Trial Outcomes & Findings for Study to Evaluate the Efficacy of Tenapanor as Adjunctive Therapy to Phosphate Binder Therapy (NCT NCT03824587)
NCT ID: NCT03824587
Last Updated: 2023-03-06
Results Overview
Difference in mean change from baseline in s-P level at Week 4 between the tenapanor and placebo groups.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
236 participants
Primary outcome timeframe
4 Weeks (28 days randomization period; from baseline to week 4)
Results posted on
2023-03-06
Participant Flow
Participant milestones
| Measure |
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
|
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
|
|---|---|---|
|
Run-in Period
STARTED
|
0
|
511
|
|
Run-in Period
COMPLETED
|
0
|
236
|
|
Run-in Period
NOT COMPLETED
|
0
|
275
|
|
Treatment Period
STARTED
|
117
|
119
|
|
Treatment Period
COMPLETED
|
112
|
116
|
|
Treatment Period
NOT COMPLETED
|
5
|
3
|
Reasons for withdrawal
| Measure |
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
|
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
|
|---|---|---|
|
Run-in Period
Screen Failure
|
0
|
275
|
|
Treatment Period
Adverse Event
|
4
|
1
|
|
Treatment Period
Withdrawal by Subject
|
0
|
1
|
|
Treatment Period
Kidney Transplant
|
1
|
1
|
Baseline Characteristics
Study to Evaluate the Efficacy of Tenapanor as Adjunctive Therapy to Phosphate Binder Therapy
Baseline characteristics by cohort
| Measure |
Tenapanor 30 mg BID
n=117 Participants
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
|
Placebo
n=119 Participants
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
|
Total
n=236 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.10 years
STANDARD_DEVIATION 12.326 • n=5 Participants
|
53.88 years
STANDARD_DEVIATION 12.673 • n=7 Participants
|
54.49 years
STANDARD_DEVIATION 12.491 • n=5 Participants
|
|
Sex: Female, Male
Female
|
52 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
97 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
65 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
139 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
37 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
79 Participants
n=5 Participants
|
88 Participants
n=7 Participants
|
167 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
52 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
102 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
57 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
117 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Serum Phosphorus < 7.5 mg/dL
|
76 Participants
n=5 Participants
|
77 Participants
n=7 Participants
|
153 Participants
n=5 Participants
|
|
Serum Phosphorus >= 7.5 mg/d:
|
41 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
83 Participants
n=5 Participants
|
|
Sevelamer
|
57 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
115 Participants
n=5 Participants
|
|
Non-Sevelamer
|
60 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
121 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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
Difference in mean change from baseline in s-P level at Week 4 between the tenapanor and placebo groups.
Outcome measures
| Measure |
Tenapanor 30 mg BID
n=116 Participants
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
|
Placebo
n=119 Participants
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
|
|---|---|---|
|
Change in Serum Phosphorus (s-P) Level From Baseline to Week 4.
|
-0.84 mg/dL
Standard Error 0.131
|
-0.19 mg/dL
Standard Error 0.130
|
SECONDARY outcome
Timeframe: 4 Weeks (28 days randomization period)Population: One patient did not receive study drug so was therefore not included in the modified ITT analysis
Achieving an s-P level \<5.5 mg/dL
Outcome measures
| Measure |
Tenapanor 30 mg BID
n=116 Participants
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
|
Placebo
n=119 Participants
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
|
|---|---|---|
|
s-P Response at Week 4
|
43 Participants
|
26 Participants
|
SECONDARY outcome
Timeframe: 4 Weeks (28 days randomization period)Population: One patient did not receive study drug so was therefore not included in the modified ITT analysis
iFGF23 at Week 4/baseline iFGF23 - 1
Outcome measures
| Measure |
Tenapanor 30 mg BID
n=116 Participants
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
|
Placebo
n=119 Participants
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
|
|---|---|---|
|
Relative Change From Baseline in iFGF23 at Week 4
|
0.756 pg/mL
Interval 0.686 to 0.834
|
0.931 pg/mL
Interval 0.845 to 1.025
|
SECONDARY outcome
Timeframe: 4 Weeks (28 days randomization period)Population: One patient did not receive study drug so was therefore not included in the modified ITT analysis
cFGF23 at Week 4/baseline cFGF23 - 1
Outcome measures
| Measure |
Tenapanor 30 mg BID
n=115 Participants
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
|
Placebo
n=119 Participants
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
|
|---|---|---|
|
Relative Change From Baseline in cFGF23 at Week 4
|
0.779 pg/mL
Interval 0.716 to 0.848
|
0.947 pg/mL
Interval 0.871 to 1.03
|
Adverse Events
Tenapanor 30 mg BID
Serious events: 3 serious events
Other events: 50 other events
Deaths: 0 deaths
Placebo
Serious events: 5 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tenapanor 30 mg BID
n=117 participants at risk
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
|
Placebo
n=119 participants at risk
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
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Edema
|
0.85%
1/117 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
0.84%
1/119 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
0.00%
0/117 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
0.84%
1/119 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Edema
|
0.85%
1/117 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
0.00%
0/119 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
|
Cardiac disorders
Cardiorespiratory Arrest
|
0.85%
1/117 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
0.00%
0/119 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
|
Cardiac disorders
Nodal Arrhythmia
|
0.00%
0/117 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
0.84%
1/119 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
|
Injury, poisoning and procedural complications
Arteriovenous Fistula Aneurysm
|
0.00%
0/117 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
0.84%
1/119 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
|
Infections and infestations
Pneumonia
|
0.00%
0/117 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
0.84%
1/119 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
Other adverse events
| Measure |
Tenapanor 30 mg BID
n=117 participants at risk
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
|
Placebo
n=119 participants at risk
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
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
42.7%
50/117 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
6.7%
8/119 • Adverse events were collected for the 4 week (28 days) treatment period.
Adverse events were NOT collected during the run-in period since patients were receiving standard of care; any changes to health status during bhis period were reported in the medical history prior to randomization. The safety analysis includes all patients randomized (whether they received study drug or not).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60