Autosomal Dominant Polycystic Kidney DiseasePhase 2NOCTURNENCT01451827

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

A Phase 2 study testing Tolvaptan MR and Tolvaptan IR in people with Autosomal Dominant Polycystic Kidney Disease, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 35 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 18 to 50 years
Conditions the study is for: Autosomal Dominant Polycystic Kidney Disease
What is being tested?: Tolvaptan MR and Tolvaptan IR
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 178 participants
Where: 35 sitesUnited States
Study dates: Oct 2011to Jul 2013
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Age 18 to 50
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

Show all 10Show fewer

an eGFR > 45 mL/min/1.73 m2 by the CKD-EPI equation
Subjects not planning to become pregnant willing to comply with birth control requirements.
Subjects must be in good health as determined by screening tests.
Subjects providing informed consent and able to comply with all trial requirements.

Who cannot join

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

Show all 19Show fewer

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)
Subjects having taken an investigational drug within 30 days preceding randomization on Day 0
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
Subjects on antihypertensives that have not been on the same antihypertensive regimen for at least 30 days prior to the first dose of IMP
Subjects having contraindications to, or interference with, MRI assessments
Subjects with a history of serious mental disorders that, in the opinion of the investigator, would exclude the subject from participating in this trial
Subjects with previous exposure to tolvaptan

Trial locations and contacts

35 sites in 1 country.

City, postcode or hospital

35 sites in 1 country

United States35 sites

Otsuka Investigational Site
Anderson, South Carolina, 29621
Otsuka Investigational Site
Arlington, Texas, 76015
Otsuka Investigational Site
Atlanta, Georgia, 30322
Otsuka Investigational Site
Augusta, Georgia, 30901
Otsuka Investigational Site 2
Aurora, Colorado, 80045
Otsuka Investigational Site
Aurora, Colorado, 80045
Otsuka Investigational Site
Baltimore, Maryland, 21224
Otsuka Investigational Site
Bethlehem, Pennsylvania, 18017
Otsuka Investigational Site
Boston, Massachusetts, 02111
Otsuka Investigational Site
Buffalo, New York, 14215
Otsuka Investigational Site
Chapel Hill, North Carolina, 27599
Otsuka Investigational Site
Charlottesville, Virginia, 22908
Otsuka Investigational Site
Cleveland, Ohio, 44106
Otsuka Investigational Site
Denver, Colorado, 80210
Otsuka Investigational Site
Detroit, Michigan, 48236
Otsuka Investigational Site
Huntsville, Alabama, 35802
Otsuka Investigational Site
Jacksonville, Florida, 32216
Otsuka Investigational Site
Kansas City, Kansas, 66160
Otsuka Investigational Site
Los Angeles, California, 90025
Otsuka Investigational Site
Melbourne, Florida, 32935
Otsuka Investigational Site
Mishawaka, Indiana, 46545
Otsuka Investigational Site
Mission, Texas, 78572
Otsuka Investigational Site
Mobile, Alabama, 36617
Otsuka Investigational Site
Nashville, Tennessee, 37205
Otsuka Investigational Site
New Haven, Connecticut, 06510
Otsuka Investigational Site
Paducah, Kentucky, 42003
Otsuka Investigational Site
Peoria, Arizona, 85381
Otsuka Investigational Site
Peoria, Illinois, 61602
Otsuka Investigational Site
Philadelphia, Pennsylvania, 19104
Otsuka Investigational Site
Rochester, Minnesota, 55905
Otsuka Investigational Site
Rockville, Maryland, 20850
Otsuka Investigational Site
San Diego, California, 92108
Otsuka Investigational Site
Shreveport, Louisiana, 71101
Otsuka Investigational Site
Tempe, Arizona, 85284
Otsuka Investigational Site
Voorhees Township, New Jersey, 08043

Other trials in United States

About this study

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

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

Conditions: Autosomal Dominant Polycystic Kidney Disease
Being tested: Tolvaptan MR, Tolvaptan IR, Placebo
Keywords: Kidney Disease, Polycystic Kidney Disease, Autosomal Dominant Polycystic Kidney Disease, PKD, ADPKD
Medical subject headings: Polycystic Kidney, Autosomal Dominant, Kidney Diseases, Polycystic Kidney Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Tolvaptan MRDrug
Also called OPC-41061
50/80 mg capsules
Tolvaptan IRDrug
Also called OPC-41061
60/30 mg capsules
PlaceboDrug
tablet

Study groups in NCT01451827
Study group	Role	What they receive
Tolvaptan MR 50 mg	Experimental	Tolvaptan MR 50 mg capsule and 2 placebo IR tablets ( 8 AM) and 1 placebo IR tablet (4 PM) daily. Receives: Drug: Tolvaptan MR; Drug: Placebo
Tolvaptan MR 80 mg	Experimental	Tolvaptan MR 80 mg capsule and 2 placebo IR tablets (8 AM) and 1 placebo IR tablet (4 PM) daily. Receives: Drug: Tolvaptan MR; Drug: Placebo
Tolvaptan IR 60/30 mg	Experimental	Two tolvaptan IR 30-mg tablets and 1 placebo MR capsule (8 AM) and 1 tolvaptan IR 30-mg tablet (4 PM) daily. Receives: Drug: Tolvaptan IR; Drug: Placebo
Placebo	Placebo comparator	Placebo MR capsule and 2 placebo IR tablets (8 AM) and 1 placebo IR tablet (4 PM) daily. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline to Week 3

Secondary outcomes (2)

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.
Measured: Baseline to Week 8
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.
Measured: Baseline to Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2011Jul 2013

First posted14 Oct 2011 (estimated)
Study startOct 2011
Primary completionJul 2013
Study completionJul 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Autosomal Dominant Polycystic Kidney DiseaseStudies of the same condition, open and under way.
More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 178 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01451827
Sponsor's protocol ID: 156-09-290
Acronym: NOCTURNE
Status last verified: Aug 2018
First submitted: 11 Oct 2011
Last updated: 27 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
PubMed 39356039

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Hypertension in Children and Young People at Risk of Autosomal Dominant Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease (ADPKD
Active, not recruitingObservational study
Role of ROS and cAMP-PKA Biomarkers in ADPKD
Autosomal Dominant Polycystic Kidney Disease
Not yet recruitingPhase 1
A Study to Investigate the Pharmacokinetics of JMKX003142 in Healthy Participants and Participants With Hepatic Impairment
ADPKD (Autosomal Dominant Polycystic Kidney Disease), Renal Edema
RecruitingPhase 1
Absorption, Distribution, Metabolism, and Excretion of 14C-VX-407 After a Single Oral Dose
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
RecruitingObservational study
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All Autosomal Dominant Polycystic Kidney Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01451827
Acronym / sponsor ID: NOCTURNE / 156-09-290
Conditions: Autosomal Dominant Polycystic Kidney Disease
Keywords: Kidney Disease, Polycystic Kidney Disease, Autosomal Dominant Polycystic Kidney Disease, PKD, ADPKD
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 178 participants (actual)
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
Study start: Oct 2011
Primary completion: Jul 2013 (actual)
Study completion: Jul 2013 (actual)
First posted: 14 Oct 2011 (estimated)
Results: Posted 13 Aug 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 4

Arm	Type	Receives
Tolvaptan MR 50 mg	Experimental	Drug: Tolvaptan MR, Drug: PlaceboTolvaptan MR 50 mg capsule and 2 placebo IR tablets ( 8 AM) and 1 placebo IR tablet (4 PM) daily.
Tolvaptan MR 80 mg	Experimental	Drug: Tolvaptan MR, Drug: PlaceboTolvaptan MR 80 mg capsule and 2 placebo IR tablets (8 AM) and 1 placebo IR tablet (4 PM) daily.
Tolvaptan IR 60/30 mg	Experimental	Drug: Tolvaptan IR, Drug: PlaceboTwo tolvaptan IR 30-mg tablets and 1 placebo MR capsule (8 AM) and 1 tolvaptan IR 30-mg tablet (4 PM) daily.
Placebo	Placebo comparator	Drug: PlaceboPlacebo MR capsule and 2 placebo IR tablets (8 AM) and 1 placebo IR tablet (4 PM) daily.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (10 listed)

Age 18 to 50
Subjects with:
Subjects not planning to become pregnant willing to comply with birth control requirements.
Subjects must be in good health as determined by screening tests.
Subjects providing informed consent and able to comply with all trial requirements.

Key exclusion criteria (19 listed)

Subjects using diuretics within 14 days prior to randomization, or the requirement for intermittent or constant diuretic use for any reason
Subjects who had an eGFR < 45 mL/min/1.73 m2 calculated based on the most recent historical creatinine during the last 12 months
Subjects with:
Subjects having taken an investigational drug within 30 days preceding randomization on Day 0
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Tolvaptan MRAlso: OPC-4106150/80 mg capsules	Drug	Tolvaptan MR 50 mg, Tolvaptan MR 80 mg
Tolvaptan IRAlso: OPC-4106160/30 mg capsules	Drug	Tolvaptan IR 60/30 mg
Placebotablet	Drug	Placebo, Tolvaptan IR 60/30 mg, Tolvaptan MR 50 mg, Tolvaptan MR 80 mg

Primary outcome

Percent Change From Baseline in Total Kidney Volume (TKV) at Week 3
Time frame: Baseline to 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.

2 secondary outcomes

Change From Baseline in Total Score of the Autosomal Dominant Polycystic Kidney Disease Urinary Impact Scale (ADPKD-UIS)
Time frame: Baseline to Week 8
Percent Change From Baseline in TKV at Week 8.
Time frame: Baseline to Week 8

Results and safety

Results posted to the registry on 13 Aug 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tolvaptan Modifed Release (MR) 50 mg	45	42
Tolvaptan MR 80 mg	45	40
Tolvaptan Immediate Release (IR) 60/30 mg	44	42
Placebo	43	39

Primary outcome: Percent Change From Baseline in Total Kidney Volume (TKV) at Week 3

Time frame: Baseline to Week 3. Mean (Standard Deviation). Unit: Percentage change

Measure	Tolvaptan MR 50 mg n = 41	Tolvaptan MR 80 mg n = 43	Tolvaptan IR 60/30 mg n = 41	Placebo n = 39
Value	-2.46 (4.40)	-2.55 (3.85)	-1.17 (4.52)	0.09 (5.31)

Tolvaptan MR 50 mg vs Tolvaptan MR 80 mg vs Tolvaptan IR 60/30 mg vs Placebo: Ratio of geometric means: 0.98 (95% CI 0.96 to 1.00), p = 0.0127, ANCOVA
Tolvaptan MR 80 mg vs Placebo: Ratio of geometric means: 0.97 (95% CI 0.95 to 0.99), p = 0.0108, ANCOVA
Tolvaptan MR 50 mg vs Placebo: Ratio of geometric means: 0.98 (95% CI 0.96 to 1.00), p = 0.0155, ANCOVA

Population analysed: Participants who were randomized and had baseline and post-baseline observations in the total renal volume.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from the time of signing the informed consent, throughout the 8 week treatment period and for 7 days after the last dose of study medication.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tolvaptan MR 50 mg	3 of 45 (6.7%)	27 of 45 (60%)	0 of 45
Tolvaptan MR 80 mg	1 of 44 (2.3%)	25 of 44 (56.8%)	0 of 44
Tolvaptan IR 60/30 mg	1 of 44 (2.3%)	32 of 44 (72.7%)	0 of 44
Placebo	1 of 42 (2.4%)	18 of 42 (42.9%)	0 of 42

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39356039St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

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Hypertension in Children and Young People at Risk of Autosomal Dominant Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease (ADPKD
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Role of ROS and cAMP-PKA Biomarkers in ADPKD
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Frank Czerwiec, M.D., Ph.D. study director

Otsuka Pharmaceutical Development & Commercialization, Inc.

35 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Total Kidney Volume (TKV) at Week 3 (time frame: Baseline to Week 3). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01451827, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2018.