Healthy VolunteersPhase 1NCT03808298
Study to Investigate the Effect of Balovaptan on the QTC Interval in Healthy Subjects
A Phase 1 study testing Balovaptan therapeutic dose Treatment A and Balovaptan supra-therapeutic dose Treatment B in people with Healthy Volunteers, run by Hoffmann-La Roche at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Balovaptan therapeutic dose Treatment A and Balovaptan supra-therapeutic dose Treatment B
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Feb 2019to 13 Jul 2019
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
PRA International Clinical Pharmacology Center (EDS US Clinic)
Lenexa, Kansas, 66219
About this study
Official title: A Single-Center, Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study to Investigate the Effect of Balovaptan on the QTC Interval in Healthy Subjects
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.
- Conditions
- Healthy Volunteers
- Being tested
- Balovaptan therapeutic dose Treatment A, Balovaptan supra-therapeutic dose Treatment B, Active control [moxifloxacin] on Day 2 Treatment C, Active control [Moxifloxacin] on Day 15 Treatment D, Placebo for Balovaptan Treatment C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Balovaptan therapeutic dose Treatment ADrug
Days 1-14: A single once daily dose at dose level A of balovaptan for 14 days
Balovaptan supra-therapeutic dose Treatment BDrug
Days 1-14: A single once daily oral dose at dose level B of balovaptan for 14 days.
Active control [moxifloxacin] on Day 2 Treatment CDrug
Day 2: A single oral dose of 400 mg moxifloxacin capsule.
Active control [Moxifloxacin] on Day 15 Treatment DDrug
Day 15: A single oral dose of 400 mg moxifloxacin capsule.
Placebo for Balovaptan Treatment CDrug
Days 1-14: Matching placebo for balovaptan for 14 days.
Placebo for Balovaptan Treatment DDrug
Days 1-14: Matching placebo for balovaptan for 14 days.
Placebo for Moxifloxacin Treatment ADrug
Day 2 and 15: A single oral dose of a matching placebo capsule for moxifloxacin.
Placebo for Moxifloxacin Treatment BDrug
Days 2 and 15: Single oral dose of a matching placebo capsule of moxifloxacin.
Moxifloxacin Treatment CDrug
Day 2: A single oral dose of 400 mg moxifloxacin capsule.
Placebo for Moxifloxacin Treatment CDrug
Day 15: A single oral dose of a matching placebo capsule for moxifloxacin.
Placebo for Moxifloxacin Treatment DDrug
Day 2: A single oral dose of a matching placebo capsule for moxifloxacin.
Moxifloxacin Treatment DDrug
Day 15: A single oral dose of 400 mg moxifloxacin capsule.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Sequence 1: A, B, C | Experimental | Not described Receives: Drug: Balovaptan therapeutic dose Treatment A; Drug: Balovaptan supra-therapeutic dose Treatment B; Drug: Active control [moxifloxacin] on Day 2 Treatment C; Drug: Placebo for Balovaptan Treatment C; Drug: Placebo for Moxifloxacin Treatment A; Drug: Placebo for Moxifloxacin Treatment B; Drug: Moxifloxacin Treatment C; Drug: Placebo for Moxifloxacin Treatment C |
| Treatment Sequence 2: A, C, B | Experimental | Not described Receives: Drug: Balovaptan therapeutic dose Treatment A; Drug: Balovaptan supra-therapeutic dose Treatment B; Drug: Active control [moxifloxacin] on Day 2 Treatment C; Drug: Placebo for Balovaptan Treatment C; Drug: Placebo for Moxifloxacin Treatment A; Drug: Placebo for Moxifloxacin Treatment B; Drug: Moxifloxacin Treatment C; Drug: Placebo for Moxifloxacin Treatment C |
| Treatment Sequence 3: B, A, C | Experimental | Not described Receives: Drug: Balovaptan therapeutic dose Treatment A; Drug: Balovaptan supra-therapeutic dose Treatment B; Drug: Active control [moxifloxacin] on Day 2 Treatment C; Drug: Placebo for Balovaptan Treatment C; Drug: Placebo for Moxifloxacin Treatment A; Drug: Placebo for Moxifloxacin Treatment B; Drug: Moxifloxacin Treatment C; Drug: Placebo for Moxifloxacin Treatment C |
| Treatment Sequence 4: B, C, A | Experimental | Not described Receives: Drug: Balovaptan therapeutic dose Treatment A; Drug: Balovaptan supra-therapeutic dose Treatment B; Drug: Active control [moxifloxacin] on Day 2 Treatment C; Drug: Placebo for Balovaptan Treatment C; Drug: Placebo for Moxifloxacin Treatment A; Drug: Placebo for Moxifloxacin Treatment B; Drug: Moxifloxacin Treatment C; Drug: Placebo for Moxifloxacin Treatment C |
| Treatment Sequence 5: C, A, B | Experimental | Not described Receives: Drug: Balovaptan therapeutic dose Treatment A; Drug: Balovaptan supra-therapeutic dose Treatment B; Drug: Active control [moxifloxacin] on Day 2 Treatment C; Drug: Placebo for Balovaptan Treatment C; Drug: Placebo for Moxifloxacin Treatment A; Drug: Placebo for Moxifloxacin Treatment B; Drug: Moxifloxacin Treatment C; Drug: Placebo for Moxifloxacin Treatment C |
| Treatment Sequence 6: C, B, A | Experimental | Not described Receives: Drug: Balovaptan therapeutic dose Treatment A; Drug: Balovaptan supra-therapeutic dose Treatment B; Drug: Active control [moxifloxacin] on Day 2 Treatment C; Drug: Placebo for Balovaptan Treatment C; Drug: Placebo for Moxifloxacin Treatment A; Drug: Placebo for Moxifloxacin Treatment B; Drug: Moxifloxacin Treatment C; Drug: Placebo for Moxifloxacin Treatment C |
| Treatment Sequence 7: A, B, D | Experimental | Not described Receives: Drug: Balovaptan therapeutic dose Treatment A; Drug: Balovaptan supra-therapeutic dose Treatment B; Drug: Active control [Moxifloxacin] on Day 15 Treatment D; Drug: Placebo for Balovaptan Treatment D; Drug: Placebo for Moxifloxacin Treatment A; Drug: Placebo for Moxifloxacin Treatment B; Drug: Placebo for Moxifloxacin Treatment D; Drug: Moxifloxacin Treatment D |
| Treatment Sequence 8: A, D, B | Experimental | Not described Receives: Drug: Balovaptan therapeutic dose Treatment A; Drug: Balovaptan supra-therapeutic dose Treatment B; Drug: Active control [Moxifloxacin] on Day 15 Treatment D; Drug: Placebo for Balovaptan Treatment D; Drug: Placebo for Moxifloxacin Treatment A; Drug: Placebo for Moxifloxacin Treatment B; Drug: Placebo for Moxifloxacin Treatment D; Drug: Moxifloxacin Treatment D |
| Treatment Sequence 9: B, A, D | Experimental | Not described Receives: Drug: Balovaptan therapeutic dose Treatment A; Drug: Balovaptan supra-therapeutic dose Treatment B; Drug: Active control [Moxifloxacin] on Day 15 Treatment D; Drug: Placebo for Balovaptan Treatment D; Drug: Placebo for Moxifloxacin Treatment A; Drug: Placebo for Moxifloxacin Treatment B; Drug: Placebo for Moxifloxacin Treatment D; Drug: Moxifloxacin Treatment D |
| Treatment Sequence 10: B, D, A | Experimental | Not described Receives: Drug: Balovaptan therapeutic dose Treatment A; Drug: Balovaptan supra-therapeutic dose Treatment B; Drug: Active control [Moxifloxacin] on Day 15 Treatment D; Drug: Placebo for Balovaptan Treatment D; Drug: Placebo for Moxifloxacin Treatment A; Drug: Placebo for Moxifloxacin Treatment B; Drug: Placebo for Moxifloxacin Treatment D; Drug: Moxifloxacin Treatment D |
| Treatment Sequence 11: D, A, B | Experimental | Not described Receives: Drug: Balovaptan therapeutic dose Treatment A; Drug: Balovaptan supra-therapeutic dose Treatment B; Drug: Active control [Moxifloxacin] on Day 15 Treatment D; Drug: Placebo for Balovaptan Treatment D; Drug: Placebo for Moxifloxacin Treatment A; Drug: Placebo for Moxifloxacin Treatment B; Drug: Placebo for Moxifloxacin Treatment D; Drug: Moxifloxacin Treatment D |
| Treatment Sequence 12: D, B, A | Experimental | Not described Receives: Drug: Balovaptan therapeutic dose Treatment A; Drug: Balovaptan supra-therapeutic dose Treatment B; Drug: Active control [Moxifloxacin] on Day 15 Treatment D; Drug: Placebo for Balovaptan Treatment D; Drug: Placebo for Moxifloxacin Treatment A; Drug: Placebo for Moxifloxacin Treatment B; Drug: Placebo for Moxifloxacin Treatment D; Drug: Moxifloxacin Treatment D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Change-from-baseline QTcF (ΔΔQTcF) at dose level B of balovaptan measured on 12-lead ECGs extracted from continuous recordings at the specified time points on Day 14.
Measured: Baseline (Predose Day 1), Day 14. (Each treatment period is 15 days.)
Secondary outcomes (28)
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Change-from-baseline QTcF (ΔΔQTcF) at dose level B of balovaptan measured on 12-lead ECGs extracted from continuous recordings at the specified time points on Day 1.
Measured: Baseline (Predose Day 1), Day 1. (Each treatment period is 15 days.)
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Change-from-baseline QTcF (ΔΔQTcF) at dose level A of balovaptan measured on 12-lead ECGs extracted from continuous recordings at the specified time points on Days 1 and 14.
Measured: Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Change-from-baseline heart rate at dose level A and dose level B of balovaptan measured on 12-Lead ECGs extracted from continuous recordings on Days 1 and 14.
Measured: Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Change-from-baseline PR interval at dose level A and dose level B of balovaptan measured on 12-Lead ECGs extracted from continuous recordings on Day 1 and 14.
Measured: Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Change-from-baseline QRS interval at dose level A and dose level B of balovapton measured on 12-Lead ECGs extracted from continuous recordings on Days 1 and 14.
Measured: Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)
Number of Categorical Outliers for QTcF
The number (percentage) of categorical outliers were participants who had increases in absolute QTcF values > 450 and ≤ 480 ms, > 480 and ≤ 500 ms, or > 500 ms.
Measured: Up to approximately 20 weeks
Number of Categorical Outliers for HR
Number (percentage) of categorical outliers were participants with a decrease in HR from pre-dose baseline > 25% to a HR < 50 bpm; and increase in HR from pre-dose baseline > 25% to a HR > 100 bpm.
Measured: Up to approximately 20 weeks
Number of Categorical Outliers for PR
PR outliers criteria is as an increase of PR from baseline >25% resulting in PR >200 ms.
Measured: Up to approximately 20 weeks
Number of Categorical Outliers for QRS
QRS outlier criteria is an increase of QRS from baseline >25% resulting in QRS >120 ms.
Measured: Up to approximately 20 weeks
Number of Treatment Emergent Changes of T-Wave Morphology
Number (%) of participants falling into each of the T-wave categories: Normal (+), Flat, Notched (+), Biphasic, Normal (-), Notched (-).
Measured: Up to approximately 20 weeks
Number of Treatment Emergent Changes of U-Wave Presence
Number (percentage) of participants with treatment emergent changes of U-wave presence.
Measured: Up to approximately 20 weeks
Tmax of Balovaptan
Measured: Day 1 and Day 14. (Each treatment period is 15 days.)
Tmax of M2 Metabolite
Measured: Day 1 and Day 14. (Each treatment period is 15 days.)
Tmax M3 Metabolite
Measured: Day 1 and Day 14. (Each treatment period is 15 days.)
Cmax of Balovaptan
Measured: Day 1 and Day 14. (Each treatment period is 15 days.)
Cmax of M2 Metabolite
Measured: Day 1 and Day 14. (Each treatment period is 15 days.)
Cmax of M3 Metabolite
Measured: Day 1 and Day 14. (Each treatment period is 15 days.)
AUC0-24 of Balovaptan
Measured: Day 1 and Day 14 (Each treatment period is 15 days.)
AUC0-24 of M2 Metabolite
Measured: Day 1 and Day 14 (Each treatment period is 15 days.)
AUC0-24 of M3 Metabolite
Measured: Day 1 and Day 14 (Each treatment period is 15 days.)
Tmax of Moxifloxacin
Measured: Days 2 (Treatment C) or 15 (Treatment D). (Each treatment period is 15 days.)
Cmax of Moxifloxacin
Measured: Days 2 (Treatment C) or 15 (Treatment D) (Each treatment period is 15 days.)
AUC0-24 of Moxifloxacin
Measured: Days 2 (Treatment C) or 15 (Treatment D) (Each treatment period is 15 days.)
Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of Balovaptan From Concentration-QTc Analysis
Measured: Baseline, Day 14. (Each treatment period is 15 days.)
Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of M2 From Concentration-QTc Analysis
Measured: Baseline, Day 14. (Each treatment period is 15 days.)
Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentration for M3 From Concentration-QTc Analysis
Measured: Baseline, Day 14. (Each treatment period is 15 days.)
Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records
Measured: Baseline, Day 15. (Each treatment period is 15 days.)
Percentage of Participants With Treatment Emergent Adverse Events
Measured: Up to approximately 20 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2019
- Study start7 Feb 2019
- Primary completion14 Jun 2019
- Study completion13 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03808298
- Sponsor's protocol ID
- WP40734
- Status last verified
- Jul 2020
- First submitted
- 7 Jan 2019
- Last updated
- 24 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No