Hyperphosphatemia
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled study to evaluate the effect of tenapanor on change in s-P levels when tenapanor is administered orally, twice daily for 28 days as adjunctive therapy to ESRD subjects with hyperphosphatemia on stable phosphate binder therapy.
Detailed description
The study consists of a Screening visit; a Run-in Period of at least 2 weeks and up to 4 weeks, where existing phosphate binder treatment is maintained; and a 4-week Double-Blind Treatment Period. At Screening, a subject must be on thrice daily phosphate binder therapy and have a serum phosphate (s-P) level ≥5.5 and ≤10.0 mg/dL to qualify for entering the study. s-P will be measured at each visit during the run-in period to enable the evaluation of the s-P randomization criteria. Subjects who qualify to enroll in the study will be randomized in a 1:1 ratio to receive tenapanor or placebo while continuing their existing phosphate binder treatment. During the Double-Blind Treatment Period, subjects will receive tenapanor or placebo starting at a dose of 30 mg bid
Interventions
DRUGPlacebo
Inactive Drug
DRUGTenapanor
Active Drug
DRUGPhosphate Binder Agents
standard of care phosphate binder use at study entry was maintained throughout the entire study
Sponsors
Ardelyx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Signed and dated informed consent prior to any study specific procedures. * Males or females aged 18 to 80 years, inclusive, at Screening * Females must be non-pregnant, non-lactating and either be post-menopausal for at least -2 months, have documentation of irreversible surgical sterilization, use of acceptable -contraceptive method, or sexual abstinence, or a sterile sexual partner from Screening -until 30 days after the last subject visit. * Males must agree to avoid fathering a child (or donating sperm), and therefore be either sterile (documented) or agree to use approved methods of contraception, from the time of enrollment until 30 days after end of study. * Chronic maintenance hemodialysis (HD) 3x/week for at least 3 months or chronic maintenance peritoneal dialysis (PD) for a minimum of 6 months. * If receiving active vitamin D or calcimimetics, the dose should have been unchanged for the last 4 weeks prior to Screening. * Kt/V ≥1.2 at most recent measurement prior to Screening. * Prescribed and taking phosphate binder medication at least 3 times per day, and the prescribed dose should have been unchanged during the last 4 weeks prior to Screening. * Serum phosphorus levels must be ≥5.5 and ≤10.0 mg/dL at Screening and the end of the run-in period, analyzed at the central laboratory used in the study.
Exclusion criteria
* Severe hyperphosphatemia defined as having an s-P level \>10.0 mg/dL on phosphate-binders at any time point during routine clinical monitoring for the 3 preceding months before Screening. * Serum/plasma parathyroid hormone \>1200 pg/mL. * Clinical signs of hypovolemia at Screening as judged by the Investigator. * History of inflammatory bowel disease (IBD) or irritable bowel syndrome with diarrhea (IBS-D). * Scheduled for living donor kidney transplant or plans to relocate to another center during the study period. * Use of an investigational agent within 30 days prior to Screening. * 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). * If, in the opinion of the Investigator, the subject 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 |
|---|---|---|
| Change in Serum Phosphorus (s-P) Level From Baseline to Week 4. | 4 Weeks (28 days randomization period; from baseline to week 4) | Difference in mean change from baseline in s-P level at Week 4 between the tenapanor and placebo groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| s-P Response at Week 4 | 4 Weeks (28 days randomization period) | Achieving an s-P level \<5.5 mg/dL |
| Relative Change From Baseline in iFGF23 at Week 4 | 4 Weeks (28 days randomization period) | iFGF23 at Week 4/baseline iFGF23 - 1 |
| Relative Change From Baseline in cFGF23 at Week 4 | 4 Weeks (28 days randomization period) | cFGF23 at Week 4/baseline cFGF23 - 1 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tenapanor 30 mg BID During the Double-Blind Treatment Period, subjects will receive tenapanor starting at a dose of 30 mg bid (three 10 mg tablets each time).
Investigators may decrease or increase the dose of study medication based on s-P levels and/or gastrointestinal (GI) tolerability in 10 mg increments to a minimum of 10 mg bid or a maximum of 30 mg bid at any time during the Double-Blind Treatment Period.
Tenapanor: Active Drug
Phosphate Binder Agents: standard of care phosphate binder use at study entry was maintained throughout the entire study | 117 |
| Placebo same size, weight and appearance of experimental drug
Placebo: Inactive Drug
Phosphate Binder Agents: standard of care phosphate binder use at study entry was maintained throughout the entire study | 119 |
| Total | 236 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Run-in Period | Screen Failure | 0 | 275 |
| Treatment Period | Adverse Event | 4 | 1 |
| Treatment Period | Kidney Transplant | 1 | 1 |
| Treatment Period | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Tenapanor 30 mg BID | Placebo |
|---|---|---|---|
| Age, Continuous | 54.49 years STANDARD_DEVIATION 12.491 | 55.10 years STANDARD_DEVIATION 12.326 | 53.88 years STANDARD_DEVIATION 12.673 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 67 Participants | 37 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 167 Participants | 79 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants |
| Non-Sevelamer | 121 Participants | 60 Participants | 61 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 102 Participants | 52 Participants | 50 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 117 Participants | 57 Participants | 60 Participants |
| Serum Phosphorus >= 7.5 mg/d: | 83 Participants | 41 Participants | 42 Participants |
| Serum Phosphorus < 7.5 mg/dL | 153 Participants | 76 Participants | 77 Participants |
| Sevelamer | 115 Participants | 57 Participants | 58 Participants |
| Sex: Female, Male Female | 97 Participants | 52 Participants | 45 Participants |
| Sex: Female, Male Male | 139 Participants | 65 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 117 | 0 / 119 |
| other Total, other adverse events | 50 / 117 | 8 / 119 |
| serious Total, serious adverse events | 3 / 117 | 5 / 119 |
Outcome results
Primary
Change in Serum Phosphorus (s-P) Level From Baseline to Week 4.
Difference in mean change from baseline in s-P level at Week 4 between the tenapanor and placebo groups.
Time frame: 4 Weeks (28 days randomization period; from baseline to week 4)
Population: One patient did not receive study drug so was therefore not included in the modified ITT analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tenapanor 30 mg BID | Change in Serum Phosphorus (s-P) Level From Baseline to Week 4. | -0.84 mg/dL | Standard Error 0.131 |
| Placebo | Change in Serum Phosphorus (s-P) Level From Baseline to Week 4. | -0.19 mg/dL | Standard Error 0.13 |
p-value: 0.000499% CI: [-1.13, -0.18]Mixed Models Analysis
Secondary
Relative Change From Baseline in cFGF23 at Week 4
cFGF23 at Week 4/baseline cFGF23 - 1
Time frame: 4 Weeks (28 days randomization period)
Population: One patient did not receive study drug so was therefore not included in the modified ITT analysis
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Tenapanor 30 mg BID | Relative Change From Baseline in cFGF23 at Week 4 | 0.779 pg/mL |
| Placebo | Relative Change From Baseline in cFGF23 at Week 4 | 0.947 pg/mL |
p-value: 0.0011ANOVA
Secondary
Relative Change From Baseline in iFGF23 at Week 4
iFGF23 at Week 4/baseline iFGF23 - 1
Time frame: 4 Weeks (28 days randomization period)
Population: One patient did not receive study drug so was therefore not included in the modified ITT analysis
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Tenapanor 30 mg BID | Relative Change From Baseline in iFGF23 at Week 4 | 0.756 pg/mL |
| Placebo | Relative Change From Baseline in iFGF23 at Week 4 | 0.931 pg/mL |
p-value: 0.0027ANOVA
Secondary
s-P Response at Week 4
Achieving an s-P level \<5.5 mg/dL
Time frame: 4 Weeks (28 days randomization period)
Population: One patient did not receive study drug so was therefore not included in the modified ITT analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tenapanor 30 mg BID | s-P Response at Week 4 | 43 Participants |
| Placebo | s-P Response at Week 4 | 26 Participants |
p-value: 0.0097Cochran-Mantel-Haenszel