Tenapanor for Irritable Bowel Syndrome with Constipation

Recruiting at 31 trial locations

Overseen By Jon Vanderhoof, MD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Ardelyx

Must not be taking: Fiber supplements, Anti-diarrheals

Disqualifiers: Celiac disease, Cystic fibrosis, Hypothyroidism, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 12 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication, tenapanor, to determine if it helps children and teens with irritable bowel syndrome with constipation (IBS-C), a condition causing stomach pain and difficulty with bowel movements. The study compares tenapanor at two different doses against a placebo (a pill with no active medicine) to assess its effectiveness and safety. It targets those aged 12 to 18 who regularly experience constipation and stomach pain associated with IBS-C. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tenapanor is generally safe for people with IBS-C, which stands for Irritable Bowel Syndrome with Constipation. In past studies, tenapanor remained safe even with long-term use. Most participants did not experience serious side effects. Some common side effects, such as diarrhea, were mild and occurred in only a few cases. The treatment is considered safe for adults, and this trial is now examining its use in younger people. Overall, evidence suggests that tenapanor is a safe option for managing IBS-C symptoms. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for IBS-C?

Researchers are excited about tenapanor for irritable bowel syndrome with constipation (IBS-C) because it offers a new mechanism of action compared to current treatments like fiber supplements, laxatives, and prescription medications such as linaclotide or lubiprostone. Unlike these options, tenapanor works by blocking sodium absorption in the gut, which helps increase water secretion into the intestines and speeds up bowel movements. This unique approach not only targets the root cause of constipation in IBS-C but also has the potential to improve abdominal pain and discomfort. By addressing these symptoms more effectively, tenapanor could significantly enhance the quality of life for those suffering from this condition.

What evidence suggests that tenapanor might be an effective treatment for IBS-C?

Studies have shown that tenapanor can effectively manage symptoms of Irritable Bowel Syndrome with Constipation (IBS-C). One study demonstrated that tenapanor significantly reduced abdominal pain and increased the number of complete bowel movements. Patients taking tenapanor increased from about 0.1 complete bowel movements per week to more than 3 per week. Another study found that tenapanor improved IBS-C symptoms over 26 weeks and was generally well tolerated, though some patients experienced diarrhea, which may limit its use for some. Overall, tenapanor shows promise as a treatment for IBS-C. Participants in this trial will be randomized to receive either 25 mg or 50 mg of tenapanor twice daily, or a placebo, to further evaluate its effectiveness and safety. ^{1 2 6 7 8}

Who Is on the Research Team?

David Rosenbaum, PhD

Principal Investigator

Ardelyx

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Tenapanor

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.

How Is the Trial Designed?

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

Tenapanor is already approved in United States for the following indications:

Approved in United States as Ibsrela for:

• Irritable Bowel Syndrome with Constipation (IBS-C)
• Chronic Kidney Disease

Who Is Running the Clinical Trial?

Ardelyx

Lead Sponsor

Trials

31

Recruited

6,100+

Published Research Related to This Trial

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]

Tenapanor is a newly FDA-approved medication for treating irritable bowel syndrome with constipation (IBS-C) that works by inhibiting the sodium/hydrogen exchanger isoform 3 (NHE3), leading to increased fluid retention and softer stools.

In addition to improving bowel symptoms, tenapanor also helps reduce abdominal pain and visceral hypersensitivity, making it a promising option for IBS-C patients who do not respond to first-line treatments like soluble fiber.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenapanor in the Treatment of Irritable Bowel Syndrome with Constipation: Discovery, Efficacy, and Role in Management. Herekar, A., Shimoga, D., Jehangir, A., et al.[2023]

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]

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]

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]

Citations

1. ir.ardelyx.com ir.ardelyx.com/news-releases/news-release-details/ardelyx-presents-data-continues-support-benefits-ibsrelar

Release Details Overall, the findings support the effectiveness of tenapanor in the management of IBS-C, with a majority of patients reporting treatment ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12557657/

Tenapanor for Irritable Bowel Syndrome With Constipation ... The primary endpoint was the FDA composite (≥30% abdominal pain reduction and ≥1 additional complete spontaneous bowel movement in the same week ...

3. aafp.org aafp.org/pubs/afp/issues/2022/0600/p656.html

Tenapanor (Ibsrela) for the Treatment of Irritable Bowel ... Tenapanor provides a modest improvement in IBS-C symptoms in adults, although diarrhea will limit its use for some patients.

4. journals.lww.com journals.lww.com/ajg/fulltext/2021/06000/efficacy_of_tenapanor_in_treating_patients_with.29.aspx

Efficacy of Tenapanor in Treating Patients With Irritable... Tenapanor 50 mg bid improved IBS-C symptoms over 26 weeks and was generally well tolerated, offering a potential new long-term treatment option for patients ...

5. gi.org gi.org/journals-publications/ebgi/schoenfeld-june-2022/

Tenapanor (IBSRELA) for Treatment of IBS-C It's notable that tenapanor-treated patients improved from mean of 0.1 CSBMs/week to more than 3 CSBMs/week, which was consistent through 26 ...

6. ibsrela-hcp.com ibsrela-hcp.com/safety/

IBSRELA® (tenapanor) Clinical Safety Data | For US HCPs *Reported in at least 2% of IBSRELA-treated patients and at an incidence greater than placebo. †The adverse reaction profile was similar during the 12-week, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10257918/

Tenapanor in the Treatment of Irritable Bowel Syndrome ... Tenapanor is a proven, safe, and efficacious treatment option for IBS-C subjects. It provides global IBS symptom relief with both an increase in complete ...

8. ibsrela-hcp.com ibsrela-hcp.com/

IBSRELA® (tenapanor) | For US HCPs Review IBSRELA safety data. See safety ... IBSRELA (tenapanor) is indicated for the treatment of Irritable Bowel Syndrome with Constipation (IBS-C) in adults.