A 26-Wk Study to Assess Safety & Efficacy of Tenapanor for T/t of Chronic Idiopathic Constipation in Adults

Ardelyx

Status and phase: Enrolling; Phase 3

Conditions: Chronic Idiopathic Constipation (CIC)

Treatments: Drug: Tenapanor 50 mg BID; Drug: Tenapanor 5 mg BID; Drug: Tenapanor 25 mg BID; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07382167

TEN-03-301

Details and patient eligibility

About

This is a 26-week, multi-center, randomized, double-blind, placebo-controlled study with a 4-week treatment-free Safety Follow-up period to assess the safety and efficacy of tenapanor (5 mg, 25mg, and 50 mg) in adult patients with Chronic Idiopathic Constipation (CIC) when administered twice daily for 26 consecutive weeks.

Full description

This study consists of a 2-week Screening period, followed by a 26-week randomized treatment period (RTP), and a 4-week treatment-free Safety Follow-up period.

After obtaining study informed consent from patients, the 2-week Screening period starts. Patients will be fully assessed for eligibility into the study. The assessments will include evaluation of inclusion/exclusion criteria, including medical histories, physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests.

Patients will also self-report, on information about the status of their constipation symptoms and severity via an electronic diary (eDiary). Patient compliance with the eDiary will be monitored to determine eligibility at the end of screening.

Eligible patients will be randomized (Visit 2) to receive tenapanor 5 mg BID, 25 mg BID, 50 mg BID, or placebo for 26 consecutive weeks as the double-blind RTP. During this period, patients will continue recording daily assessments of constipation symptoms and weekly assessments of constipation severity in the eDiary. Patients will have return visits every two to six weeks at Weeks 2, 4, 8, 12, 16, 20 and 26(Visit 3-9) to undergo safety assessments.

Upon completion of the 26-week RTP, patients will be monitored for AEs during the 4-week treatment-free Safety Follow-up period and complete the Follow-up visit (Visit 10) at the end of this period to undergo safety assessments.

Enrollment: 692 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients that are ≥18 to ≤80 years old at the Screening visit (Visit 1).
2. Meet the Rome IV Diagnostic Criteria for functional constipation.
3. Females of non-childbearing potential, or agree to the use of an acceptable means of contraception for up to 30 days following the last dose of study medication.
4. Males must agree to use an appropriate method of barrier contraception (e.g., latex condom with a spermicidal agent) or have documented surgical sterilization.
5. Meets the entry criteria assessed during the Screening period.
6. Ability to understand and provide input on the assessments in the eDiary.
7. Provide written informed consent before the initiation of any study-specific procedures.
8. Must agree to have daily access to eDiary via a computer, tablet or smart phone

Exclusion criteria

1. Loose or watery stool (BSFS of 6 or 7) in the absence of any medication that is known to affect stool consistency (i.e., prohibited medicine) for >25% of bowel movements (BMs) during the 3 months prior to the Screening visit
2. Fecal impaction within 6 months prior to the Screening visit
3. Unexplained and clinically significant "alarm symptoms" including lower gastrointestinal (GI) bleeding, iron-deficiency anemia, weight loss or fever of unknown origin
4. Functional diarrhea as defined by Rome IV criteria
5. IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed IBS (IBS-M), or unsubtyped IBS as defined by Rome IV criteria
6. Diagnosis or treatment of any clinically symptomatic biochemical or structural abnormality of the GI tract within 6 months prior to the Screening visit, or active disease within 6 months prior to the Screening visit
7. Patient with central nervous system disorder (e.g., Parkinson's disease, spinal cord injury, or multiple sclerosis)
8. Use of prohibited medications defined by protocol
9. Patient has a history or current evidence of laxative abuse
10. Hepatic dysfunction (ALT [SGPT] or AST [SGOT] >2.5 times the upper limit of normal) or renal impairment (serum creatinine >2 mg/dL)
11. Positive HIV, hepatitis B or hepatitis C test at screening
12. Positive urinary drug test at Screening, with the exception of cannabis and cannabidiol (CBD)
13. Any evidence of or treatment of malignancy within 1 year prior to the Screening visit
14. Any surgery on the stomach, small intestine or colon; appendectomy or cholecystectomy are not excluded unless within 60 days prior to the Screening visit
15. Pregnant women or women planning to become pregnant during trial participation
16. A major psychiatric disorder (DSM-III-R or DSM-IV) including major depression or other psychoses that has required hospitalization in the last year prior to the Screening visit.
17. Alcohol or substance abuse within 1 year prior to the Screening visit
18. Participation in other clinical trials within 1 month prior to the Screening visit
19. Clinical evidence of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematologic, neurologic, psychiatric or any disease that may interfere with the patient's successful completion of the trial
20. Patient is involved in the conduct and/or administration of this trial as an Investigator, Sub-Investigator or other staff member, or is a first-degree family member or relative residing with one of the above persons involved in the trial
21. If, in the opinion of the Investigator, the patient is unable or unwilling to fulfill the requirements of the protocol or has a condition, which would render the results uninterpretable

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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692 participants in 4 patient groups, including a placebo group

Tenapanor 5 mg BID

Experimental group

Description:

Patients will be randomized to receive 5 mg tenapanor twice daily.

Treatment:

Drug: Tenapanor 5 mg BID

Tenapanor 25 mg BID

Experimental group

Description:

Patients will be randomized to receive 25 mg tenapanor twice daily.

Treatment:

Drug: Tenapanor 25 mg BID

Tenapanor 50 mg BID

Experimental group

Description:

Patients will be randomized to receive 50 mg tenapanor twice daily.

Treatment:

Drug: Tenapanor 50 mg BID

Placebo Comparator

Placebo Comparator group

Description:

Patients will be randomized to receive matching placebo twice daily.

Treatment:

Drug: Placebo