Tenapanor for Irritable Bowel Syndrome

Overseen By Kyle D. Staller, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Kyle Staller, MD, MPH

Must not be taking: Opioids, Antidiabetics, IBS-C agents, others

Disqualifiers: Diabetes, Cardiovascular disease, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how tenapanor affects gut health in people with irritable bowel syndrome with constipation (IBS-C). Tenapanor is a new medication that increases bowel movements and reduces stomach pain by altering how the intestines absorb water and sodium. Participants will take the medication for eight weeks and provide stool samples to offer researchers further insights. This trial suits those who have had IBS-C for at least six months, according to specific criteria, and can maintain a consistent diet and medication routine during the study. As a Phase 4 trial, tenapanor is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop all current medications, but you must not use certain IBS-C treatments like linaclotide, lubiprostone, or plecanatide within a month before the trial. If you are taking probiotics, bulk laxatives, fiber, or stool softeners, your dose must be stable for at least 30 days before the trial and remain the same or decrease during the study.

What is the safety track record for tenapanor?

Research shows that tenapanor is generally well-tolerated by adults with irritable bowel syndrome with constipation (IBS-C). In studies involving over 1,200 adults, diarrhea was the most common side effect, occurring in about 16% of those taking tenapanor, compared to 4% of those taking a placebo (a sugar pill). This indicates that diarrhea occurs more frequently with tenapanor, though most people do not experience it.

Long-term studies have not revealed any unexpected safety issues with tenapanor. It is important to note that tenapanor is unsafe for children under 6 years old due to serious risks observed in animal studies. However, for adults with IBS-C, research so far suggests that tenapanor is safe and can alleviate symptoms like constipation and stomach pain. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for IBS-C, which often include laxatives and fiber supplements, Tenapanor offers a novel approach by targeting the sodium/hydrogen exchanger 3 (NHE3) in the intestines. This mechanism helps reduce the absorption of sodium, leading to increased water in the gut and thereby easing constipation. Researchers are excited about Tenapanor because it not only addresses constipation but could also improve abdominal pain, making it a potentially more comprehensive treatment for IBS-C symptoms compared to current options.

What is the effectiveness track record for tenapanor in treating IBS-C?

Research has shown that tenapanor, which participants in this trial will receive, effectively treats irritable bowel syndrome with constipation (IBS-C). In earlier studies, a 50 mg dose of tenapanor taken twice daily increased bowel movement frequency and reduced stomach pain. Patients experienced an increase from about 0.1 complete bowel movements per week to over 3 per week. The treatment was well-tolerated over 26 weeks, suggesting it as a promising long-term option. Tenapanor works by blocking a receptor in the gut, reducing the absorption of sodium and water, which helps relieve constipation. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults aged 18-75 with IBS-C, as per Rome IV criteria for at least 6 months. Participants must be able to submit stool samples, follow instructions, record daily bowel habits, and have a BMI between >18.5 and <35 kg/m2. They should not make major dietary changes or use probiotics during the study.

Inclusion Criteria

I have been diagnosed with constipation-predominant IBS for at least 6 months.

You have submitted a stool sample prior to starting medication.

You are willing to maintain your current dietary habits and use probiotics during the study period.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tenapanor (50 mg per dose) twice daily for 8 weeks, with stool samples submitted at 0, 4, and 8 weeks

8 weeks

3 visits (sample submission)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tenapanor

Trial Overview The trial is testing Tenapanor's effects on gut bacteria and metabolism in IBS-C patients over an 8-week period. Subjects will take one capsule of Tenapanor (50 mg) twice daily and provide stool samples after weeks 4 and 8.

How Is the Trial Designed?

Group I: Patients with IBS-C Experimental Treatment 1 Intervention

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?

Kyle Staller, MD, MPH

Lead Sponsor

Trials

1

Recruited

30+

Ardelyx

Industry Sponsor

Trials

31

Recruited

6,100+

Published Research Related to This Trial

Tenapanor, a medication approved by the FDA in 2019 for treating IBS with constipation (IBS-C), works by inhibiting the intestinal sodium/hydrogen exchanger 3 (NHE3), which helps increase fluid in the gut and improve bowel movement frequency and abdominal pain.

The treatment of IBS typically starts with dietary and lifestyle changes, but when these are ineffective, tenapanor offers a pharmacological option that targets the underlying mechanisms of IBS-C, enhancing patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenapanor for constipation-predominant irritable bowel syndrome. Siddiqui, S., Cash, BD.[2020]

Tenapanor, a selective NHE3 inhibitor, has been approved in the USA for treating constipation-predominant irritable bowel syndrome (IBS-C) in adults, based on positive results from the phase III T3MPO trial program.

In addition to IBS-C, tenapanor is also being developed for managing hyperphosphataemia in patients with chronic kidney disease, indicating its potential for multiple therapeutic uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenapanor: First Approval. Markham, A.[2020]

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 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 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]

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/PMC8183489/

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 ...

3. ibsrela-hcp.com ibsrela-hcp.com/efficacy/

IBSRELA® (tenapanor) Clinical Efficacy Data | For US HCPs Key secondary efficacy endpoints included the risk difference in (1) complete spontaneous bowel movement (CSBM) responder rate and (2) abdominal pain responder ...

4. 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 ...

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 IBSRELA is contraindicated in patients less than 6 years of age; in nonclinical studies in young juvenile rats administration of tenapanor caused deaths ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/211801s014lbl.pdf

IBSRELA (tenapanor) tablets, for oral use - accessdata.fda.gov The safety data described below reflect data from 1203 adult patients with IBS-C in two randomized, double-blind, placebo-controlled clinical trials (Trial 1 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11005483/

Long-term safety of tenapanor in people with irritable ... This study, called T3MPO-3, was undertaken to investigate whether there are any possible side effects associated with the long-term use of tenapanor in adults ...

9. ir.ardelyx.com ir.ardelyx.com/news-releases/news-release-details/ardelyx-presents-data-supporting-ibsrelar-tenapanor-digestive

Ardelyx Presents Data Supporting IBSRELA® (tenapanor) ... The most common adverse reactions in IBSRELA-treated patients (incidence ≥2% and greater than placebo) were: diarrhea (16% vs 4% placebo), ...

10. ibsrela.com ibsrela.com/

IBSRELA® (tenapanor) | IBS-C Treatment For Adult Patients Learn about IBSRELA® (tenapanor) for irritable bowel syndrome with constipation (IBS-C) in adults. View Safety Info, Prescribing Info, And Boxed Warning.