Tenapanor for Irritable Bowel Syndrome with Constipation

Recruiting in Palo Alto (17 mi)

+30 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Ardelyx

Must not be taking: Fiber supplements, Anti-diarrheals

Disqualifiers: Celiac disease, Cystic fibrosis, Hypothyroidism, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called tenapanor in children who have IBS-C. The medication helps to soften stools, making it easier to relieve constipation.

Will I have to stop taking my current medications?

Participants will need to stop using laxatives and any medications that affect stool consistency, like fiber supplements and anti-diarrheals, unless specified as rescue medication by the study doctor.

What data supports the effectiveness of the drug Tenapanor for treating irritable bowel syndrome with constipation?

Research shows that Tenapanor, a drug that helps reduce sodium absorption in the gut, has been effective in treating irritable bowel syndrome with constipation (IBS-C) in multiple clinical trials, including both short-term (12-week) and long-term (26-week) studies, by improving symptoms like abdominal pain and bowel movement frequency. ^{1 2 3 4 5}

Is Tenapanor safe for humans?

Tenapanor has been studied in clinical trials for treating irritable bowel syndrome with constipation, and these trials have assessed its safety. It is minimally absorbed in the body, which may reduce the risk of side effects, and it has been approved by the FDA for this condition, indicating it has met safety standards. ^{1 2 3 5 6}

How is the drug Tenapanor unique for treating IBS-C?

Tenapanor is unique because it is a first-in-class drug that works by inhibiting a specific protein in the gut (NHE3), which reduces the absorption of sodium and water, helping to relieve constipation. Unlike other treatments that mainly address symptoms, Tenapanor targets the underlying process in the intestines, offering a novel approach for managing IBS-C. ^{1 2 3 4 5}

Research Team

David Rosenbaum, PhD

Principal Investigator

Ardelyx

Eligibility Criteria

This trial is for kids and teens aged 12 to under 18 with IBS-C (constipation type). They must weigh at least 18 kg, not be pregnant, agree to use birth control if applicable, and can't have had certain surgeries or conditions that affect the gut. Participants need to stop other laxatives and follow study rules including using an eDiary.

Inclusion Criteria

I am between 12 and 17 years old.

Patient meets the entry criteria assessed during the 2-week Screening period

I and my guardian can communicate with the doctor and follow the study's requirements, including using an eDiary.

Exclusion Criteria

I have needed help to relieve severe constipation before joining the study.

I have been diagnosed with functional diarrhea according to Rome IV criteria.

History of non-retentive fecal incontinence

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive tenapanor or placebo twice daily for 12 weeks, with ongoing eDiary assessments and safety evaluations every two to four weeks

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, unless they enter the Long Term Safety Extension Study

2 weeks

1 visit (in-person)

Long Term Safety Extension

Participants may opt into a 40-week extension study to continue receiving treatment and monitoring

40 weeks

Treatment Details

Interventions

• Placebo (Other)
• Tenapanor (Phosphate Absorption Inhibitor)

Trial Overview The trial tests two doses of Tenapanor (25 mg and 50 mg) against a placebo in young patients with IBS-C. It's randomized and double-blind, meaning neither the participants nor the researchers know who gets which treatment. The medication is taken twice daily for three months.

Participant Groups

Group I: Tenpanor 50 mg BID Experimental Treatment 1 Intervention

Patients will be randomized to receive 50 mg tenapanor twice daily

Group II: Tenpanor 25 mg BID Experimental Treatment 1 Intervention

Patients will be randomized to receive 25 mg tenapanor twice daily

Group III: Placebo Comparator Placebo Group 1 Intervention

Patients will be randomized to receive matching placebo twice daily

Who Is Running the Clinical Trial?

Ardelyx

Lead Sponsor

Trials

31

Recruited

6,100+

Findings from Research

In a phase 3 trial involving 629 patients with constipation-predominant irritable bowel syndrome (IBS-C), tenapanor 50 mg twice daily significantly improved symptoms, with 27% of patients achieving the primary endpoint compared to 18.7% in the placebo group.

While tenapanor was generally well tolerated, diarrhea was the most common side effect, leading to discontinuation in 6.5% of patients, indicating a need for monitoring in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 12-Week, Placebo-Controlled Phase 3 Trial (T3MPO-1). Chey, WD., Lembo, AJ., Rosenbaum, DP.[2022]

In a phase 3 trial involving 620 patients with irritable bowel syndrome with constipation (IBS-C), tenapanor 50 mg twice daily significantly improved abdominal pain and bowel movement frequency compared to placebo, with 36.5% of patients responding positively versus 23.7% in the placebo group.

Tenapanor was generally well tolerated, with diarrhea being the most common side effect, but it was usually mild to moderate and led to discontinuation in only 6.5% of patients on tenapanor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2). Chey, WD., Lembo, AJ., Yang, Y., et al.[2023]

Tenapanor is a first-in-class oral medication for treating irritable bowel syndrome with constipation (IBS-C) that works locally in the gut by inhibiting the NHE3 transporter, which may lead to fewer systemic side effects and drug interactions.

Clinical trials (Phase 2b and 3) have demonstrated that tenapanor effectively meets both primary and secondary treatment goals, suggesting it could be a promising new option for patients with IBS-C who find conventional laxatives unsatisfactory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenapanor for the treatment of irritable bowel syndrome with constipation. Sinagra, E., Rossi, F., Raimondo, D., et al.[2022]

In a phase 2 study involving 356 patients with constipation-predominant irritable bowel syndrome (IBS-C), tenapanor 50 mg taken twice daily significantly improved bowel movement frequency, with a complete spontaneous bowel movement (CSBM) responder rate of 60.7% compared to 33.7% in the placebo group.

Tenapanor also effectively reduced abdominal symptoms, with a composite responder rate of 50.0% in the 50 mg group versus 23.6% in the placebo group, although diarrhea was noted as a common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenapanor Treatment of Patients With Constipation-Predominant Irritable Bowel Syndrome: A Phase 2, Randomized, Placebo-Controlled Efficacy and Safety Trial. Chey, WD., Lembo, AJ., Rosenbaum, DP.[2018]

Tenapanor is a promising treatment for constipation-predominant irritable bowel syndrome (IBS-C) as it effectively inhibits the Na(+)/H(+) exchanger 3 (NHE3), which helps regulate sodium and water absorption in the intestines.

It has shown an excellent safety profile in preclinical studies with no serious side effects reported, and its non-systemic action reduces the risk of adverse effects and drug interactions, although further Phase III trials are needed to confirm its efficacy and optimize dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenapanor hydrochloride for the treatment of constipation-predominant irritable bowel syndrome. Zielińska, M., Wasilewski, A., Fichna, J.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 12-Week, Placebo-Controlled Phase 3 Trial (T3MPO-1). [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2). [2023]

3. England pubmed.ncbi.nlm.nih.gov

Tenapanor for the treatment of irritable bowel syndrome with constipation. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Tenapanor Treatment of Patients With Constipation-Predominant Irritable Bowel Syndrome: A Phase 2, Randomized, Placebo-Controlled Efficacy and Safety Trial. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Tenapanor hydrochloride for the treatment of constipation-predominant irritable bowel syndrome. [2018]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Tenapanor in the Treatment of Irritable Bowel Syndrome with Constipation: Discovery, Efficacy, and Role in Management. [2023]