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Completed

NCT Number: NCT04560816

A Study of the Cardiac Effects of ALXN1840 in Healthy Adults

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.

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Key information

Conditions

Healthy Basal Ganglia Diseases Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Hepatolenticular Degeneration Heredodegenerative Disorders, Nervous System Liver Diseases Metabolic Diseases Metabolism, Inborn Errors Metal Metabolism, Inborn Errors Movement Disorders Nervous System Diseases Neurodegenerative Diseases Nutritional and Metabolic Diseases

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

PPD Development, LP

Austin, Texas, 78744, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

ALXN1840

Drug

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

Other names: WTX101, Bis-choline tetrathiomolybdate, Tiomolibdate choline

Placebo

Drug

Placebo will be administered orally.

Other names: Placebo-matching ALXN1840

moxifloxacin

Drug

Moxifloxacin (400 milligrams) will be administered orally.

Primary outcomes

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

    Time frame: 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

    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.

Secondary outcomes

  1. ΔΔQTcF For Moxifloxacin Using The By-time Point Analysis

    Time frame: 1, 2, and 3 hours postdose at Day 1

    Assay sensitivity was evaluated using the by-time point analysis of the effect on ΔΔQTc of moxifloxacin.

    If ΔΔQTcF was larger than 5 ms at 1, 2, and 3 hours postdose, assay sensitivity was considered to be demonstrated.

  2. Change From Baseline For Heart Rate (ΔHR)

    Time frame: 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

    Twelve-lead 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.

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

    Time frame: 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

    Twelve-lead 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.

  4. Change From Baseline PR Interval (ΔPR)

    Time frame: 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

    Twelve-lead 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.

  5. Change From Baseline QRS Interval (ΔQRS)

    Time frame: 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

    Twelve-lead 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.

  6. Placebo-corrected Change From Baseline Heart Rate (ΔΔHR)

    Time frame: 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

    Twelve-lead 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.

    Least square mean difference and its 90% CI were calculated based on MMRM with fixed effects for period, sequence, timepoint, treatment, time-by-treatment interaction as fixed effect and baseline value and sex as covariates.

  7. Placebo-corrected Change From Baseline PR Interval (ΔΔPR)

    Time frame: 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

    Twelve-lead 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.

  8. Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS)

    Time frame: 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

    Twelve-lead 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.

    Least square mean difference and its 90% CI were calculated based on MMRM with fixed effects for period, sequence, timepoint, treatment, time-by-treatment interaction as fixed effect and baseline value and sex as covariates.

  9. Number of Participants With Treatment-emergent T-wave Morphology Abnormalities and U-waves

    Time frame: Day 1 (after dosing) through 24 hours postdose

    Twelve-lead 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.

  10. ALXN1840 PK Parameter: Area Under The Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUC0-t) Of Total Molybdenum And Plasma Ultrafiltrate (PUF) Molybdenum Following a Single Oral Dose of ALXN1840

    Time frame: Predose (0) to 96 hours post-dose

    Blood samples for PK analysis of total molybdenum and PUF molybdenum were collected as close as possible to nominal time after completion of the ECG extraction period.

  11. ALXN1840 PK Parameter: Maximum Observed Concentration (Cmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840

    Time frame: Predose (0) to 96 hours post-dose

    Blood samples for PK analysis of total molybdenum and PUF molybdenum were collected as close as possible to nominal time after completion of the ECG extraction period.

  12. ALXN1840 PK Parameter: Time To Maximum Observed Concentration (Tmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840

    Time frame: Pre-dose to 96 hours post-dose

    Blood samples for PK analysis of total molybdenum and PUF molybdenum were collected as close as possible to nominal time after completion of the ECG extraction period.

  13. Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    Time frame: Day 1 (after dosing) through Day 70

    An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE was an AE that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. A related TEAE was defined as having a reasonable possibility the study intervention caused the AE as assessed by the investigator. Serious AEs were defined as any untoward medical occurrence that met at least 1 of the following serious criteria: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, other medically important serious event.

Sponsors and collaborators

Lead sponsor

Alexion Pharmaceuticals, Inc.

Industry

Collaborators

  • ERT: Clinical Trial Technology Solutions
  • PPD Development, LP

Registry information

Official study title

A Randomized, 3-Treatment, 3-Period, 6-Sequence, Crossover, Placebo- and Active-Controlled, Double-Blind for ALXN1840 (Open-Label for Moxifloxacin) Thorough QT/QTc Study to Evaluate ALXN1840 on Cardiac Repolarization in Healthy Adults

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Sep 23, 2020
Registry last updated
Aug 14, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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