Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2018-001454-10 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study was a non-randomized, open-label, one-sequence, two-period within-subject study to investigate the effect of CYP3A inhibition on the PK of balovaptan in healthy male and female volunteers using itraconazole as a CYP3A inhibitor. The study was conducted at 1 site in the Netherlands.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Balovaptan + Itraconzole | Experimental | Dosing in Period 1 was separated by at least a 7 day washout period before dosing starts in Period 2. Participants received the study drugs in 2 periods over a total of 37 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Balovaptan | Drug | In Period 1, balovaptan was administered orally once daily (qd) on Days 1 to 10. In Period 2, balovaptan was administered qd on Days 6 to 20. |
|
| 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, Day 10 and Day 15 of Period 2 |
| Maximum Plasma Concentration (Cmax) for M2 Metabolite (as Applicable) | Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. | Day 10 of Period 1, Day 10 and Day 15 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, Day 10 and Day 15 of Period 2 |
| Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for Balovaptan | Day 10 of Period 1, Day 10 and Day 15 of Period 2 | |
| Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for M2 Metabolite (as Applicable) | Day 10 of Period 1, Day 10 and Day 15 of Period 2 | |
| Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for M3 Metabolite | Day 10 of Period 1, Day 10 and Day 15 of Period 2 | |
| Time to Maximum Observed Plasma Concentration (Tmax) for Balovaptan | Day 10 of Period 1; Day 10 and Day 15 of Period 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Trough Plasma Concentration (Ctrough) for Balovaptan | Day 10 of Period 1; Day 10 and Day 15 of Period 2 | |
| Trough Plasma Concentration (Ctrough) for M2 Metabolite (as Applicable) | Day 10 of Period 1; Day 10 and Day 15 of Period 2 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Participants in this study included healthy volunteers.
The study was conducted at 1 site in the Netherlands.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Balovaptan + Itraconzole | Dosing in Period 1 was separated by at least a 7 day washout period before dosing started in Period 2. Participants received the study drugs in 2 periods over a total of 37 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Balovaptan + Itraconzole | Dosing in Period 1 was separated by at least a 7 day washout period before dosing started in Period 2. Participants received the study drugs in 2 periods over a total of 37 days. |
| Units | Counts |
|---|---|
| Participants |
|
| 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 1 dose of balovaptan. Subjects 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, Day 10 and Day 15 of Period 2 |
|
From the first study drug to the data cutoff date: 9 Nov 2018 (up to 21 days postdose)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Balovaptan + Itraconzole | Dosing in Period 1 was separated by at least a 7 day washout period before dosing started in Period 2. Participants received the study drugs in 2 periods over a total of 37 days. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800-821-8590 | genentech@druginfo.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 18, 2018 | Oct 14, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 20, 2018 | Oct 14, 2019 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| C000708839 | balovaptan |
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Itraconazole | Drug | In Period 2, 200 mg itraconzole was administered bid for 4 days and qd on Days 5-20, approximately 12 hours apart. On Days 6-20, 200 mg itraconazole was administered qd. |
|
| Time to Maximum Observed Plasma Concentration (Tmax) for M2 Metabolite (as Applicable) | Day 10 of Period 1; Day 10 and Day 15 of Period 2 |
| Time to Maximum Observed Plasma Concentration (Tmax) for M3 Metabolite | Day 10 of Period 1; Day 10 and Day 15 of Period 2 |
| Trough Plasma Concentration (Ctrough) for M3 Metabolite | Day 10 of Period 1; Day 10 and Day 15 of Period 2 |
| Time to Steady State for Balovaptan | Days 1, 3, 5, 8, 9, 10 in Period 1 and Days 1, 3, 5, 8, 9, 10, 13, 14, 15 in Period 2 |
| Percentage of Participants With Adverse Events | Up to 21 days postdose |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| Primary | Maximum Plasma Concentration (Cmax) for M2 Metabolite (as Applicable) | 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 1 dose of balovaptan. Subjects 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, Day 10 and Day 15 of Period 2 |
|
|
|
| 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 1 dose of balovaptan. Subjects 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, Day 10 and Day 15 of Period 2 |
|
|
|
| Primary | Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for Balovaptan | The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least 1 dose of balovaptan. Subjects 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 of Period 1, Day 10 and Day 15 of Period 2 |
|
|
|
| Primary | Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for M2 Metabolite (as Applicable) | The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least 1 dose of balovaptan. Subjects 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 of Period 1, Day 10 and Day 15 of Period 2 |
|
|
|
| Primary | Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for M3 Metabolite | The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least 1 dose of balovaptan. Subjects 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 of Period 1, Day 10 and Day 15 of Period 2 |
|
|
|
| Secondary | Trough Plasma Concentration (Ctrough) for Balovaptan | The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least 1 dose of balovaptan. Subjects 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 | Mean | Standard Deviation | ng/mL | Day 10 of Period 1; Day 10 and Day 15 of Period 2 |
|
|
|
| Secondary | Trough Plasma Concentration (Ctrough) for M2 Metabolite (as Applicable) | The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least 1 dose of balovaptan. Subjects 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 | Mean | Standard Deviation | ng/mL | Day 10 of Period 1; Day 10 and Day 15 of Period 2 |
|
|
|
| Secondary | Trough Plasma Concentration (Ctrough) for M3 Metabolite | The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least 1 dose of balovaptan. Subjects 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 | Mean | Standard Deviation | ng/mL | Day 10 of Period 1; Day 10 and Day 15 of Period 2 |
|
|
|
| Secondary | Time to Steady State for Balovaptan | The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least 1 dose of balovaptan. Subjects 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 | Number | Day | Days 1, 3, 5, 8, 9, 10 in Period 1 and Days 1, 3, 5, 8, 9, 10, 13, 14, 15 in Period 2 |
|
|
|
| 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 |
|
|
|
| Primary | Time to Maximum Observed Plasma Concentration (Tmax) for Balovaptan | The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least 1 dose of balovaptan. Subjects 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; Day 10 and Day 15 of Period 2 |
|
|
|
| Primary | Time to Maximum Observed Plasma Concentration (Tmax) for M2 Metabolite (as Applicable) | The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least 1 dose of balovaptan. Subjects 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; Day 10 and Day 15 of Period 2 |
|
|
|
| Primary | Time to Maximum Observed Plasma Concentration (Tmax) for M3 Metabolite | The Pharmacokinetic (PK) analysis population consisted of all subjects who received at least 1 dose of balovaptan. Subjects 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; Day 10 and Day 15 of Period 2 |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 11 |
| 15 |
| Head discomfort | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Medical device site pruritus | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Catheter site haematoma | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Anal pruritus | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
|
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.
| D010879 |
| Piperazines |
|
|
|
|
|
|
|
|
|
|
|