Phase 1
N=57
Study to Investigate the Effect of Balovaptan on the QTC Interval in Healthy Subjects
Healthy Volunteers
Bottom Line
View on ClinicalTrials.gov: NCT03808298 ↗Enrolled (actual)
57
Serious AEs
0.0%
Results posted
Jul 2020
Primary outcome: Primary: Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings — -0.1; -0.6; -0.1; 0.1 ms
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Balovaptan therapeutic dose Treatment A (Drug); Balovaptan supra-therapeutic dose Treatment B (Drug); Active control [moxifloxacin] on Day 2 Treatment C (Drug); Active control [Moxifloxacin] on Day 15 Treatment D (Drug); Placebo for Balovaptan Treatment C (Drug); Placebo for Balovaptan Treatment D (Drug); Placebo for Moxifloxacin Treatment A (Drug); Placebo for Moxifloxacin Treatment B (Drug); Moxifloxacin Treatment C (Drug); Placebo for Moxifloxacin Treatment C (Drug); Placebo for Moxifloxacin Treatment D (Drug); Moxifloxacin Treatment D (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Jun 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings |
-2.3; -3.5; -1.8; -2.9; -0.2; -2.2 | — |
| SECONDARY Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings |
-2.3; -3.5; -1.8; -2.9; -0.2; -2.2 | — |
| SECONDARY Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings |
-2.7; -3.5; -1.6; -2.9; -0.6; -2.2 | — |
| SECONDARY Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings |
0.2; 0.5; 0.4; 0.1; 0.0; 0.2 | — |
| SECONDARY Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings |
-1.4; -0.9; -0.2; -0.3; -0.4; -0.3 | — |
| SECONDARY Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings |
-0.1; -0.1; 0.0; 0.1; 0.1; -0.1 | — |
| SECONDARY Number of Categorical Outliers for QTcF |
0; 1; 0; 0; 0; 00 | — |
| SECONDARY Number of Categorical Outliers for HR |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Categorical Outliers for PR |
0; 0; 0 | — |
| SECONDARY Number of Categorical Outliers for QRS |
0; 0; 0 | — |
| SECONDARY Number of Treatment Emergent Changes of T-Wave Morphology |
0; 1; 1; 0; 0; 0 | — |
| SECONDARY Number of Treatment Emergent Changes of U-Wave Presence |
0; 0; 0 | — |
| SECONDARY Tmax of Balovaptan |
2.50; 1.00; 1.00; 1.00 | — |
| SECONDARY Tmax of M2 Metabolite |
23.92; 23.92; 6.00; 6.00 | — |
| SECONDARY Tmax M3 Metabolite |
23.92; 8.00; 4.00; 4.01 | — |
| SECONDARY Cmax of Balovaptan |
32.5; 362.7; 89.8; 613.4 | — |
| SECONDARY Cmax of M2 Metabolite |
5.69; 42.75; 24.77; 152.83 | — |
| SECONDARY Cmax of M3 Metabolite |
6.83; 71.12; 1005.2; 5456.9 | — |
| SECONDARY AUC0-24 of Balovaptan |
440.7; 3524.8; 1127.6; 6377.9 | — |
| SECONDARY AUC0-24 of M2 Metabolite |
90.8; 766.6; 527.5; 3127.0 | — |
| SECONDARY AUC0-24 of M3 Metabolite |
131.2; 1404.2; 1005.2; 5456.9 | — |
| SECONDARY Tmax of Moxifloxacin |
2.50; 1.78 | — |
| SECONDARY Cmax of Moxifloxacin |
2056.9; 2058.8 | — |
| SECONDARY AUC0-24 of Moxifloxacin |
22503.9; 24103.1 | — |
| SECONDARY Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of Balovaptan From Concentration-QTc Analysis |
1.06; 0.70 | — |
| SECONDARY Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of M2 From Concentration-QTc Analysis |
1.01; 0.27 | — |
| SECONDARY Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentration for M3 From Concentration-QTc Analysis |
1.05; 0.23 | — |
| SECONDARY Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records |
-2.0; -3.2; 3.4; -2.0; 6.2; -2.3 | — |
| SECONDARY Percentage of Participants With Treatment Emergent Adverse Events |
42.1 | — |
Summary
This was a single-center, multiple-dose, randomized, double-blind, placebo-controlled, positive-controlled, twelve sequence, 3-period cross-over study to investigate the effect of balovaptan on the QTc interval in healthy subjects.
Eligibility Criteria
Inclusion Criteria
- Healthy male and female subjects. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, urinalysis, and serology.
- Body Mass Index of 18 to 30 kg/m2, inclusive.
- For women of childbearing potential: agreement to use at least 1 acceptable form of contraception during the entire study and for 90 days following last dose of study drug.
- For men: vasectomized, agreement to remain abstinent or use of a condom during intercourse. Must also agree to refrain from donating sperm.
- Fluent in English.
Exclusion Criteria
- If female, a positive pregnancy test at screening or prior to Day 1 of any Treatment Period.
- Lactating women.
- Any condition or disease detected during the medical interview / physical examination that would render the subject unsuitable for the study, place the subject at undue risk or interfere with the ability of the subject to complete the study in the opinion of the Investigator or designee.
Data sourced from ClinicalTrials.gov (NCT03808298). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.