A Phase 2a, Single-Center Study Investigating the Short-Term Renal Hemodynamic Effects, Safety and Pharmacokinetics/ Pharmacodynamics of Oral Tolvaptan in Subjects with Autosomal Dominant Polycystic Kidney Disease at Various Stages of Renal Function

A Phase 2a, Single-Center Study Investigating the Short-Term Renal Hemodynamic Effects, Safety and Pharmacokinetics/ Pharmacodynamics of Oral Tolvaptan in Subjects with Autosomal Dominant Polycystic Kidney Disease at Various Stages of Renal Function - Phase 2a study in adult subjects with ADPKD

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON34527

Enrollment

Registered

2010-07-26

Start date

2011-09-01

Completion date

Unknown

Last updated

2024-05-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Genetic Disease whereby the kidneys contain multiple cysts filled with fluid

Interventions

During the 3-week treatment phase, each subject will receive a daily split dose of 45/15 mg tolvaptan for 1 week, with the larger dose upon awakening each day followed by the smaller dose approximat

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: This study will be started in subjects with eGFR >30 mL/min*1.73m2. Other important inclusion criteria are: confirmed diagnosis of ADPKD, body mass index of 30 mL/min*1.73m2, subjects with eGFR

Exclusion criteria

Exclusion criteria: - Subjects with previous exposure to tolvaptan - Subjects with recent (within last 6 months) renal surgery - Subjects with evidence of renal cystic disease other than ADPKD (e.g. renal cancer) - Safety contraindications including: reproductive precautions, unawareness of thirst, severe allergic reactions to compounds with similar chemical structure as tolvaptan, significant risk factors for renal impairment other than ADPKD (e.g. advanced diabetes), a history of significant coagulation defects, critical electrolyte inbalances, low blood volume, clinically significant anemia, history of substance abuse, uncontrolled hypertension. - Contraindications to or interference with MRI assessments See protocol page 30 for further details.

Design outcomes

Primary

Measure	Time frame
Pharmacodynamics: GFR as determined by iothalamate clearance, ERPF as determined by hippuran clearance and filtration fraction (GFR/ERPF).	—

Secondary

Measure	Time frame
- Pharmacodynamics: Urine concentrations of sodium, potassium, osmoles, creatinine, urea, uric acid, aldosterone and albumin and urine volume. The calculated urinary excretion of sodium, potassium, creatinine, urea, uric acid, albumin and aldosterone. Serum or plasma concentrations of sodium, potassium, osmoles, creatinine, urea, uric acid, albumin, cystatin C, active plasma renin, copeptin, and aldosterone. The calculated clearances of free water, sodium, potassium, osmoles, creatinine, urea, and uric acid and the fractional clearances of free water, sodium, potassium, urea and uric acid to creatinine clearance. The calculated ratio of urine albumin to creatinine. Mean arterial blood pressure. Short-term changes in total kidney volume (TKV) as percent change from baseline at the Final Treatment Visit (after approximately 3 weeks of treatment) and at the Post Treatment Visit (after approximately 3 weeks off treatment) measured by MRI. - Safety: Adverse events (AEs), vital signs, clinical laboratory tests, physical examinations, and electrocardiograms (ECG). - Pharmacokinetics: Peak plasma concentration (Cmax), time to peak plasma concentration (tmax), and area under the concentration-time curve calculated to the time of the last observable concentration (AUCt*) of tolvaptan and its metabolites (DM-4103 and DM-4107) in plasma.	—

Measure

Time frame

- Pharmacodynamics: Urine concentrations of sodium, potassium, osmoles, creatinine, urea, uric acid, aldosterone and albumin and urine volume. The calculated urinary excretion of sodium, potassium, creatinine, urea, uric acid, albumin and aldosterone. Serum or plasma concentrations of sodium, potassium, osmoles, creatinine, urea, uric acid, albumin, cystatin C, active plasma renin, copeptin, and aldosterone. The calculated clearances of free water, sodium, potassium, osmoles, creatinine, urea, and uric acid and the fractional clearances of free water, sodium, potassium, urea and uric acid to creatinine clearance. The calculated ratio of urine albumin to creatinine. Mean arterial blood pressure. Short-term changes in total kidney volume (TKV) as percent change from baseline at the Final Treatment Visit (after approximately 3 weeks of treatment) and at the Post Treatment Visit (after approximately 3 weeks off treatment) measured by MRI. - Safety: Adverse events (AEs), vital signs, clinical laboratory tests, physical examinations, and electrocardiograms (ECG). - Pharmacokinetics: Peak plasma concentration (Cmax), time to peak plasma concentration (tmax), and area under the concentration-time curve calculated to the time of the last observable concentration (AUCt*) of tolvaptan and its metabolites (DM-4103 and DM-4107) in plasma.

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)