Trial Outcomes & Findings for A Study to Investigate the Effect of Rifampicin on the PK of Multiple Doses of Balovaptin In Healthy Volunteers (NCT NCT03586726)
NCT ID: NCT03586726
Last Updated: 2019-11-07
Results Overview
Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units.
COMPLETED
PHASE1
16 participants
Day 10 of Period 1 and Day 16 of Period 2
2019-11-07
Participant Flow
Participant milestones
| Measure |
Balovaptan + Rifampicin
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Overall Study
STARTED
|
16
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Balovaptan + Rifampicin
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
A Study to Investigate the Effect of Rifampicin on the PK of Multiple Doses of Balovaptin In Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Age, Continuous
|
39.0 Years
STANDARD_DEVIATION 14.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 10 of Period 1 and Day 16 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Maximum Plasma Concentration (Cmax) for Balovaptan
Balovaptan (Period 1)
|
94.2 ng/mL
Geometric Coefficient of Variation 33.4
|
|
Maximum Plasma Concentration (Cmax) for Balovaptan
Balovaptan + rifampicin (Period 2)
|
12.9 ng/mL
Geometric Coefficient of Variation 22.8
|
PRIMARY outcome
Timeframe: Day 10 of Period 1 and Day 16 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Maximum Plasma Concentration (Cmax) for M2 Metabolite
Balovaptan (Period 1)
|
22.0 ng/mL
Geometric Coefficient of Variation 22.7
|
|
Maximum Plasma Concentration (Cmax) for M2 Metabolite
Balovaptan + rifampicin (Period 2)
|
8.09 ng/mL
Geometric Coefficient of Variation 20.5
|
PRIMARY outcome
Timeframe: Day 10 of Period 1 and Day 16 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Maximum Plasma Concentration (Cmax) for M3 Metabolite
Balovaptan (Period 1)
|
49.6 ng/mL
Geometric Coefficient of Variation 26.4
|
|
Maximum Plasma Concentration (Cmax) for M3 Metabolite
Balovaptan + rifampicin (Period 2)
|
10.9 ng/mL
Geometric Coefficient of Variation 23.2
|
PRIMARY outcome
Timeframe: Day 10 and 11 of Period 1; Day 16 and 17 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Area Under the Plasma Concentration Curve From Time 0 to 24 Hours (AUC0-24) for Balovaptan
Balovaptan (Period 1)
|
1000 ng.h/mL
Geometric Coefficient of Variation 29.6
|
|
Area Under the Plasma Concentration Curve From Time 0 to 24 Hours (AUC0-24) for Balovaptan
Balovaptan + rifampicin (Period 2)
|
67.0 ng.h/mL
Geometric Coefficient of Variation 16.3
|
PRIMARY outcome
Timeframe: Day 10 and 11 of Period 1; Day 16 and 17 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M2 Metabolite
Balovaptan (Period 1)
|
448 ng.h/mL
Geometric Coefficient of Variation 22.7
|
|
Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M2 Metabolite
Balovaptan + rifampicin (Period 2)
|
149 ng.h/mL
Geometric Coefficient of Variation 21.9
|
PRIMARY outcome
Timeframe: Day 10 and 11 of Period 1; Day 16 and 17 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M3 Metabolite
Balovaptan (Period 1)
|
844 ng.h/mL
Geometric Coefficient of Variation 20.8
|
|
Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M3 Metabolite
Balovaptan + rifampicin (Period 2)
|
110 ng.h/mL
Geometric Coefficient of Variation 13.3
|
SECONDARY outcome
Timeframe: Up to 21 days postdosePopulation: The safety analysis population consisted of subjects who received at least one dose of balovaptan.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Percentage of Participants With Adverse Events
|
94 Percentage
|
SECONDARY outcome
Timeframe: Day 10 of Period 1 and Day 16 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Time to Maximum Observed Plasma Concentration (Tmax) for Balovaptan
Balovaptan (Period 1)
|
1.00 Hour
Interval 0.5 to 1.1
|
|
Time to Maximum Observed Plasma Concentration (Tmax) for Balovaptan
Balovaptan + rifampicin (Period 2)
|
1.00 Hour
Interval 0.5 to 1.02
|
SECONDARY outcome
Timeframe: Day 10 of Period 1 and Day 16 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Time to Maximum Observed Plasma Concentration for M2 Metabolite
Balovaptan (Period 1)
|
2.50 Hours
Interval 0.0 to 16.0
|
|
Time to Maximum Observed Plasma Concentration for M2 Metabolite
Balovaptan + rifampicin (Period 2)
|
3.00 Hours
Interval 1.5 to 12.0
|
SECONDARY outcome
Timeframe: Day 10 of Period 1 and Day 16 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Time to Maximum Observed Plasma Concentration for M3 Metabolite
Balovaptan (Period 1)
|
1.00 Hour(s)
Interval 0.5 to 4.0
|
|
Time to Maximum Observed Plasma Concentration for M3 Metabolite
Balovaptan + rifampicin (Period 2)
|
1.00 Hour(s)
Interval 1.0 to 4.0
|
SECONDARY outcome
Timeframe: Day 10 and 11 of Period 1; Day 16 and 17 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Metabolite to Parent Ratio for M2 Metabolite Based on AUC0-24
Balovaptan (Period 1)
|
0.430 Ratio
Geometric Coefficient of Variation 32.3
|
|
Metabolite to Parent Ratio for M2 Metabolite Based on AUC0-24
Balovaptan + rifampicin (Period 2)
|
2.14 Ratio
Geometric Coefficient of Variation 14.8
|
SECONDARY outcome
Timeframe: Day 10 of Period 1 and Day 16 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Metabolite to Parent Ratio for M2 Metabolite Based on Cmax
Balovaptan (Period 1)
|
0.225 Ratio
Geometric Coefficient of Variation 30.9
|
|
Metabolite to Parent Ratio for M2 Metabolite Based on Cmax
Balovaptan + rifampicin (Period 2)
|
0.606 Ratio
Geometric Coefficient of Variation 20.7
|
SECONDARY outcome
Timeframe: Day 10 and 11 of Period 1; Day 16 and 17 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Metabolite to Parent Ratio for M3 Metabolite Based on AUC0-24
Balovaptan (Period 1)
|
0.872 Ratio
Geometric Coefficient of Variation 16.6
|
|
Metabolite to Parent Ratio for M3 Metabolite Based on AUC0-24
Balovaptan + rifampicin (Period 2)
|
1.70 Ratio
Geometric Coefficient of Variation 6.9
|
SECONDARY outcome
Timeframe: Day 10 of Period 1 and Day 16 of Period 2Population: The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
Outcome measures
| Measure |
Balovaptan + Rifampicin
n=16 Participants
Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.
|
|---|---|
|
Metabolite to Parent Ratio for M3 Metabolite Based on Cmax
Balovaptan (Period 1)
|
0.545 Ratio
Geometric Coefficient of Variation 16.5
|
|
Metabolite to Parent Ratio for M3 Metabolite Based on Cmax
Balovaptan + rifampicin (Period 2)
|
0.873 Ratio
Geometric Coefficient of Variation 9.0
|
Adverse Events
BALOVAPTAN+RIFAMPICIN
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
BALOVAPTAN+RIFAMPICIN
n=16 participants at risk
In Period 1, balovaptan was administered alone as a once daily (qd) dose on Days 1 to 10.
In Period 2, balovaptan was administered as a qd dose on Days 7 to 16.
In Period 2, 600 mg of rifampicin was administered alone as a qd dose on Days 7 to 16.
|
|---|---|
|
Nervous system disorders
Headache
|
37.5%
6/16 • Number of events 11 • Up to 21 days postdose (15 November 2018).
|
|
Nervous system disorders
Dizziness
|
25.0%
4/16 • Number of events 5 • Up to 21 days postdose (15 November 2018).
|
|
Nervous system disorders
Head discomfort
|
6.2%
1/16 • Number of events 3 • Up to 21 days postdose (15 November 2018).
|
|
Nervous system disorders
Paraesthesia
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Nervous system disorders
Somnolence
|
6.2%
1/16 • Number of events 2 • Up to 21 days postdose (15 November 2018).
|
|
Renal and urinary disorders
Chromaturia
|
75.0%
12/16 • Number of events 14 • Up to 21 days postdose (15 November 2018).
|
|
Gastrointestinal disorders
Abdominal pain
|
25.0%
4/16 • Number of events 4 • Up to 21 days postdose (15 November 2018).
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
2/16 • Number of events 3 • Up to 21 days postdose (15 November 2018).
|
|
Gastrointestinal disorders
Nausea
|
12.5%
2/16 • Number of events 3 • Up to 21 days postdose (15 November 2018).
|
|
Gastrointestinal disorders
Frequent bowel movements
|
12.5%
2/16 • Number of events 2 • Up to 21 days postdose (15 November 2018).
|
|
Gastrointestinal disorders
Abdominal distension
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Gastrointestinal disorders
Anorectal discomfort
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Gastrointestinal disorders
Eructation
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Gastrointestinal disorders
Flatulence
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Gastrointestinal disorders
Glossodynia
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Gastrointestinal disorders
Lip pain
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Psychiatric disorders
Insomnia
|
31.2%
5/16 • Number of events 7 • Up to 21 days postdose (15 November 2018).
|
|
Psychiatric disorders
Nightmare
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Psychiatric disorders
Panic attack
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Psychiatric disorders
Persistent depressive disorder
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Psychiatric disorders
Restlessness
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Psychiatric disorders
Stress
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
12.5%
2/16 • Number of events 4 • Up to 21 days postdose (15 November 2018).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.5%
2/16 • Number of events 2 • Up to 21 days postdose (15 November 2018).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stifness
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
General disorders
Fatigue
|
18.8%
3/16 • Number of events 3 • Up to 21 days postdose (15 November 2018).
|
|
General disorders
Catheter site pain
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
2/16 • Number of events 2 • Up to 21 days postdose (15 November 2018).
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Ear and labyrinth disorders
Vertigo
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Eye disorders
Eye irritation
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
|
Vascular disorders
Hot flush
|
6.2%
1/16 • Number of events 1 • Up to 21 days postdose (15 November 2018).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER