- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04560816
A Study of the Cardiac Effects of ALXN1840 in Healthy Adults
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Austin, Texas, United States, 78744
- PPD Development, LP
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / 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. |
Placebo will be administered orally.
Other Names:
ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose).
Other Names:
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. |
Placebo will be administered orally.
Other Names:
ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose).
Other Names:
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. |
Placebo will be administered orally.
Other Names:
ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose).
Other Names:
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. |
Placebo will be administered orally.
Other Names:
ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose).
Other Names:
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. |
Placebo will be administered orally.
Other Names:
ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose).
Other Names:
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. |
Placebo will be administered orally.
Other Names:
ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose).
Other Names:
Moxifloxacin (400 milligrams) will be administered orally.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
1, 2, and 3 hours postdose at Day 1
|
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.
|
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)
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.
|
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)
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.
|
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)
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.
|
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
|
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. |
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
|
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.
|
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
|
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. |
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
|
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.
|
Day 1 (after dosing) through 24 hours postdose
|
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.
|
Predose (0) to 96 hours post-dose
|
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.
|
Predose (0) to 96 hours post-dose
|
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.
|
Pre-dose to 96 hours post-dose
|
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.
|
Day 1 (after dosing) through Day 70
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Eugene S. Swenson, MD, PhD, Alexion
- Study Chair: Masood Sadaat, MD, MSc, Alexion
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antimetabolites
- Antineoplastic Agents
- Gastrointestinal Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Hypolipidemic Agents
- Lipid Regulating Agents
- Anti-Bacterial Agents
- Chelating Agents
- Sequestering Agents
- Nootropic Agents
- Lipotropic Agents
- Moxifloxacin
- Choline
- Tetrathiomolybdate
Other Study ID Numbers
- ALXN1840-HV-107
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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