Trial Outcomes & Findings for A Phase 3 Study of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis (NCT NCT03427125)
NCT ID: NCT03427125
Last Updated: 2023-06-29
Results Overview
Patients with at least a 1.2 mg/dL decrease in serum phosphorus during the first 26 weeks of the study were defined as the responder population.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1559 participants
Primary outcome timeframe
12 weeks (randomized withdrawal period)
Results posted on
2023-06-29
Participant Flow
Participant milestones
| Measure |
Tenapanor 10 mg, 20 mg, 30 mg BID
During the 26-week open label part, all enrolled subjects will receive 30 mg BID doses of tenapanor. Investigators may decrease or increase the dose in 10 mg increments to a minimum of 10 g BIDor a maximum of 30 mg BID
Tenapanor: Active Drug
|
Placebo
Placebo
Placebo: Inactive Drug
|
Sevelamer Carbonate
Subjects randomized into the active control group, for safety analysis, will receive sevelamer carbonate, open label, for the entire 52-week study period. Sevelamer carbonate will be dosed based on package insert instructions (standard of care)
Sevelamer Carbonate: Active control
|
|---|---|---|---|
|
2 to 4 Week Washout Period
STARTED
|
0
|
1559
|
0
|
|
2 to 4 Week Washout Period
COMPLETED
|
0
|
564
|
0
|
|
2 to 4 Week Washout Period
NOT COMPLETED
|
0
|
995
|
0
|
|
26-Week Treatment Period
STARTED
|
423
|
0
|
141
|
|
26-Week Treatment Period
COMPLETED
|
256
|
0
|
117
|
|
26-Week Treatment Period
NOT COMPLETED
|
167
|
0
|
24
|
|
12-Week Randomized Withdrawal Period
STARTED
|
129
|
127
|
117
|
|
12-Week Randomized Withdrawal Period
COMPLETED
|
99
|
99
|
112
|
|
12-Week Randomized Withdrawal Period
NOT COMPLETED
|
30
|
28
|
5
|
|
14-Week Safety Extension
STARTED
|
222
|
0
|
112
|
|
14-Week Safety Extension
COMPLETED
|
205
|
0
|
109
|
|
14-Week Safety Extension
NOT COMPLETED
|
17
|
0
|
3
|
Reasons for withdrawal
| Measure |
Tenapanor 10 mg, 20 mg, 30 mg BID
During the 26-week open label part, all enrolled subjects will receive 30 mg BID doses of tenapanor. Investigators may decrease or increase the dose in 10 mg increments to a minimum of 10 g BIDor a maximum of 30 mg BID
Tenapanor: Active Drug
|
Placebo
Placebo
Placebo: Inactive Drug
|
Sevelamer Carbonate
Subjects randomized into the active control group, for safety analysis, will receive sevelamer carbonate, open label, for the entire 52-week study period. Sevelamer carbonate will be dosed based on package insert instructions (standard of care)
Sevelamer Carbonate: Active control
|
|---|---|---|---|
|
2 to 4 Week Washout Period
Screen failure (did not meet study entry requirements)
|
0
|
995
|
0
|
Baseline Characteristics
A Phase 3 Study of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis
Baseline characteristics by cohort
| Measure |
Tenapanor 10 mg, 20 mg, 30 mg BID
n=419 Participants
During the 26-week open label part, all enrolled subjects will receive 30 mg BID doses of tenapanor. Investigators may decrease or increase the dose in 10 mg increments to a minimum of 10 g BIDor a maximum of 30 mg BID
Tenapanor: Active Drug
|
Placebo
Placebo
Placebo: Inactive Drug
|
Sevelamer Carbonate
n=137 Participants
Subjects randomized into the active control group, for safety analysis, will receive sevelamer carbonate, open label, for the entire 52-week study period. Sevelamer carbonate will be dosed based on package insert instructions (standard of care)
Sevelamer Carbonate: Active control
|
Total
n=556 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
57.74 years
STANDARD_DEVIATION 12.639 • n=93 Participants
|
—
|
59.00 years
STANDARD_DEVIATION 12.638 • n=27 Participants
|
58.05 years
STANDARD_DEVIATION 12.639 • n=483 Participants
|
|
Sex: Female, Male
Female
|
154 Participants
n=93 Participants
|
—
|
46 Participants
n=27 Participants
|
200 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
265 Participants
n=93 Participants
|
—
|
91 Participants
n=27 Participants
|
356 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
115 Participants
n=93 Participants
|
—
|
41 Participants
n=27 Participants
|
156 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
302 Participants
n=93 Participants
|
—
|
96 Participants
n=27 Participants
|
398 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=93 Participants
|
—
|
0 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
11 Participants
n=93 Participants
|
—
|
0 Participants
n=27 Participants
|
11 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
21 Participants
n=93 Participants
|
—
|
7 Participants
n=27 Participants
|
28 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
2 Participants
n=93 Participants
|
—
|
0 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
195 Participants
n=93 Participants
|
—
|
60 Participants
n=27 Participants
|
255 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
189 Participants
n=93 Participants
|
—
|
70 Participants
n=27 Participants
|
259 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
—
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
—
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
BMI
|
31.30 kg/m^2
STANDARD_DEVIATION 7.505 • n=93 Participants
|
—
|
31.41 kg/m^2
STANDARD_DEVIATION 9.918 • n=27 Participants
|
31.33 kg/m^2
STANDARD_DEVIATION 8.159 • n=483 Participants
|
PRIMARY outcome
Timeframe: 12 weeks (randomized withdrawal period)Population: The sevalmer arm was not included in the randomized withdrawal period. They were treated as an active safety comparator.
Patients with at least a 1.2 mg/dL decrease in serum phosphorus during the first 26 weeks of the study were defined as the responder population.
Outcome measures
| Measure |
Tenapanor 10 mg, 20 mg, 30 mg BID
n=63 Participants
During the 26-week open label part, all enrolled subjects will receive 30 mg BID doses of tenapanor. Investigators may decrease or increase the dose in 10 mg increments to a minimum of 10 g BIDor a maximum of 30 mg BID
Tenapanor: Active Drug
|
Placebo
n=68 Participants
Placebo
Placebo: Inactive Drug
|
Sevelamer Carbonate
Subjects randomized into the active control group, for safety analysis, will receive sevelamer carbonate, open label, for the entire 52-week study period. Sevelamer carbonate will be dosed based on package insert instructions (standard of care)
Sevelamer Carbonate: Active control
|
|---|---|---|---|
|
Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the Responder Population
|
0.43 mg/dL
Standard Deviation 0.199
|
1.80 mg/dL
Standard Deviation 0.196
|
—
|
SECONDARY outcome
Timeframe: 12 weeks (randomized withdrawal period)Population: The sevelamer group did not participate in the randomized withdrawal period
Placebo Adjusted Change in Serum Phosphorus from the beginning to the end of the Randomized Withdrawal Period in all patients
Outcome measures
| Measure |
Tenapanor 10 mg, 20 mg, 30 mg BID
n=120 Participants
During the 26-week open label part, all enrolled subjects will receive 30 mg BID doses of tenapanor. Investigators may decrease or increase the dose in 10 mg increments to a minimum of 10 g BIDor a maximum of 30 mg BID
Tenapanor: Active Drug
|
Placebo
n=123 Participants
Placebo
Placebo: Inactive Drug
|
Sevelamer Carbonate
Subjects randomized into the active control group, for safety analysis, will receive sevelamer carbonate, open label, for the entire 52-week study period. Sevelamer carbonate will be dosed based on package insert instructions (standard of care)
Sevelamer Carbonate: Active control
|
|---|---|---|---|
|
Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the ITT Population
|
0.22 mg/dL
Standard Deviation 0.149
|
0.88 mg/dL
Standard Deviation 0.150
|
—
|
SECONDARY outcome
Timeframe: 26 weeks (open label treatment period)Population: There were no placebo during this period and the sevelamer arm was a safety comparator only
Serum Phosphorus from baseline (post washout) to end of 26 week period
Outcome measures
| Measure |
Tenapanor 10 mg, 20 mg, 30 mg BID
n=407 Participants
During the 26-week open label part, all enrolled subjects will receive 30 mg BID doses of tenapanor. Investigators may decrease or increase the dose in 10 mg increments to a minimum of 10 g BIDor a maximum of 30 mg BID
Tenapanor: Active Drug
|
Placebo
Placebo
Placebo: Inactive Drug
|
Sevelamer Carbonate
Subjects randomized into the active control group, for safety analysis, will receive sevelamer carbonate, open label, for the entire 52-week study period. Sevelamer carbonate will be dosed based on package insert instructions (standard of care)
Sevelamer Carbonate: Active control
|
|---|---|---|---|
|
Serum Phosphorus From Baseline
Baseline Serum Phosphorus
|
7.44 mg/dL
Standard Deviation 1.439
|
—
|
—
|
|
Serum Phosphorus From Baseline
End of Period serum Phosphorus
|
5.88 mg/dL
Standard Deviation 1,455
|
—
|
—
|
Adverse Events
Tenapanor 10 mg, 20 mg, 30 mg BID
Serious events: 47 serious events
Other events: 222 other events
Deaths: 12 deaths
Placebo
Serious events: 4 serious events
Other events: 2 other events
Deaths: 1 deaths
Sevelamer Carbonate
Serious events: 39 serious events
Other events: 10 other events
Deaths: 5 deaths
Serious adverse events
| Measure |
Tenapanor 10 mg, 20 mg, 30 mg BID
n=419 participants at risk
During the 26-week open label part, all enrolled subjects will receive 30 mg BID doses of tenapanor. Investigators may decrease or increase the dose in 10 mg increments to a minimum of 10 g BIDor a maximum of 30 mg BID
Tenapanor: Active Drug
|
Placebo
n=126 participants at risk
Placebo
Placebo: Inactive Drug
|
Sevelamer Carbonate
n=137 participants at risk
Subjects randomized into the active control group, for safety analysis, will receive sevelamer carbonate, open label, for the entire 52-week study period. Sevelamer carbonate will be dosed based on package insert instructions (standard of care)
Sevelamer Carbonate: Active control
|
|---|---|---|---|
|
Infections and infestations
pneumonia
|
1.4%
6/419 • Number of events 6 • 1 year
|
0.00%
0/126 • 1 year
|
5.8%
8/137 • Number of events 8 • 1 year
|
|
Infections and infestations
Cellulitis
|
1.4%
6/419 • Number of events 6 • 1 year
|
0.79%
1/126 • Number of events 1 • 1 year
|
3.6%
5/137 • Number of events 5 • 1 year
|
|
Infections and infestations
Sepsis
|
1.4%
6/419 • Number of events 6 • 1 year
|
0.79%
1/126 • Number of events 1 • 1 year
|
1.5%
2/137 • Number of events 2 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
1.9%
8/419 • Number of events 8 • 1 year
|
0.79%
1/126 • Number of events 1 • 1 year
|
3.6%
5/137 • Number of events 5 • 1 year
|
|
Metabolism and nutrition disorders
Fluid Overload
|
1.7%
7/419 • Number of events 7 • 1 year
|
0.79%
1/126 • Number of events 1 • 1 year
|
4.4%
6/137 • Number of events 6 • 1 year
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
1.2%
5/419 • Number of events 5 • 1 year
|
0.00%
0/126 • 1 year
|
3.6%
5/137 • Number of events 5 • 1 year
|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.72%
3/419 • Number of events 3 • 1 year
|
0.00%
0/126 • 1 year
|
5.1%
7/137 • Number of events 7 • 1 year
|
|
Cardiac disorders
Atrial Fibrillation
|
1.4%
6/419 • Number of events 6 • 1 year
|
0.00%
0/126 • 1 year
|
0.73%
1/137 • Number of events 1 • 1 year
|
Other adverse events
| Measure |
Tenapanor 10 mg, 20 mg, 30 mg BID
n=419 participants at risk
During the 26-week open label part, all enrolled subjects will receive 30 mg BID doses of tenapanor. Investigators may decrease or increase the dose in 10 mg increments to a minimum of 10 g BIDor a maximum of 30 mg BID
Tenapanor: Active Drug
|
Placebo
n=126 participants at risk
Placebo
Placebo: Inactive Drug
|
Sevelamer Carbonate
n=137 participants at risk
Subjects randomized into the active control group, for safety analysis, will receive sevelamer carbonate, open label, for the entire 52-week study period. Sevelamer carbonate will be dosed based on package insert instructions (standard of care)
Sevelamer Carbonate: Active control
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
53.0%
222/419 • Number of events 222 • 1 year
|
1.6%
2/126 • Number of events 2 • 1 year
|
7.3%
10/137 • Number of events 10 • 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor must approve all proposed publications.
- Publication restrictions are in place
Restriction type: OTHER