Tenapanor for Constipation

Overseen By Harichandana Punukula, PharmD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cedar Valley Digestive Health Center

Disqualifiers: Diarrhea, GI abnormalities, Hepatic dysfunction, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests tenapanor as a potential treatment for constipation linked to synucleinopathy, a disorder affecting the nervous system. The study aims to determine if tenapanor can improve bowel movements in participants by comparing it to a placebo (a harmless, inactive substance). It seeks individuals with doctor-confirmed Parkinson's disease who experience fewer than five bowel movements weekly and have constipation issues impacting their daily life. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that tenapanor has been tested for safety in people with irritable bowel syndrome with constipation (IBS-C). In these studies, diarrhea was the most common side effect. However, no serious or unexpected safety issues emerged. Other research found that tenapanor was safe for use over a year, with safety results similar to shorter studies. This suggests that tenapanor is generally well-tolerated by patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for constipation?

Unlike the standard treatments for constipation, which often include fiber supplements, stool softeners, and laxatives, Tenapanor offers a novel approach. It works by inhibiting the NHE3 transporter in the intestines, which helps to increase water content in the stool, making it easier to pass. This unique mechanism could provide relief without the side effects commonly associated with traditional laxatives. Researchers are excited about Tenapanor because it targets the condition at a cellular level, potentially offering a more effective and gentler option for those suffering from constipation.

What evidence suggests that tenapanor might be an effective treatment for synucleinopathy-associated constipation?

Research has shown that tenapanor, which participants in this trial may receive, effectively relieves constipation symptoms. In studies involving individuals with Irritable Bowel Syndrome with Constipation (IBS-C), tenapanor improved the frequency and ease of bowel movements. It also reduced stomach pain, a common symptom of constipation. Another study found tenapanor to be a promising long-term treatment for constipation. These findings suggest that tenapanor might also help treat constipation linked to synucleinopathy, a condition affecting nerve cells. ^{3 6 7 8 9}

Who Is on the Research Team?

Ravindra Mallavarapu, MD

Principal Investigator

Cedar Valley Digestive Health Center

Harichandana Punukula, PharmD, MS

Principal Investigator

Cedar Valley Digestive Health Center

Richard A. Manfready, MD, AM, FACP

Principal Investigator

Cedar Valley Digestive Health Center

Are You a Good Fit for This Trial?

This trial is for people aged 50-89 with Parkinson's disease (PD) stages 1-3, experiencing constipation. Participants must not be planning to conceive and should use contraception if applicable. They must have fewer than six bowel movements weekly, with less than three feeling complete, despite using laxatives.

Inclusion Criteria

I am between 50 and 89 years old, can prevent pregnancy, and have Parkinson's disease stages 1-3.

I have had 5 or fewer bowel movements a week and often feel I haven't completely emptied.

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 or placebo orally twice daily for 12 weeks

12 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 study tests Tenapanor against a placebo in treating constipation related to synucleinopathies like PD. It aims to see if Tenapanor can increase bowel movement frequency and improve stool consistency compared to no active treatment.

How Is the Trial Designed?

Group I: Tenapanor Experimental Treatment 1 Intervention

Tenapanor 50 mg orally twice daily for 12 weeks

Group II: Placebo Placebo Group 1 Intervention

Placebo orally twice daily for 12 weeks

Who Is Running the Clinical Trial?

Cedar Valley Digestive Health Center

Lead Sponsor

Trials

1

Recruited

30+

Ardelyx

Industry Sponsor

Trials

31

Recruited

6,100+

Published Research Related to This Trial

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 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, a new treatment for irritable bowel syndrome with constipation (IBS-C), was found to be tolerable over a long-term period of up to 52 weeks, with a safety profile similar to that observed in shorter studies.

In a study involving 312 patients, the most common side effect was diarrhea, reported in 10.6% of participants, mostly mild or moderate, indicating that while side effects can occur, they are generally manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of tenapanor in patients with irritable bowel syndrome with constipation in the T3MPO-3 study. Lembo, AJ., Friedenberg, KA., Fogel, RP., 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]

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.

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 ...

2.

journals.lww.com

journals.lww.com/ajg/fulltext/2022/10002/s556_potential_of_tenapanor_as_a_treatment_for.556.aspx

S556 Potential of Tenapanor as a Treatment for Chronic...

Recognizing this overlap we performed a post hoc analysis, evaluating the efficacy of tenapanor for FC by utilizing the primary endpoint for chronic idiopathic ...

3.

pmc.ncbi.nlm.nih.gov

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

Tenapanor in the Treatment of Irritable Bowel Syndrome ...

Although PEG improves stool frequency and consistency, it has not shown improvement in abdominal pain, leading to recommendation against its use ...

4.

cureus.com

cureus.com/articles/411587-tenapanor-for-irritable-bowel-syndrome-with-constipation-ibs-c-a-systematic-review-of-randomized-trials-assessing-food-and-drug-administration-fda-composite-response-durability-and-risk-of-bias-rob-2

Tenapanor for Irritable Bowel Syndrome With Constipation ...

Tenapanor improved the FDA composite endpoint [≥30% reduction in abdominal pain and ≥1 additional complete spontaneous bowel movement (CSBM) ...

5.

ir.ardelyx.com

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

Ardelyx Presents Data Supporting IBSRELA® (tenapanor) ...

IBSRELA has also been shown to reduce abdominal pain by decreasing visceral hypersensitivity and by decreasing intestinal permeability in animal ...

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.

pmc.ncbi.nlm.nih.gov

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

Long-term safety of tenapanor in people with irritable ...

In Studies 1 and 2, tenapanor significantly improved people's symptoms of abdominal pain and constipation. ○ Diarrhea was the most common side effect. ○ Most ...

8.

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 ...

9.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1111/nmo.14658

Long‐term safety of tenapanor in patients with irritable ...

Tenapanor was tolerable over ≥52 weeks of treatment and showed similar safety to that seen in shorter studies.