Autosomal Dominant Polycystic Kidney DiseasePhase 2NCT01210560
Dose-finding Study of New Tolvaptan Formulation in Subjects With 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 6 sites in United States.
Trial summary
To establish pharmacokinetics (PK), pharmacodynamics (PD), and adverse event (AE) profile of tolvaptan administered as the modified-release (MR) formulation in ADPKD subjects. The goals of this trial are two-fold: 1. To directly compare the immediate release (IR) and MR formulations 2. 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?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 6 sitesUnited States
- Study dates
- Oct 2010to Jun 2011
- 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
- Subjects (male or female) who are surgically sterile (ie, have undergone hysterectomy) or using contraception or agree to remain abstinent
- Subjects between the ages of 18 and 50, inclusive
- Subjects with a body mass index between 19 to 35 kg/m2 (inclusive)
- Subjects with a diagnosis of ADPKD by modified Ravine criteria
- Subjects must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests
- Subjects with the ability to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principle investigator, to comply with all requirements of the trial
- Subjects who expect to be able to complete all dosing periods and assessments within 42 (+2) days after dosing on Day 1
Who cannot join
- Subjects using diuretics within 14 days prior to check in on Day -1
- Subjects with incontinence, overactive bladder, or urinary retention (eg, benign prostatic hyperplasia)
- Subjects (male or female) with nocturia/urgency (outside of the 2 to 4 times awakening per night expected for ADPKD patients) at screening
- Subjects with liver disease, liver function abnormalities or serology other than that expected for ADPKD with cystic liver disease at baseline
- Subjects with clinically significant abnormality in past medical history, or at the Screening physical examination, that in the investigator's or sponsor's opinion may place the volunteer at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of drug. This includes, but is not limited to, history of or concurrent cardiac, hepatic, renal, neurologic, endocrine, gastrointestinal, respiratory, hematologic, and immunologic disease
- Subjects with a history of drug and/or alcohol abuse within 2 years prior to screening
Show all 17Show fewer
- Subjects who have a history of or test positive at screening for hepatitis B surface antigen (HBsAg), hepatitis C antibodies (anti-HCV), and/or human immunodeficiency virus (HIV)
- Subjects who have clinically significant allergic reactions to tolvaptan or chemically related structures such as benzazepines (eg, benzazepril, conivaptan, fenoldopam mesylate or mirtazapine)
- Subjects who have taken an investigational drug within 30 days preceding trial entry
- Subjects with any history of significant bleeding or hemorrhagic tendencies
- Subjects with a history of difficulty in donating blood
- Subjects who have donated blood or plasma within 30 days prior to dosing
- Subjects who have consumed alcohol and/or food or beverages containing methylxanthines, grapefruit, grapefruit juice, Seville oranges, or Seville orange juice within 72 hours prior to Day 1 dosing
- Subjects taking CYP3A4 inhibitors, with the exception of amiodarone, taken within 30 days of dosing (eg, amprenavir, atorvastatin, aprepitant, chloramphenicol [not eye drops], cimetidine, clarithromycin, clotrimazole [if used orally], danazol, delavirdine, diltiazem, erythromycin, fluconazole, fluvoxamine, indinavir, isoniazid, itraconazole, josamycin, ketoconazole, nelfinavir, nefazadone, quinupristin/dalfopristin, ritonavir, saquinavir, troleandomycin, verapamil)
- Subjects taking CYP3A4 inducers taken within 7 days of dosing (eg, rifampin, St. Johns Wort)
- Subjects with a history of serious mental disorders
- Subjects with previous exposure to tolvaptan
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Tufts-New England Medical Center
Boston, Massachusetts, 02111
University Hospitals of Cleveland/Case
Cleveland, Ohio, 44106
Davita Clinical Research
Minneapolis, Minnesota, 55404
University of Pennsylvania Medical Center
Philadelphia, Pennsylvania, 19104
Northwest Renal Clinic Inc.
Portland, Oregon, 97210
Mayo Medical Center
Rochester, Minnesota, 55905
About this study
Official title: A Multi-center, Parallel-group, Randomized, Double-blind, Placebo-masked, Multiple Dose Trial of Modified-release (MR) and Immediate-release (IR) Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
To establish pharmacokinetics (PK), pharmacodynamics (PD), and adverse event (AE) profile of tolvaptan administered as the modified-release (MR) formulation in ADPKD subjects. The goals of this trial are two-fold:
- To directly compare the immediate release (IR) and MR formulations
- To determine the dose range and dose regimen for MR (dose finding)
Read the detailed description
Group 1 will have 12 subjects enrolled in a 3-period, randomized, crossover to compare multiple doses of a 90-30 mg split-dose of the tolvaptan IR formulation, a 120 mg once daily (QD) dose of the tolvaptan MR formulation, and, in an incomplete block randomization, multiple doses of either 20 mg QD, 60 mg QD, or 20 mg twice daily (BID) tolvaptan MR formulation. All dose regimens will be administered for 7 days. Placebo doses will be administered in order to mask QD vs BID treatments.
Group 2 will have 12 subjects enrolled in a 3-period, randomized, crossover to compare multiple oral doses of the tolvaptan MR formulation administered for 7 days as 20 mg QD, 60 mg QD, and 20 mg BID. Placebo capsules will be administered in order to mask QD vs BID treatments.
Subjects will have in-clinic assessments on 12 days to obtain 24-hour PK and PD data. Subjects will visit the clinic from the afternoon of Day -1 through the morning of Day 1. They will return at the end of each dosing period for a similar inpatient period (ie, from the afternoon of Day 6 through the morning of Day 8, from the afternoon of Day 13 through the morning of Day 15, from the afternoon of Day 20 through the morning of Day 22). Except for the first dose of each period and the doses taken in the clinic on the last day of each regimen and the afternoon of Days 6, 13 and 20, all other doses will be taken by the subject as an outpatient.
- Being tested
- Tolvaptan MR, Tolvaptan IR
- Keywords
- Kidney Disease, Polycystic Kidney Disease
- 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
20 mg Tolvaptan MR capsule(morning); Placebo capsules/tablets (morning and afternoon) for 7 days
Tolvaptan MRDrug
Also called OPC-41061
20 mg Tolvaptan MR capsule(morning and afternoon); Placebo capsules/tablets (morning and afternoon) for 7 days
Tolvaptan MRDrug
Also called OPC-41061
60 mg Tolvaptan MR capsule(morning); Placebo capsules/tablets (morning and afternoon) for 7 days
Tolvaptan IRDrug
Also called OPC-41061
90 mg Tolvaptan IR tablet(morning); 30 mg Tolvaptan IR tablet (afternoon); Placebo capsules (morning and afternoon) for 7 days
Tolvaptan MRDrug
Also called OPC-41061
120 mg Tolvaptan MR capsule(morning); Placebo capsules/tablets (morning and afternoon) for 7 days
| Study group | Role | What they receive |
|---|---|---|
| 20 mg MR | Experimental | Not described Receives: Drug: Tolvaptan MR |
| 40 mg MR | Experimental | Not described Receives: Drug: Tolvaptan MR |
| 60 mg MR | Experimental | Not described Receives: Drug: Tolvaptan MR |
| 120 mg MR | Experimental | Not described Receives: Drug: Tolvaptan MR |
| 120 mg IR | Experimental | Not described Receives: Drug: Tolvaptan IR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum (Peak) Plasma Concentration of the Drug [Cmax] and Minimum (Trough) Plasma Concentration of the Drug [Cmin] After Tolvaptan Treatment on Day 7.
Blood samples (6 mL) for determination of tolvaptan PK parameters were collected on Day 1 predose, and on Days 7, 14 and 21 at predose, and 1, 2, 4, 6, 8, 9, 10, 12, 16, and 24 hours postdose. If a sample was not drawn at the designated time, a window of ± 3 minutes for each blood draw was acceptable. Maximum and minimum plasma concentration of the drug was calculated.
Measured: Day 7
Time to Maximum (Peak) Plasma Concentration (Tmax) After Tolvaptan Treatment on Day 7.
Blood samples (6 mL) for determination of tolvaptan PK parameters were collected on Day 1 predose, and on Days 7, 14 and 21 at predose, and 1, 2, 4, 6, 8, 9, 10, 12, 16, and 24 hours postdose. If a sample was not drawn at the designated time, a window of ± 3 minutes for each blood draw was acceptable. Time to maximum plasma concentration was calculated.
Measured: Day 7
Area Under the Concentration-time Curve During the Dosing Interval at Steady State and Area Under the Concentration-time Curve From Time 0 to 24 Hours Postdose (AUCT & AUC0-24h) After Tolvaptan Treatment on Day 7.
Blood samples (6 mL) for determination of tolvaptan PK parameters were collected on Day 1 predose, and on Days 7, 14 and 21 at predose, and 1, 2, 4, 6, 8, 9, 10, 12, 16, and 24 hours postdose. If a sample was not drawn at the designated time, a window of ± 3 minutes for each blood draw was acceptable. Hence, both AUCT and AUC0-24h values were calculated.
Measured: Day 7
Secondary outcomes (14)
Number of Participants With Urine Osmolality < 300 mOsm/kg at 23.5 Hours Postdose.
For determination of duration of urine osmolality <300 mOsm/kg, the value was the end time of the last collection interval in which urine osmolality was <300 mOsm/kg. Day 8 in the table below was defined as Day 8 of Period 1, Day 15 of Period 2, and Day 22 of period 3.
Measured: 23.5 hours post-dose
Change From Baseline in Urine Osmolality Area Under the Concentration-time Curve From Time 0 to 24 Hours Postdose (AUC0-24h) at Day 7.
The AUC0-24h for urine osmolality was determined by multiplying the concentration by the collection interval duration for each collection interval and summing all the intervals in the 24-hour period. If the urine volume for an interval is zero, the duration of that interval will be added to the next collection interval. Day 7 was defined as Day 7 of Period 1, Day 14 of Period 2 and Day 21 of Period 3.
Measured: Day 7
Change From Baseline in Urine Osmolality at Day 7.
To determine the tolerability and nighttime urinary suppression of osmolality. The urine osmolality was summarized by collection interval (0 to 4, 4 to 8, 8 to 12, 12 to 16, and 16 to 24 hours)
Measured: 0-4, 4-8, 8-12, 12-16, 16-24 Hours at Day 7
Change From Baseline in Urine Volume at 24 Hours at Day 7.
Urine volume was collected by 0 to 24-hour interval at Day 7. Day 7 was defined as Day 7 of Period 1, Day 14 of Period 2 and Day 21 of Period 3.
Measured: Day 7
Change From Baseline in Urine Volume by Interval at Day 7.
Urine volume collected was by interval (0-4, 4-8, 8-12, 12-16, 16-24 hours). Day 7 was defined as Day 7 of Period 1, Day 14 of Period 2 and Day 21 of Period 3.
Measured: 0-4, 4-8, 8-12, 12-16, 16-24 Hours at Day 7
Duration of Urine Osmolality Less Than 300 mOsm/kg at Baseline and Day 7.
Duration of urine osmolality remains below 300 mOsm/kg was the sum of the durations (nominal times) of all intervals where the urine concentration was < 300 mOsm/kg. Day 7 was defined as Day 7 of Period 1, Day 14 of Period 2, and Day 21 of Period 3.
Measured: Baseline and Day 7
Change From Baseline in Number of Urine Voids During Awake Periods.
Average number of daily urine voids during awake periods for each dose group. Day 1 was defined as Day1 of Period 1, Day 8 of Period 2 adn Day 15 of Period 3; Day 7 was defined as Day 7 of Period 1, Day 14 of Period 2 and Day 21 of Period 3; Same rule applied to Day 2 and Day 6.
Measured: Days 1, 2, 3, 4, 5, 6 and 7
Change From Baseline in Number of Urine Voids During Sleep Periods.
Average number of daily urine voids during sleep periods for each dose group. Day 1 was defined as Day 1 of Period 1, Day 8 of Period 2, Day 15 of Period 3; Day 7 was defined as Day 7 of Period 1, Day 14 of Period 2 and Day 21 of Period 3; Same rule applied to Day 2 to 6.
Measured: Days 1, 2, 3, 4, 5, 6 and 7
Change From Baseline in Symptom Burden by Autosomal Dominant Polycystic Kidney Disease (ADPKD) Nocturia Quality of Life Questionnaire at Day 6.
In ADPKD Nocturia Quality of Life Questionnaire, questions 1 to 11 (with possible scores ranging from 0 to 4 and higher scores indicating better quality of life) were pooled to provide a total score (maximum of 44 points). Response scores of Question 12 (with possible scores ranging from 1 to 10, with higher scores indicating more interference (worse quality of life) with everyday life due to urination at night) were pooled separately. Day 6 was defined as Day 6 of Period 1, Day 13 of Period 2 and Day 20 of Period 3.
Measured: Day 6
Number of Participants Experiencing Urinary Urgency Based on Urinary Urgency Questionnaire (Question 1) at Baseline and Day 6.
For the ADPKD Urinary Urgency Questionnaire, Question 1 (currently experiencing urgency?) was assigned 'Yes' or 'No' to measure current urine urgency status. Baseline was defined as last pre-dose evaluation; Day 6 was defined as Day 6 of Period 1, Day 13 of Period 2 and Day 20 of Period 3.
Measured: Baseline and Day 6
Change From Baseline in Urinary Urgency Questionnaire (Questions 2 to 5 and Questions 7 to 14) at Day 6.
Question 2 to Question 6 were assigned scores of 0 to 4 with higher scores indicating worse cases in experience of urinary urgency. Scores for Question 2 to Question 5 were pooled, with a maximum possible score of 16.
Question 6 was excluded from the analysis since it was only asked at screening. Question 7 to Question 14 were also assigned scores of 0 to 4 with higher scores indicating worse cases in impact of urinary urgency on life; scores for these questions were pooled, with a maximum possible score of 32.
Baseline was defined as last pre-dose evaluation; Day 6 was defined as Day 6 of Period 1, Day 13 of Period 2 and Day 20 of Period 3.
Measured: Day 6
Number of Participants Experiencing Urinary Frequency Based on Urinary Frequency Questionnaire (Question 1) at Baseline and Day 6.
The ADPKD Urinary Frequency Questionnaire: Question 1 (currently experiencing frequency) was assigned 'Yes' or 'No' to measure current urine frequency status.
Baseline was defined as last pre-dose evaluation; Day 6 was defined as Day 6 of Period 1, Day 13 of Period 2 and Day 20 of Period 3.
Measured: Baseline and Day 6
Change From Baseline in Urinary Frequency Questionnaire (Question 2 and Questions 3 to 10) at Day 6.
Question 2 asked, "During the last 5 days, how much has urinary frequency bothered you?" In order to score the response, the written answers were assigned values from 0 to 4 as follows: 0) Not at all, 1) Somewhat, 2) Moderately, 3) Quite a bit, and 4) Constantly.
Question 3 to Question 10 were assigned scores of 0 to 4 with higher scores indicating worse cases in impact of urinary frequency on life; scores for these questions were pooled, with a maximum possible score of 32.
Baseline was defined as last pre-dose evaluation; Day 6 was defined as Day 6 of Period 1, Day 13 of Period 2 and Day 20 of Period 3.
Measured: Day 6
Ranking of Treatment Tolerability.
Ranking of treatment tolerability was evaluated based on a questionnaire. At Day 22, participants were asked the following questions and their responses recorded on the eCRF: "Which treatment period did you find most tolerable?" and "Which treatment period did you find the least tolerable?".
Measured: Day 22/Early Termination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2010 (estimated)
- Study startOct 2010
- Primary completionJun 2011
- Study completionJun 2011
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 (2)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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Frank Czerwiec, M.D., Ph.D., Study director, Otsuka Pharmaceutical Development & Commercialization, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01210560
- Sponsor's protocol ID
- 156-09-285
- Status last verified
- May 2018
- First submitted
- 21 Sep 2010
- Last updated
- 14 Jun 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 39356039Gobburu J, Ivaturi V, Wang X, Shoaf SE, Jadhav P, Perrone RD. Comparing Effects of Tolvaptan and Instruction to Increase Water Consumption in ADPKD: Post Hoc Analysis of TEMPO 3:4. Kidney360. 2023 Dec 1;4(12):1702-1707. doi: 10.34067/KID.0000000000000302. Epub 2023 Nov 21.
PubMed 37986188
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Parallel-group, Randomized, Double-blind, Placebo-masked, Multiple Dose Trial of Modified-release (MR) and Immediate-release (IR) Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
- ClinicalTrials.gov ID
- NCT01210560
- Acronym / sponsor ID
- 156-09-285
- Keywords
- Kidney Disease, Polycystic Kidney Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2010
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 28 Sep 2010 (estimated)
- Results
- Posted 14 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To establish pharmacokinetics (PK), pharmacodynamics (PD), and adverse event (AE) profile of tolvaptan administered as the modified-release (MR) formulation in ADPKD subjects. The goals of this trial are two-fold:
- To directly compare the immediate release (IR) and MR formulations
- To determine the dose range and dose regimen for MR (dose finding)
Detailed description
Group 1 will have 12 subjects enrolled in a 3-period, randomized, crossover to compare multiple doses of a 90-30 mg split-dose of the tolvaptan IR formulation, a 120 mg once daily (QD) dose of the tolvaptan MR formulation, and, in an incomplete block randomization, multiple doses of either 20 mg QD, 60 mg QD, or 20 mg twice daily (BID) tolvaptan MR formulation. All dose regimens will be administered for 7 days. Placebo doses will be administered in order to mask QD vs BID treatments.
Group 2 will have 12 subjects enrolled in a 3-period, randomized, crossover to compare multiple oral doses of the tolvaptan MR formulation administered for 7 days as 20 mg QD, 60 mg QD, and 20 mg BID. Placebo capsules will be administered in order to mask QD vs BID treatments.
Subjects will have in-clinic assessments on 12 days to obtain 24-hour PK and PD data. Subjects will visit the clinic from the afternoon of Day -1 through the morning of Day 1. They will return at the end of each dosing period for a similar inpatient period (ie, from the afternoon of Day 6 through the morning of Day 8, from the afternoon of Day 13 through the morning of Day 15, from the afternoon of Day 20 through the morning of Day 22). Except for the first dose of each period and the doses taken in the clinic on the last day of each regimen and the afternoon of Days 6, 13 and 20, all other doses will be taken by the subject as an outpatient.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 20 mg MR | Experimental | Drug: Tolvaptan MR |
| 40 mg MR | Experimental | Drug: Tolvaptan MR |
| 60 mg MR | Experimental | Drug: Tolvaptan MR |
| 120 mg MR | Experimental | Drug: Tolvaptan MR |
| 120 mg IR | Experimental | Drug: Tolvaptan IR |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Subjects (male or female) who are surgically sterile (ie, have undergone hysterectomy) or using contraception or agree to remain abstinent
- Subjects between the ages of 18 and 50, inclusive
- Subjects with a body mass index between 19 to 35 kg/m2 (inclusive)
- Subjects with a diagnosis of ADPKD by modified Ravine criteria
- Subjects must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests
Key exclusion criteria (17 listed)
- Subjects using diuretics within 14 days prior to check in on Day -1
- Subjects with incontinence, overactive bladder, or urinary retention (eg, benign prostatic hyperplasia)
- Subjects (male or female) with nocturia/urgency (outside of the 2 to 4 times awakening per night expected for ADPKD patients) at screening
- Subjects with liver disease, liver function abnormalities or serology other than that expected for ADPKD with cystic liver disease at baseline
- Subjects with clinically significant abnormality in past medical history, or at the Screening physical examination, that in the investigator's or sponsor's opinion may place the volunteer at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of drug. This includes, but is not limited to, history of or concurrent cardiac, hepatic, renal, neurologic, endocrine, gastrointestinal, respiratory, hematologic, and immunologic disease
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-4106120 mg Tolvaptan MR capsule(morning); Placebo capsules/tablets (morning and afternoon) for 7 days | Drug | 20 mg MR |
| Tolvaptan MRAlso: OPC-4106120 mg Tolvaptan MR capsule(morning and afternoon); Placebo capsules/tablets (morning and afternoon) for 7 days | Drug | 40 mg MR |
| Tolvaptan MRAlso: OPC-4106160 mg Tolvaptan MR capsule(morning); Placebo capsules/tablets (morning and afternoon) for 7 days | Drug | 60 mg MR |
| Tolvaptan IRAlso: OPC-4106190 mg Tolvaptan IR tablet(morning); 30 mg Tolvaptan IR tablet (afternoon); Placebo capsules (morning and afternoon) for 7 days | Drug | 120 mg IR |
| Tolvaptan MRAlso: OPC-41061120 mg Tolvaptan MR capsule(morning); Placebo capsules/tablets (morning and afternoon) for 7 days | Drug | 120 mg MR |
Primary outcome
Maximum (Peak) Plasma Concentration of the Drug [Cmax] and Minimum (Trough) Plasma Concentration of the Drug [Cmin] After Tolvaptan Treatment on Day 7.
Time frame: Day 7
Blood samples (6 mL) for determination of tolvaptan PK parameters were collected on Day 1 predose, and on Days 7, 14 and 21 at predose, and 1, 2, 4, 6, 8, 9, 10, 12, 16, and 24 hours postdose. If a sample was not drawn at the designated time, a window of ± 3 minutes for each blood draw was acceptable. Maximum and minimum plasma concentration of the drug was calculated.
Time to Maximum (Peak) Plasma Concentration (Tmax) After Tolvaptan Treatment on Day 7.
Time frame: Day 7
Blood samples (6 mL) for determination of tolvaptan PK parameters were collected on Day 1 predose, and on Days 7, 14 and 21 at predose, and 1, 2, 4, 6, 8, 9, 10, 12, 16, and 24 hours postdose. If a sample was not drawn at the designated time, a window of ± 3 minutes for each blood draw was acceptable. Time to maximum plasma concentration was calculated.
Area Under the Concentration-time Curve During the Dosing Interval at Steady State and Area Under the Concentration-time Curve From Time 0 to 24 Hours Postdose (AUCT & AUC0-24h) After Tolvaptan Treatment on Day 7.
Time frame: Day 7
Blood samples (6 mL) for determination of tolvaptan PK parameters were collected on Day 1 predose, and on Days 7, 14 and 21 at predose, and 1, 2, 4, 6, 8, 9, 10, 12, 16, and 24 hours postdose. If a sample was not drawn at the designated time, a window of ± 3 minutes for each blood draw was acceptable. Hence, both AUCT and AUC0-24h values were calculated.
14 secondary outcomes
Number of Participants With Urine Osmolality < 300 mOsm/kg at 23.5 Hours Postdose.
Time frame: 23.5 hours post-dose
Change From Baseline in Urine Osmolality Area Under the Concentration-time Curve From Time 0 to 24 Hours Postdose (AUC0-24h) at Day 7.
Time frame: Day 7
Change From Baseline in Urine Osmolality at Day 7.
Time frame: 0-4, 4-8, 8-12, 12-16, 16-24 Hours at Day 7
Change From Baseline in Urine Volume at 24 Hours at Day 7.
Time frame: Day 7
Change From Baseline in Urine Volume by Interval at Day 7.
Time frame: 0-4, 4-8, 8-12, 12-16, 16-24 Hours at Day 7
Duration of Urine Osmolality Less Than 300 mOsm/kg at Baseline and Day 7.
Time frame: Baseline and Day 7
Change From Baseline in Number of Urine Voids During Awake Periods.
Time frame: Days 1, 2, 3, 4, 5, 6 and 7
Change From Baseline in Number of Urine Voids During Sleep Periods.
Time frame: Days 1, 2, 3, 4, 5, 6 and 7
Change From Baseline in Symptom Burden by Autosomal Dominant Polycystic Kidney Disease (ADPKD) Nocturia Quality of Life Questionnaire at Day 6.
Time frame: Day 6
Number of Participants Experiencing Urinary Urgency Based on Urinary Urgency Questionnaire (Question 1) at Baseline and Day 6.
Time frame: Baseline and Day 6
Change From Baseline in Urinary Urgency Questionnaire (Questions 2 to 5 and Questions 7 to 14) at Day 6.
Time frame: Day 6
Number of Participants Experiencing Urinary Frequency Based on Urinary Frequency Questionnaire (Question 1) at Baseline and Day 6.
Time frame: Baseline and Day 6
Change From Baseline in Urinary Frequency Questionnaire (Question 2 and Questions 3 to 10) at Day 6.
Time frame: Day 6
Ranking of Treatment Tolerability.
Time frame: Day 22/Early Termination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 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.
- Derived from this study: PubMed 37986188Gobburu J, Ivaturi V, Wang X, Shoaf SE, Jadhav P, Perrone RD. Comparing Effects of Tolvaptan and Instruction to Increase Water Consumption in ADPKD: Post Hoc Analysis of TEMPO 3:4. Kidney360. 2023 Dec 1;4(12):1702-1707. doi: 10.34067/KID.0000000000000302. Epub 2023 Nov 21.
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RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
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.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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 6 sites in United States.
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 7 inclusion and 17 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 14 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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. 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 14 Jun 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?
Maximum (Peak) Plasma Concentration of the Drug [Cmax] and Minimum (Trough) Plasma Concentration of the Drug [Cmin] After Tolvaptan Treatment on Day 7. (time frame: Day 7). The study lists 3 primary outcomes in all. 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 NCT01210560, which also lists 2 linked publications.
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 14 Jun 2018.