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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-001783-40 | EudraCT Number |
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This study was a single-center, non-randomized, open-label, one-sequence, two-period, within-subject study to investigate the effects of multiple doses of rifampicin on the PK and safety of multiple doses of balovaptan in healthy subjects. The study was conducted at 1 site in the Netherlands.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Balovaptan + Rifampicin | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Balovaptan | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) for Balovaptan | Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. | Day 10 of Period 1 and Day 16 of Period 2 |
| Maximum Plasma Concentration (Cmax) for M2 Metabolite | Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. | Day 10 of Period 1 and Day 16 of Period 2 |
| Maximum Plasma Concentration (Cmax) for M3 Metabolite | Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. | Day 10 of Period 1 and Day 16 of Period 2 |
| Area Under the Plasma Concentration Curve From Time 0 to 24 Hours (AUC0-24) for Balovaptan | AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose. | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 |
| Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M2 Metabolite | AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose. | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 |
| Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M3 Metabolite | AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose. | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Adverse Events | Up to 21 days postdose | |
| Time to Maximum Observed Plasma Concentration (Tmax) for Balovaptan | Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units. |
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Inclusion Criteria:
Exclusion Criteria:
Rifampicin-related Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pra International Group B.V | Groningen | 9728 NZ | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32935287 | Derived | Derks MGM, Wandel C, Young A, Bolt SK, Meyenberg C. Open-Label Assessment of the Effects of Itraconazole and Rifampicin on Balovaptan Pharmacokinetics in Healthy Volunteers. Adv Ther. 2020 Nov;37(11):4720-4729. doi: 10.1007/s12325-020-01491-y. Epub 2020 Sep 15. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Plasma Concentration (Cmax) for Balovaptan | Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 10 of Period 1 and Day 16 of Period 2 |
|
Up to 21 days postdose (15 November 2018).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BALOVAPTAN+RIFAMPICIN | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA version 21.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800-821-8590 | genentech@druginfo.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 3, 2018 | Oct 15, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 9, 2018 | Oct 15, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000708839 | balovaptan |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Rifampicin | Drug | In Period 2, 600 mg of rifampicin will be administered alone as a qd dose from Day 1 to Day 6, and as a qd dose on Days 7 to 16. |
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| Day 10 of Period 1 and Day 16 of Period 2 |
| Time to Maximum Observed Plasma Concentration for M2 Metabolite | Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units. | Day 10 of Period 1 and Day 16 of Period 2 |
| Time to Maximum Observed Plasma Concentration for M3 Metabolite | Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units. | Day 10 of Period 1 and Day 16 of Period 2 |
| Metabolite to Parent Ratio for M2 Metabolite Based on AUC0-24 | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 |
| Metabolite to Parent Ratio for M2 Metabolite Based on Cmax | Day 10 of Period 1 and Day 16 of Period 2 |
| Metabolite to Parent Ratio for M3 Metabolite Based on AUC0-24 | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 |
| Metabolite to Parent Ratio for M3 Metabolite Based on Cmax | Day 10 of Period 1 and Day 16 of Period 2 |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Primary | Maximum Plasma Concentration (Cmax) for M2 Metabolite | Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 10 of Period 1 and Day 16 of Period 2 |
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| Primary | Maximum Plasma Concentration (Cmax) for M3 Metabolite | Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 10 of Period 1 and Day 16 of Period 2 |
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| Primary | Area Under the Plasma Concentration Curve From Time 0 to 24 Hours (AUC0-24) for Balovaptan | AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.h/mL | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 |
|
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| Primary | Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M2 Metabolite | AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.h/mL | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 |
|
|
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| Primary | Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M3 Metabolite | AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.h/mL | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 |
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| Secondary | Percentage of Participants With Adverse Events | The safety analysis population consisted of subjects who received at least one dose of balovaptan. | Posted | Number | Percentage | Up to 21 days postdose |
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| Secondary | Time to Maximum Observed Plasma Concentration (Tmax) for Balovaptan | Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units. | 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. | Posted | Median | Full Range | Hour | Day 10 of Period 1 and Day 16 of Period 2 |
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| Secondary | Time to Maximum Observed Plasma Concentration for M2 Metabolite | Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units. | 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. | Posted | Median | Full Range | Hours | Day 10 of Period 1 and Day 16 of Period 2 |
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| Secondary | Time to Maximum Observed Plasma Concentration for M3 Metabolite | Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units. | 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. | Posted | Median | Full Range | Hour(s) | Day 10 of Period 1 and Day 16 of Period 2 |
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| Secondary | Metabolite to Parent Ratio for M2 Metabolite Based on AUC0-24 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 |
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| Secondary | Metabolite to Parent Ratio for M2 Metabolite Based on Cmax | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Day 10 of Period 1 and Day 16 of Period 2 |
|
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| Secondary | Metabolite to Parent Ratio for M3 Metabolite Based on AUC0-24 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 |
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| Secondary | Metabolite to Parent Ratio for M3 Metabolite Based on Cmax | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Day 10 of Period 1 and Day 16 of Period 2 |
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| 0 |
| 16 |
| 0 |
| 16 |
| 15 |
| 16 |
| Dizziness | Nervous system disorders | MedDRA version 21.1 | Systematic Assessment |
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| Head discomfort | Nervous system disorders | MedDRA version 21.1 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA version 21.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA version 21.1 | Systematic Assessment |
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| Chromaturia | Renal and urinary disorders | MedDRA version 21.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Frequent bowel movements | Gastrointestinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Anorectal discomfort | Gastrointestinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Eructation | Gastrointestinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Glossodynia | Gastrointestinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Lip pain | Gastrointestinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA version 21.1 | Systematic Assessment |
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| Nightmare | Psychiatric disorders | MedDRA version 21.1 | Systematic Assessment |
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| Panic attack | Psychiatric disorders | MedDRA version 21.1 | Systematic Assessment |
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| Persistent depressive disorder | Psychiatric disorders | MedDRA version 21.1 | Systematic Assessment |
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| Restlessness | Psychiatric disorders | MedDRA version 21.1 | Systematic Assessment |
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| Stress | Psychiatric disorders | MedDRA version 21.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 21.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 21.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 21.1 | Systematic Assessment |
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| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA version 21.1 | Systematic Assessment |
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| Musculoskeletal stifness | Musculoskeletal and connective tissue disorders | MedDRA version 21.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA version 21.1 | Systematic Assessment |
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| Catheter site pain | General disorders | MedDRA version 21.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.1 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA version 21.1 | Systematic Assessment |
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| Eye irritation | Eye disorders | MedDRA version 21.1 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA version 21.1 | Systematic Assessment |
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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.
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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