A Phase IIa, Single-Center Study, Investigating the Short-Term Renal Hemodynamic Effects, Safety and Pharmacokinetics/Pharmacodynamics of Oral Tolvaptan (OPC-41061) in Subjects with Autosomal Dominant Polycystic Kidney Disease at Various Stages of Renal Functio

• Conditions: Autosomal Dominant Polycystic Kidney Disease (ADPKD); MedDRA version: 12.1Level: LLTClassification code 10036046Term: Polycystic kidney, autosomal dominant

• Registration Number: EUCTR2010-019025-33-NL
• Lead Sponsor: Otsuka Pharmaceutical Development Commercialization, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07-27
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1) Males and females between 18 and 70 years of age, inclusive

2) Diaganosis of ADPKD by Ravine criteria:
With family history: several cysts per kidney (3 if by sonography, 5 if by CT or MRI)
Without family history: 10 cysts (by an radiologic method) per kidney and exclusion of other cystic kidney diseases

3) eGFR as assessed by the MDRD equation based on an average of 2 measurements (one may be historical within 3 months prior to enrollment) that falls into one of the following strata:
Group A must have an eGFR of > 60 mL/min * 1.73 m2
Group B must have an eGFR of 30-60 ml/min * 1.73 m2
Group C must have an eGFR of < 30 ml/min * 1.73m2

4) Must have a negative serum pregnancy test prior to the first dose for all women of child-bearing potential (WOCBP)

5) Must have a body mass index (BMI) between 19-32 kg/m2

6) Must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry , hematology and serology tests

7) Subjects using diuretics may be eligible to participate if, after signing the informed consent , diuretic use is discontinued and the subject's blood pressure is stabilized on new antihypertension medication prior to the baseline visit

8) Ability to provide written, informed consent prior to initiation of any study-related procedures, and ability, in the opinion of the principle investigator, to comply with all requirements of the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Men or women who will not adhere to the reproductive precautions as outlined in the informed consent form.

2.Subject who is pregnant or breast-feeding.
3.Inability to take oral medications.
4.Subjects who have clinically significant allergic reactions to tolvaptan or chemically related structures such as benzazepines (benzazepril, conivaptan, fenoldopam mesylate or mirtazapine)
5.Subjects with a history of substance abuse (within the last 3 years).
6.Subjects taking other experimental (ie, nonmarketed) therapies or current participation in another clinical drug or device trial within 30 days prior to dosing.
Efficacy Endpoint Specific Exclusion
7.Subjects on any form of renal replacement therapy (e.g. dialysis, renal transplantation)
8.Subjects taking approved therapies for the purpose of affecting PKD cysts, including but not limited to, anti-sense RNA therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs ( ie, octreotide, sandostatin).
9.Prior use of a vasopressin antagonist for greater than 10 days or within 6 months of randomization.
10.Previous exposure to tolvaptan.
11.Subjects with a history of renal cystic disease likely to call into question the diagnosis of ADPKD, including multiple simple renal cysts, renal tubular acidosis, cystic dysplasia of the kidney, multicystic kidney, multilocular cysts of the kidney, medullary cystic kidney and acquired cystic disease of the kidney.
12.Subjects with evidence of significant renal disease other than ADPKD, such as currently active glomerular nephritidies, renal cancer, single kidney.
13.Subjects with significant risk-factors for renal impairment other than ADPKD, such as chronic use of diuretics, advanced diabetes (ie, those with poor glycemic control evidenced by a history of severely elevated hemoglobin A1C, or with evidence of advanced retinopathy, nephropathy or peripheral vascular disease due to micro-or-macro vascular disease), use of nephrotoxic drugs.
14.Subjects having recent (within last 6 months) renal surgery
15.Subjects with a history of persistent non-compliance with anti-hypertensive or other important medical therapy.
16.Subjects who may not safely be discontinued from diuretic medication for any reason.
17.Consumption of alcohol and/or food and beverages containing methyl xanthines within 24 hours of renal function testing and grapefruit, grapefruit juice, Seville oranges or Seville orange juice within 72 hours prior to dosing.
18.Exposure to any substances known to stimulate hepatic microsomal enzymes within 30 days prior to screening through the end of the study (eg, occupational exposure to pesticides, organic solvents, etc).
Patient Safety Specific Exclusion
19.Allergy to iodine.
20.Subjects with diabetes mellitus (fasting glucose > 126 mg/dL or on treatment with insulin or oral hypoglycemics).
21.Any history of significant coagulation defects or hemorrhagic diathesis (ie, von Willebrand disease).
22.A history of difficulty in donating blood.
23.Donation of blood or plasma within 30 days prior to dosing.
23.History of or current hepatitis or acquired immunodeficiency syndrome (AIDS) or carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HCV), or human immunodeficiency virus (HIV) antibodies.
24.Urine cotinine concentrations > 200 ng/mL or serum cotinine concentrations > 20 ng/mL at screening or upon admission to the study center.
25.Subjects having disorders in thirst recognition or inab

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified