End Stage Renal Disease, Hyperphosphatemia
Conditions
Brief summary
The study is designed to evaluate the ability of tenapanor alone or in combination with sevelamer to achieve serum phosphorus concentration (sP) within the population reference range (sP \>2.5 and ≤4.5 mg/dL) in patients with end-stage renal disease (ESRD) on dialysis with hyperphosphatemia (\>4.5 mg/dL).
Detailed description
Patients who complete the TEN-02-301 study (PHREEDOM) may be eligible to enroll into TEN-02-401 (NORMALIZE). Patients from the TEN-02-301 tenapanor arm will either receive only tenapanor or be given sevelamer in addition to tenapanor based on their sP. Patients from the TEN-02-301 sevelamer arm will be given tenapanor in addition to their sevelamer dose and the sevelamer dose will then be adjusted based on their sP following a protocol-specified dose titration schedule. Patients will be monitored for safety and efficacy with in-office and telephone visits for up to an additional 18 months. Laboratory assessments will be measured at every visit (Weeks 1, 2, 3, 4, 6 and 8 and Months 3, 6, 9, 12, 15 and 18) using a central laboratory. Safety assessments will be performed during the study and will include physical examinations, vital signs (blood pressure and pulse), body weights, clinical laboratory evaluations, 12-lead electrocardiograms (ECGs), and adverse event (AE) monitoring.
Interventions
DRUGTenapanor
NHE3 Inhibitor
DRUGSevelamer Carbonate
Phosphate binder
Sponsors
Ardelyx
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Must complete TEN-02-301 (PHREEDOM)
Exclusion criteria
1. Schedlued for kidney transplant 2. Life expectancy \<12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Achieving Normal Serum Phosphorus Level | 18 months | Proportion of patients with serum phosphorus between 2.5 and 4.5 mg/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Phosphorus (s-P) From TEN-02-301 (Parent Study) Baseline | up to 2.5 years | The change from the baseline s-P from the parent study until the endpoint visit which was up to 2.5 years after the baseline |
| Change From Baseline in Serum Phosphorus (of Extension Study; TEN-02-401) to Endpoint Visit | up to 18 months | Baseline upon enrollment in the 18-month long-term extension study |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tenapanor w/Sevelamer Tenapanor will be administered QD or BID and sevelamer can be added to achieve desired serum phosphorus level
Tenapanor: NHE3 Inhibitor
Sevelamer Carbonate: Phosphate binder | 111 |
| Sevelamer w/Tenapanor Sevelamer will be administered QD, BID or TID and tenapanor will be added to achieve desired serum phosphorus level and sevelamer dose will be decreased as needed
Tenapanor: NHE3 Inhibitor
Sevelamer Carbonate: Phosphate binder | 61 |
| Total | 172 |
Baseline characteristics
| Characteristic | Tenapanor w/Sevelamer | Sevelamer w/Tenapanor | Total |
|---|---|---|---|
| Age, Continuous | 55.97 years STANDARD_DEVIATION 12.146 | 58.48 years STANDARD_DEVIATION 14.028 | 56.85 years STANDARD_DEVIATION 12.861 |
| BMI | 31.90 kg/m^2 STANDARD_DEVIATION 7.36 | 29.33 kg/m^2 STANDARD_DEVIATION 7.472 | 30.98 kg/m^2 STANDARD_DEVIATION 7.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 31 Participants | 20 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 80 Participants | 41 Participants | 121 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 7 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 59 Participants | 27 Participants | 86 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 44 Participants | 31 Participants | 75 Participants |
| Region of Enrollment United States | 111 participants | 61 participants | 172 participants |
| Sex: Female, Male Female | 46 Participants | 17 Participants | 63 Participants |
| Sex: Female, Male Male | 65 Participants | 44 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 111 | 4 / 61 |
| other Total, other adverse events | 91 / 111 | 52 / 61 |
| serious Total, serious adverse events | 56 / 111 | 22 / 61 |
Outcome results
Primary
Achieving Normal Serum Phosphorus Level
Proportion of patients with serum phosphorus between 2.5 and 4.5 mg/dL
Time frame: 18 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tenapanor w/Sevelamer | Achieving Normal Serum Phosphorus Level | 36 Participants |
| Sevelamer w/Tenapanor | Achieving Normal Serum Phosphorus Level | 21 Participants |
p-value: 0.7439Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Serum Phosphorus (of Extension Study; TEN-02-401) to Endpoint Visit
Baseline upon enrollment in the 18-month long-term extension study
Time frame: up to 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tenapanor w/Sevelamer | Change From Baseline in Serum Phosphorus (of Extension Study; TEN-02-401) to Endpoint Visit | -0.47 mg/dL | Standard Deviation 2.084 |
| Sevelamer w/Tenapanor | Change From Baseline in Serum Phosphorus (of Extension Study; TEN-02-401) to Endpoint Visit | -0.57 mg/dL | Standard Deviation 2.422 |
Secondary
Change in Serum Phosphorus (s-P) From TEN-02-301 (Parent Study) Baseline
The change from the baseline s-P from the parent study until the endpoint visit which was up to 2.5 years after the baseline
Time frame: up to 2.5 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tenapanor w/Sevelamer | Change in Serum Phosphorus (s-P) From TEN-02-301 (Parent Study) Baseline | -2.00 mg/dL | Standard Deviation 2.248 |
| Sevelamer w/Tenapanor | Change in Serum Phosphorus (s-P) From TEN-02-301 (Parent Study) Baseline | -1.91 mg/dL | Standard Deviation 1.982 |