Back to resultsDose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD
Primary Purpose
Autosomal Dominant Polycystic Kidney Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tolvaptan MR
Tolvaptan MR
Tolvaptan MR
Tolvaptan IR
Tolvaptan MR
Sponsored by
About this trial
This is an interventional treatment trial for Autosomal Dominant Polycystic Kidney Disease focused on measuring Kidney Disease, Polycystic Kidney Disease
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
- Tufts-New England Medical Center
- Davita Clinical Research
- Mayo Medical Center
- University Hospitals of Cleveland/Case
- Northwest Renal Clinic Inc.
- University of Pennsylvania Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
20 mg MR
40 mg MR
60 mg MR
120 mg MR
120 mg IR
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
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)
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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?".
Full Information
NCT ID
NCT01210560
First Posted
September 21, 2010
Last Updated
May 16, 2018
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01210560
Brief Title
Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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:
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autosomal Dominant Polycystic Kidney Disease
Keywords
Kidney Disease, Polycystic Kidney Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
20 mg MR
Arm Type
Experimental
Arm Title
40 mg MR
Arm Type
Experimental
Arm Title
60 mg MR
Arm Type
Experimental
Arm Title
120 mg MR
Arm Type
Experimental
Arm Title
120 mg IR
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Tolvaptan MR
Other Intervention Name(s)
OPC-41061
Intervention Description
20 mg Tolvaptan MR capsule(morning); Placebo capsules/tablets (morning and afternoon) for 7 days
Intervention Type
Drug
Intervention Name(s)
Tolvaptan MR
Other Intervention Name(s)
OPC-41061
Intervention Description
20 mg Tolvaptan MR capsule(morning and afternoon); Placebo capsules/tablets (morning and afternoon) for 7 days
Intervention Type
Drug
Intervention Name(s)
Tolvaptan MR
Other Intervention Name(s)
OPC-41061
Intervention Description
60 mg Tolvaptan MR capsule(morning); Placebo capsules/tablets (morning and afternoon) for 7 days
Intervention Type
Drug
Intervention Name(s)
Tolvaptan IR
Other Intervention Name(s)
OPC-41061
Intervention Description
90 mg Tolvaptan IR tablet(morning); 30 mg Tolvaptan IR tablet (afternoon); Placebo capsules (morning and afternoon) for 7 days
Intervention Type
Drug
Intervention Name(s)
Tolvaptan MR
Other Intervention Name(s)
OPC-41061
Intervention Description
120 mg Tolvaptan MR capsule(morning); Placebo capsules/tablets (morning and afternoon) for 7 days
Primary Outcome Measure Information:
Title
Maximum (Peak) Plasma Concentration of the Drug [Cmax] and Minimum (Trough) Plasma Concentration of the Drug [Cmin] After Tolvaptan Treatment on Day 7.
Description
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 Frame
Day 7
Title
Time to Maximum (Peak) Plasma Concentration (Tmax) After Tolvaptan Treatment on Day 7.
Description
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.
Time Frame
Day 7
Title
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.
Description
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.
Time Frame
Day 7
Secondary Outcome Measure Information:
Title
Number of Participants With Urine Osmolality < 300 mOsm/kg at 23.5 Hours Postdose.
Description
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.
Time Frame
23.5 hours post-dose
Title
Change From Baseline in Urine Osmolality Area Under the Concentration-time Curve From Time 0 to 24 Hours Postdose (AUC0-24h) at Day 7.
Description
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.
Time Frame
Day 7
Title
Change From Baseline in Urine Osmolality at Day 7.
Description
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)
Time Frame
0-4, 4-8, 8-12, 12-16, 16-24 Hours at Day 7
Title
Change From Baseline in Urine Volume at 24 Hours at Day 7.
Description
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.
Time Frame
Day 7
Title
Change From Baseline in Urine Volume by Interval at Day 7.
Description
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.
Time Frame
0-4, 4-8, 8-12, 12-16, 16-24 Hours at Day 7
Title
Duration of Urine Osmolality Less Than 300 mOsm/kg at Baseline and Day 7.
Description
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.
Time Frame
Baseline and Day 7
Title
Change From Baseline in Number of Urine Voids During Awake Periods.
Description
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.
Time Frame
Days 1, 2, 3, 4, 5, 6 and 7
Title
Change From Baseline in Number of Urine Voids During Sleep Periods.
Description
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.
Time Frame
Days 1, 2, 3, 4, 5, 6 and 7
Title
Change From Baseline in Symptom Burden by Autosomal Dominant Polycystic Kidney Disease (ADPKD) Nocturia Quality of Life Questionnaire at Day 6.
Description
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.
Time Frame
Day 6
Title
Number of Participants Experiencing Urinary Urgency Based on Urinary Urgency Questionnaire (Question 1) at Baseline and Day 6.
Description
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.
Time Frame
Baseline and Day 6
Title
Change From Baseline in Urinary Urgency Questionnaire (Questions 2 to 5 and Questions 7 to 14) at Day 6.
Description
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.
Time Frame
Day 6
Title
Number of Participants Experiencing Urinary Frequency Based on Urinary Frequency Questionnaire (Question 1) at Baseline and Day 6.
Description
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.
Time Frame
Baseline and Day 6
Title
Change From Baseline in Urinary Frequency Questionnaire (Question 2 and Questions 3 to 10) at Day 6.
Description
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.
Time Frame
Day 6
Title
Ranking of Treatment Tolerability.
Description
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?".
Time Frame
Day 22/Early Termination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Czerwiec, M.D., Ph.D.
Organizational Affiliation
Otsuka Pharmaceutical Development & Commercialization, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Tufts-New England Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Davita Clinical Research
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Mayo Medical Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University Hospitals of Cleveland/Case
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Northwest Renal Clinic Inc.
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
University of Pennsylvania Medical Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD
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