Polycystic Kidney, Autosomal Dominant
Conditions
Brief summary
This study's purpose is to evaluate the long-term safety of open-label tolvaptan regimens to determine the maximally-tolerated dose and acquire pilot efficacy data in patients with autosomal dominant polycystic kidney disease (ADPKD).
Detailed description
Autosomal Dominant Polycystic Kidney Disease is a genetic disease classified by the formation of fluid-filled cysts in the kidneys. The accumulation of these cysts causes the kidneys to enlarge several times the normal size and leads to the eventual loss of renal function and ultimately results in renal failure in end-stage patients. This is a disease with life-threatening implications to those who have it, and their family members who may also be affected. Aside from early anti-hypertensive control and dietary protein restriction, which are presumed to offer a modest degree of protection, most surviving patients require renal replacement therapy (dialysis and transplant) and suffer from high morbidity and mortality. A rationale for use of tolvaptan in these genetic disorders has been proven, in principle, through use of a variety of animal models. In these models, tolvaptan is effective in halting or reversing the progression of this renal disease. The current study is being undertaken in order to evaluate whether tolvaptan, an oral vasopressin V2 receptor inhibitor, will maintain an adequate safety profile and show a potential clinical benefit by reducing total renal volume in the hopes of making an impact upon disease progression.
Interventions
DRUGTolvaptan
Participants were titrated to either the tolvaptan 45/15 or 60/30 mg split-dose over a 2-month Titration Period. They received the titrated dose for 34 months during the Fixed-dose Period. Following a planned off-treatment period, participants had the option to enter an Extension Period for an additional 12 months. Tolvaptan was supplied as tablets.
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Prior participation in designated tolvaptan ADPKD studies (156-04-248, 156-04-249). * Able to give Informed Consent.
Exclusion criteria
* Women who are breast feeding and females of childbearing potential who are not using acceptable contraceptive methods. * In the opinion of the study investigator or sponsor may present a safety risk. * Patients who are unlikely to adequately comply with study procedures. * Patients who at Day 1 have an estimated glomerular filtration rate (GFR) below 30 mL/min or who anticipate renal-replacement therapy within one year of study entry. * Patients having contraindications to magnetic resonance imaging (MRI) or gadolinium contrast will be eligible but will not be able to participate in MRI. * Patients taking a diuretic within 1 week of enrollment or likely to need diuretic therapy prior to Month 2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Assessments Based on Vital Signs, Electrocardiogram (ECG's), Clinical Laboratory Tests, Physical Examinations Are Reported as Adverse Events (AEs) Upon Study Physician Discretion. | AEs were recorded from screening (ICF was signed) until 7-Day follow-up | An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in a study , whether or not it was considered drug-related by the study physician. A treatment-emergent AE (TEAE) was defined as an AE that started after start of study drug treatment; or if the event was continuous from Baseline and was serious, study drug related, or resulted in death, discontinuation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose. | Baseline to Month 24 | Urine osmolality at steady state (after at least 4 days of dosing) including absolute trough prior to the second daily dose. Samples for this assessment were taken as closely coincident to PK blood sample as practical. During Weeks 1, 2, 3 and 4 of the Titration Period and at Month 6, additional samples were collected for the preceding day immediately preceding the second daily dose. These samples allowed derivation of an average nadir of spot urine osmolality concentrations at each dose level and while at steady state during extended tolvaptan administration. |
| Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime. | Baseline to Month 24 | Urine osmolality at steady state (after at least 4 days of dosing) including average of troughs (the mean urine osmolality prior to bedtime). Samples for this assessment were to be taken as closely coincident to PK blood sample as practical. During Weeks 1, 2, 3 and 4 of the Titration Period and at Month 6, additional samples were collected for the preceding day at bedtime. These samples allowed derivation of an average nadir of spot urine osmolality concentrations at each dose level and while at steady state during extended tolvaptan administration. |
| Percent Change From Baseline in Renal Volume. | Baseline to Month 36 | Total Kidney Volume (TKV) was assessed by the central magnetic resonance imaging (MRI) rater. |
| Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Baseline to Month 36 | GFR was estimated using reciprocal serum creatinine formula. The formula does not adjust for body weight or height, but this may be done to normalize to body surface area. The formula for reciprocal Serum creatinine is: 1/Pcr. (Pcr = serum creatinine concentration \[mg/dL\]). Clinic weight scales were calibrated at least yearly. |
| Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Baseline to Months 2, 6, 12, 24, 36, Extension Day 1, Extension Month 12 | Spot urine osmolality at trough was determined for urine samples collected immediately prior to morning dosing for Day 1 (Baseline), Months 2, 6, 12, 24, 36, Extension Day 1, and Extension Month 12 for all participants. Sample was taken after the first morning's void and was provided as a mid-stream, clean catch sample. During the titration period (Weeks 1, 2, 3 and 4) and at Month 6, additional samples were collected for the preceding day immediately preceding the 2nd daily dose and at bed-time. These samples allowed derivation of an average nadir of spot urine osmolality concentrations at each dose level and while at steady state during extended tolvaptan administration. At the Month 36 visit, participants were given a urine container and brought back the specimen at Extension Day 1. All participants were fasting. |
| Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose- Extension. | Baseline to Month 24 | Urine osmolality at steady state (after at least 4 days of dosing) including absolute trough prior to the second daily dose. Samples for this assessment were taken as closely coincident to PK blood sample as practical. During Weeks 1, 2, 3 and 4 of the Titration Period and at Month 6, additional samples were collected for the preceding day immediately preceding the second daily dose. These samples allowed derivation of an average nadir of spot urine osmolality concentrations at each dose level and while at steady state during extended tolvaptan administration. |
| Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime- Extension. | Baseline to Month 24 | Urine osmolality at steady state (after at least 4 days of dosing) including average of troughs (the mean urine osmolality prior to bedtime). Samples for this assessment were to be taken as closely coincident to PK blood sample as practical. During Weeks 1, 2, 3 and 4 of the Titration Period and at Month 6, additional samples were collected for the preceding day at bedtime. These samples allowed derivation of an average nadir of spot urine osmolality concentrations at each dose level and while at steady state during extended tolvaptan administration. |
| Percent Change From Baseline in Renal Volume-Extension. | Baseline to Months 2, 12, 24, 36, Extension Day 1, Extension Month 12 | TKV was assessed by the central magnetic resonance imaging (MRI) rater. |
| Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Baseline to Months 2, 6, 9, 12, 16, 20, 24, 28, 32, 36, Extension Day 1, Extension Month 12 | GFR was estimated using reciprocal serum creatinine formula. The formula does not adjust for body weight or height, but this may be done to normalize to body surface area. The formula for reciprocal Serum creatinine is: 1/Pcr. (Pcr = serum creatinine concentration \[mg/dL\]). Clinic weight scales were calibrated at least yearly. |
| Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose. | Baseline to Month 36 | Spot urine osmolality at trough was determined for urine samples collected immediately prior to morning dosing for Day 1 (Baseline), Months 2, 6, 12, 24, 36 for all participants. Sample was taken after the first morning's void and was provided as a mid-stream, clean catch sample. During the titration period (Weeks 1, 2, 3 and 4) and at Month 6, additional samples were collected for the preceding day immediately preceding the 2nd daily dose and at bed-time. These samples allowed derivation of an average nadir of spot urine osmolality concentrations at each dose level and while at steady state during extended tolvaptan administration. At the Month 36 visit, participants were given a urine container and brought back the specimen at Extension Day 1. All participants were fasting. |
| Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Baseline to Month 36 | The participants were seated and resting systolic and diastolic BP for each scheduled assessment was recorded. At each assessment, participants were categorized (based on repeated blood pressure measurements as being normotensive (MAP \< 100 mm Hg and off therapy), high normal (sBP \> 129 and or dBP \> 84 mm Hg off therapy) or hypertensive (sBP \>140 and/or dBP \> 90 mm Hg). The mean arterial pressure (MAP) was derived from these values and were not recorded (MAP = diastolic pressure + \[1/3 x pulse pressure (ie systolic - diastolic pressure)\] in mm Hg). |
| Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Baseline to Month 36 | The participants were seated and resting systolic and diastolic BP for each scheduled assessment was recorded. At each assessment, participants were categorized (based on repeated blood pressure measurements as being normotensive (MAP \< 100 mm Hg and off therapy), high normal (sBP \> 129 and or dBP \> 84 mm Hg off therapy) or hypertensive (sBP \>140 and/or dBP \> 90 mm Hg). The mean arterial pressure (MAP) was derived from these values and were not recorded (MAP = diastolic pressure + \[1/3 x pulse pressure (ie systolic - diastolic pressure)\] in mm Hg). |
| Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Baseline to Months 2, 6, 9, 12, 16, 20, 24, 28, 32, 36, Extension Day 1, Extension Month 4, Extension Month 8, Extension Month 12 | The participants were seated and resting systolic and diastolic BP for each scheduled assessment was recorded. At each assessment, participants were categorized (based on repeated blood pressure measurements as being normotensive (MAP \< 100 mm Hg and off therapy), high normal (sBP \> 129 and or dBP \> 84 mm Hg off therapy) or hypertensive (sBP \>140 and/or dBP \> 90 mm Hg). The mean arterial pressure (MAP) was derived from these values and were not recorded (MAP = diastolic pressure + \[1/3 x pulse pressure (ie systolic - diastolic pressure)\] in mm Hg). |
| Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Baseline to Months 2, 6, 9, 12, 16, 20, 24, 28, 32, 36, Extension Day 1, Extension Month 4, Extension Month 8, Extension Month 12 | The participants were seated and resting systolic and diastolic BP for each scheduled assessment was recorded. At each assessment, participants were categorized (based on repeated blood pressure measurements as being normotensive (MAP \< 100 mm Hg and off therapy), high normal (sBP \> 129 and or dBP \> 84 mm Hg off therapy) or hypertensive (sBP \>140 and/or dBP \> 90 mm Hg). The mean arterial pressure (MAP) was derived from these values and were not recorded (MAP = diastolic pressure + \[1/3 x pulse pressure (ie systolic - diastolic pressure)\] in mm Hg). |
| Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Baseline to Months 2, 6, 9, 12, 16, 20, 24, 28, 32, 36, Extension Day 1, Extension Month 4, Extension Month 8, Extension Month 12 | The participants were seated and resting systolic and diastolic BP for each scheduled assessment was recorded. At each assessment, participants were categorized (based on repeated blood pressure measurements as being normotensive (MAP \< 100 mm Hg and off therapy), high normal (sBP \> 129 and or dBP \> 84 mm Hg off therapy) or hypertensive (sBP \>140 and/or dBP \> 90 mm Hg). The mean arterial pressure (MAP) was derived from these values and were not recorded (MAP = diastolic pressure + \[1/3 x pulse pressure (ie systolic - diastolic pressure)\] in mm Hg). |
| Mean Change From Baseline in Patient-assessed Renal Pain Scale. | Baseline to Month 36 | Participants were asked the question to assess the relative level of pain attributed to their kidneys. This question was, On a scale of 0 to 10, with zero represented no pain at all and 10 represented the worst pain ever experienced, what was the worst kidney pain experienced in the last 4 months? If the latest assessment was less than 4 months prior, the question was substituted since your last visit for in the last 4 months. The same interrogator designated to this task was used throughout the study for each participant. |
| Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Baseline to Months 2, 6, 12, 24, 36, Extension Day 1, Extension Month 12 | Participants were asked the question to assess the relative level of pain attributed to their kidneys. This question was, On a scale of 0 to 10, with zero represented no pain at all and 10 represented the worst pain ever experienced, what was the worst kidney pain experienced in the last 4 months? If the latest assessment was less than 4 months prior, the question was substituted since your last visit for in the last 4 months. The same interrogator designated to this task was used throughout the study for each participant. |
| Mean Change From Baseline in Abdominal Girth Measurement. | Baseline to Month 36 | The participant had a measurement of their abdominal girth recorded. The measurement will be taken with a tape measure extending around the abdomen at the level of the iliac crests laterally and the umbilicus anteriorly. The examiner should also palpate for each kidney and liver edge, noting presence or enlargement. (By definition if the kidneys are palpable they are enlarged, the liver edge may be palpable but not enlarged). |
| Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Baseline to Extension Day 1, Extension Month 12 | The participant had a measurement of their abdominal girth recorded. The measurement will be taken with a tape measure extending around the abdomen at the level of the iliac crests laterally and the umbilicus anteriorly. The examiner should also palpate for each kidney and liver edge, noting presence or enlargement. (By definition if the kidneys are palpable they are enlarged, the liver edge may be palpable but not enlarged). |
| Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Baseline to Month 36 | The participants were seated and resting systolic and diastolic BP for each scheduled assessment was recorded. At each assessment, participants were categorized (based on repeated blood pressure measurements as being normotensive (MAP \< 100 mm Hg and off therapy), high normal (sBP \> 129 and or dBP \> 84 mm Hg off therapy) or hypertensive (sBP \>140 and/or dBP \> 90 mm Hg). The mean arterial pressure (MAP) was derived from these values and were not recorded (MAP = diastolic pressure + \[1/3 x pulse pressure (ie systolic - diastolic pressure)\] in mm Hg). |
Countries
United States
Participant flow
Recruitment details
A phase 2, multi-center, open-label trial, to determine the safety, tolerability, and efficacy study of split-dose oral regimens of tolvaptan tablets in a range of 30 to 120 mg/d in autosomal dominant polycystic kidney disease (ADPKD) participants.
Pre-assignment details
This was an open-label study with a 30-day Screening period, Titration period (Day 1 to Month 2), Fixed-dose period (Month 2 to Month 36), and Extension period (12 Months).
Participants by arm
| Arm | Count |
|---|---|
| Tolvaptan 45+15 mg Participants had received tolvaptan tablets of 45+15 mg orally twice daily during the fixed-dose period from Month 2 to Month 36 followed by a planned extension period for an additional 12 Months. | 22 |
| Tolvaptan 60+30 mg Participants had received tolvaptan tablets of 60+30 mg orally twice daily during the fixed-dose period from Month 2 to Month 36 followed by a planned extension period for an additional 12 Months. | 24 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Fixed-dose Period | Adverse Event | 2 | 1 |
| Fixed-dose Period | Lost to Follow-up | 1 | 1 |
| Fixed-dose Period | Met Withdrawal Criteria | 1 | 0 |
| Fixed-dose Period | Withdrew Consent | 0 | 1 |
Baseline characteristics
| Characteristic | Tolvaptan 45+15 mg | Tolvaptan 60+30 mg | Total |
|---|---|---|---|
| Age, Continuous | 39.3 Years STANDARD_DEVIATION 8.4 | 43.9 Years STANDARD_DEVIATION 7.8 | 41.7 Years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 16 Participants | 18 Participants | 34 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 22 | 23 / 24 |
| serious Total, serious adverse events | 3 / 22 | 8 / 24 |
Outcome results
Primary
Safety Assessments Based on Vital Signs, Electrocardiogram (ECG's), Clinical Laboratory Tests, Physical Examinations Are Reported as Adverse Events (AEs) Upon Study Physician Discretion.
An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in a study , whether or not it was considered drug-related by the study physician. A treatment-emergent AE (TEAE) was defined as an AE that started after start of study drug treatment; or if the event was continuous from Baseline and was serious, study drug related, or resulted in death, discontinuation.
Time frame: AEs were recorded from screening (ICF was signed) until 7-Day follow-up
Population: Safety dataset was defined as all participants who consumed at least 1 dose of study medication. Safety variables analyzed included physical examinations, laboratory tests, vital signs, ECG's and AEs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tolvaptan 45+15 mg | Safety Assessments Based on Vital Signs, Electrocardiogram (ECG's), Clinical Laboratory Tests, Physical Examinations Are Reported as Adverse Events (AEs) Upon Study Physician Discretion. | Participants with serious TEAEs | 3 participants |
| Tolvaptan 45+15 mg | Safety Assessments Based on Vital Signs, Electrocardiogram (ECG's), Clinical Laboratory Tests, Physical Examinations Are Reported as Adverse Events (AEs) Upon Study Physician Discretion. | Participants with severe TEAEs | 6 participants |
| Tolvaptan 45+15 mg | Safety Assessments Based on Vital Signs, Electrocardiogram (ECG's), Clinical Laboratory Tests, Physical Examinations Are Reported as Adverse Events (AEs) Upon Study Physician Discretion. | Participants discontinued due to AEs | 3 participants |
| Tolvaptan 60+30 mg | Safety Assessments Based on Vital Signs, Electrocardiogram (ECG's), Clinical Laboratory Tests, Physical Examinations Are Reported as Adverse Events (AEs) Upon Study Physician Discretion. | Participants with serious TEAEs | 8 participants |
| Tolvaptan 60+30 mg | Safety Assessments Based on Vital Signs, Electrocardiogram (ECG's), Clinical Laboratory Tests, Physical Examinations Are Reported as Adverse Events (AEs) Upon Study Physician Discretion. | Participants with severe TEAEs | 10 participants |
| Tolvaptan 60+30 mg | Safety Assessments Based on Vital Signs, Electrocardiogram (ECG's), Clinical Laboratory Tests, Physical Examinations Are Reported as Adverse Events (AEs) Upon Study Physician Discretion. | Participants discontinued due to AEs | 1 participants |
Secondary
Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension.
GFR was estimated using reciprocal serum creatinine formula. The formula does not adjust for body weight or height, but this may be done to normalize to body surface area. The formula for reciprocal Serum creatinine is: 1/Pcr. (Pcr = serum creatinine concentration \[mg/dL\]). Clinic weight scales were calibrated at least yearly.
Time frame: Baseline to Months 2, 6, 9, 12, 16, 20, 24, 28, 32, 36, Extension Day 1, Extension Month 12
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 2 (N= 17, 18) | -0.09 dL/mg | Standard Deviation 0.11 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 6 (N= 17, 16) | -0.03 dL/mg | Standard Deviation 0.11 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 9 (N= 16, 18) | -0.01 dL/mg | Standard Deviation 0.11 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 12 (N= 16, 17) | -0.03 dL/mg | Standard Deviation 0.12 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 16 (N= 17, 16) | -0.06 dL/mg | Standard Deviation 0.12 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 20 (N= 17, 18) | -0.06 dL/mg | Standard Deviation 0.1 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 24 (N= 17, 17) | -0.04 dL/mg | Standard Deviation 0.11 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 28 (N= 17, 18) | -0.06 dL/mg | Standard Deviation 0.1 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 32 (N= 17, 18) | -0.09 dL/mg | Standard Deviation 0.14 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 36 (N= 17, 18) | -0.07 dL/mg | Standard Deviation 0.11 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Extension Day 1 (N= 17, 18) | -0.04 dL/mg | Standard Deviation 0.13 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Extension Month 12 (N= 17, 18) | -0.05 dL/mg | Standard Deviation 0.17 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Extension Day 1 (N= 17, 18) | -0.01 dL/mg | Standard Deviation 0.17 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 2 (N= 17, 18) | -0.04 dL/mg | Standard Deviation 0.15 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 24 (N= 17, 17) | -0.02 dL/mg | Standard Deviation 0.14 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 6 (N= 17, 16) | -0.00 dL/mg | Standard Deviation 0.13 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 36 (N= 17, 18) | -0.05 dL/mg | Standard Deviation 0.14 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 9 (N= 16, 18) | -0.01 dL/mg | Standard Deviation 0.14 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 28 (N= 17, 18) | -0.02 dL/mg | Standard Deviation 0.14 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 12 (N= 16, 17) | -0.00 dL/mg | Standard Deviation 0.21 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Extension Month 12 (N= 17, 18) | -0.04 dL/mg | Standard Deviation 0.14 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 16 (N= 17, 16) | -0.01 dL/mg | Standard Deviation 0.13 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 32 (N= 17, 18) | -0.05 dL/mg | Standard Deviation 0.12 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension. | Month 20 (N= 17, 18) | -0.02 dL/mg | Standard Deviation 0.16 |
Secondary
Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR).
GFR was estimated using reciprocal serum creatinine formula. The formula does not adjust for body weight or height, but this may be done to normalize to body surface area. The formula for reciprocal Serum creatinine is: 1/Pcr. (Pcr = serum creatinine concentration \[mg/dL\]). Clinic weight scales were calibrated at least yearly.
Time frame: Baseline to Month 36
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 2 (N= 22, 24) | -0.09 dL/mg | Standard Deviation 0.11 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 6 (N= 19, 21) | -0.03 dL/mg | Standard Deviation 0.1 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 9 (N= 18, 23) | -0.01 dL/mg | Standard Deviation 0.12 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 12 (N= 17, 22) | -0.03 dL/mg | Standard Deviation 0.11 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 16 (N= 18, 21) | -0.06 dL/mg | Standard Deviation 0.12 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 20 (N= 18, 21) | -0.06 dL/mg | Standard Deviation 0.1 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 24 (N= 18, 20) | -0.04 dL/mg | Standard Deviation 0.1 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 28 (N= 18, 21) | -0.07 dL/mg | Standard Deviation 0.1 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 32 (N= 18, 21) | -0.09 dL/mg | Standard Deviation 0.14 |
| Tolvaptan 45+15 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 36 (N= 18, 21) | -0.07 dL/mg | Standard Deviation 0.11 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 28 (N= 18, 21) | -0.02 dL/mg | Standard Deviation 0.14 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 2 (N= 22, 24) | -0.05 dL/mg | Standard Deviation 0.13 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 20 (N= 18, 21) | -0.03 dL/mg | Standard Deviation 0.15 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 6 (N= 19, 21) | -0.01 dL/mg | Standard Deviation 0.12 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 36 (N= 18, 21) | -0.06 dL/mg | Standard Deviation 0.13 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 9 (N= 18, 23) | -0.03 dL/mg | Standard Deviation 0.13 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 24 (N= 18, 20) | -0.02 dL/mg | Standard Deviation 0.13 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 12 (N= 17, 22) | -0.01 dL/mg | Standard Deviation 0.18 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 32 (N= 18, 21) | -0.06 dL/mg | Standard Deviation 0.12 |
| Tolvaptan 60+30 mg | Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR). | Month 16 (N= 18, 21) | -0.02 dL/mg | Standard Deviation 0.12 |
Secondary
Mean Change From Baseline in Abdominal Girth Measurement.
The participant had a measurement of their abdominal girth recorded. The measurement will be taken with a tape measure extending around the abdomen at the level of the iliac crests laterally and the umbilicus anteriorly. The examiner should also palpate for each kidney and liver edge, noting presence or enlargement. (By definition if the kidneys are palpable they are enlarged, the liver edge may be palpable but not enlarged).
Time frame: Baseline to Month 36
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Abdominal Girth Measurement. | Month 6 (N= 18, 23) | 1.4 cm | Standard Deviation 6.5 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Abdominal Girth Measurement. | Month 24 (N= 17, 21) | 2.0 cm | Standard Deviation 7.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Abdominal Girth Measurement. | Month 12 (N= 18, 23) | 1.3 cm | Standard Deviation 4.7 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Abdominal Girth Measurement. | Month 36 (N= 18, 21) | 3.1 cm | Standard Deviation 7.2 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Abdominal Girth Measurement. | Month 2 (N= 22, 24) | 0.6 cm | Standard Deviation 5 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Abdominal Girth Measurement. | Month 36 (N= 18, 21) | 0.3 cm | Standard Deviation 7.3 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Abdominal Girth Measurement. | Month 2 (N= 22, 24) | -2.3 cm | Standard Deviation 6.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Abdominal Girth Measurement. | Month 6 (N= 18, 23) | 0.5 cm | Standard Deviation 4.6 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Abdominal Girth Measurement. | Month 12 (N= 18, 23) | -2.8 cm | Standard Deviation 11.5 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Abdominal Girth Measurement. | Month 24 (N= 17, 21) | -0.6 cm | Standard Deviation 6.7 |
Secondary
Mean Change From Baseline in Abdominal Girth Measurement- Extension.
The participant had a measurement of their abdominal girth recorded. The measurement will be taken with a tape measure extending around the abdomen at the level of the iliac crests laterally and the umbilicus anteriorly. The examiner should also palpate for each kidney and liver edge, noting presence or enlargement. (By definition if the kidneys are palpable they are enlarged, the liver edge may be palpable but not enlarged).
Time frame: Baseline to Extension Day 1, Extension Month 12
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Month 12 (N= 17, 18) | 1.1 cm | Standard Deviation 4.8 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Month 36 (N= 17, 18) | 2.5 cm | Standard Deviation 6.9 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Month 6 (N= 16, 18) | 0.3 cm | Standard Deviation 5.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Extension Day 1 (N= 17, 18) | 4.2 cm | Standard Deviation 7.2 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Month 24 (N= 17, 21) | 2.0 cm | Standard Deviation 7.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Extension Month 12 (N= 17, 18) | 4.6 cm | Standard Deviation 9.5 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Month 2 (N= 17, 18) | -0.8 cm | Standard Deviation 3.9 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Extension Month 12 (N= 17, 18) | 1.6 cm | Standard Deviation 6.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Month 2 (N= 17, 18) | -2.8 cm | Standard Deviation 7 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Month 6 (N= 16, 18) | 0.3 cm | Standard Deviation 5.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Month 12 (N= 17, 18) | -3.5 cm | Standard Deviation 12.9 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Month 24 (N= 17, 21) | -1.1 cm | Standard Deviation 7.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Month 36 (N= 17, 18) | 0.1 cm | Standard Deviation 7.7 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Abdominal Girth Measurement- Extension. | Extension Day 1 (N= 17, 18) | 2.9 cm | Standard Deviation 7.9 |
Secondary
Mean Change From Baseline in dBP for Hypertension Assessment- Extension.
The participants were seated and resting systolic and diastolic BP for each scheduled assessment was recorded. At each assessment, participants were categorized (based on repeated blood pressure measurements as being normotensive (MAP \< 100 mm Hg and off therapy), high normal (sBP \> 129 and or dBP \> 84 mm Hg off therapy) or hypertensive (sBP \>140 and/or dBP \> 90 mm Hg). The mean arterial pressure (MAP) was derived from these values and were not recorded (MAP = diastolic pressure + \[1/3 x pulse pressure (ie systolic - diastolic pressure)\] in mm Hg).
Time frame: Baseline to Months 2, 6, 9, 12, 16, 20, 24, 28, 32, 36, Extension Day 1, Extension Month 4, Extension Month 8, Extension Month 12
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 2 (N= 17, 18) | -5.5 mmHg | Standard Deviation 12.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 6 (N= 17, 18) | -4.5 mmHg | Standard Deviation 8.2 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 9 (N= 16, 18) | -5.3 mmHg | Standard Deviation 9.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 12 (N= 16, 18) | -10.1 mmHg | Standard Deviation 12.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 16 (N= 17, 18) | -6.9 mmHg | Standard Deviation 10.1 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 20 (N= 17, 18) | -7.5 mmHg | Standard Deviation 10 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 24 (N= 17, 18) | -3.9 mmHg | Standard Deviation 11.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 28 (N= 17, 18) | -5.6 mmHg | Standard Deviation 10.8 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 32 (N= 17, 18) | -5.4 mmHg | Standard Deviation 11 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 36 (N= 17, 18) | -5.7 mmHg | Standard Deviation 10.2 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Extension Day 1 (N= 17, 18) | -7.9 mmHg | Standard Deviation 7.3 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Extension Month 4 (N= 17, 18) | -6.8 mmHg | Standard Deviation 10.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Extension Month 8 (N= 17, 18) | -5.0 mmHg | Standard Deviation 7.9 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Extension Month 12 (N= 17, 18) | -6.0 mmHg | Standard Deviation 8.9 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Extension Day 1 (N= 17, 18) | -4.0 mmHg | Standard Deviation 10.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 2 (N= 17, 18) | 0.3 mmHg | Standard Deviation 9.7 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 28 (N= 17, 18) | -2.9 mmHg | Standard Deviation 8.4 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 6 (N= 17, 18) | -2.4 mmHg | Standard Deviation 12.6 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Extension Month 8 (N= 17, 18) | -6.7 mmHg | Standard Deviation 12.7 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 9 (N= 16, 18) | -2.9 mmHg | Standard Deviation 11.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 32 (N= 17, 18) | -3.6 mmHg | Standard Deviation 11.4 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 12 (N= 16, 18) | -1.9 mmHg | Standard Deviation 13 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Extension Month 4 (N= 17, 18) | -6.1 mmHg | Standard Deviation 10.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 16 (N= 17, 18) | -2.1 mmHg | Standard Deviation 12 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 36 (N= 17, 18) | -4.8 mmHg | Standard Deviation 14 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 20 (N= 17, 18) | -6.1 mmHg | Standard Deviation 12.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Extension Month 12 (N= 17, 18) | -5.6 mmHg | Standard Deviation 11.7 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in dBP for Hypertension Assessment- Extension. | Month 24 (N= 17, 18) | -0.6 mmHg | Standard Deviation 12.7 |
Secondary
Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment.
The participants were seated and resting systolic and diastolic BP for each scheduled assessment was recorded. At each assessment, participants were categorized (based on repeated blood pressure measurements as being normotensive (MAP \< 100 mm Hg and off therapy), high normal (sBP \> 129 and or dBP \> 84 mm Hg off therapy) or hypertensive (sBP \>140 and/or dBP \> 90 mm Hg). The mean arterial pressure (MAP) was derived from these values and were not recorded (MAP = diastolic pressure + \[1/3 x pulse pressure (ie systolic - diastolic pressure)\] in mm Hg).
Time frame: Baseline to Month 36
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 2 (N= 22, 24) | -4.0 mmHg | Standard Deviation 11.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 6 (N= 19, 23) | -3.6 mmHg | Standard Deviation 8.2 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 9 (N= 18, 23) | -4.8 mmHg | Standard Deviation 8.9 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 12 (N= 17, 23) | -9.2 mmHg | Standard Deviation 12.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 16 (N= 18, 23) | -5.6 mmHg | Standard Deviation 11.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 20 (N= 18, 21) | -7.4 mmHg | Standard Deviation 9.8 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 24 (N= 18, 21) | -3.1 mmHg | Standard Deviation 11.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 28 (N= 18, 21) | -5.3 mmHg | Standard Deviation 10.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 32 (N= 18, 21) | -4.6 mmHg | Standard Deviation 11.2 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 36 (N= 18, 21) | -5.4 mmHg | Standard Deviation 10 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 28 (N= 18, 21) | -2.2 mmHg | Standard Deviation 8.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 2 (N= 22, 24) | -0.2 mmHg | Standard Deviation 9.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 20 (N= 18, 21) | -5.6 mmHg | Standard Deviation 12.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 6 (N= 19, 23) | -2.5 mmHg | Standard Deviation 11.2 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 36 (N= 18, 21) | -4.0 mmHg | Standard Deviation 13.2 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 9 (N= 18, 23) | -2.8 mmHg | Standard Deviation 11.4 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 24 (N= 18, 21) | -0.1 mmHg | Standard Deviation 12.4 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 12 (N= 17, 23) | -1.1 mmHg | Standard Deviation 12.6 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 32 (N= 18, 21) | -3.0 mmHg | Standard Deviation 10.9 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment. | Month 16 (N= 18, 23) | -2.3 mmHg | Standard Deviation 10.7 |
Secondary
Mean Change From Baseline in MAP for Hypertension Assessment- Extension.
The participants were seated and resting systolic and diastolic BP for each scheduled assessment was recorded. At each assessment, participants were categorized (based on repeated blood pressure measurements as being normotensive (MAP \< 100 mm Hg and off therapy), high normal (sBP \> 129 and or dBP \> 84 mm Hg off therapy) or hypertensive (sBP \>140 and/or dBP \> 90 mm Hg). The mean arterial pressure (MAP) was derived from these values and were not recorded (MAP = diastolic pressure + \[1/3 x pulse pressure (ie systolic - diastolic pressure)\] in mm Hg).
Time frame: Baseline to Months 2, 6, 9, 12, 16, 20, 24, 28, 32, 36, Extension Day 1, Extension Month 4, Extension Month 8, Extension Month 12
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 2 (N= 17, 18) | -4.1 mmHg | Standard Deviation 11.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 6 (N= 17, 18) | -4.2 mmHg | Standard Deviation 7.7 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 9 (N= 16, 18) | -4.8 mmHg | Standard Deviation 9.8 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 12 (N= 17, 18) | -13.1 mmHg | Standard Deviation 18.9 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 16 (N= 17, 18) | -6.8 mmHg | Standard Deviation 10.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 20 (N= 17, 18) | -7.5 mmHg | Standard Deviation 10 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 24 (N= 17, 18) | -3.1 mmHg | Standard Deviation 13.2 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 28 (N= 17, 18) | -5.5 mmHg | Standard Deviation 11.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 32 (N= 17, 18) | -6.2 mmHg | Standard Deviation 10 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 36 (N= 17, 18) | -4.1 mmHg | Standard Deviation 9.8 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Extension Day 1 (N= 17, 18) | -6.8 mmHg | Standard Deviation 7.8 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Extension Month 4 (N= 17, 18) | -5.1 mmHg | Standard Deviation 10.7 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Extension Month 8 (N= 17, 18) | -2.8 mmHg | Standard Deviation 8.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Extension Month 12 (N= 17, 18) | -4.2 mmHg | Standard Deviation 9.3 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Extension Day 1 (N= 17, 18) | -4.4 mmHg | Standard Deviation 11 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 2 (N= 17, 18) | -0.6 mmHg | Standard Deviation 10 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 28 (N= 17, 18) | -2.9 mmHg | Standard Deviation 10.2 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 6 (N= 17, 18) | -3.4 mmHg | Standard Deviation 12.5 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Extension Month 8 (N= 17, 18) | -6.8 mmHg | Standard Deviation 12.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 9 (N= 16, 18) | -3.4 mmHg | Standard Deviation 11.5 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 32 (N= 17, 18) | -4.6 mmHg | Standard Deviation 12 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 12 (N= 17, 18) | -2.3 mmHg | Standard Deviation 12.9 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Extension Month 4 (N= 17, 18) | -6.9 mmHg | Standard Deviation 10.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 16 (N= 17, 18) | -1.9 mmHg | Standard Deviation 11.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 36 (N= 17, 18) | -5.1 mmHg | Standard Deviation 14.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 20 (N= 17, 18) | -7.2 mmHg | Standard Deviation 12.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Extension Month 12 (N= 17, 18) | -6.0 mmHg | Standard Deviation 10.9 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in MAP for Hypertension Assessment- Extension. | Month 24 (N= 17, 18) | 0.1 mmHg | Standard Deviation 12.6 |
Secondary
Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment.
The participants were seated and resting systolic and diastolic BP for each scheduled assessment was recorded. At each assessment, participants were categorized (based on repeated blood pressure measurements as being normotensive (MAP \< 100 mm Hg and off therapy), high normal (sBP \> 129 and or dBP \> 84 mm Hg off therapy) or hypertensive (sBP \>140 and/or dBP \> 90 mm Hg). The mean arterial pressure (MAP) was derived from these values and were not recorded (MAP = diastolic pressure + \[1/3 x pulse pressure (ie systolic - diastolic pressure)\] in mm Hg).
Time frame: Baseline to Month 36
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 9 (N= 18, 23) | -4.7 mmHg | Standard Deviation 9.2 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 6 (N= 19, 23) | -3.6 mmHg | Standard Deviation 7.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 24 (N= 18, 21) | -2.7 mmHg | Standard Deviation 13 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 12 (N= 18, 23) | -12.0 mmHg | Standard Deviation 18.9 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 28 (N= 18, 21) | -5.2 mmHg | Standard Deviation 11.2 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 2 (N= 22, 24) | -3.7 mmHg | Standard Deviation 10.5 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 32 (N= 18, 21) | -5.6 mmHg | Standard Deviation 10 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 16 (N= 18, 23) | -5.8 mmHg | Standard Deviation 11 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 36 (N= 18, 21) | -3.8 mmHg | Standard Deviation 9.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 20 (N= 18, 21) | -7.6 mmHg | Standard Deviation 9.7 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 36 (N= 18, 21) | -4.4 mmHg | Standard Deviation 13.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 2 (N= 22, 24) | -1.0 mmHg | Standard Deviation 10.5 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 6 (N= 19, 23) | -3.3 mmHg | Standard Deviation 11.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 9 (N= 18, 23) | -3.0 mmHg | Standard Deviation 10.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 12 (N= 18, 23) | -1.8 mmHg | Standard Deviation 12.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 16 (N= 18, 23) | -2.5 mmHg | Standard Deviation 10.6 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 20 (N= 18, 21) | -7.0 mmHg | Standard Deviation 12.3 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 24 (N= 18, 21) | -0.1 mmHg | Standard Deviation 12 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 28 (N= 18, 21) | -2.7 mmHg | Standard Deviation 10.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment. | Month 32 (N= 18, 21) | -4.3 mmHg | Standard Deviation 11.2 |
Secondary
Mean Change From Baseline in Patient-assessed Renal Pain Scale.
Participants were asked the question to assess the relative level of pain attributed to their kidneys. This question was, On a scale of 0 to 10, with zero represented no pain at all and 10 represented the worst pain ever experienced, what was the worst kidney pain experienced in the last 4 months? If the latest assessment was less than 4 months prior, the question was substituted since your last visit for in the last 4 months. The same interrogator designated to this task was used throughout the study for each participant.
Time frame: Baseline to Month 36
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale. | Month 6 (N= 19, 23) | 0.4 Units on a scale | Standard Deviation 2.8 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale. | Month 24 (N= 18, 21) | 0.2 Units on a scale | Standard Deviation 1.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale. | Month 12 (N= 18, 23) | 1.2 Units on a scale | Standard Deviation 3.3 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale. | Month 36 (N= 18, 21) | 0.6 Units on a scale | Standard Deviation 2.3 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale. | Month 2 (N= 22, 24) | 0.6 Units on a scale | Standard Deviation 3.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale. | Month 36 (N= 18, 21) | 0.5 Units on a scale | Standard Deviation 2.2 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale. | Month 2 (N= 22, 24) | 0.0 Units on a scale | Standard Deviation 1.6 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale. | Month 6 (N= 19, 23) | -0.1 Units on a scale | Standard Deviation 1.7 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale. | Month 12 (N= 18, 23) | -0.1 Units on a scale | Standard Deviation 2.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale. | Month 24 (N= 18, 21) | 1.0 Units on a scale | Standard Deviation 3.3 |
Secondary
Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension.
Participants were asked the question to assess the relative level of pain attributed to their kidneys. This question was, On a scale of 0 to 10, with zero represented no pain at all and 10 represented the worst pain ever experienced, what was the worst kidney pain experienced in the last 4 months? If the latest assessment was less than 4 months prior, the question was substituted since your last visit for in the last 4 months. The same interrogator designated to this task was used throughout the study for each participant.
Time frame: Baseline to Months 2, 6, 12, 24, 36, Extension Day 1, Extension Month 12
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Month 12 (N= 17, 18) | 1.2 Units on a scale | Standard Deviation 3.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Month 36 (N= 17, 18) | 0.6 Units on a scale | Standard Deviation 2.3 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Month 6 (N=17, 18) | 0.8 Units on a scale | Standard Deviation 2.5 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Extension Day 1 (N= 17, 18) | -0.3 Units on a scale | Standard Deviation 0.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Month 24 (N= 17, 18) | 0.2 Units on a scale | Standard Deviation 1.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Extension Month 12 (N= 17, 18) | -0.4 Units on a scale | Standard Deviation 1.3 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Month 2 (N= 17, 18) | 0.9 Units on a scale | Standard Deviation 2.7 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Extension Month 12 (N= 17, 18) | -0.6 Units on a scale | Standard Deviation 2.2 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Month 2 (N= 17, 18) | 0.3 Units on a scale | Standard Deviation 1.3 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Month 6 (N=17, 18) | -0.2 Units on a scale | Standard Deviation 1.9 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Month 12 (N= 17, 18) | -0.3 Units on a scale | Standard Deviation 2 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Month 24 (N= 17, 18) | 0.8 Units on a scale | Standard Deviation 3.3 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Month 36 (N= 17, 18) | 0.5 Units on a scale | Standard Deviation 2.4 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension. | Extension Day 1 (N= 17, 18) | 0.8 Units on a scale | Standard Deviation 2.1 |
Secondary
Mean Change From Baseline in sBP for Hypertension Assessment- Extension.
The participants were seated and resting systolic and diastolic BP for each scheduled assessment was recorded. At each assessment, participants were categorized (based on repeated blood pressure measurements as being normotensive (MAP \< 100 mm Hg and off therapy), high normal (sBP \> 129 and or dBP \> 84 mm Hg off therapy) or hypertensive (sBP \>140 and/or dBP \> 90 mm Hg). The mean arterial pressure (MAP) was derived from these values and were not recorded (MAP = diastolic pressure + \[1/3 x pulse pressure (ie systolic - diastolic pressure)\] in mm Hg).
Time frame: Baseline to Months 2, 6, 9, 12, 16, 20, 24, 28, 32, 36, Extension Day 1, Extension Month 4, Extension Month 8, Extension Month 12
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 2 (N= 17, 18) | -1.6 mmHg | Standard Deviation 13 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 6 (N= 17, 18) | -3.4 mmHg | Standard Deviation 11.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 9 (N= 16, 18) | -4.1 mmHg | Standard Deviation 13.2 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 12 (N= 17, 18) | -8.9 mmHg | Standard Deviation 14.5 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 16 (N= 17, 18) | -6.5 mmHg | Standard Deviation 14.5 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 20 (N= 17, 18) | -7.7 mmHg | Standard Deviation 11.7 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 24 (N= 17, 18) | -1.8 mmHg | Standard Deviation 18.9 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 28 (N= 17, 18) | -4.9 mmHg | Standard Deviation 14.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 32 (N= 17, 18) | -7.6 mmHg | Standard Deviation 11.1 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 36 (N= 17, 18) | -0.6 mmHg | Standard Deviation 13.5 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Extension Day 1 (N= 17, 18) | -4.4 mmHg | Standard Deviation 11.8 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Extension Month 4 (N= 17, 18) | -1.1 mmHg | Standard Deviation 16.1 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Extension Month 8 (N= 17, 18) | 1.8 mmHg | Standard Deviation 13.1 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Extension Month 12 (N= 17, 18) | -0.5 mmHg | Standard Deviation 13.5 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Extension Day 1 (N= 17, 18) | -5.1 mmHg | Standard Deviation 14.9 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 2 (N= 17, 18) | -2.7 mmHg | Standard Deviation 15 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 28 (N= 17, 18) | -3.4 mmHg | Standard Deviation 17.7 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 6 (N= 17, 18) | -5.6 mmHg | Standard Deviation 13.7 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Extension Month 8 (N= 17, 18) | -7.3 mmHg | Standard Deviation 14.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 9 (N= 16, 18) | -4.3 mmHg | Standard Deviation 13.7 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 32 (N= 17, 18) | -6.8 mmHg | Standard Deviation 16 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 12 (N= 17, 18) | -3.3 mmHg | Standard Deviation 15.5 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Extension Month 4 (N= 17, 18) | -8.7 mmHg | Standard Deviation 11.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 16 (N= 17, 18) | -1.7 mmHg | Standard Deviation 13.9 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 36 (N= 17, 18) | -5.4 mmHg | Standard Deviation 18.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 20 (N= 17, 18) | -9.3 mmHg | Standard Deviation 17.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Extension Month 12 (N= 17, 18) | -7.1 mmHg | Standard Deviation 12.2 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in sBP for Hypertension Assessment- Extension. | Month 24 (N= 17, 18) | 1.4 mmHg | Standard Deviation 15.2 |
Secondary
Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment.
The participants were seated and resting systolic and diastolic BP for each scheduled assessment was recorded. At each assessment, participants were categorized (based on repeated blood pressure measurements as being normotensive (MAP \< 100 mm Hg and off therapy), high normal (sBP \> 129 and or dBP \> 84 mm Hg off therapy) or hypertensive (sBP \>140 and/or dBP \> 90 mm Hg). The mean arterial pressure (MAP) was derived from these values and were not recorded (MAP = diastolic pressure + \[1/3 x pulse pressure (ie systolic - diastolic pressure)\] in mm Hg).
Time frame: Baseline to Month 36
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 2 (N= 22, 24) | -3.2 mmHg | Standard Deviation 12.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 6 (N= 19, 23) | -3.6 mmHg | Standard Deviation 10.8 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 9 (N= 18, 23) | -4.6 mmHg | Standard Deviation 12.5 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 12 (N= 18, 23) | -8.0 mmHg | Standard Deviation 14.6 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 16 (N= 18, 23) | -6.2 mmHg | Standard Deviation 14.2 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 20 (N= 18, 21) | -7.9 mmHg | Standard Deviation 11.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 24 (N= 18, 21) | -2.1 mmHg | Standard Deviation 18.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 28 (N= 18, 21) | -4.7 mmHg | Standard Deviation 14.2 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 32 (N= 18, 21) | -7.3 mmHg | Standard Deviation 10.9 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 36 (N= 18, 21) | -0.2 mmHg | Standard Deviation 13.2 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 28 (N= 18, 21) | -4.1 mmHg | Standard Deviation 17.1 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 2 (N= 22, 24) | -3.0 mmHg | Standard Deviation 15.4 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 20 (N= 18, 21) | -10.0 mmHg | Standard Deviation 16.4 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 6 (N= 19, 23) | -5.0 mmHg | Standard Deviation 12.4 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 36 (N= 18, 21) | -5.4 mmHg | Standard Deviation 17.6 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 9 (N= 18, 23) | -3.5 mmHg | Standard Deviation 12.5 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 24 (N= 18, 21) | -0.1 mmHg | Standard Deviation 14.7 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 12 (N= 18, 23) | -3.5 mmHg | Standard Deviation 14.2 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 32 (N= 18, 21) | -7.2 mmHg | Standard Deviation 14.8 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment. | Month 16 (N= 18, 23) | -2.9 mmHg | Standard Deviation 12.6 |
Secondary
Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime.
Urine osmolality at steady state (after at least 4 days of dosing) including average of troughs (the mean urine osmolality prior to bedtime). Samples for this assessment were to be taken as closely coincident to PK blood sample as practical. During Weeks 1, 2, 3 and 4 of the Titration Period and at Month 6, additional samples were collected for the preceding day at bedtime. These samples allowed derivation of an average nadir of spot urine osmolality concentrations at each dose level and while at steady state during extended tolvaptan administration.
Time frame: Baseline to Month 24
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime. | Month 2 (N= 21, 22) | -275.00 mOsm/kg | Standard Deviation 219.37 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime. | Month 6 (N= 19, 23) | -327.41 mOsm/kg | Standard Deviation 217.15 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime. | Month 12 (16, 18) | -283.21 mOsm/kg | Standard Deviation 230.81 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime. | Month 24 (N= 1, 7) | -263.00 mOsm/kg | — |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime. | Month 24 (N= 1, 7) | -246.00 mOsm/kg | Standard Deviation 208.5 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime. | Month 2 (N= 21, 22) | -291.09 mOsm/kg | Standard Deviation 194.88 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime. | Month 12 (16, 18) | -245.83 mOsm/kg | Standard Deviation 234.46 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime. | Month 6 (N= 19, 23) | -301.83 mOsm/kg | Standard Deviation 210.55 |
Secondary
Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime- Extension.
Urine osmolality at steady state (after at least 4 days of dosing) including average of troughs (the mean urine osmolality prior to bedtime). Samples for this assessment were to be taken as closely coincident to PK blood sample as practical. During Weeks 1, 2, 3 and 4 of the Titration Period and at Month 6, additional samples were collected for the preceding day at bedtime. These samples allowed derivation of an average nadir of spot urine osmolality concentrations at each dose level and while at steady state during extended tolvaptan administration.
Time frame: Baseline to Month 24
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime- Extension. | Month 2 (N= 17, 17) | -322.27 mOsm/kg | Standard Deviation 207.32 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime- Extension. | Month 6 (N= 17, 18) | -309.73 mOsm/kg | Standard Deviation 225.4 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime- Extension. | Month 12 (16, 15) | -283.21 mOsm/kg | Standard Deviation 230.81 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime- Extension. | Month 24 (N= 1, 6) | -263.00 mOsm/kg | — |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime- Extension. | Month 24 (N= 1, 6) | -187.50 mOsm/kg | Standard Deviation 153.04 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime- Extension. | Month 2 (N= 17, 17) | -258.88 mOsm/kg | Standard Deviation 174.51 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime- Extension. | Month 12 (16, 15) | -206.00 mOsm/kg | Standard Deviation 200.36 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime- Extension. | Month 6 (N= 17, 18) | -264.50 mOsm/kg | Standard Deviation 180.12 |
Secondary
Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose.
Spot urine osmolality at trough was determined for urine samples collected immediately prior to morning dosing for Day 1 (Baseline), Months 2, 6, 12, 24, 36 for all participants. Sample was taken after the first morning's void and was provided as a mid-stream, clean catch sample. During the titration period (Weeks 1, 2, 3 and 4) and at Month 6, additional samples were collected for the preceding day immediately preceding the 2nd daily dose and at bed-time. These samples allowed derivation of an average nadir of spot urine osmolality concentrations at each dose level and while at steady state during extended tolvaptan administration. At the Month 36 visit, participants were given a urine container and brought back the specimen at Extension Day 1. All participants were fasting.
Time frame: Baseline to Month 36
Population: The intent-to-treat (ITT) dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. Observed cases (OC) dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose. | Month 6 (N= 19, 23) | -288.42 mOsm/kg | Standard Deviation 219.55 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose. | Month 24 (N= 18, 20) | -170.17 mOsm/kg | Standard Deviation 272.21 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose. | Month 12 (N= 17, 21) | -227.29 mOsm/kg | Standard Deviation 226.63 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose. | Month 36 (N= 18, 21) | -222.50 mOsm/kg | Standard Deviation 229.91 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose. | Month 2 (N= 21, 22) | -274.10 mOsm/kg | Standard Deviation 223.14 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose. | Month 36 (N= 18, 21) | -208.90 mOsm/kg | Standard Deviation 194.19 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose. | Month 2 (N= 21, 22) | -228.00 mOsm/kg | Standard Deviation 238.19 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose. | Month 6 (N= 19, 23) | -263.78 mOsm/kg | Standard Deviation 221.05 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose. | Month 12 (N= 17, 21) | -178.43 mOsm/kg | Standard Deviation 228.43 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose. | Month 24 (N= 18, 20) | -189.75 mOsm/kg | Standard Deviation 229.33 |
Secondary
Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension.
Spot urine osmolality at trough was determined for urine samples collected immediately prior to morning dosing for Day 1 (Baseline), Months 2, 6, 12, 24, 36, Extension Day 1, and Extension Month 12 for all participants. Sample was taken after the first morning's void and was provided as a mid-stream, clean catch sample. During the titration period (Weeks 1, 2, 3 and 4) and at Month 6, additional samples were collected for the preceding day immediately preceding the 2nd daily dose and at bed-time. These samples allowed derivation of an average nadir of spot urine osmolality concentrations at each dose level and while at steady state during extended tolvaptan administration. At the Month 36 visit, participants were given a urine container and brought back the specimen at Extension Day 1. All participants were fasting.
Time frame: Baseline to Months 2, 6, 12, 24, 36, Extension Day 1, Extension Month 12
Population: The intent-to-treat (ITT) dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. Observed cases (OC) dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Month 12 (N= 16, 17) | -234.56 mOsm/kg | Standard Deviation 232.01 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Month 36 (N= 17, 18) | -234.71 mOsm/kg | Standard Deviation 230.9 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Month 6 (N= 17, 18) | -270.94 mOsm/kg | Standard Deviation 200.29 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Extension Day 1 (N= 17, 17) | -54.59 mOsm/kg | Standard Deviation 236.96 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Month 24 (N= 17, 17) | -164.06 mOsm/kg | Standard Deviation 279.32 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Extension Month 12 (N= 17, 18) | -115.59 mOsm/kg | Standard Deviation 278.19 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Month 2 (N= 17, 17) | -328.06 mOsm/kg | Standard Deviation 207.05 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Extension Month 12 (N= 17, 18) | -202.44 mOsm/kg | Standard Deviation 227.92 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Month 2 (N= 17, 17) | -176.88 mOsm/kg | Standard Deviation 225.54 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Month 6 (N= 17, 18) | -223.50 mOsm/kg | Standard Deviation 211.61 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Month 12 (N= 16, 17) | -155.65 mOsm/kg | Standard Deviation 242.53 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Month 24 (N= 17, 17) | -160.06 mOsm/kg | Standard Deviation 196.5 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Month 36 (N= 17, 18) | -196.33 mOsm/kg | Standard Deviation 175.23 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension. | Extension Day 1 (N= 17, 17) | -157.18 mOsm/kg | Standard Deviation 229.19 |
Secondary
Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose.
Urine osmolality at steady state (after at least 4 days of dosing) including absolute trough prior to the second daily dose. Samples for this assessment were taken as closely coincident to PK blood sample as practical. During Weeks 1, 2, 3 and 4 of the Titration Period and at Month 6, additional samples were collected for the preceding day immediately preceding the second daily dose. These samples allowed derivation of an average nadir of spot urine osmolality concentrations at each dose level and while at steady state during extended tolvaptan administration.
Time frame: Baseline to Month 24
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose. | Month 12 (N= 16, 20) | -288.20 mOsm/kg | Standard Deviation 216.85 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose. | Month 6 (N= 19, 23) | -321.78 mOsm/kg | Standard Deviation 242.53 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose. | Month 24 (N= 1, 7) | -405.00 mOsm/kg | — |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose. | Month 2 (N= 21, 21) | -263.95 mOsm/kg | Standard Deviation 220.4 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose. | Month 24 (N= 1, 7) | -227.14 mOsm/kg | Standard Deviation 334.13 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose. | Month 6 (N= 19, 23) | -294.13 mOsm/kg | Standard Deviation 215.95 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose. | Month 12 (N= 16, 20) | -234.65 mOsm/kg | Standard Deviation 238.82 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose. | Month 2 (N= 21, 21) | -298.71 mOsm/kg | Standard Deviation 257.53 |
Secondary
Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose- Extension.
Urine osmolality at steady state (after at least 4 days of dosing) including absolute trough prior to the second daily dose. Samples for this assessment were taken as closely coincident to PK blood sample as practical. During Weeks 1, 2, 3 and 4 of the Titration Period and at Month 6, additional samples were collected for the preceding day immediately preceding the second daily dose. These samples allowed derivation of an average nadir of spot urine osmolality concentrations at each dose level and while at steady state during extended tolvaptan administration.
Time frame: Baseline to Month 24
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose- Extension. | Month 2 (N= 17, 17) | -281.63 mOsm/kg | Standard Deviation 235.9 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose- Extension. | Month 6 (N= 17, 18) | -305.25 mOsm/kg | Standard Deviation 223.9 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose- Extension. | Month 12 (N= 16, 16) | -288.20 mOsm/kg | Standard Deviation 216.85 |
| Tolvaptan 45+15 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose- Extension. | Month 24 (N= 1, 6) | -405.00 mOsm/kg | — |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose- Extension. | Month 24 (N= 1, 6) | -120.50 mOsm/kg | Standard Deviation 196.05 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose- Extension. | Month 2 (N= 17, 17) | -254.82 mOsm/kg | Standard Deviation 217.14 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose- Extension. | Month 12 (N= 16, 16) | -190.69 mOsm/kg | Standard Deviation 201.16 |
| Tolvaptan 60+30 mg | Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose- Extension. | Month 6 (N= 17, 18) | -261.61 mOsm/kg | Standard Deviation 201.49 |
Secondary
Percent Change From Baseline in Renal Volume.
Total Kidney Volume (TKV) was assessed by the central magnetic resonance imaging (MRI) rater.
Time frame: Baseline to Month 36
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Percent Change From Baseline in Renal Volume. | Month 2 (N= 21, 24) | -1.0 Percentage change per month | Standard Deviation 5.2 |
| Tolvaptan 45+15 mg | Percent Change From Baseline in Renal Volume. | Month 12 (N= 18, 22) | 0.3 Percentage change per month | Standard Deviation 6 |
| Tolvaptan 45+15 mg | Percent Change From Baseline in Renal Volume. | Month 24 (N= 18, 21) | 4.6 Percentage change per month | Standard Deviation 8.4 |
| Tolvaptan 45+15 mg | Percent Change From Baseline in Renal Volume. | Month 36 (N= 18, 20) | 9.9 Percentage change per month | Standard Deviation 11.8 |
| Tolvaptan 60+30 mg | Percent Change From Baseline in Renal Volume. | Month 36 (N= 18, 20) | 5.3 Percentage change per month | Standard Deviation 10 |
| Tolvaptan 60+30 mg | Percent Change From Baseline in Renal Volume. | Month 2 (N= 21, 24) | -1.3 Percentage change per month | Standard Deviation 5.3 |
| Tolvaptan 60+30 mg | Percent Change From Baseline in Renal Volume. | Month 24 (N= 18, 21) | 1.0 Percentage change per month | Standard Deviation 8.3 |
| Tolvaptan 60+30 mg | Percent Change From Baseline in Renal Volume. | Month 12 (N= 18, 22) | 2.4 Percentage change per month | Standard Deviation 6.6 |
Secondary
Percent Change From Baseline in Renal Volume-Extension.
TKV was assessed by the central magnetic resonance imaging (MRI) rater.
Time frame: Baseline to Months 2, 12, 24, 36, Extension Day 1, Extension Month 12
Population: The ITT dataset was defined as a dataset that included data from all participants who enrolled to the study with observations at Baseline and Post Baseline. OC dataset were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan 45+15 mg | Percent Change From Baseline in Renal Volume-Extension. | Month 36 (N= 17, 18) | 7.9 Percentage change per month | Standard Deviation 8.7 |
| Tolvaptan 45+15 mg | Percent Change From Baseline in Renal Volume-Extension. | Month 12 (N= 17, 18) | -0.7 Percentage change per month | Standard Deviation 4.5 |
| Tolvaptan 45+15 mg | Percent Change From Baseline in Renal Volume-Extension. | Extension Day 1 (N= 17, 18) | 14.1 Percentage change per month | Standard Deviation 10.5 |
| Tolvaptan 45+15 mg | Percent Change From Baseline in Renal Volume-Extension. | Month 2 (N= 17, 18) | -1.3 Percentage change per month | Standard Deviation 5.4 |
| Tolvaptan 45+15 mg | Percent Change From Baseline in Renal Volume-Extension. | Extension Month 12 (N= 17, 18) | 15.7 Percentage change per month | Standard Deviation 12.7 |
| Tolvaptan 45+15 mg | Percent Change From Baseline in Renal Volume-Extension. | Month 24 (N= 17, 18) | 3.2 Percentage change per month | Standard Deviation 6 |
| Tolvaptan 60+30 mg | Percent Change From Baseline in Renal Volume-Extension. | Extension Month 12 (N= 17, 18) | 10.7 Percentage change per month | Standard Deviation 10.4 |
| Tolvaptan 60+30 mg | Percent Change From Baseline in Renal Volume-Extension. | Month 2 (N= 17, 18) | -1.4 Percentage change per month | Standard Deviation 3.9 |
| Tolvaptan 60+30 mg | Percent Change From Baseline in Renal Volume-Extension. | Month 12 (N= 17, 18) | 1.9 Percentage change per month | Standard Deviation 5.7 |
| Tolvaptan 60+30 mg | Percent Change From Baseline in Renal Volume-Extension. | Month 36 (N= 17, 18) | 3.8 Percentage change per month | Standard Deviation 7.4 |
| Tolvaptan 60+30 mg | Percent Change From Baseline in Renal Volume-Extension. | Extension Day 1 (N= 17, 18) | 8.4 Percentage change per month | Standard Deviation 7.9 |
| Tolvaptan 60+30 mg | Percent Change From Baseline in Renal Volume-Extension. | Month 24 (N= 17, 18) | 0.2 Percentage change per month | Standard Deviation 7.2 |