Phase 2
N=30
A PK Study of 3 Dosages of Tolvaptan in Patients With Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Bottom Line
View on ClinicalTrials.gov: NCT02009878 ↗Enrolled (actual)
30
Serious AEs
3.5%
Results posted
May 2016
Primary outcome: Primary: Maximal Increase From Baseline in Serum Sodium Concentration Following Tolvaptan Administration. — 3.6; 5.3; 7.9 mmol/L
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- tolvaptan (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.
- Primary completion
- Jun 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximal Increase From Baseline in Serum Sodium Concentration Following Tolvaptan Administration. |
3.6; 5.3; 7.9 | — |
| PRIMARY Time of Maximal Increase From Baseline in Serum Sodium Concentration Following Tolvaptan Administration. |
24.13; 6.38; 24.02 | — |
| SECONDARY Cmax (Maximum (Peak) Plasma Concentration) for Tolvaptan in Plasma. |
37.7; 107; 157 | — |
| SECONDARY Tmax (Time to Maximum (Peak) Plasma Concentration) for Tolvaptan in Plasma |
1.50; 2.00; 2.00 | — |
| SECONDARY AUC Infinity (Area Under the Concentration-time Curve From Time Zero to Infinity) for Tolvaptan in Plasma |
244; 655; 1000 | — |
| SECONDARY Change From Baseline in Serum Sodium Concentrations |
-2.5; -2.3; -2.6; -2.0; 2.4; 1.7 | — |
| SECONDARY Change From Baseline in Fluid Intake From 0-6 Hours, 0-12 Hours and 0-24 Hours |
97.5; -255.0; -103.0; 210.0; -65.0; 118.8 | — |
| SECONDARY Change From Baseline in Fluid Balance (Fluid Intake Minus Urine Output) From 0-6 Hours, 0-12 Hours and 0-24 Hours. |
-403.7; -856.8; -1478.8; -588.8; -839.8; -1897.5 | — |
| SECONDARY Change From Baseline in Cumulative Urine Volume at 0-6 Hours, 0-12 Hours and 0-24 Hours. |
501.2; 601.8; 1375.6; 798.8; 774.8; 2016.3 | — |
Summary
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
Eligibility Criteria
Inclusion Criteria
- Male or female subjects greater than or equal to 18 years of age or the age of legal consent.
- Must have a BMI less than or equal to 32.0 kg/m2.
- Subjects must have a diagnosis of SIADH prior to randomization.
- Persistent euvolemic hyponatremia, evidenced by 3 serum sodium assessments of between 120 and 133 mmol/L, inclusive drawn locally as follows: one during the screening period, a second at check-in on Day -1, a third on Day 0 (12-24 hours prior to dosing), which will serve as the baseline value for efficacy endpoints
- Subjects with relatively intact renal function, ie, estimated glomerular filtration rate using the CKD-EPI formula of greater than or equal to 60 mL/min/1.73m2.
- Ability to provide written, informed consent prior to initiation of any trial related procedures, and ability, in the opinion of the PI, to comply with all the requirements of the trial.
- Sexually active males who are practicing a highly effective method of birth control during the trial and for 30 days after the last dose of trial medication or who will remain abstinent during the trial and for 30 days after the last dose, or sexually active females of childbearing potential who are practicing a highly effective method of birth control during the trial and for 30 days after the last dose of trial medication or who will remain abstinent during the trial and for 30 days after the last dose, or female subjects of nonchildbearing potential (surgically sterile or postmenopausal [1 year post menses]). If employing birth control, 1 of the following highly effective methods (failure rate 3 x ULN.
- Has primary polydipsia.
- Inability to take oral medications.
- Subjects who have supine blood pressure, after resting for greater than or equal to 3 minutes, higher than 140/90 mmHg or lower than 100/50 mmHg. The sponsor may allow exceptions if they are not deemed clinically significant.
- Subjects who have a supine pulse rate, after resting for greater than or equal to 3 minutes, outside the range of 40 to 90 bpm. The sponsor may allow exceptions significant.
- History of serious mental disorders that, in the opinion of the investigator, would exclude the subject from participating in this trial.
- Any subject who, in the opinion of the investigator, should not participate in the trial.
- Subjects who are pregnant or breastfeeding. A negative serum pregnancy test must be confirmed prior to randomization for all female subjects of childbearing potential.
- Subjects with Type 1 diabetes.
Data sourced from ClinicalTrials.gov (NCT02009878). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.