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This is a study to evaluate how the body handles and metabolizes (PK) the various doses of the drug Tolvaptan, and what the effect (PD) of the various doses of Tolvaptan are on the content of "salt" in blood and urine
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| tolvaptan 3.75 mg | Other | tolvaptan 3.75 mg |
|
| tolvaptan 7.5 mg | Other | tolvaptan 7.5 mg |
|
| tolvaptan 15 mg | Other | tolvaptan 15 mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tolvaptan | Drug | Subjects will receive a single dose of 3.75, 7.5 or 15 mg of tolvaptan on study Day 1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximal Increase From Baseline in Serum Sodium Concentration Following Tolvaptan Administration. | Maximal increase in serum sodium is summarized below by tolvaptan dose. Blood samples for determination of plasma concentrations of tolvaptan were collected predose and at 1, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose on Day 1 or at Early Termination (ET). | Baseline to Day 2 |
| Time of Maximal Increase From Baseline in Serum Sodium Concentration Following Tolvaptan Administration. | Time of maximal increase in serum sodium is summarized in the table below by tolvaptan dose. Samples were taken on Day 0 (baseline) at the corresponding Day 1 predose time and 12 hours postdose time; and on Day 1 at predose and at 2, 4, 6, 8, 12, and 24 hours postdose. | Baseline to Day 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax (Maximum (Peak) Plasma Concentration) for Tolvaptan in Plasma. | Blood samples for determination of plasma concentrations of tolvaptan were collected predose and 1, 2, 3, 4, 8, 12, 16, and 24 hours postdose on Day 1 or at ET. PK parameters in participants with SIADH following tolvaptan administration for three different doses are presented below. | Baseline to Day 2 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vseobecna fakultni nemocnice V Praze | Prague | 128 08 | Czechia | |||
| Holstebro Regionhospital |
Participants with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and a serum sodium concentration between 120 and 133 mmol/L were randomized to single doses of 3.75, 7.5, or 15 mg tolvaptan. Baseline pharmacodynamics (PD) was assessed for 24 hours predose. Pharmacokinetic (PK) and PD assessments were obtained 24 hours postdose.
The study was conducted in 30 participants (29 received treatment) at 14 trial sites in 7 countries.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tolvaptan 3.75 mg | Participants had received a single dose of 3.75 mg oral tolvaptan. |
| FG001 | Tolvaptan 7.5 mg | Participants had received a single dose of 7.5 mg oral tolvaptan. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Tmax (Time to Maximum (Peak) Plasma Concentration) for Tolvaptan in Plasma | Blood samples for determination of plasma concentrations of tolvaptan were collected predose and 1, 2, 3, 4, 8, 12, 16, and 24 hours postdose on Day 1 or at ET. PK parameters in participants with SIADH following tolvaptan administration for three different doses are presented below. | Baseline to Day 2 |
| AUC Infinity (Area Under the Concentration-time Curve From Time Zero to Infinity) for Tolvaptan in Plasma | Blood samples for determination of plasma concentrations of tolvaptan were collected predose and 1, 2, 3, 4, 8, 12, 16, and 24 hours postdose on Day 1 or at ET. If an indwelling catheter was utilized, saline flushes were used. PK parameters in participants with SIADH following tolvaptan administration for three different doses are presented below. | Baseline to Day 2 |
| Change From Baseline in Serum Sodium Concentrations | Samples were taken on Day 0 (baseline) at the corresponding Day 1 predose time and 12 hours postdose time; and on Day 1 at predose and at 2, 4, 6, 8, 12, and 24 hours postdose. | Baseline and Day 2 |
| Change From Baseline in Fluid Intake From 0-6 Hours, 0-12 Hours and 0-24 Hours | Fluid intake was monitored on Day 0 (times relative to Day 1 dosing), and Day 1 at intervals of 0 to 6, 6 to 12, and 12 to 24 hours postdose. Fluid intake included fluid used for dosing (study medication and any concomitant medication); food items that included any significant amounts of water (e.g., Jello [including Gelatin and Jelly dessert] and soup) was added to the total fluid intake. Samples were taken on Day 0 (baseline) at the corresponding Day 1 predose time and 12 hours postdose time; and on Day 1 at predose and at 2, 4, 6, 8, 12, and 24 hours postdose. | Baseline and Day 2 |
| Change From Baseline in Fluid Balance (Fluid Intake Minus Urine Output) From 0-6 Hours, 0-12 Hours and 0-24 Hours. | Fluid intake was monitored on Day 0 (times relative to Day 1 dosing), and Day 1 at intervals of 0 to 6, 6 to 12, and 12 to 24 hours postdose. Fluid intake included fluid used for dosing (study medication and any concomitant medication); food items that included any significant amounts of water (e.g., Jello [including Gelatin and Jelly dessert] and soup) was added to the total fluid intake. Urine was collected for baseline comparison on Day 0 for the 24 hour prior to Day 1 dosing at intervals of 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12 hours, and 12 to 24 hours relative to the Day 1 dosing time. Fluid balance was determined as fluid intake minus urine output. | 2 days |
| Change From Baseline in Cumulative Urine Volume at 0-6 Hours, 0-12 Hours and 0-24 Hours. | Urine was collected for baseline comparison on Day 0 for the 24 hour prior to Day 1 dosing at intervals of 0 to 2, 2 to 4, 4, to 6, 6, to 8, 8, to 12, and 12 to 24 hours relative to Day 1 dosing time. Urine was collected on Day 1 at intervals of 0 to 2,2 to 4, 4 to 6, 6 to 8, 8 to 12, and 12 to 24 hours postdose. For the start of the urine collection on Day 0, a window of 15 to 40 minutes prior to the assigned dosing time was acceptable, with the 0 to 24 hour collection period on Day 1 starting 24 hours after the start time on Day 0. Participants were asked to void immediately prior to the end of the collection interval. The volume of individual voids were measured and recorded prior to refrigerating. All voids in a collection interval were pooled at the end of the collection interval, at which time the volume was determined, recorded and an aliquot taken for osmolality, sodium, potassium, and creatinine assessments. | 2 days |
| Holstebro |
| 7500 |
| Denmark |
| Medizinische Klinik im Klinikum Hannover | Hanover | Lower Saxony | 30167 | Germany |
| Universitätsklinikum C.-G.-Carus | Dresden | Saxony | 01307 | Germany |
| Evangelische Lungenklinik Berlin | Berlin | 13125 | Germany |
| Universitaetsklinikum Koeln | Cologne | 50937 | Germany |
| Universitaetsklinikum Schleswig-Holstein - Campus Luebeck | Lübeck | 23538 | Germany |
| Semmelweis Egyetem AOK | Budapest | 1083 | Hungary |
| Hospital Clinic i Provincial de Barcelona | Barcelona | 08036 | Spain |
| Hospital Universitario Clinico San Carlos | Madrid | 28040 | Spain |
| Sahlgrenska Universitetssjukhuset | Gothenburg | 41345 | Sweden |
| Birmingham Heartlands Hospital | Birmingham | B9 5SS | United Kingdom |
| Royal Free Hospital | London | NW3 2QG | United Kingdom |
| The Christie Hospital | Manchester | M20 4BX | United Kingdom |
| FG002 | Tolvaptan 15 mg | Participants had received a single dose of 15 mg oral tolvaptan. |
| COMPLETED |
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| NOT COMPLETED |
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The baseline analysis population comprised of all participants who had taken one dose of the study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tolvaptan 3.75 mg | Participants had received a single dose of 3.75 mg oral tolvaptan. |
| BG001 | Tolvaptan 7.5 mg | Participants had received a single dose of 7.5 mg oral tolvaptan. |
| BG002 | Tolvaptan 15 mg | Participants had received a single dose of 15 mg oral tolvaptan. |
| BG003 | Total | Total of all reporting groups |
| 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 | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| 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 | Maximal Increase From Baseline in Serum Sodium Concentration Following Tolvaptan Administration. | Maximal increase in serum sodium is summarized below by tolvaptan dose. Blood samples for determination of plasma concentrations of tolvaptan were collected predose and at 1, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose on Day 1 or at Early Termination (ET). | PD dataset comprised of all participants who had taken 1 dose of study medication and had all observed measurements. | Posted | Mean | Standard Deviation | mmol/L | Baseline to Day 2 |
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| Secondary | Cmax (Maximum (Peak) Plasma Concentration) for Tolvaptan in Plasma. | Blood samples for determination of plasma concentrations of tolvaptan were collected predose and 1, 2, 3, 4, 8, 12, 16, and 24 hours postdose on Day 1 or at ET. PK parameters in participants with SIADH following tolvaptan administration for three different doses are presented below. | PK parameter dataset comprised of all participants who had taken 1 dose of study medication and had evaluable PK data. | Posted | Mean | Standard Deviation | ng/mL | Baseline to Day 2 |
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| Secondary | Tmax (Time to Maximum (Peak) Plasma Concentration) for Tolvaptan in Plasma | Blood samples for determination of plasma concentrations of tolvaptan were collected predose and 1, 2, 3, 4, 8, 12, 16, and 24 hours postdose on Day 1 or at ET. PK parameters in participants with SIADH following tolvaptan administration for three different doses are presented below. | PK parameter dataset comprised of all participants who had taken 1 dose of study medication and had evaluable PK data. | Posted | Median | Full Range | hours | Baseline to Day 2 |
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| Secondary | AUC Infinity (Area Under the Concentration-time Curve From Time Zero to Infinity) for Tolvaptan in Plasma | Blood samples for determination of plasma concentrations of tolvaptan were collected predose and 1, 2, 3, 4, 8, 12, 16, and 24 hours postdose on Day 1 or at ET. If an indwelling catheter was utilized, saline flushes were used. PK parameters in participants with SIADH following tolvaptan administration for three different doses are presented below. | PK parameter dataset comprised of all participants who had taken 1 dose of study medication and had evaluable PK data. | Posted | Mean | Standard Deviation | ng·h/mL | Baseline to Day 2 |
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| Secondary | Change From Baseline in Serum Sodium Concentrations | Samples were taken on Day 0 (baseline) at the corresponding Day 1 predose time and 12 hours postdose time; and on Day 1 at predose and at 2, 4, 6, 8, 12, and 24 hours postdose. | PD dataset comprised of all participants who had taken 1 dose of study medication and had all observed measurements. | Posted | Mean | Standard Deviation | mmol/L | Baseline and Day 2 |
|
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| Primary | Time of Maximal Increase From Baseline in Serum Sodium Concentration Following Tolvaptan Administration. | Time of maximal increase in serum sodium is summarized in the table below by tolvaptan dose. Samples were taken on Day 0 (baseline) at the corresponding Day 1 predose time and 12 hours postdose time; and on Day 1 at predose and at 2, 4, 6, 8, 12, and 24 hours postdose. | PD dataset comprised of all participants who had taken 1 dose of study medication and had all observed measurements. | Posted | Median | Full Range | hours | Baseline to Day 2 |
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| Secondary | Change From Baseline in Fluid Intake From 0-6 Hours, 0-12 Hours and 0-24 Hours | Fluid intake was monitored on Day 0 (times relative to Day 1 dosing), and Day 1 at intervals of 0 to 6, 6 to 12, and 12 to 24 hours postdose. Fluid intake included fluid used for dosing (study medication and any concomitant medication); food items that included any significant amounts of water (e.g., Jello [including Gelatin and Jelly dessert] and soup) was added to the total fluid intake. Samples were taken on Day 0 (baseline) at the corresponding Day 1 predose time and 12 hours postdose time; and on Day 1 at predose and at 2, 4, 6, 8, 12, and 24 hours postdose. | PD dataset comprised of all participants who had taken 1 dose of study medication and had all observed measurements. | Posted | Mean | Standard Deviation | mL | Baseline and Day 2 |
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| Secondary | Change From Baseline in Fluid Balance (Fluid Intake Minus Urine Output) From 0-6 Hours, 0-12 Hours and 0-24 Hours. | Fluid intake was monitored on Day 0 (times relative to Day 1 dosing), and Day 1 at intervals of 0 to 6, 6 to 12, and 12 to 24 hours postdose. Fluid intake included fluid used for dosing (study medication and any concomitant medication); food items that included any significant amounts of water (e.g., Jello [including Gelatin and Jelly dessert] and soup) was added to the total fluid intake. Urine was collected for baseline comparison on Day 0 for the 24 hour prior to Day 1 dosing at intervals of 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12 hours, and 12 to 24 hours relative to the Day 1 dosing time. Fluid balance was determined as fluid intake minus urine output. | PD dataset comprised of all participants who had taken 1 dose of study medication and had all observed measurements. | Posted | Mean | Standard Deviation | mL | 2 days |
| |||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Cumulative Urine Volume at 0-6 Hours, 0-12 Hours and 0-24 Hours. | Urine was collected for baseline comparison on Day 0 for the 24 hour prior to Day 1 dosing at intervals of 0 to 2, 2 to 4, 4, to 6, 6, to 8, 8, to 12, and 12 to 24 hours relative to Day 1 dosing time. Urine was collected on Day 1 at intervals of 0 to 2,2 to 4, 4 to 6, 6 to 8, 8 to 12, and 12 to 24 hours postdose. For the start of the urine collection on Day 0, a window of 15 to 40 minutes prior to the assigned dosing time was acceptable, with the 0 to 24 hour collection period on Day 1 starting 24 hours after the start time on Day 0. Participants were asked to void immediately prior to the end of the collection interval. The volume of individual voids were measured and recorded prior to refrigerating. All voids in a collection interval were pooled at the end of the collection interval, at which time the volume was determined, recorded and an aliquot taken for osmolality, sodium, potassium, and creatinine assessments. | PD dataset comprised of all participants who had taken 1 dose of study medication and had all observed measurements. | Posted | Mean | Standard Deviation | mL | 2 days |
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Adverse events were reported from the signing of the informed consent throughout the study and were followed for 7 (+2) days post last dose of study medication.
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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 | Tolvaptan 3.75 mg | Subjects will receive a single dose of 3.75, 7.5 or 15 mg of tolvaptan on study Day 1 | 0 | 10 | 0 | 10 | ||
| EG001 | Tolvaptan 7.5 mg | Subjects will receive a single dose of 3.75, 7.5 or 15 mg of tolvaptan on study Day 1 | 0 | 10 | 1 | 10 | ||
| EG002 | Tolvaptan 15 mg | Subjects will receive a single dose of 3.75, 7.5 or 15 mg of tolvaptan on study Day 1 | 1 | 9 | 3 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Small cell lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA (18.0) | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (18.0) | Non-systematic Assessment |
| |
| Polyuria | Renal and urinary disorders | MedDRA (18.0) | Non-systematic Assessment |
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Center may publish study results but ≥ 60 days prior to any public presentation, a copy is sent to Sponsor for review and Center can delay publication for 60 days to permit Sponsor to protect its intellectual property rights or confidential information contained within the publication. The first publication is a joint publication, if Center is part of a multi-center study. Center is free to publish, if there is no multi-center publication within 18 months of completion/ termination of study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Medical Affairs | Otsuka Pharmaceutical Development and Commercialization, Inc. | 800 562-3974 |
| ID | Term |
|---|---|
| D007177 | Inappropriate ADH Syndrome |
| ID | Term |
|---|---|
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014883 | Water-Electrolyte Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000077602 | Tolvaptan |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Male |
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| Counts |
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| OG002 |
| Tolvaptan 15 mg |
Participants had received a single dose of 15 mg oral tolvaptan. |
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