Tenapanor for Irritable Bowel Syndrome with Constipation

Recruiting at 16 trial locations

Overseen By Susan Edelstein, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Ardelyx

Must not be taking: Fiber supplements, Anti-diarrheals

Disqualifiers: Celiac, Cystic fibrosis, Hypothyroidism, others

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: 6

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of tenapanor for children with irritable bowel syndrome with constipation (IBS-C), a condition causing abdominal pain and infrequent bowel movements. Researchers are evaluating different doses of tenapanor to determine the most effective and safe option. The study includes a placebo group for comparison. Children with IBS-C who frequently experience constipation may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that tenapanor is likely to be safe for humans?

Research shows that tenapanor is already approved for treating adults with irritable bowel syndrome with constipation (IBS-C). Studies have found that it usually improves symptoms, though some people may experience side effects. Diarrhea is the most common side effect, occurring in about 16% of patients, compared to 4% who took a placebo. Other side effects are less common.

Tenapanor is currently in a phase 2 trial for use in children, indicating existing evidence of its safety in adults. This trial aims to understand how well children handle the treatment. Previous studies on adults provide a good starting point, but children's reactions can differ, highlighting the importance of this study. ^{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 novel approach compared to current treatments like fiber supplements, laxatives, and other medications targeting serotonin receptors. Unlike these standard options, Tenapanor works by inhibiting the NHE3 transporter in the gut, which reduces sodium absorption and increases water secretion, softening stools and easing constipation. This unique mechanism of action could potentially provide faster relief and better symptom management for IBS-C patients. Additionally, Tenapanor is available in various dosage options, allowing for tailored treatment based on individual patient needs.

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

Studies have shown that tenapanor can help manage symptoms of Irritable Bowel Syndrome with Constipation (IBS-C). Research indicates that many patients experience less abdominal pain and have more regular bowel movements. One study found that tenapanor led to modest improvements in IBS-C symptoms for adults, although it sometimes caused diarrhea. Another study showed that tenapanor was well-tolerated over 26 weeks and provided long-term relief from symptoms. Most patients using tenapanor reported satisfaction with their treatment and noticed improvements in constipation. ^{1 2 3 6 7}

Who Is on the Research Team?

Susan Edelstein, PhD

Principal Investigator

Ardelyx

Are You a Good Fit for This Trial?

This trial is for children aged 6 to less than 12 years who have Irritable Bowel Syndrome with Constipation (IBS-C). The key eligibility details are not provided, so it's important to check the specific requirements before joining.

Inclusion Criteria

Meet the entry criteria assessed during the 2-week Screening period

I am willing to stop my current laxatives for the study's approved treatment.

Meet the Modified Diagnostic Rome IV criteria for child/adolescent diagnosis of IBS-C

Exclusion Criteria

Involvement in the conduct or administration of the trial by patient or parent/guardian/LAR

History of non-retentive fecal incontinence

I have undergone manual disimpaction before joining the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Randomized Treatment Period

Participants receive tenapanor or placebo and record daily assessments in the eDiary

4 weeks

4 visits (in-person)

Follow-up

Participants undergo a treatment-free period with safety assessments

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Tenapanor

Trial Overview

The study is testing the safety and effectiveness of a medication called Tenapanor compared to a placebo. It's designed as a double-blind test, meaning neither the participants nor the researchers know who receives the real drug or placebo.

How Is the Trial Designed?

Group I: Tenapanor Cohort 6 Experimental Treatment 1 Intervention

Tenapanor 25 mg BID

Group II: Tenapanor Cohort 5 Experimental Treatment 1 Intervention

Tenapanor 20 mg BID

Group III: Tenapanor Cohort 4 Experimental Treatment 1 Intervention

Tenapanor 15 mg BID

Group IV: Tenapanor Cohort 3 Experimental Treatment 1 Intervention

Tenapanor 10 mg BID

Group V: Tenapanor Cohort 2 Experimental Treatment 1 Intervention

Tenapanor 5 mg BID

Group VI: Tenapanor Cohort 1 Experimental Treatment 1 Intervention

Tenapanor 2 mg BID

Group VII: Placebo Placebo Group 1 Intervention

Matching placebo

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

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]

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]

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]

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.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8183489/

Efficacy of Tenapanor in Treating Patients With Irritable ...

Tenapanor 50 mg b.i.d. improved IBS-C symptoms over 26 weeks and was generally well tolerated, offering a potential new long-term treatment option for patients ...

5.

journals.lww.com

journals.lww.com/10.14309/01.ajg.0001132184.84018.f7

S1181 Treatment Satisfaction With Tenapanor (IBSRELA ...

Of the 4252 invites sent, 537 patients completed the survey. Most patients reported treatment satisfaction with TEN (88%) as well as improved constipation (95%) ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05905926

Safety Study of Tenapanor for the Treatment of Pediatric ...

An open-label long-term safety study of tenapanor for the treatment of irritable bowel syndrome with constipation (IBS-C) in pediatric patients 6 to less than ...

7.

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.