8-Week Study of Tolvaptan Dose Forms in Autosomal Dominant Polycystic Kidney Disease (ADPKD) (NOCTURNE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01451827
First received: October 11, 2011
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to compare the short-term effects of two tolvaptan formulations in patients with ADPKD.


Condition Intervention Phase
Autosomal Dominant Polycystic Kidney Disease
Drug: Tolvaptan MR
Drug: Tolvaptan IR
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Placebo-controlled, Double-blind, Placebo-masked, Parallel-group Pilot Trial to Compare the Efficacy, Tolerability, and Safety of Tolvaptan Modified-release and Immediate-release Formulations in Subjects With Autosomal Dominant Polycystic Kidney Disease

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Percent change in Total Kidney Volume (TKV) [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in total score of the ADPKD-Urinary Impact Scale (UIS) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Percent change in Total Kidney Volume (TKV) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 178
Study Start Date: October 2011
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tolvaptan MR 50 mg
Tolvaptan MR 50 mg capsule and 2 placebo IR tablets (AM) and 1 placebo IR tablet (PM)
Drug: Tolvaptan MR
50/80 mg capsules
Other Name: OPC-41061
Drug: Placebo
tablet
Experimental: Tolvaptan MR 80 mg
Tolvaptan MR 80 mg capsule and 2 placebo IR tablets (AM) and 1 placebo IR tablet (PM)
Drug: Tolvaptan MR
50/80 mg capsules
Other Name: OPC-41061
Drug: Placebo
tablet
Experimental: Tolvaptan IR 60/30 mg
Two tolvaptan IR 30-mg tablets and 1 placebo MR capsule (AM) and 1 tolvaptan IR 30-mg tablet (PM)
Drug: Tolvaptan IR
60/30 mg capsules
Other Name: OPC-41061
Drug: Placebo
tablet
Placebo Comparator: Placebo
Placebo MR capsule and 2 placebo IR tablets (AM) and 1 placebo IR tablet (PM)
Drug: Placebo
tablet

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18 to 50
  2. Subjects with:

    • BMI between 19 and 35 kg/m2
    • diagnosis of ADPKD by modified Ravine criteria:

      • family history: 3cysts/kidney if by sonography or 5 by CT or MRI
      • Without family history: 10 cysts per kidney
    • an eGFR > 45 mL/min/1.73 m2 by the CKD-EPI equation
  3. Subjects not planning to become pregnant willing to comply with birth control requirements.
  4. Subjects must be in good health as determined by screening tests.
  5. Subjects providing informed consent and able to comply with all trial requirements.

Exclusion Criteria:

  1. Subjects using diuretics within 14 days prior to randomization, or the requirement for intermittent or constant diuretic use for any reason
  2. Subjects who had an eGFR < 45 mL/min/1.73 m2 calculated based on the most recent historical creatinine during the last 12 months
  3. Subjects with:

    • incontinence, overactive bladder, or urinary retention (eg, BPH), meaning subjects with symptoms of frequent nocturia, as determined by medical history or urinary urgency should be carefully evaluated to exclude non-ADPKD GU issues prior to entry.
    • liver disease, liver function abnormalities, or serology other than that expected for ADPKD with cystic liver disease at baseline
    • a history of renal surgery or cyst drainage within 6 months of randomization
    • blood pressure 150/95 mmHg or < 90/40 mmHg.
    • heart rate outside the range of 40 to 90 bpm.
    • advanced diabetes with a history of poor control, evidence of significant renal disease renal cancer, single kidney, or recent renal surgery
    • other significant medical history that may interfere with the study objectives
    • significant abnormalities in serum sodium concentration (< 135 or > 145 mEq/L)
    • a history of drug and/or alcohol abuse within 2 years prior to screening
    • clinically significant allergic reactions to tolvaptan or chemically related structures such as benzazepines (eg, benzazepril, conivaptan, fenoldopam mesylate, or mirtazapine)
  4. Subjects having taken an investigational drug within 30 days preceding randomization on Day 0
  5. Subjects taking medications or having concomitant illnesses likely to confound endpoint assessments, including taking approved (ie, marketed) therapies for the purpose of affecting PKD cysts such as tolvaptan, somatostatin agonists (ie, octreotide, sandostatin), Rapamune (sirolimus), anti-sense RNA therapies, other vasopressin antagonists (eg, OPC-31260 [mozavaptan] and Vaprisol® [conivaptan]) or agonists (eg, desmopressin), and cyst reduction surgery
  6. Subjects on antihypertensives that have not been on the same antihypertensive regimen for at least 30 days prior to the first dose of IMP
  7. Subjects having contraindications to, or interference with, MRI assessments
  8. Subjects with a history of serious mental disorders that, in the opinion of the investigator, would exclude the subject from participating in this trial
  9. Subjects with previous exposure to tolvaptan
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01451827

  Show 35 Study Locations
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Frank Czerwiec, M.D., Ph.D. Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01451827     History of Changes
Other Study ID Numbers: 156-09-290
Study First Received: October 11, 2011
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Kidney Disease
Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease
PKD
ADPKD

Additional relevant MeSH terms:
Kidney Diseases
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Kidney Diseases, Cystic

ClinicalTrials.gov processed this record on April 17, 2014