Not provided
Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 20141663 | Other Grant/Funding Number | Otsuka America Pharmaceutical, Inc. |
Not provided
Not provided
Not provided
Slow subject enrollment and contracting issues; sponsor decided to abort study
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Otsuka America Pharmaceutical | INDUSTRY |
| Medical University of South Carolina | OTHER |
| Barnes-Jewish Hospital | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
To assess the pharmacokinetic profile of tolvaptan in critically ill acute brain injury patients and to secondarily evaluate the clinical response and safety of tolvaptan in acute brain injured patients
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Brain injured patients with hyponatremia | Patients with acute brain injury who develop hyponatremia and are administered tolvaptan via the nasogastric tube, deemed necessary by the primary medical team. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tolvaptan | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum observed plasma concentration (Cmax) and time to maximum observed plasma concentration (Tmax) of tolvaptan over 36 hours post-dose | Cmax will be derived from plasma concentrations versus time using a validated LS/MS/MS assay is sodium heparinized plasma. The tolvaptan assay has a range of 1.00 - 200 mg/mL. Blood samples will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of tolvaptan is administered. The first 15 patients will receive single dose 15mg of tolvaptan via a gastric tube and if determined not bioequivalent and no clinical response to oral administration and safe to administer, then last 15 patients will receive 30mg single dose via a gastric tube. | Over 36 hours from drug administration |
| The elimination rate constant (ke) of tolvaptan over 36 hours post-dose | Ke derived from plasma concentrations versus time using a validated LS/MS/MS assay is sodium heparinized plasma. The tolvaptan assay has a range of 1.00 - 200 mg/mL. Blood samples will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of tolvaptan is administered. The first 15 patients will receive single dose 15mg of tolvaptan via a gastric tube and if determined not bioequivalent and no clinical response to oral administration and safe to administer, then last 15 patients will receive 30mg single dose via a gastric tube. | Over 36 hours from drug administration |
| Area under the plasma concentration time curve (AUC) of tolvaptan from time zero to 36 hours post-dose | AUC will be computed from 0 to 36 hours using the linear-log trapezoidal method and extrapolated to infinity. Tolvaptan concentrations will be determined using a validated LS/MS/MS assay is sodium heparinized plasma. The tolvaptan assay has a range of 1.00 - 200 mg/mL. Blood samples will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of tolvaptan is administered. The first 15 patients will receive single dose 15mg of tolvaptan via a gastric tube and if determined not bioequivalent and no clinical response to oral administration and safe to administer, then last 15 patients will receive 30mg single dose via a gastric tube. |
| Measure | Description | Time Frame |
|---|---|---|
| The clinical response of tolvaptan administered through the nasogastric tube in acute brain injured patients | Clinical response is defined as a change in serum sodium of 4 - 6 mEq/L | Over 36 hours from drug administration |
| The safety of tolvaptan administered via a nasogastric tube in acute brain injured patients |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
The population will be comprised of 30 acute brain injury patients in the ICU.
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Kathryn A Morbitzer, PharmD | University of North Carolina, Chapel Hill | Principal Investigator |
| Denise H. Rhoney, PharmD | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barnes-Jewish Hospital | St Louis | Missouri | 63110 | United States | ||
| University of North Carolina Hospitals |
Not provided
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D007010 | Hyponatremia |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077602 | Tolvaptan |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Blood samples for pharmacokinetic sampling will be collected in serum separator tubes at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of study drug is administered. Serum sodium will be collected at baseline and 2, 4, 6, 8, 12, 24, and 36 hours after study drug administration. Approximately 180 mL of blood will be collected over 36 hours. Urinary output and urine specific gravity will be collected 0-2, 2-4, 3-6, 6-8, 8-12, and 12-24 hours after tolvaptan administration.
| Over 36 hours from drug administration |
Safety assessments will include: vital signs, clinical laboratory tests, concomitant medications, and reported or observed adverse events. The rate of sodium correction will also be assessed. Excessive correction in sodium is defined as ≥ 12 mE/L increased in serum sodium within 24 hours of the dose. Excessive drop in blood pressure will be defined as >20% reduction in MAP from baseline. |
| Over 36 hours from drug administration |
| Chapel Hill |
| North Carolina |
| 27599 |
| United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D014883 | Water-Electrolyte Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |