Chronic Kidney Disease Stage 5, End Stage Renal Disease, ESRD
Conditions
Keywords
Hemodialysis
Brief summary
The purpose of this study is to determine if the study drug is safe, tolerable and active in reducing fluid overload/weight gain between dialysis sessions for patients with End Stage Renal Disease on Hemodialysis.
Detailed description
This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacodynamics of the study drug in male and female patients with end-stage renal disease on hemodialysis. The study consists of a 2 week treatment-free run-in period where entry criteria are verified, a 4-week treatment period, of which the first week of treatment will be performed as an in-patient study in a clinical pharmacology unit (CPU) and the remaining three weeks of treatment will performed as an out-patient study, and a 2-week treatment-free follow-up period. Safety assessments will be performed at regular intervals and will include clinical and vital signs, clinical laboratory evaluations, ECGs, and AE monitoring. Pharmacodynamic assessments will include, but are not limited to, interdialytic weight gain (IDWG), blood pressure, and stool sodium excretion. Pharmacokinetic assessments will include blood sampling for measurement of study drug plasma concentrations.
Interventions
DRUGAZD1722 (in-patient)
doses between 5 and 60 mg BID may be administered based on tolerability in a CPU setting
DRUGPlacebo (in-patient)
Placebo, size and color matched to experimental drug administered in a CPU
DRUGAZD1722 (out-patient)
doses between 5 and 45 mg BID
DRUGPlacebo
Placebo, size and color matched to experimental drug
Sponsors
AstraZeneca
Ardelyx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Males or females aged 18 to 80 years, inclusive; * Body mass index between 18 and 45 kg/m2, inclusive; * Ambulatory (≥ 6 months) maintenance hemodialysis; * Stable dialysis treatment regimen 3x/week for ≥ 2 months prior to screening visit.
Exclusion criteria
* Currently taking diuretic medication; * Has a urine production of ≥ 200 ml/day (based on a 24-hour measurement starting on Day -1 and completed prior to randomization); * Predialysis systolic BP \>200 mmHg or diastolic BP \>110 mmHg on two successive occasions during the 2-week run-in period; * Predialysis SBP \< 110 mmHg on two successive occasions during the 2-week run-in period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Weekly Interdialytic Weight Gain (IDWG) | Run-in period (Weeks -2 and -1) versus Week 4 (end of treatment) | Patients are weighed pre dialysis prior to their first dialysis of the week. This measure looks at the change in pre-dialysis weight over time |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stool Sodium Content | Days 1 through 7 | The amount of sodium in a days worth of stool output |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AZD1722- in Patient Tenapanor administered in a clinical pharmacology unit
AZD1722 (in-patient): doses between 5 and 60 mg BID may be administered based on tolerability in a CPU setting | 8 |
| Placebo- in Patient Placebo (size and color matched to experimental drug) administered in a clinical pharmacology unit
Placebo (in-patient): Placebo, size and color matched to experimental drug administered in a CPU | 8 |
| AZD1722 Out-patient Tenapanor
AZD1722 (out-patient): doses between 5 and 45 mg BID | 37 |
| Placebo Out-patient Placebo
Placebo: Placebo, size and color matched to experimental drug | 35 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 2 |
| Overall Study | relocation | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | AZD1722- in Patient | Placebo- in Patient | AZD1722 Out-patient | Placebo Out-patient | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.9 years STANDARD_DEVIATION 8.3 | 54.4 years STANDARD_DEVIATION 6.5 | 51.5 years STANDARD_DEVIATION 11.5 | 49.3 years STANDARD_DEVIATION 11.8 | 50.6 years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 13 Participants | 10 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 8 Participants | 24 Participants | 25 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 172.89 centimeters STANDARD_DEVIATION 9.31 | 172.05 centimeters STANDARD_DEVIATION 16.48 | 170.23 centimeters STANDARD_DEVIATION 10.8 | 170.20 centimeters STANDARD_DEVIATION 10.39 | 170.63 centimeters STANDARD_DEVIATION 10.84 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 6 Participants | 14 Participants | 19 Participants | 45 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 18 Participants | 16 Participants | 38 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 13 Participants | 15 Participants | 33 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 24 Participants | 20 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 37 | 0 / 35 |
| other Total, other adverse events | 6 / 8 | 2 / 8 | 3 / 37 | 21 / 35 |
| serious Total, serious adverse events | 0 / 8 | 3 / 8 | 2 / 37 | 1 / 35 |
Outcome results
Primary
Change in Mean Weekly Interdialytic Weight Gain (IDWG)
Patients are weighed pre dialysis prior to their first dialysis of the week. This measure looks at the change in pre-dialysis weight over time
Time frame: Run-in period (Weeks -2 and -1) versus Week 4 (end of treatment)
Population: The out-patient arms were the only groups that were pre-specified to be included in this analysis since the in-patient arms were only treated for one week.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1722 Out-patient | Change in Mean Weekly Interdialytic Weight Gain (IDWG) | -0.26 kilograms | Standard Deviation 0.939 |
| Placebo Out-patient | Change in Mean Weekly Interdialytic Weight Gain (IDWG) | -0.23 kilograms | Standard Deviation 0.871 |
Comparison: AZD1722 in-patient and Placebo in-patient are not included in this analysis since it was only a one week evaluation period and an effect was not expected. Also the size (n=8) of the group was too small to .perform this analysis.p-value: 0.46ANCOVA
Secondary
Stool Sodium Content
The amount of sodium in a days worth of stool output
Time frame: Days 1 through 7
Population: The in-patient arms were the only groups pre-specified to be used in this analysis since stool could only be collected in the clinical pharmacology unit (in-patient).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1722 Out-patient | Stool Sodium Content | 36.62 mEq/day | Standard Deviation 21.809 |
| Placebo Out-patient | Stool Sodium Content | 2.82 mEq/day | Standard Deviation 2.655 |
Comparison: AZD1722 out-patient and Placebo out-patient were not included in this analysis since stool was only collected in the clinical pharmacology unit of the in-patient groups.p-value: <0.0001t-test, 2 sided