continuous (Holter) recordings on Day -1 of Treatment Period 1 and Days 1 and 2 in each treatment period.
Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) For ALXN1840 [Baseline, 24 hours postdose]
Twelve-lead ECGs will be extracted from approximately 25-hour continuous (Holter) recordings on Day -1 of Treatment Period 1 and Days 1 and 2 in each treatment period.
Placebo-corrected Change From Baseline PR Interval (ΔΔPR) For ALXN1840 [Baseline, 24 hours postdose]
Twelve-lead ECGs will be extracted from approximately 25-hour continuous (Holter) recordings on Day -1 of Treatment Period 1 and Days 1 and 2 in each treatment period.
Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) For ALXN1840 [Baseline, 24 hours postdose]
Twelve-lead ECGs will be extracted from approximately 25-hour continuous (Holter) recordings on Day -1 of Treatment Period 1 and Days 1 and 2 in each treatment period.
Treatment-emergent T-wave Morphology Abnormalities And U-waves [Day 1 (after dosing) through 24 hours postdose]
Twelve-lead ECGs will be extracted from approximately 25-hour continuous (Holter) recordings on Day -1 of Treatment Period 1 and Days 1 and 2 in each treatment period.
Area Under The Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUC0-t) Of Total Molybdenum And Plasma Ultrafiltrate Molybdenum [Baseline, up to 96 hours post-dose]
Maximum Observed Concentration (Cmax) Of Total Molybdenum And Plasma Ultrafiltrate Molybdenum [Baseline, up to 96 hours post-dose]
Time To Maximum Observed Concentration (Tmax) Of Total Molybdenum And Plasma Ultrafiltrate Molybdenum [Baseline, up to 96 hours post-dose]
Incidence Of Treatment-emergent Adverse Events [Day 1 (after dosing) through Day 70]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Nonsmoker.
Body weight at least 60 kilograms (kg) for males or 52 kg for females and body mass index ≥18.0 and ≤30.0 kg/meter squared.
Willing and able to follow protocol-specified contraception requirements.
Participant has no clinically significant history or presence of ECG findings.

Exclusion Criteria:

History or presence of clinical and/or lab disorders.
Lymphoma, leukemia, or any malignancy within the past 5 years, or breast cancer within the past 10 years.
Participant has abnormal blood pressure, defined as a supine blood pressure <90/50 millimeters of mercury (mm Hg) or >140/90 mm Hg.
Serum potassium, calcium, or magnesium levels outside the normal range.
Serum copper and/or ceruloplasmin values below the lower limit of normal at Screening.
Female participant has hemoglobin <10.8 grams/deciliter (g/dL) and male participant has hemoglobin <12.5 g/dL.
Clinically significant multiple or severe allergies.
Alanine aminotransferase, aspartate aminotransferase, serum creatinine, or total bilirubin greater than upper limit of normal (with the exception of Gilbert's syndrome).