Healthy
Conditions
Keywords
Electrocardiogram, Cardiac Repolarization, ALXN1840, Optimized QT Correction, QT Interval Correction, Thorough QT, QT Correction by Fridericia, Individual QT Correction, Wilson Disease
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.
Interventions
DRUGALXN1840
ALXN1840 (120 milligrams) will be administered orally (supratherapeutic dose).
DRUGPlacebo
Placebo will be administered orally.
DRUGMoxifloxacin
Moxifloxacin (400 milligrams) will be administered orally.
Sponsors
PPD Development, LP
ERT: Clinical Trial Technology Solutions
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
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.
Intervention model description
This will be a 3-treatment, 3-period, 6-sequence, crossover study in healthy adults.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | 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. |
| Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | 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. |
| ΔΔQTcF For Moxifloxacin Using The By-time Point Analysis | 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. |
| Number of Participants With Treatment-emergent T-wave Morphology Abnormalities and U-waves | 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. |
| 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 | 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. |
| ALXN1840 PK Parameter: Maximum Observed Concentration (Cmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840 | 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. |
| ALXN1840 PK Parameter: Time To Maximum Observed Concentration (Tmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840 | 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. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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. |
| Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | 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. |
Countries
United States
Participant flow
Recruitment details
Only healthy participants were eligible for enrollment. Participants with cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurologic disorders; abnormal blood pressure, history of cardiac abnormalities, or abnormal clinical laboratory results were excluded from the study.
Pre-assignment details
One participant was excluded from the pharmacokinetic (PK)/corrected QT interval (QTc) set as a result of having no postdose data for PK concentration and QTc data at matching time points.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study All participants were randomly assigned to receive a single dose of each the following 3 treatments in 1 of 6 treatment sequences:
* ALXN1840 120 mg administered as 15 mg enteric-coated tablets (supratherapeutic dose)
* Enteric-coated placebo tablets matching ALXN1840
* Moxifloxacin 400 mg tablet | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 34.4 years STANDARD_DEVIATION 7.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 56 | 0 / 53 | 0 / 57 |
| other Total, other adverse events | 9 / 57 | 3 / 56 | 6 / 53 | 16 / 57 |
| serious Total, serious adverse events | 0 / 57 | 0 / 56 | 0 / 53 | 0 / 57 |
Outcome results
Primary
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.
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
Population: All participants who received at least 1 dose of study treatment with measurements at baseline as well as on-treatment with evaluable data at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ALXN1840 | Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | Day 1, 3 hours postdose | -0.64 ms |
| ALXN1840 | Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | Day 1, 4 hours postdose | -1.08 ms |
| ALXN1840 | Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | Day 1, 10 hours postdose | 0.76 ms |
| ALXN1840 | Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | Day 1, 5 hours postdose | -0.90 ms |
| ALXN1840 | Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | Day 1, 6 hours postdose | -0.71 ms |
| ALXN1840 | Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | Day 1, 7 hours postdose | 0.25 ms |
| ALXN1840 | Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | Day 1, 8 hours postdose | -0.93 ms |
| ALXN1840 | Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | Day 1, 0.5 hours postdose | -0.21 ms |
| ALXN1840 | Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | Day 1, 1 hour postdose | -0.31 ms |
| ALXN1840 | Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | Day 1, 2 hours postdose | 0.07 ms |
| ALXN1840 | Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | Day 1, 12 hours postdose | 0.05 ms |
| ALXN1840 | Placebo-corrected Change From Baseline For QTcF (ΔΔQTcF) for ALXN1840 Using The By-time Point Analysis | Day 2, 24 hours postdose | 2.30 ms |
Secondary
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
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.
Time frame: Predose (0) to 96 hours post-dose
Population: All participants who received at least 1 dose of study treatment with evaluable data. It was pre-specified to collect data for only the ALXN1840 Arm for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1840 | 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 | Total Molybdenum | 18450 h*ng/mL | Geometric Coefficient of Variation 44.5 |
| ALXN1840 | 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 | Plasma Ultrafiltrate Molybdenum | 1763 h*ng/mL | Geometric Coefficient of Variation 84.8 |
Secondary
ALXN1840 PK Parameter: Maximum Observed Concentration (Cmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840
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.
Time frame: Predose (0) to 96 hours post-dose
Population: All participants who received at least 1 dose of study treatment with evaluable data. It was pre-specified to collect data for only the ALXN1840 Arm for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1840 | ALXN1840 PK Parameter: Maximum Observed Concentration (Cmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840 | Total Molybdenum | 504.1 ng/mL | Geometric Coefficient of Variation 46.8 |
| ALXN1840 | ALXN1840 PK Parameter: Maximum Observed Concentration (Cmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840 | Plasma Ultrafiltrate Molybdenum | 127.9 ng/mL | Geometric Coefficient of Variation 120.5 |
Secondary
ALXN1840 PK Parameter: Time To Maximum Observed Concentration (Tmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840
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.
Time frame: Pre-dose to 96 hours post-dose
Population: All participants who received at least 1 dose of study treatment with evaluable data. It was pre-specified to collect data for only the ALXN1840 Arm for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ALXN1840 | ALXN1840 PK Parameter: Time To Maximum Observed Concentration (Tmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840 | Total Molybdenum | 5.00 hours |
| ALXN1840 | ALXN1840 PK Parameter: Time To Maximum Observed Concentration (Tmax) Of Total Molybdenum And PUF Molybdenum Following a Single Oral Dose of ALXN1840 | Plasma Ultrafiltrate Molybdenum | 6.00 hours |
Secondary
Change From Baseline For Heart Rate (ΔHR)
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.
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
Population: All participants who received at least 1 dose of study treatment with measurements at baseline as well as on-treatment with evaluable data at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ALXN1840 | Change From Baseline For Heart Rate (ΔHR) | Day 1, 6 hours postdose | 7.07 bpm |
| ALXN1840 | Change From Baseline For Heart Rate (ΔHR) | Day 1, 12 hours postdose | 5.76 bpm |
| ALXN1840 | Change From Baseline For Heart Rate (ΔHR) | Day 1, 5 hours postdose | 5.85 bpm |
| ALXN1840 | Change From Baseline For Heart Rate (ΔHR) | Day 1, 2 hours postdose | -0.12 bpm |
| ALXN1840 | Change From Baseline For Heart Rate (ΔHR) | Day 1, 10 hours postdose | 7.71 bpm |
| ALXN1840 | Change From Baseline For Heart Rate (ΔHR) | Day 1, 8 hours postdose | 4.69 bpm |
| ALXN1840 | Change From Baseline For Heart Rate (ΔHR) | Day 1, 1 hour postdose | -0.02 bpm |
| ALXN1840 | Change From Baseline For Heart Rate (ΔHR) | Day 1, 0.5 hours postdose | -0.27 bpm |
| ALXN1840 | Change From Baseline For Heart Rate (ΔHR) | Day 1, 3 hours postdose | 0.41 bpm |
| ALXN1840 | Change From Baseline For Heart Rate (ΔHR) | Day 1, 7 hours postdose | 5.59 bpm |
| ALXN1840 | Change From Baseline For Heart Rate (ΔHR) | Day 2, 24 hours postdose | 2.32 bpm |
| ALXN1840 | Change From Baseline For Heart Rate (ΔHR) | Day 1, 4 hours postdose | 0.51 bpm |
| Placebo | Change From Baseline For Heart Rate (ΔHR) | Day 1, 0.5 hours postdose | 0.50 bpm |
| Placebo | Change From Baseline For Heart Rate (ΔHR) | Day 1, 1 hour postdose | 0.38 bpm |
| Placebo | Change From Baseline For Heart Rate (ΔHR) | Day 1, 2 hours postdose | 0.19 bpm |
| Placebo | Change From Baseline For Heart Rate (ΔHR) | Day 1, 3 hours postdose | -1.17 bpm |
| Placebo | Change From Baseline For Heart Rate (ΔHR) | Day 1, 4 hours postdose | 0.24 bpm |
| Placebo | Change From Baseline For Heart Rate (ΔHR) | Day 1, 5 hours postdose | 4.83 bpm |
| Placebo | Change From Baseline For Heart Rate (ΔHR) | Day 1, 8 hours postdose | 3.97 bpm |
| Placebo | Change From Baseline For Heart Rate (ΔHR) | Day 1, 10 hours postdose | 7.44 bpm |
| Placebo | Change From Baseline For Heart Rate (ΔHR) | Day 1, 12 hours postdose | 5.18 bpm |
| Placebo | Change From Baseline For Heart Rate (ΔHR) | Day 2, 24 hours postdose | 1.60 bpm |
| Placebo | Change From Baseline For Heart Rate (ΔHR) | Day 1, 6 hours postdose | 6.95 bpm |
| Placebo | Change From Baseline For Heart Rate (ΔHR) | Day 1, 7 hours postdose | 4.32 bpm |
| Moxifloxacin | Change From Baseline For Heart Rate (ΔHR) | Day 1, 6 hours postdose | 7.43 bpm |
| Moxifloxacin | Change From Baseline For Heart Rate (ΔHR) | Day 1, 12 hours postdose | 6.93 bpm |
| Moxifloxacin | Change From Baseline For Heart Rate (ΔHR) | Day 1, 3 hours postdose | 2.14 bpm |
| Moxifloxacin | Change From Baseline For Heart Rate (ΔHR) | Day 1, 0.5 hours postdose | 1.27 bpm |
| Moxifloxacin | Change From Baseline For Heart Rate (ΔHR) | Day 2, 24 hours postdose | 2.92 bpm |
| Moxifloxacin | Change From Baseline For Heart Rate (ΔHR) | Day 1, 2 hours postdose | 1.97 bpm |
| Moxifloxacin | Change From Baseline For Heart Rate (ΔHR) | Day 1, 1 hour postdose | 3.87 bpm |
| Moxifloxacin | Change From Baseline For Heart Rate (ΔHR) | Day 1, 8 hours postdose | 5.37 bpm |
| Moxifloxacin | Change From Baseline For Heart Rate (ΔHR) | Day 1, 5 hours postdose | 5.82 bpm |
| Moxifloxacin | Change From Baseline For Heart Rate (ΔHR) | Day 1, 7 hours postdose | 6.61 bpm |
| Moxifloxacin | Change From Baseline For Heart Rate (ΔHR) | Day 1, 10 hours postdose | 9.15 bpm |
| Moxifloxacin | Change From Baseline For Heart Rate (ΔHR) | Day 1, 4 hours postdose | 2.30 bpm |
Secondary
Change From Baseline PR Interval (ΔPR)
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.
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
Population: All participants who received at least 1 dose of study treatment with measurements at baseline as well as on-treatment with evaluable data at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ALXN1840 | Change From Baseline PR Interval (ΔPR) | Day 1, 4 hours postdose | -0.75 ms |
| ALXN1840 | Change From Baseline PR Interval (ΔPR) | Day 1, 1 hour postdose | 0.41 ms |
| ALXN1840 | Change From Baseline PR Interval (ΔPR) | Day 1, 2 hours postdose | 1.30 ms |
| ALXN1840 | Change From Baseline PR Interval (ΔPR) | Day 1, 3 hours postdose | 0.46 ms |
| ALXN1840 | Change From Baseline PR Interval (ΔPR) | Day 1, 5 hours postdose | -1.72 ms |
| ALXN1840 | Change From Baseline PR Interval (ΔPR) | Day 1, 6 hours postdose | -3.64 ms |
| ALXN1840 | Change From Baseline PR Interval (ΔPR) | Day 1, 7 hours postdose | -5.76 ms |
| ALXN1840 | Change From Baseline PR Interval (ΔPR) | Day 1, 8 hours postdose | -4.52 ms |
| ALXN1840 | Change From Baseline PR Interval (ΔPR) | Day 1, 10 hours postdose | -3.94 ms |
| ALXN1840 | Change From Baseline PR Interval (ΔPR) | Day 1, 12 hours postdose | -2.89 ms |
| ALXN1840 | Change From Baseline PR Interval (ΔPR) | Day 2, 24 hours postdose | -0.13 ms |
| ALXN1840 | Change From Baseline PR Interval (ΔPR) | Day 1, 0.5 hours postdose | -0.13 ms |
| Placebo | Change From Baseline PR Interval (ΔPR) | Day 1, 0.5 hours postdose | 1.26 ms |
| Placebo | Change From Baseline PR Interval (ΔPR) | Day 1, 10 hours postdose | -3.34 ms |
| Placebo | Change From Baseline PR Interval (ΔPR) | Day 1, 1 hour postdose | 1.66 ms |
| Placebo | Change From Baseline PR Interval (ΔPR) | Day 1, 7 hours postdose | -4.05 ms |
| Placebo | Change From Baseline PR Interval (ΔPR) | Day 1, 6 hours postdose | -3.43 ms |
| Placebo | Change From Baseline PR Interval (ΔPR) | Day 1, 2 hours postdose | 1.54 ms |
| Placebo | Change From Baseline PR Interval (ΔPR) | Day 2, 24 hours postdose | 0.69 ms |
| Placebo | Change From Baseline PR Interval (ΔPR) | Day 1, 8 hours postdose | -3.83 ms |
| Placebo | Change From Baseline PR Interval (ΔPR) | Day 1, 3 hours postdose | 1.32 ms |
| Placebo | Change From Baseline PR Interval (ΔPR) | Day 1, 5 hours postdose | -1.12 ms |
| Placebo | Change From Baseline PR Interval (ΔPR) | Day 1, 4 hours postdose | -0.10 ms |
| Placebo | Change From Baseline PR Interval (ΔPR) | Day 1, 12 hours postdose | -2.98 ms |
| Moxifloxacin | Change From Baseline PR Interval (ΔPR) | Day 1, 4 hours postdose | -3.38 ms |
| Moxifloxacin | Change From Baseline PR Interval (ΔPR) | Day 1, 5 hours postdose | -4.22 ms |
| Moxifloxacin | Change From Baseline PR Interval (ΔPR) | Day 1, 12 hours postdose | -4.60 ms |
| Moxifloxacin | Change From Baseline PR Interval (ΔPR) | Day 1, 6 hours postdose | -5.52 ms |
| Moxifloxacin | Change From Baseline PR Interval (ΔPR) | Day 1, 7 hours postdose | -7.16 ms |
| Moxifloxacin | Change From Baseline PR Interval (ΔPR) | Day 1, 8 hours postdose | -7.07 ms |
| Moxifloxacin | Change From Baseline PR Interval (ΔPR) | Day 2, 24 hours postdose | -1.68 ms |
| Moxifloxacin | Change From Baseline PR Interval (ΔPR) | Day 1, 1 hour postdose | -1.37 ms |
| Moxifloxacin | Change From Baseline PR Interval (ΔPR) | Day 1, 10 hours postdose | -6.61 ms |
| Moxifloxacin | Change From Baseline PR Interval (ΔPR) | Day 1, 2 hours postdose | -0.77 ms |
| Moxifloxacin | Change From Baseline PR Interval (ΔPR) | Day 1, 0.5 hours postdose | -1.33 ms |
| Moxifloxacin | Change From Baseline PR Interval (ΔPR) | Day 1, 3 hours postdose | -2.66 ms |
Secondary
Change From Baseline QRS Interval (ΔQRS)
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.
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
Population: All participants who received at least 1 dose of study treatment with measurements at baseline as well as on-treatment with evaluable data at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ALXN1840 | Change From Baseline QRS Interval (ΔQRS) | Day 1, 4 hours postdose | 0.14 ms |
| ALXN1840 | Change From Baseline QRS Interval (ΔQRS) | Day 1, 8 hours postdose | -0.66 ms |
| ALXN1840 | Change From Baseline QRS Interval (ΔQRS) | Day 1, 6 hours postdose | -1.01 ms |
| ALXN1840 | Change From Baseline QRS Interval (ΔQRS) | Day 1, 5 hours postdose | -0.23 ms |
| ALXN1840 | Change From Baseline QRS Interval (ΔQRS) | Day 1, 0.5 hours postdose | -0.01 ms |
| ALXN1840 | Change From Baseline QRS Interval (ΔQRS) | Day 1, 7 hours postdose | -0.89 ms |
| ALXN1840 | Change From Baseline QRS Interval (ΔQRS) | Day 1, 2 hours postdose | 0.08 ms |
| ALXN1840 | Change From Baseline QRS Interval (ΔQRS) | Day 1, 1 hour postdose | 0.04 ms |
| ALXN1840 | Change From Baseline QRS Interval (ΔQRS) | Day 2, 24 hours postdose | -0.14 ms |
| ALXN1840 | Change From Baseline QRS Interval (ΔQRS) | Day 1, 3 hours postdose | 0.10 ms |
| ALXN1840 | Change From Baseline QRS Interval (ΔQRS) | Day 1, 12 hours postdose | -0.42 ms |
| ALXN1840 | Change From Baseline QRS Interval (ΔQRS) | Day 1, 10 hours postdose | -0.89 ms |
| Placebo | Change From Baseline QRS Interval (ΔQRS) | Day 1, 7 hours postdose | -1.08 ms |
| Placebo | Change From Baseline QRS Interval (ΔQRS) | Day 1, 0.5 hours postdose | -0.07 ms |
| Placebo | Change From Baseline QRS Interval (ΔQRS) | Day 1, 1 hour postdose | -0.04 ms |
| Placebo | Change From Baseline QRS Interval (ΔQRS) | Day 1, 2 hours postdose | -0.09 ms |
| Placebo | Change From Baseline QRS Interval (ΔQRS) | Day 1, 3 hours postdose | -0.05 ms |
| Placebo | Change From Baseline QRS Interval (ΔQRS) | Day 1, 6 hours postdose | -0.73 ms |
| Placebo | Change From Baseline QRS Interval (ΔQRS) | Day 1, 8 hours postdose | -0.39 ms |
| Placebo | Change From Baseline QRS Interval (ΔQRS) | Day 1, 10 hours postdose | -0.71 ms |
| Placebo | Change From Baseline QRS Interval (ΔQRS) | Day 2, 24 hours postdose | 0.02 ms |
| Placebo | Change From Baseline QRS Interval (ΔQRS) | Day 1, 4 hours postdose | 0.16 ms |
| Placebo | Change From Baseline QRS Interval (ΔQRS) | Day 1, 5 hours postdose | -0.28 ms |
| Placebo | Change From Baseline QRS Interval (ΔQRS) | Day 1, 12 hours postdose | -0.30 ms |
| Moxifloxacin | Change From Baseline QRS Interval (ΔQRS) | Day 1, 1 hour postdose | 0.06 ms |
| Moxifloxacin | Change From Baseline QRS Interval (ΔQRS) | Day 1, 10 hours postdose | -0.87 ms |
| Moxifloxacin | Change From Baseline QRS Interval (ΔQRS) | Day 1, 12 hours postdose | -0.50 ms |
| Moxifloxacin | Change From Baseline QRS Interval (ΔQRS) | Day 1, 2 hours postdose | -0.10 ms |
| Moxifloxacin | Change From Baseline QRS Interval (ΔQRS) | Day 2, 24 hours postdose | -0.18 ms |
| Moxifloxacin | Change From Baseline QRS Interval (ΔQRS) | Day 1, 0.5 hours postdose | -0.08 ms |
| Moxifloxacin | Change From Baseline QRS Interval (ΔQRS) | Day 1, 6 hours postdose | -1.13 ms |
| Moxifloxacin | Change From Baseline QRS Interval (ΔQRS) | Day 1, 7 hours postdose | -1.16 ms |
| Moxifloxacin | Change From Baseline QRS Interval (ΔQRS) | Day 1, 5 hours postdose | -0.35 ms |
| Moxifloxacin | Change From Baseline QRS Interval (ΔQRS) | Day 1, 4 hours postdose | 0.01 ms |
| Moxifloxacin | Change From Baseline QRS Interval (ΔQRS) | Day 1, 8 hours postdose | -0.48 ms |
| Moxifloxacin | Change From Baseline QRS Interval (ΔQRS) | Day 1, 3 hours postdose | -0.19 ms |
Secondary
Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF)
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.
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
Population: All participants who received at least 1 dose of study treatment with measurements at baseline as well as on-treatment with evaluable data at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ALXN1840 | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 0.5 hours postdose | -2.56 ms |
| ALXN1840 | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 1 hour postdose | -0.49 ms |
| ALXN1840 | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 2 hours postdose | -0.69 ms |
| ALXN1840 | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 3 hours postdose | -1.04 ms |
| ALXN1840 | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 4 hours postdose | -1.06 ms |
| ALXN1840 | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 5 hours postdose | -0.64 ms |
| ALXN1840 | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 6 hours postdose | -6.05 ms |
| ALXN1840 | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 7 hours postdose | -7.60 ms |
| ALXN1840 | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 8 hours postdose | -7.66 ms |
| ALXN1840 | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 10 hours postdose | -4.96 ms |
| ALXN1840 | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 12 hours postdose | -5.05 ms |
| ALXN1840 | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 2, 24 hours postdose | 0.52 ms |
| Placebo | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 10 hours postdose | -5.73 ms |
| Placebo | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 0.5 hours postdose | -2.36 ms |
| Placebo | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 12 hours postdose | -5.10 ms |
| Placebo | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 8 hours postdose | -6.73 ms |
| Placebo | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 1 hour postdose | -0.19 ms |
| Placebo | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 6 hours postdose | -5.35 ms |
| Placebo | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 2, 24 hours postdose | -1.78 ms |
| Placebo | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 2 hours postdose | -0.76 ms |
| Placebo | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 5 hours postdose | -0.55 ms |
| Placebo | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 7 hours postdose | -7.85 ms |
| Placebo | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 3 hours postdose | -0.41 ms |
| Placebo | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 4 hours postdose | 0.02 ms |
| Moxifloxacin | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 3 hours postdose | 10.96 ms |
| Moxifloxacin | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 4 hours postdose | 10.03 ms |
| Moxifloxacin | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 5 hours postdose | 9.54 ms |
| Moxifloxacin | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 6 hours postdose | 4.00 ms |
| Moxifloxacin | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 12 hours postdose | 0.94 ms |
| Moxifloxacin | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 7 hours postdose | 2.05 ms |
| Moxifloxacin | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 0.5 hours postdose | 2.29 ms |
| Moxifloxacin | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 1 hour postdose | 9.47 ms |
| Moxifloxacin | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 8 hours postdose | 1.49 ms |
| Moxifloxacin | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 2 hours postdose | 10.28 ms |
| Moxifloxacin | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 2, 24 hours postdose | 3.48 ms |
| Moxifloxacin | Change From Baseline QT Interval Using Fridericia's Formula (ΔQTcF) | Day 1, 10 hours postdose | 1.70 ms |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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.
Time frame: Day 1 (after dosing) through Day 70
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALXN1840 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 9 Participants |
| ALXN1840 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any serious TEAE (SAE) | 0 Participants |
| ALXN1840 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any related TEAE | 4 Participants |
| ALXN1840 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to death | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any serious TEAE (SAE) | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to death | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 3 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any related TEAE | 0 Participants |
| Moxifloxacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any related TEAE | 3 Participants |
| Moxifloxacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any serious TEAE (SAE) | 0 Participants |
| Moxifloxacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 6 Participants |
| Moxifloxacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to death | 0 Participants |
Secondary
Number of Participants With Treatment-emergent T-wave Morphology Abnormalities and U-waves
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.
Time frame: Day 1 (after dosing) through 24 hours postdose
Population: All participants who received at least 1 dose of study treatment with measurements at baseline as well as on-treatment with at least 1 postdose time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALXN1840 | Number of Participants With Treatment-emergent T-wave Morphology Abnormalities and U-waves | At least one treatment-emergent T-wave abnormality | 0 Participants |
| ALXN1840 | Number of Participants With Treatment-emergent T-wave Morphology Abnormalities and U-waves | At least one treatment-emergent U-wave | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent T-wave Morphology Abnormalities and U-waves | At least one treatment-emergent T-wave abnormality | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent T-wave Morphology Abnormalities and U-waves | At least one treatment-emergent U-wave | 0 Participants |
| Moxifloxacin | Number of Participants With Treatment-emergent T-wave Morphology Abnormalities and U-waves | At least one treatment-emergent T-wave abnormality | 1 Participants |
| Moxifloxacin | Number of Participants With Treatment-emergent T-wave Morphology Abnormalities and U-waves | At least one treatment-emergent U-wave | 0 Participants |
Secondary
Placebo-corrected Change From Baseline Heart Rate (ΔΔHR)
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.
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
Population: All participants who received at least 1 dose of study treatment with measurements at baseline as well as on-treatment with evaluable data at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ALXN1840 | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 1 hour postdose | -0.40 bpm |
| ALXN1840 | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 2 hours postdose | -0.31 bpm |
| ALXN1840 | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 2, 24 hours postdose | 0.73 bpm |
| ALXN1840 | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 0.5 hours postdose | -0.77 bpm |
| ALXN1840 | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 3 hours postdose | 1.58 bpm |
| ALXN1840 | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 4 hours postdose | 0.27 bpm |
| ALXN1840 | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 5 hours postdose | 1.02 bpm |
| ALXN1840 | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 6 hours postdose | 0.13 bpm |
| ALXN1840 | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 7 hours postdose | 1.27 bpm |
| ALXN1840 | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 8 hours postdose | 0.72 bpm |
| ALXN1840 | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 10 hours postdose | 0.27 bpm |
| ALXN1840 | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 12 hours postdose | 0.58 bpm |
| Placebo | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 4 hours postdose | 2.06 bpm |
| Placebo | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 1 hour postdose | 3.50 bpm |
| Placebo | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 7 hours postdose | 2.29 bpm |
| Placebo | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 2 hours postdose | 1.78 bpm |
| Placebo | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 12 hours postdose | 1.75 bpm |
| Placebo | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 5 hours postdose | 0.99 bpm |
| Placebo | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 2, 24 hours postdose | 1.32 bpm |
| Placebo | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 10 hours postdose | 1.71 bpm |
| Placebo | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 0.5 hours postdose | 0.77 bpm |
| Placebo | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 6 hours postdose | 0.48 bpm |
| Placebo | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 3 hours postdose | 3.31 bpm |
| Placebo | Placebo-corrected Change From Baseline Heart Rate (ΔΔHR) | Day 1, 8 hours postdose | 1.40 bpm |
Secondary
Placebo-corrected Change From Baseline PR Interval (ΔΔPR)
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.
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
Population: All participants who received at least 1 dose of study treatment with measurements at baseline as well as on-treatment with evaluable data at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ALXN1840 | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 10 hours postdose | -0.61 ms |
| ALXN1840 | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 1 hour postdose | -1.25 ms |
| ALXN1840 | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 2 hours postdose | -0.24 ms |
| ALXN1840 | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 6 hours postdose | -0.21 ms |
| ALXN1840 | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 12 hours postdose | 0.09 ms |
| ALXN1840 | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 2, 24 hours postdose | -0.82 ms |
| ALXN1840 | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 3 hours postdose | -0.87 ms |
| ALXN1840 | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 4 hours postdose | -0.65 ms |
| ALXN1840 | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 5 hours postdose | -0.60 ms |
| ALXN1840 | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 7 hours postdose | -1.71 ms |
| ALXN1840 | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 8 hours postdose | -0.69 ms |
| ALXN1840 | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 0.5 hours postdose | -1.39 ms |
| Placebo | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 4 hours postdose | -3.28 ms |
| Placebo | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 0.5 hours postdose | -2.60 ms |
| Placebo | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 2, 24 hours postdose | -2.37 ms |
| Placebo | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 1 hour postdose | -3.03 ms |
| Placebo | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 7 hours postdose | -3.10 ms |
| Placebo | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 2 hours postdose | -2.31 ms |
| Placebo | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 5 hours postdose | -3.11 ms |
| Placebo | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 3 hours postdose | -3.99 ms |
| Placebo | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 6 hours postdose | -2.09 ms |
| Placebo | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 10 hours postdose | -3.28 ms |
| Placebo | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 8 hours postdose | -3.24 ms |
| Placebo | Placebo-corrected Change From Baseline PR Interval (ΔΔPR) | Day 1, 12 hours postdose | -1.62 ms |
Secondary
Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS)
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.
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
Population: All participants who received at least 1 dose of study treatment with measurements at baseline as well as on-treatment with evaluable data at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ALXN1840 | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 6 hours postdose | -0.27 ms |
| ALXN1840 | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 10 hours postdose | -0.18 ms |
| ALXN1840 | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 0.5 hours postdose | 0.07 ms |
| ALXN1840 | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 4 hours postdose | -0.02 ms |
| ALXN1840 | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 2 hours postdose | 0.17 ms |
| ALXN1840 | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 7 hours postdose | 0.19 ms |
| ALXN1840 | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 5 hours postdose | 0.05 ms |
| ALXN1840 | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 3 hours postdose | 0.15 ms |
| ALXN1840 | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 12 hours postdose | -0.12 ms |
| ALXN1840 | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 8 hours postdose | -0.27 ms |
| ALXN1840 | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 2, 24 hours postdose | -0.16 ms |
| ALXN1840 | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 1 hour postdose | 0.08 ms |
| Placebo | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 2, 24 hours postdose | -0.20 ms |
| Placebo | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 1 hour postdose | 0.10 ms |
| Placebo | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 2 hours postdose | -0.01 ms |
| Placebo | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 3 hours postdose | -0.13 ms |
| Placebo | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 5 hours postdose | -0.07 ms |
| Placebo | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 6 hours postdose | -0.40 ms |
| Placebo | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 7 hours postdose | -0.08 ms |
| Placebo | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 8 hours postdose | -0.10 ms |
| Placebo | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 0.5 hours postdose | -0.01 ms |
| Placebo | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 4 hours postdose | -0.15 ms |
| Placebo | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 10 hours postdose | -0.15 ms |
| Placebo | Placebo-corrected Change From Baseline QRS Interval (ΔΔQRS) | Day 1, 12 hours postdose | -0.20 ms |
Secondary
ΔΔQTcF For Moxifloxacin Using The By-time Point Analysis
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.
Time frame: 1, 2, and 3 hours postdose at Day 1
Population: All participants who received at least 1 dose of moxifloxacin with measurements at baseline as well as on-treatment with evaluable data at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ALXN1840 | ΔΔQTcF For Moxifloxacin Using The By-time Point Analysis | Day 1, 1 hour postdose | 9.65 ms |
| ALXN1840 | ΔΔQTcF For Moxifloxacin Using The By-time Point Analysis | Day 1, 2 hours postdose | 11.04 ms |
| ALXN1840 | ΔΔQTcF For Moxifloxacin Using The By-time Point Analysis | Day 1, 3 hours postdose | 11.37 ms |