The Efficacy of AZD1722 in Constipation Predominant Irritable Bowel Syndrome (IBS-C)

• Sponsor: Ardelyx (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01923428
• Collaborator: (none)
• Enrollment: 356
• Locations: 4
• Arms: 4
• Duration (Months): 14
• Patients Per Site: 89
• Patients Per Site Per Month: 6.4

Study Details

Study Description

Brief Summary

This phase 2, randomized, double blind, placebo-controlled, multi-center study will evaluate the safety and efficacy of three dose levels of AZD1722 in subjects with constipation predominant IBS (IBS-C) as defined by the ROME III criteria and who have active disease as determined during a two-week screening period. Subjects who qualify and are randomized into the study will receive 5, 20, or 50 mg of AZD1722 BID or placebo BID for 12 consecutive weeks. At the end of this treatment period, subjects will be followed for an additional 4 weeks.

Condition or Disease	Intervention/Treatment	Phase
Constipation Predominant Irritable Bowel Syndrome	Drug: AZD1722; Drug: Placebo	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 356 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of AZD1722 for the Treatment of Constipation-Predominant Irritable Bowel Syndrome (IBS-C)
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 5 mg BID AZD1722	Drug: AZD1722; Other Names: RDX5791, Tenapanor
Experimental: 20 mg BID AZD1722	Drug: AZD1722; Other Names: RDX5791, Tenapanor
Experimental: 50 mg BID AZD1722	Drug: AZD1722; Other Names: RDX5791, Tenapanor
Placebo Comparator: Placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Percent Complete Spontaneous Bowel Movement Responders vs Placebo [12 weeks]

   Weekly complete spontaneous bowel movement resaponders defined as an increase of one or more bowel movement per week from baseline for 6 of the 12 weeks

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Females and males must agree to use appropriate methods of contraception or be sterile (with appropriate documentation)

• Subject is ambulatory

• Subject meets definition of IBS-C using Rome III Criteria for the Diagnosis of IBS with a history of <5 SBMs per week

• Subject meets Screening eligibility criteria (see below)

• A colonoscopy based on AGA guidelines; every 10 years at ≥ 50 years old, or the occurrence of any warning signs (i.e., unexplained weight loss, non-hemorrhoid blood in stools)

• Ability to communicate well with the Investigator and to comply with the requirements of the entire study, including an understanding of how to use the touch-tone telephone electronic diary.

• Written informed consent and a willingness to participate in the study as it is described.

• Daily access to a touch tone telephone.

Exclusion Criteria:

• Functional diarrhea as defined by Rome III criteria

• IBS with diarrhea (IBS-D), mixed IBS (IBS-M), or unsubtyped IBS as defined by Rome III criteria

• Diagnosis or treatment of any clinically symptomatic biochemical or structural abnormality of the GI tract within 6 months prior to screening, or active disease within 6 months prior to screening. Including but not limited to cancer, inflammatory bowel disease, diverticulitis, duodenal ulcer, erosive esophagitis, gastric ulcer, pancreatitis (within 12 months of screening), cholelithiasis, amyloidosis, ileus, non-controlled GERD, gastrointestinal obstruction or carcinoid syndrome.

• Use of medications that are known to affect stool consistency (Prohibited Medications), including fiber supplements, anti-diarrheals, cathartics, antacids, opiates, prokinetic drugs, laxatives, enemas, antibiotics within 4 weeks of enrollment, probiotics (including probiotic yogurt); or salt or electrolyte supplements containing sodium, potassium, chloride, or bicarbonate formulations during the seven days prior to treatment; unless specified as rescue medication, and used accordingly.

• Clinical evidence of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematologic, neurologic, psychiatric or any disease that may interfere with the subject successfully completing the trial.

• The subject has a history or current evidence of laxative abuse (in the clinical judgment of the physician).

• Hepatic dysfunction (ALT [SGPT] or AST [SGOT] >2.5 times the upper limit of normal) or renal impairment (serum creatinine > 2mg/dL).

• Any evidence of or treatment of malignancy (other than localized basal cell, squamous cell skin cancer or cancer in situ that has been resected) within the previous year.

• Any surgery on the stomach, small intestine or colon, excluding appendectomy.

• Pregnant or lactating women.

• A major psychiatric disorder (DSM-III-R or DSM-IV) including major depression or other psychoses that has required hospitalization in the last 3 years. History of attempted suicide or uncontrolled bipolar disorder. Alcohol or substance abuse in the last year.

• Participation in other clinical trials within 1 month prior to Day -14 (beginning of screening period).

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Boulder	Colorado	United States
2		Greensboro	North Carolina	United States
3		Winston-Salem	North Carolina	United States
4		Chattanooga	Tennessee	United States

Sponsors and Collaborators

• Ardelyx

Investigators

• Study Director: David P Rosenbaum, Ph.D., Ardelyx, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ardelyx
• ClinicalTrials.gov Identifier: NCT01923428
• Other Study ID Numbers: D5612C00001
• First Posted: Aug 15, 2013
• Last Update Posted: Apr 8, 2020
• Last Verified: Mar 1, 2020

• Additional relevant MeSH terms: Irritable Bowel Syndrome; Syndrome; Constipation

Study Results

Participant Flow

Arm/Group Title	5 mg BID	20 mg BID	50 mg BID	Placebo
Arm/Group Description	AZD1722	AZD1722	AZD1722	Placebo
Period Title: Overall Study
STARTED	88	89	89	90
COMPLETED	69	77	78	80
NOT COMPLETED	19	12	11	10

Baseline Characteristics

Arm/Group Title	5 mg BID	20 mg BID	50 mg BID	Placebo	Total
Arm/Group Description	AZD1722	AZD1722	AZD1722	Placebo	Total of all reporting groups
Overall Participants	88	89	89	90	356
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	84 95.5%	82 92.1%	84 94.4%	81 90%	331 93%
>=65 years	4 4.5%	7 7.9%	5 5.6%	9 10%	25 7%
Sex: Female, Male (Count of Participants)
Female	76 86.4%	77 86.5%	79 88.8%	77 85.6%	309 86.8%
Male	12 13.6%	12 13.5%	10 11.2%	13 14.4%	47 13.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	22 25%	30 33.7%	24 27%	29 32.2%	105 29.5%
Not Hispanic or Latino	66 75%	59 66.3%	65 73%	61 67.8%	251 70.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	3 3.4%	2 2.2%	1 1.1%	6 1.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	18 20.5%	19 21.3%	17 19.1%	22 24.4%	76 21.3%
White	69 78.4%	67 75.3%	69 77.5%	65 72.2%	270 75.8%
More than one race	1 1.1%	0 0%	1 1.1%	2 2.2%	4 1.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.5 (5.65)	28.5 (5.27)	28.3 (4.87)	28.7 (5.63)	28.7 (5.36)

Outcome Measures

1. Primary Outcome

Title	Percent Complete Spontaneous Bowel Movement Responders vs Placebo
Description	Weekly complete spontaneous bowel movement resaponders defined as an increase of one or more bowel movement per week from baseline for 6 of the 12 weeks
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	5 mg BID	20 mg BID	50 mg BID	Placebo
Arm/Group Description	AZD1722	AZD1722	AZD1722	Placebo
Measure Participants	87	87	84	89
Count of Participants [Participants]	35 39.8%	38 42.7%	51 57.3%	30 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	50 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	27
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	5 mg BID		20 mg BID		50 mg BID		Placebo
Arm/Group Description	AZD1722 AZD1722		AZD1722 AZD1722		AZD1722 AZD1722		Placebo
All Cause Mortality
	5 mg BID		20 mg BID		50 mg BID		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	5 mg BID		20 mg BID		50 mg BID		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/88 (2.3%)		1/89 (1.1%)		0/89 (0%)		1/90 (1.1%)
Gastrointestinal disorders
small intestinal obstruction	0/88 (0%)	0	1/89 (1.1%)	1	0/89 (0%)	0	0/90 (0%)	0
Infections and infestations
Urinary Tract Infection	1/88 (1.1%)	1	0/89 (0%)	0	0/89 (0%)	0	0/90 (0%)	0
Musculoskeletal and connective tissue disorders
Osteomyelitis	0/88 (0%)	0	0/89 (0%)	0	0/89 (0%)	0	1/90 (1.1%)	1
Respiratory, thoracic and mediastinal disorders
Laryngeal neoplasm	1/88 (1.1%)	1	0/89 (0%)	0	0/89 (0%)	0	0/90 (0%)	0
Other (Not Including Serious) Adverse Events
	5 mg BID		20 mg BID		50 mg BID		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/88 (11.4%)		13/89 (14.6%)		15/89 (16.9%)		4/90 (4.4%)
Gastrointestinal disorders
Diarrhea	7/88 (8%)	7	11/89 (12.4%)	11	10/89 (11.2%)	10	0/90 (0%)	0
Infections and infestations
Urinary Tract Infection	3/88 (3.4%)	3	2/89 (2.2%)	2	5/89 (5.6%)	5	4/90 (4.4%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.