NCT04560816

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
57

participants targeted

Target at P75+ for phase_1 healthy

Timeline
Completed

Started Jul 2020

Typical duration for phase_1 healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 24, 2020

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

September 18, 2020

Completed
5 days until next milestone

First Posted

Study publicly available on registry

September 23, 2020

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 24, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 24, 2021

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

August 14, 2023

Completed
Last Updated

August 14, 2023

Status Verified

September 1, 2022

Enrollment Period

8 months

First QC Date

September 18, 2020

Results QC Date

March 25, 2022

Last Update Submit

September 30, 2022

Conditions

Healthy

Keywords

ElectrocardiogramCardiac RepolarizationALXN1840Optimized QT CorrectionQT Interval CorrectionThorough QTQT Correction by FridericiaIndividual QT CorrectionWilson Disease

Outcome Measures

Primary Outcomes (1)

  • Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis

    Twelve-lead electrocardiograms (ECGs) were 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 in the QT interval was corrected for heart rate using Fridericia's formula (ΔQTcF). ΔQTcF was based on a mixed-effects model for repeated measures (MMRM) with ΔQTcF as the dependent variable; period, sequence, time, treatment, and time-by-treatment interaction as fixed effects; and baseline QTc and sex as covariates. ΔΔQTc = LS mean ΔQTcF after ALXN1840 dosing minus LS mean ΔQTcF after placebo. If the upper bound of the confidence interval (CI) of ΔΔQTcF was \< 10 ms for all postdose time points, ALXN1840 was concluded to not have a significant effect on QT interval prolongation.

    Baseline (average of samples taken at -45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose

Secondary Outcomes (13)

  • ΔΔQTcF For Moxifloxacin Using The By-time Point Analysis

    1, 2, and 3 hours postdose at Day 1

  • Change From Baseline For Heart Rate (ΔHR)

    Baseline (average of samples taken at 45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose

  • Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF)

    Baseline (average of samples taken at 45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose

  • Change From Baseline PR Interval (ΔPR)

    Baseline (average of samples taken at 45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose

  • Change From Baseline QRS Interval (ΔQRS)

    Baseline (average of samples taken at 45, -30, and -15 minutes before dosing), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 (Day 2) hours postdose

  • +8 more secondary outcomes

Study Arms (6)

Treatment Sequence 1

EXPERIMENTAL

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: ALXN1840Drug: PlaceboDrug: Moxifloxacin

Treatment Sequence 2

EXPERIMENTAL

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: ALXN1840Drug: PlaceboDrug: Moxifloxacin

Treatment Sequence 3

EXPERIMENTAL

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: ALXN1840Drug: PlaceboDrug: Moxifloxacin

Treatment Sequence 4

EXPERIMENTAL

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: ALXN1840Drug: PlaceboDrug: Moxifloxacin

Treatment Sequence 5

EXPERIMENTAL

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: ALXN1840Drug: PlaceboDrug: Moxifloxacin

Treatment Sequence 6

EXPERIMENTAL

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: ALXN1840Drug: PlaceboDrug: Moxifloxacin

Interventions

ALXN1840DRUG

ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose).

Also known as: WTX101, Bis-choline tetrathiomolybdate, Tiomolibdate choline
Treatment Sequence 1Treatment Sequence 2Treatment Sequence 3Treatment Sequence 4Treatment Sequence 5Treatment Sequence 6
PlaceboDRUG

Placebo will be administered orally.

Also known as: Placebo-matching ALXN1840
Treatment Sequence 1Treatment Sequence 2Treatment Sequence 3Treatment Sequence 4Treatment Sequence 5Treatment Sequence 6
MoxifloxacinDRUG

Moxifloxacin (400 milligrams) will be administered orally.

Treatment Sequence 1Treatment Sequence 2Treatment Sequence 3Treatment Sequence 4Treatment Sequence 5Treatment Sequence 6

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

PPD Development, LP

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Hepatolenticular Degeneration

Interventions

tetrathiomolybdateMoxifloxacin

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesBrain Diseases, Metabolic, InbornBrain Diseases, MetabolicMovement DisordersHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolism, Inborn ErrorsMetal Metabolism, Inborn ErrorsMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones4-QuinolonesQuinolonesQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
Alexion Pharmaceuticals, Inc.
Organization
Alexion Pharmaceuticals, Inc.
clinicaltrials@alexion.com
855-752-2356

Study Officials

  • Eugene S. Swenson, MD, PhD

    Alexion Pharmaceuticals, Inc.

    STUDY DIRECTOR

  • Masood Sadaat, MD, MSc

    Alexion Pharmaceuticals, Inc.

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Masking Details
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.
Purpose
TREATMENT
Intervention Model
CROSSOVER
Model Details: This will be a 3-treatment, 3-period, 6-sequence, crossover study in healthy adults.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 18, 2020

First Posted

September 23, 2020

Study Start

July 24, 2020

Primary Completion

March 24, 2021

Study Completion

March 24, 2021

Last Updated

August 14, 2023

Results First Posted

August 14, 2023

Record last verified: 2022-09

Data Sharing

IPD Sharing
Will not share

Locations

US(1)