Clinical trial NCT04560816: A Study of the Cardiac Effects of ALXN1840 in Healthy Adults
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Electrocardiogram
Cardiac Repolarization
ALXN1840
Optimized QT Correction
QT Interval Correction
Thorough QT
QT Correction by Fridericia
Individual QT Correction
Wilson Disease
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
name: ERT: Clinical Trial Technology Solutions
First posted: 2020-09-23
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This will be a 3-treatment, 3-period, 6-sequence, crossover study in healthy adults.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Nonsmoker.
2. 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.
3. Willing and able to follow protocol-specified contraception requirements.
4. Participant has no clinically significant history or presence of ECG findings.

Exclusion Criteria:

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

Primary outcomes:
measure: Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis
timeFrame: 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:
measure: ΔΔQTcF For Moxifloxacin Using The By-time Point Analysis
timeFrame: 1, 2, and 3 hours postdose at Day 1
measure: Change From Baseline For Heart Rate (ΔHR)
timeFrame: 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
measure: Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF)
timeFrame: 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
measure: Change From Baseline PR Interval (ΔPR)
timeFrame: 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
measure: Change From Baseline QRS Interval (ΔQRS)
timeFrame: 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
measure: Placebo-corrected Change From Baseline Heart Rate (ΔΔHR)
timeFrame: 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
measure: Placebo-corrected Change From Baseline PR Interval (ΔΔPR)
timeFrame: 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
measure: Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS)
timeFrame: 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
measure: Number of Participants With Treatment-emergent T-wave Morphology Abnormalities and U-waves
timeFrame: Day 1 (after dosing) through 24 hours postdose
measure: 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
timeFrame: Predose (0) to 96 hours post-dose
measure: ALXN1840 PK Parameter: Maximum Observed Concentration (Cmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840
timeFrame: Predose (0) to 96 hours post-dose
measure: ALXN1840 PK Parameter: Time To Maximum Observed Concentration (Tmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840
timeFrame: Pre-dose to 96 hours post-dose
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 (after dosing) through Day 70
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD Development, LP
state: Texas
Study officials:
affiliation: Alexion Pharmaceuticals, Inc.
name: Eugene S. Swenson, MD, PhD
role: STUDY_DIRECTOR
affiliation: Alexion Pharmaceuticals, Inc.
name: Masood Sadaat, MD, MSc
role: STUDY_CHAIR
References: