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

Autosomal Dominant Polycystic Kidney Disease Clinical Trial

— NOCTURNE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01451827
• Other study ID #: 156-09-290
• Status: Completed
• Phase: Phase 2
• Start date: October 2011
• Est. completion date: July 2013

Study information

• Verified date: August 2018
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 178
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Autosomal Dominant Polycystic Kidney Disease
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Drug:
• Tolvaptan MR
50/80 mg capsules
• Tolvaptan IR
60/30 mg capsules
• Placebo
tablet

Locations

Country	Name	City	State
United States	Otsuka Investigational Site	Anderson	South Carolina
United States	Otsuka Investigational Site	Arlington	Texas
United States	Otsuka Investigational Site	Atlanta	Georgia
United States	Otsuka Investigational Site	Augusta	Georgia
United States	Otsuka Investigational Site	Aurora	Colorado
United States	Otsuka Investigational Site 2	Aurora	Colorado
United States	Otsuka Investigational Site	Baltimore	Maryland
United States	Otsuka Investigational Site	Bethlehem	Pennsylvania
United States	Otsuka Investigational Site	Boston	Massachusetts
United States	Otsuka Investigational Site	Buffalo	New York
United States	Otsuka Investigational Site	Chapel Hill	North Carolina
United States	Otsuka Investigational Site	Charlottesville	Virginia
United States	Otsuka Investigational Site	Cleveland	Ohio
United States	Otsuka Investigational Site	Denver	Colorado
United States	Otsuka Investigational Site	Detroit	Michigan
United States	Otsuka Investigational Site	Huntsville	Alabama
United States	Otsuka Investigational Site	Jacksonville	Florida
United States	Otsuka Investigational Site	Kansas City	Kansas
United States	Otsuka Investigational Site	Los Angeles	California
United States	Otsuka Investigational Site	Melbourne	Florida
United States	Otsuka Investigational Site	Mishawaka	Indiana
United States	Otsuka Investigational Site	Mission	Texas
United States	Otsuka Investigational Site	Mobile	Alabama
United States	Otsuka Investigational Site	Nashville	Tennessee
United States	Otsuka Investigational Site	New Haven	Connecticut
United States	Otsuka Investigational Site	Paducah	Kentucky
United States	Otsuka Investigational Site	Peoria	Illinois
United States	Otsuka Investigational Site	Peoria	Arizona
United States	Otsuka Investigational Site	Philadelphia	Pennsylvania
United States	Otsuka Investigational Site	Rochester	Minnesota
United States	Otsuka Investigational Site	Rockville	Maryland
United States	Otsuka Investigational Site	San Diego	California
United States	Otsuka Investigational Site	Shreveport	Louisiana
United States	Otsuka Investigational Site	Tempe	Arizona
United States	Otsuka Investigational Site	Voorhees	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Total Kidney Volume (TKV) at Week 3	The primary endpoint was percent change from baseline in TKV at Week 3. Total kidney volume is an important measure of disease progression. A 3-week time point is adequate to assess acute effects on kidney cyst shrinkage.	Baseline to Week 3
Secondary	Change From Baseline in Total Score of the Autosomal Dominant Polycystic Kidney Disease Urinary Impact Scale (ADPKD-UIS)	The ADPKD-UIS was a self-administered questionnaire designed to measure ADPKD-related urinary symptoms in participants with ADPKD. This instrument contained 11 items in 3 domains (Urinary Frequency, Urinary Urgency, and Nocturia). Each item was scored using a scale of 1 to 5 (a higher score indicated increased difficulty/extremely bothered). The maximum total score is 55; 1: not difficult/not bothered at all; 55: extremely difficult/extremely bothered.	Baseline to Week 8
Secondary	Percent Change From Baseline in TKV at Week 8.	Total kidney volume is an important measure of disease progression. A 3-week time point is adequate to assess acute effects on kidney cyst shrinkage.	Baseline to Week 8