Tenapanor for Pediatric IBS with Constipation

Enrolling by invitation at 21 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Ardelyx

Disqualifiers: Surgery on stomach, Pregnant, others

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

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: 6

Duration: 40 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests tenapanor to determine its long-term safety for children and teens with IBS-C (Irritable Bowel Syndrome with Constipation). The goal is to confirm that tenapanor remains safe for young patients who have already used it. This study suits young individuals who have completed a previous tenapanor study and can comfortably walk around. As a Phase 3 trial, it represents the final step before FDA approval, allowing participants to contribute to the potential availability of a new treatment for IBS-C.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

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

Research has shown that tenapanor is usually well-tolerated by people with IBS-C (irritable bowel syndrome with constipation). In previous studies, most patients found relief from symptoms like stomach pain and bloating. However, about 2.5% of patients experienced severe diarrhea. If this occurs, stopping the medication and drinking plenty of fluids is important. Overall, tenapanor is considered safe, but like any treatment, it may have side effects. ^{1 2 3 4 5}

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

Tenapanor is unique because it targets the sodium/hydrogen exchanger 3 (NHE3) in the gut, which is different from many traditional treatments for pediatric IBS with constipation that primarily focus on increasing bowel movements through fiber supplements or laxatives. This new mechanism reduces the absorption of sodium and phosphate, leading to increased water in the intestines, which can ease constipation. Researchers are excited about Tenapanor because it offers a novel approach that could provide relief more effectively and with potentially fewer side effects than current options.

What evidence suggests that tenapanor might be an effective treatment for pediatric IBS with constipation?

Research has shown that tenapanor, the investigational treatment in this trial, effectively treats irritable bowel syndrome with constipation (IBS-C). Studies have found that tenapanor can increase the number of complete spontaneous bowel movements (CSBMs) from about 0.1 per week to more than 3 per week, with this improvement lasting for 26 weeks. Many patients also reported significantly less abdominal pain. The treatment was generally well tolerated, with most patients experiencing benefits without serious side effects. Overall, tenapanor presents a promising option for effectively managing IBS-C symptoms. ^{1 2 3 6 7}

Who Is on the Research Team?

David Rosenbaum

Principal Investigator

Ardelyx

Are You a Good Fit for This Trial?

This trial is for children and teenagers aged between 6 and under 18 who have Irritable Bowel Syndrome with Constipation (IBS-C). They must have completed a previous study on this condition, followed the procedures well, and be able to walk. Girls who can have babies need a negative pregnancy test and must use birth control.

Inclusion Criteria

I am between 6 and 17 years old.

I can walk on my own.

Patient completed the parent study immediately with adequate compliance with study procedures in the opinion of the Investigator Females of child-bearing potential must have negative pregnancy test at the last visit of the parent study and confirm the use of appropriate contraception (including abstinence).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue tenapanor at the same dose assigned in the parent study, with possible titration to 50 mg BID or 25 mg BID after the first week

40 weeks

Visits approximately every 6 weeks

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, which is being considered as a long-term treatment option for young patients with IBS-C. It's an open-label study, meaning everyone knows they're getting Tenapanor without any placebo or comparison drug involved.

How Is the Trial Designed?

Group I: Tenapanor Experimental Treatment 1 Intervention

Eligible patients from the parent study will continue tenapanor at the same dose assigned in the parent study which can be titrated to either 50 mg BID or 25 mg BID per Investigator guidance after a patient's first week on the assigned dose.

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, 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 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 pilot study of 14 children aged 8-16 with obstructive sleep apnea syndrome (OSAS), nasal expiratory positive airway pressure (NEPAP) significantly improved the obstructive apnea index compared to a placebo, indicating its potential efficacy as an alternative therapy.

Despite the overall positive results, individual responses to NEPAP varied, with some children showing no improvement or worsening symptoms, highlighting the need for further evaluation of its effectiveness through polysomnography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of nasal expiratory positive airway pressure devices for the treatment of childhood obstructive sleep apnea syndrome. Kureshi, SA., Gallagher, PR., McDonough, JM., et al.[2021]

Citations

1. 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 ...

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. 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 ...

4. 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 ...

5. 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 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 ...

6. journals.lww.com journals.lww.com/10.14309/01.ajg.0001132052.38436.89

S1148 Efficacy and Safety of Tenapanor in Irritable Bowel... Tenapanor shows promise as a potential treatment for IBS-C, demonstrating superior efficacy in alleviating symptoms such as abdominal pain, bloating, and ...

7. ibsrela-hcp.com ibsrela-hcp.com/

IBSRELA® (tenapanor) | For US HCPs Severe diarrhea was reported in 2.5% of IBSRELA-treated patients. If severe diarrhea occurs, suspend dosing and rehydrate patient.