Chronic Kidney Disease Requiring Chronic Dialysis, Hyperphosphatemia
Conditions
Keywords
hyperphosphatemia
Brief summary
This is a randomized, open-label study to evaluate different methods of initiating tenapanor therapy in CKD patients on dialysis with hyperphosphatemia, when they are either phosphate binder naïve or on phosphate binder therapy. The objective to evaluate the effect of tenapanor alone or in combination with phosphate binders to achieve target serum phosphorus (s-P) levels of ≤5.5 mg/dL when tenapanor is administered as the core therapy (alone or in combination with phosphate binders) for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis.
Detailed description
Approximately 330 CKD patients on dialysis with hyperphosphatemia (\>4.5 mg/dL) will be enrolled in this study. This is a randomized, open-label study to evaluate different methods of initiating tenapanor therapy in CKD patients on dialysis with hyperphosphatemia, when they are either phosphate binder naïve or on phosphate binder therapy. The study consists of a Screening visit and a 10-week open-label Treatment Period (TP), for which * Patients with s-P \>5.5 and ≤10.0 mg/dL under stable phosphate binder treatment are randomized in a 1:1 ratio to two different treatment cohorts: * Cohort 1 (straight switch), which stops taking phosphate binders and is started on tenapanor 30 mg twice daily (BID) at Visit 2 (Day 1); * Cohort 2, which decreases phosphate binder dose by at least 50% (may be more than 50% if patient is taking an odd number of binder pills each day), with ability to switch the binder regimen from thrice daily (TID) to BID or QD; and initiates tenapanor 30 mg BID at Visit 2 (Day 1). * Phosphate binder naïve patients with s-P \>4.5 and ≤10.0 mg/dL are enrolled as Cohort 3 and receive tenapanor at Visit 2 (Day 1) with a starting dose of 30 mg BID. * Patients on phosphate binder therapy must receive phosphate binder(s) thrice daily, and both the s-P level assessed at the most recent measurement prior to the Screening visit (Visit 1) and the s-P level assessed at the Screening visit (Visit 1) must be \>5.5 and ≤10.0 mg/dL to qualify for randomization into Cohort 1 or Cohort 2 at Visit 2 (Day 1). * Phosphate binder naïve patients must have the s-P level assessed at the Screening visit (Visit 1) \>4.5 and ≤10.0 mg/dL to qualify for enrollment into Cohort 3 at Visit 2 (Day 1). Patients who do not meet the randomization/enrollment criteria on s-P will be discontinued as screen failures. During the TP, patients will receive tenapanor starting at a dose of 30 mg twice daily. Tenapanor will be taken twice daily; just prior to breakfast and dinner. The Investigator may titrate the dose of tenapanor in 10 mg increments down to a minimum of 10 mg QD or up to a maximum of 30 mg BID at any time during the study based on s-P levels and/or gastrointestinal (GI) tolerability.
Interventions
DRUGTenapanor
Use of tenapanor
Sponsors
Ardelyx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Signed and dated informed consent form prior to any study specific procedures. 2. Males or females aged 18 to 80 years, inclusive, at Screening (Visit 1). 3. Females must be non-pregnant and non-lactating. 4. Patients on phosphate binder therapy must be on chronic maintenance hemodialysis (HD) 3 times per week for at least 3 months or chronic maintenance peritoneal dialysis (PD) for a minimum of 6 months. If modality of dialysis has changed, the patient must meet one of the two dialysis criteria above and been on the new modality of dialysis for a minimum of one month. Phosphate binder naïve patients must be on chronic maintenance HD 3 times per week or chronic maintenance PD. 5. Kt/V ≥1.2 at most recent measurement prior to Screening (Visit 1). 6. Prescribed and taking phosphate binder medication at least 3 times per day or being phosphate binder naïve; defined as having not taken phosphate binders for at least 3 months prior to Screening. The patient must be taking a minimum of 6 pills per day for Renvela, Auryxia, or PhosLo; and/or a minimum of 3 pills per day for Fosrenol or Velphoro. 7. For patients taking phosphate binders, both the s-P level at the most recent measurement prior to Screening (Visit 1) and the s-P level at Screening (Visit 1) must be \>5.5 and ≤10.0 mg/dL. 8. For phosphate binder naïve patients, the s-P level at Screening (Visit 1) must be \>4.5 and ≤10.0 mg/dL. 9. Able to understand and comply with the protocol.
Exclusion criteria
1. Severe hyperphosphatemia defined as having an s-P level \>10.0 mg/dL at any time point during routine clinical monitoring for the 3 preceding months before Screening (Visit 1). 2. Serum/plasma PTH \>1200 pg/mL. The most recent value from the patient's medical records should be used. 3. Clinical signs of hypovolemia at Screening (Visit 1) as judged by the Investigator. 4. History of inflammatory bowel disease or irritable bowel syndrome with diarrhea. 5. Scheduled for living donor kidney transplant or plans to relocate to another center during the study. 6. Use of an investigational agent within 30 days prior to Screening (Visit 1). 7. Involvement in the planning and/or conduct of the study (applies to both Ardelyx/Contract Research Organization (CRO) staff and/or staff at the study site). 8. If, in the opinion of the Investigator, the patient is unable or unwilling to fulfill the requirements of the protocol or has a condition which would render the results uninterpretable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Tenapanor to Achieve Target s-P Levels of Less Than or Equal to 5.5 mg/dL | 10 weeks | To evaluate the effect of tenapanor alone or in combination with phosphate binders to achieve target serum phosphorus (s-P) levels of ≤5.5 mg/dL when tenapanor is administered as the core therapy for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Effect of Tenapanor to Achieve Various s-P Levels ≤4.5 mg/dL | 10 weeks | Evaluating the ability of different treatment regimens to lower s-P to different levels |
| To Evaluate the Effect of Tenapanor on Reducing Daily Phosphorus-lowering Therapy Pill Burden. | 10 weeks | Evaluating the ability of tenapanor to make the phosphate lowering treatment regimen better for patients by evaluating the change in pill weight or pill number from baseline to the end of the 10-week treatment period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Phosphate binders are stopped and tenapanor is started immediately upon enrollment | 151 |
| Cohort 2 Phosphate binder dose is decreased by at least 50% and tenapanor is initiated | 152 |
| Cohort 3: Phosphate Binder Naïve Phosphate binder naive patients are enrolled as Cohort 3 and receive tenapanor with a starting dose of 30 mg/BID
Tenapanor: Use of tenapanor | 30 |
| Total | 333 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3: Phosphate Binder Naïve | Total |
|---|---|---|---|---|
| Age, Continuous | 52.3 years STANDARD_DEVIATION 11.05 | 53.3 years STANDARD_DEVIATION 12.16 | 55.4 years STANDARD_DEVIATION 16.52 | 53.0 years STANDARD_DEVIATION 12.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 42 Participants | 38 Participants | 13 Participants | 93 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 109 Participants | 114 Participants | 17 Participants | 240 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 6 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 3 Participants | 0 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 66 Participants | 71 Participants | 9 Participants | 146 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 4 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 64 Participants | 62 Participants | 20 Participants | 146 Participants |
| Sex: Female, Male Female | 44 Participants | 50 Participants | 12 Participants | 106 Participants |
| Sex: Female, Male Male | 107 Participants | 102 Participants | 18 Participants | 227 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 151 | 1 / 152 | 0 / 30 |
| other Total, other adverse events | 59 / 151 | 64 / 152 | 10 / 30 |
| serious Total, serious adverse events | 20 / 151 | 26 / 152 | 4 / 30 |
Outcome results
Primary
Effect of Tenapanor to Achieve Target s-P Levels of Less Than or Equal to 5.5 mg/dL
To evaluate the effect of tenapanor alone or in combination with phosphate binders to achieve target serum phosphorus (s-P) levels of ≤5.5 mg/dL when tenapanor is administered as the core therapy for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis.
Time frame: 10 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Straight Switch | Effect of Tenapanor to Achieve Target s-P Levels of Less Than or Equal to 5.5 mg/dL | 52 Participants |
| Cohort 2: Decrease Phosphate Binder by 50% | Effect of Tenapanor to Achieve Target s-P Levels of Less Than or Equal to 5.5 mg/dL | 58 Participants |
| Cohort 3: Phosphate Binder Naive | Effect of Tenapanor to Achieve Target s-P Levels of Less Than or Equal to 5.5 mg/dL | 19 Participants |
Secondary
To Evaluate the Effect of Tenapanor on Reducing Daily Phosphorus-lowering Therapy Pill Burden.
Evaluating the ability of tenapanor to make the phosphate lowering treatment regimen better for patients by evaluating the change in pill weight or pill number from baseline to the end of the 10-week treatment period.
Time frame: 10 weeks
Population: Cohort 3 is not included since they are medication naive so there is no baseline pill weight
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Straight Switch | To Evaluate the Effect of Tenapanor on Reducing Daily Phosphorus-lowering Therapy Pill Burden. | -6262 mg | Standard Deviation 6149.7 |
| Cohort 2: Decrease Phosphate Binder by 50% | To Evaluate the Effect of Tenapanor on Reducing Daily Phosphorus-lowering Therapy Pill Burden. | -3290 mg | Standard Deviation 5263.4 |
Secondary
To Evaluate the Effect of Tenapanor to Achieve Various s-P Levels ≤4.5 mg/dL
Evaluating the ability of different treatment regimens to lower s-P to different levels
Time frame: 10 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Straight Switch | To Evaluate the Effect of Tenapanor to Achieve Various s-P Levels ≤4.5 mg/dL | 18 Participants |
| Cohort 2: Decrease Phosphate Binder by 50% | To Evaluate the Effect of Tenapanor to Achieve Various s-P Levels ≤4.5 mg/dL | 23 Participants |
| Cohort 3: Phosphate Binder Naive | To Evaluate the Effect of Tenapanor to Achieve Various s-P Levels ≤4.5 mg/dL | 13 Participants |