Trial Outcomes & Findings for An 8-Week Study to Evaluate Tenapanor in the Treatment of Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD) (NCT NCT02675998)

Last Updated: 2020-08-10

Results Overview

Serum phosphorus difference between placebo and tenapanor in the change from the end of the 8 week treatment period to the end of the randomized withdrawal period in Efficacy Analysis Set. The efficacy analysis was pre-defined to be a pooled analysis of all tenapanor treated patients with a minimum of a 1.2 mg/dL decrease in serum phosphorus during the 8-week treatment period

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

219 participants

Primary outcome timeframe

4 weeks

Results posted on

2020-08-10

Participant Flow

Participant milestones

Participant milestones
Measure	3mg BID Tenapanor, 3mg BID (6mg total) Tenapanor	10mg BID Tenapanor, 10mg BID (20mg total) Tenapanor	30 mg Dose Titration Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question Tenapanor	Randomized Withdrawal Period Placebo These were participants re-randomized to placebo during the 4-week withdrawal period.
8-Week Treatment Period STARTED	74	73	72	0
8-Week Treatment Period COMPLETED	57	54	53	0
8-Week Treatment Period NOT COMPLETED	17	19	19	0
4-Week Randomized Withdrawal Period STARTED	25	23	34	82
4-Week Randomized Withdrawal Period COMPLETED	24	22	32	74
4-Week Randomized Withdrawal Period NOT COMPLETED	1	1	2	8

Reasons for withdrawal

Reasons for withdrawal
Measure	3mg BID Tenapanor, 3mg BID (6mg total) Tenapanor	10mg BID Tenapanor, 10mg BID (20mg total) Tenapanor	30 mg Dose Titration Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question Tenapanor	Randomized Withdrawal Period Placebo These were participants re-randomized to placebo during the 4-week withdrawal period.
8-Week Treatment Period Adverse Event	6	5	6	0
8-Week Treatment Period Withdrawal by Subject	3	3	3	0
8-Week Treatment Period Lack of Efficacy	2	5	3	0
8-Week Treatment Period Physician Decision	1	0	2	0
8-Week Treatment Period GI side Effects	1	4	2	0
8-Week Treatment Period Protocol Violation	1	1	1	0
8-Week Treatment Period Other	3	1	2	0
4-Week Randomized Withdrawal Period Lack of Efficacy	0	1	1	3
4-Week Randomized Withdrawal Period Adverse Event	0	0	1	3
4-Week Randomized Withdrawal Period Protocol Violation	0	0	0	1
4-Week Randomized Withdrawal Period Physician Decision	1	0	0	0
4-Week Randomized Withdrawal Period Withdrawal by Subject	0	0	0	1

Baseline Characteristics

An 8-Week Study to Evaluate Tenapanor in the Treatment of Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	3mg BID n=74 Participants Tenapanor, 3mg BID (6mg total)	10mg BID n=73 Participants Tenapanor, 10mg BID (20mg total)	Dose Titration n=72 Participants Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question	Placebo Placebo Placebo	Total n=219 Participants Total of all reporting groups
Age, Continuous	55.7 years STANDARD_DEVIATION 11.49 • n=5 Participants	57.4 years STANDARD_DEVIATION 10.81 • n=7 Participants	54.2 years STANDARD_DEVIATION 10.87 • n=5 Participants	—	55.8 years STANDARD_DEVIATION 11.09 • n=21 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	39 Participants n=7 Participants	24 Participants n=5 Participants	—	91 Participants n=21 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	34 Participants n=7 Participants	48 Participants n=5 Participants	—	128 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants	—	40 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	61 Participants n=5 Participants	65 Participants n=7 Participants	53 Participants n=5 Participants	—	179 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	—	2 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	—	4 Participants n=21 Participants
Race (NIH/OMB) Black or African American	40 Participants n=5 Participants	45 Participants n=7 Participants	40 Participants n=5 Participants	—	125 Participants n=21 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	25 Participants n=7 Participants	31 Participants n=5 Participants	—	86 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Body Mass Index	32.5 m/kg^2 STANDARD_DEVIATION 8.52 • n=5 Participants	33.6 m/kg^2 STANDARD_DEVIATION 8.50 • n=7 Participants	33.4 m/kg^2 STANDARD_DEVIATION 8.15 • n=5 Participants	—	33.1 m/kg^2 STANDARD_DEVIATION 8.37 • n=21 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: Patients who completed the first 8-weeks and had a minimum of a 1.2 mg/dL decrease in serum phosphorus were included in the analysis. Also, it was a pre-specificied pooled analysis where all the tenapanor treated patients were combined thus all patients are included in the 30 mg dose titration group.

Outcome measures

Outcome measures
Measure	3mg BID Tenapanor, 3mg BID (6mg total) Tenapanor	10mg BID Tenapanor, 10mg BID (20mg total) Tenapanor	30 mg Dose Titration n=43 Participants Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question Tenapanor	Placebo n=37 Participants Placebo Placebo
Placebo Adjusted Change in Serum Phosphate During Randomized Withdrawal Period From Pooled Tenapanor Arms	—	—	1.4 mg/dL Standard Error 0.23	0.6 mg/dL Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline and 8 weeks

Population: There was no placebo group during the 8-week treatment period.

Serum phosphorus difference between baseline (end of washout period) to the end of the 8 week treatment period in ITT analysis set

Outcome measures

Outcome measures
Measure	3mg BID n=74 Participants Tenapanor, 3mg BID (6mg total) Tenapanor	10mg BID n=73 Participants Tenapanor, 10mg BID (20mg total) Tenapanor	30 mg Dose Titration n=72 Participants Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question Tenapanor	Placebo Placebo Placebo
Change in Serum Phosphate During 8-Week Treatment Period	-1.1 mg/dL Standard Error 0.17	-1.1 mg/dL Standard Error 0.17	-1.1 mg/dL Standard Error 0.18	—

Adverse Events

3mg BID

Serious events: 1 serious events

Other events: 22 other events

Deaths: 1 deaths

10mg BID

Serious events: 0 serious events

Other events: 30 other events

Deaths: 0 deaths

30 mg Dose Titration

Serious events: 0 serious events

Other events: 34 other events

Deaths: 0 deaths

Randomized Withdrawal Period Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	3mg BID n=74 participants at risk Tenapanor, 3mg BID (6mg total)	10mg BID n=73 participants at risk Tenapanor, 10mg BID (20mg total)	30 mg Dose Titration n=72 participants at risk Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question	Randomized Withdrawal Period Placebo n=82 participants at risk The 164 patients that ended the 8 week treatment period were re-randomized 1:1 to stay on tenapanor or receive placebo. The patients in this group were re-randomized to receive placebo for the last 4 weeks of the study
Gastrointestinal disorders Diarrhea	1.4% 1/74 • Number of events 1 • 12 weeks. The first 8 weeks were tenapanor only and during the last 4 weeks half of the tenapanor-treated patients from the first 8 weeks were randomized to receive placebo There was no placebo during the first 8-weeks	0.00% 0/73 • 12 weeks. The first 8 weeks were tenapanor only and during the last 4 weeks half of the tenapanor-treated patients from the first 8 weeks were randomized to receive placebo There was no placebo during the first 8-weeks	0.00% 0/72 • 12 weeks. The first 8 weeks were tenapanor only and during the last 4 weeks half of the tenapanor-treated patients from the first 8 weeks were randomized to receive placebo There was no placebo during the first 8-weeks	0.00% 0/82 • 12 weeks. The first 8 weeks were tenapanor only and during the last 4 weeks half of the tenapanor-treated patients from the first 8 weeks were randomized to receive placebo There was no placebo during the first 8-weeks

Other adverse events

Other adverse events
Measure	3mg BID n=74 participants at risk Tenapanor, 3mg BID (6mg total)	10mg BID n=73 participants at risk Tenapanor, 10mg BID (20mg total)	30 mg Dose Titration n=72 participants at risk Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question	Randomized Withdrawal Period Placebo n=82 participants at risk The 164 patients that ended the 8 week treatment period were re-randomized 1:1 to stay on tenapanor or receive placebo. The patients in this group were re-randomized to receive placebo for the last 4 weeks of the study
Gastrointestinal disorders Diarrhea	29.7% 22/74 • Number of events 22 • 12 weeks. The first 8 weeks were tenapanor only and during the last 4 weeks half of the tenapanor-treated patients from the first 8 weeks were randomized to receive placebo There was no placebo during the first 8-weeks	41.1% 30/73 • Number of events 30 • 12 weeks. The first 8 weeks were tenapanor only and during the last 4 weeks half of the tenapanor-treated patients from the first 8 weeks were randomized to receive placebo There was no placebo during the first 8-weeks	47.2% 34/72 • Number of events 34 • 12 weeks. The first 8 weeks were tenapanor only and during the last 4 weeks half of the tenapanor-treated patients from the first 8 weeks were randomized to receive placebo There was no placebo during the first 8-weeks	8.5% 7/82 • Number of events 7 • 12 weeks. The first 8 weeks were tenapanor only and during the last 4 weeks half of the tenapanor-treated patients from the first 8 weeks were randomized to receive placebo There was no placebo during the first 8-weeks

Additional Information

Chief Development Officer

Ardelyx

Phone: 6175134929

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60