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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The aim of this study is to better understand how tenapanor affects the metagenomics and metabolomics of patients with irritable bowel syndrome with constipation (IBS-C). Tenapanor is the newest FDA-approved agent for IBS-C. It is a small molecule that inhibits the NHE3 receptor, leading to impaired sodium and water absorption in the intestine. Previous clinical trials comparing tenapanor to placebo showed that a 50 mg dose of tenapanor led to increased bowel movements and decreased abdominal pain. This study consists of an 8-week treatment period in which subjects will ingest one capsule of tenapanor (50 mg per dose), twice daily, and send in stool samples following 4 weeks and 8 weeks of treatment.

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

Research shows that Tenapanor, a drug approved by the FDA, helps improve bowel movement frequency and form, as well as reduce abdominal pain in patients with constipation-predominant irritable bowel syndrome (IBS-C). It works by increasing sodium levels in the intestines, which helps draw fluid into the gut and relieve constipation. ^{1 2 3 4 5}

Is Tenapanor safe for humans?

Tenapanor has been tested in several clinical trials for irritable bowel syndrome with constipation (IBS-C) and has been approved by the FDA, indicating it is generally considered safe for this condition. It is minimally absorbed in the body, which may reduce the risk of side effects, but as with any medication, some people may experience side effects. ^{1 2 3 4 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 the sodium/hydrogen exchanger in the gut, which increases sodium levels and fluid in the intestines, helping to relieve constipation and abdominal pain in IBS-C patients. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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, 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 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 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]

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. Spain pubmed.ncbi.nlm.nih.gov

Tenapanor for constipation-predominant irritable bowel syndrome. [2020]

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

Tenapanor: First Approval. [2020]

5. 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]

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]