A 12-Week Study With a 4-Week Randomized Withdrawal Period to Evaluate the Efficacy and Safety of Tenapanor for the Treatment of IBS-C (T3MPO-1)

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ClinicalTrials.gov Identifier: NCT02621892

Recruitment Status : Completed

First Posted : December 4, 2015

Results First Posted : April 21, 2020

Last Update Posted : April 21, 2020

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Sponsor:

Information provided by (Responsible Party):

Ardelyx

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Constipation Predominant Irritable Bowel Syndrome
Interventions	Drug: Tenapanor Drug: Placebo
Enrollment	606

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	50mg BID	Placebo
Arm/Group Description	Tenapanor	Placebo
Arm/Group Description	Tenapanor Tenapanor	Placebo Placebo
Period Title: Treatment Period
Started	307	299
Completed	261	272
Not Completed	46	27
Period Title: Randomized Withdrawal Period
Started	261	272
Completed	250	260
Not Completed	11	12

Baseline Characteristics

Arm/Group Title		50mg BID	Placebo	Total
Arm/Group Description		Tenapanor	Placebo	Total of all reporting groups
Arm/Group Description		Tenapanor Tenapanor	Placebo Placebo	Total of all reporting groups
Overall Number of Baseline Participants		307	299	606
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	307 participants	299 participants	606 participants
		45 (13.38)	44.9 (13.04)	45 (13.20)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	307 participants	299 participants	606 participants
	Female	244 79.5%	249 83.3%	493 81.4%
	Male	63 20.5%	50 16.7%	113 18.6%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	307 participants	299 participants	606 participants
	Hispanic or Latino	98 31.9%	83 27.8%	181 29.9%
	Not Hispanic or Latino	209 68.1%	216 72.2%	425 70.1%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	307 participants	299 participants	606 participants
	American Indian or Alaska Native	0 0.0%	2 0.7%	2 0.3%
	Asian	10 3.3%	4 1.3%	14 2.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	88 28.7%	100 33.4%	188 31.0%
	White	201 65.5%	186 62.2%	387 63.9%
	More than one race	8 2.6%	7 2.3%	15 2.5%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Body Mass Index (BMI) Mean (Standard Deviation) Unit of measure: Kg/m^2
	Number Analyzed	307 participants	299 participants	606 participants
		29.88 (7.198)	29.30 (6.442)	29.60 (6.836)

Outcome Measures

1.Primary Outcome


Title	6 of 12 Week Overall Responder Rate
Description	An overall responder is defined as a weekly responder for the first 6/...
Description	An overall responder is defined as a weekly responder for the first 6/12 weeks where both CSBM and abdominal pain response criteria were met for the week. The CSBM response criteria are defined as an increase of one or more change in average weekly CSBMs from baseline. The definition of a CSBM is as follows: A CSBM is a spontaneous bowel movement (SBM) for which the subject responds "yes" to the following question; "Did you feel like you completely emptied your bowels?" The abdominal pain response criterion is defined as a decrease of 30% or more of percent change in average weekly worst abdominal pain from baseline.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	50mg BID	Placebo
Arm/Group Description:	Tenapanor	Placebo
Arm/Group Description:	Tenapanor Tenapanor	Placebo Placebo
Overall Number of Participants Analyzed	307	299
Measure Type: Count of Participants Unit of Measure: Participants
	83 27.0%	56 18.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	50mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.02
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	8.31
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	6 of 12 Week Overall Complete Spontaneous Bowel Movement (CSBM)Responder Rate
Description	An overall CSBM responder is defined as a weekly responder for the fir...
Description	An overall CSBM responder is defined as a weekly responder for the first 6/12 weeks. The CSBM response criteria are defined as an increase of one or more change in average weekly CSBMs from baseline. The definition of a CSBM is as follows: A CSBM is a spontaneous bowel movement (SBM) for which the subject responds "yes" to the following question; "Did you feel like you completely emptied your bowels?"
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	50mg BID	Placebo
Arm/Group Description:	Tenapanor	Placebo
Arm/Group Description:	Tenapanor Tenapanor	Placebo Placebo
Overall Number of Participants Analyzed	307	299
Measure Type: Count of Participants Unit of Measure: Participants
	104 33.9%	88 29.4%

3.Secondary Outcome


Title	6 of 12 Week Overall Abdominal Pain Responder Rate
Description	An overall abdominal pain responder is defined as a weekly responder f...
Description	An overall abdominal pain responder is defined as a weekly responder for the first 6/12. The abdominal pain response criterion is defined as a decrease of 30% or more of percent change in average weekly worst abdominal pain from baseline.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	50mg BID	Placebo
Arm/Group Description:	Tenapanor	Placebo
Arm/Group Description:	Tenapanor Tenapanor	Placebo Placebo
Overall Number of Participants Analyzed	307	299
Measure Type: Count of Participants Unit of Measure: Participants
	135 44.0%	99 33.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	50mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.008
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	10.86
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	9 of 12 Week Overall Responder Rate
Description	An overall responder is defined as a weekly responder for the first 9/...
Description	An overall responder is defined as a weekly responder for the first 9/12 weeks where both CSBM and abdominal pain response criteria were met for the week. The CSBM response criteria are defined as an increase of one or more change in average weekly CSBMs from baseline and a minimum of at least 3 CSBMs that same week. The definition of a CSBM is as follows: A CSBM is a spontaneous bowel movement (SBM) for which the subject responds "yes" to the following question; "Did you feel like you completely emptied your bowels?" The abdominal pain response criterion is defined as a decrease of 30% or more of percent change in average weekly worst abdominal pain from baseline.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	50mg BID	Placebo
Arm/Group Description:	Tenapanor	Placebo
Arm/Group Description:	Tenapanor Tenapanor	Placebo Placebo
Overall Number of Participants Analyzed	307	299
Measure Type: Count of Participants Unit of Measure: Participants
	42 13.7%	10 3.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	50mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	10.34
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	9 of 12 Week Overall CSBM Responder Rate
Description	An overall CSBM responder is defined as a weekly responder for the fir...
Description	An overall CSBM responder is defined as a weekly responder for the first 9/12 weeks. The CSBM response criteria are defined as an increase of one or more change in average weekly CSBMs from baseline and a minimum of at least 3 CSBMs that same week. The definition of a CSBM is as follows: A CSBM is a spontaneous bowel movement (SBM) for which the subject responds "yes" to the following question; "Did you feel like you completely emptied your bowels?"
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	50mg BID	Placebo
Arm/Group Description:	Tenapanor	Placebo
Arm/Group Description:	Tenapanor Tenapanor	Placebo Placebo
Overall Number of Participants Analyzed	307	299
Measure Type: Count of Participants Unit of Measure: Participants
	52 16.9%	15 5.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	50mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	11.92
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	9 of 12 Week Overall Abdominal Pain Responder Rate
Description	An overall abdominal pain responder is defined as a weekly responder f...
Description	An overall abdominal pain responder is defined as a weekly responder for the first 9/12 weeks. The abdominal pain response criterion is defined as a decrease of 30% or more of percent change in average weekly worst abdominal pain from baseline.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	50mg BID	Placebo
Arm/Group Description:	Tenapanor	Placebo
Arm/Group Description:	Tenapanor Tenapanor	Placebo Placebo
Overall Number of Participants Analyzed	307	299
Measure Type: Count of Participants Unit of Measure: Participants
	93 30.3%	58 19.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	50mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.003
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	10.9
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	4 months
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	50mg BID		Placebo
Arm/Group Description	Tenapanor		Placebo
Arm/Group Description	Tenapanor Tenapanor		Placebo Placebo
All-Cause Mortality
	50mg BID		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/307 (0.00%)		0/299 (0.00%)
Serious Adverse Events Serious Adverse Events
	50mg BID		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/307 (1.95%)		0/299 (0.00%)
Musculoskeletal and connective tissue disorders
Osteoarthritis ^†	1/307 (0.33%)	1	0/299 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pineal neoplasm ^†	1/307 (0.33%)	1	0/299 (0.00%)	0
Nervous system disorders
Migraine ^†	1/307 (0.33%)	1	0/299 (0.00%)	0
Psychiatric disorders
Panick Attack ^†	1/307 (0.33%)	1	0/299 (0.00%)	0
Alcohol withdrawal syndromw ^†	1/307 (0.33%)	1	0/299 (0.00%)	0
Major Depression ^†	1/307 (0.33%)	1	0/299 (0.00%)	0
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	50mg BID		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/307 (14.66%)		5/299 (1.67%)
Gastrointestinal disorders
Diarrhea ^†	45/307 (14.66%)	45	5/299 (1.67%)	5
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Chief Development Officer
Organization:	Ardelyx
Phone:	6175134929
EMail:	drosenbaum@ardelyx.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chey WD, Lembo AJ, Yang Y, Rosenbaum DP. Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2). Am J Gastroenterol. 2021 Jun 1;116(6):1294-1303. doi: 10.14309/ajg.0000000000001056.

Chey WD, Lembo AJ, Rosenbaum DP. Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 12-Week, Placebo-Controlled Phase 3 Trial (T3MPO-1). Am J Gastroenterol. 2020 Feb;115(2):281-293. doi: 10.14309/ajg.0000000000000516.

Layout table for additonal information

Responsible Party:	Ardelyx
ClinicalTrials.gov Identifier:	NCT02621892
Other Study ID Numbers:	TEN-01-301
First Submitted:	December 2, 2015
First Posted:	December 4, 2015
Results First Submitted:	March 30, 2020
Results First Posted:	April 21, 2020
Last Update Posted:	April 21, 2020

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