Tenapanor Clinical Trials

Tenapanor is a medication that works by inhibiting the NHE3 protein, a transporter found in the gastrointestinal tract. This action leads to reduced absorption of sodium and water in the intestines, which can help increase bowel movements and soften stool. For other conditions, Tenapanor works by blocking the paracellular absorption of phosphate in the intestine. It is marketed as Ibsrela for Irritable Bowel Syndrome with Constipation (IBS-C) and as Xphozah for hyperphosphatemia.

Uses and Conditions

Tenapanor is being studied or is approved for a range of conditions, primarily focusing on gastrointestinal disorders and issues related to electrolyte balance. These conditions include:

• Irritable Bowel Syndrome with Constipation (IBS-C) and Chronic Idiopathic Constipation (CIC): These are common gastrointestinal disorders characterized by abdominal pain and infrequent or difficult bowel movements. Tenapanor's mechanism of increasing water in the intestines helps alleviate these symptoms.
• Hyperphosphatemia: This condition involves abnormally high levels of phosphate in the blood, often seen in patients with chronic kidney disease (CKD) who are on dialysis. Tenapanor helps reduce phosphate absorption from the diet.
• Cystic Fibrosis (CF): Specifically, Tenapanor is being investigated for CF-related constipation (CFrC), a common complication in individuals with cystic fibrosis.
• Synucleinopathy-Related Constipation (e.g., Parkinson's Disease): This refers to constipation associated with neurological disorders like Parkinson's disease, where abnormal protein deposits (synuclein) can affect gut function.
• Hyperoxaluria: A condition characterized by excessive oxalate in the urine, which can lead to kidney stones. Tenapanor is being explored for its potential to reduce intestinal oxalate absorption.
• Lactation: Studies have also been conducted to understand the pharmacokinetics of Tenapanor in breast milk of lactating females.

Dosing

Tenapanor is typically taken orally, often twice daily (BID). The specific dosage can vary depending on the condition being treated and the patient's individual needs. Clinical trials have investigated various strengths and regimens:

• For Irritable Bowel Syndrome with Constipation (IBS-C) and Chronic Idiopathic Constipation (CIC), common dosages studied include Tenapanor 5 mg BID, Tenapanor 25 mg BID, and Tenapanor 50 mg BID. One study for IBS-C in pediatric patients is investigating a Tenapanor 5 mg/mL solution. For adult IBS-C, patients have ingested one 50 mg capsule twice daily before breakfast and dinner for 8 weeks.
• For Cystic Fibrosis-related constipation, participants in a recruiting study will ingest one 50 mg tablet of Tenapanor twice daily for 4 weeks.
• In studies for hyperphosphatemia, dosages have included Tenapanor 10 mg, 20 mg, 30 mg BID, and 3 mg BID, often with dose titration.
• A completed study for hyperoxaluria used 30 mg tablets.
• For a study evaluating pharmacokinetics in lactating females, the study drug was administered at a dose of 50 mg BID.

Side Effects

As with any medication, Tenapanor can cause side effects. The most commonly reported adverse event in clinical trials was diarrhea. Here are some of the side effects observed in trials, comparing the percentage of patients on Tenapanor to those on placebo where available:

• Diarrhea (Gastrointestinal disorders): 29.3% of patients taking Tenapanor experienced diarrhea, compared to 3.6% on placebo (across 7 trials). In another trial, 22.1% of patients experienced diarrhea, with no placebo comparison available.
• Fall (Injury, poisoning and procedural complications): 8.7% of patients taking Tenapanor experienced a fall, with no placebo comparison available.
• Hyperkalemia (Metabolism and nutrition disorders): 8.1% of patients taking Tenapanor experienced hyperkalemia, with no placebo comparison available.
• COVID-19 (Infections and infestations): 7.0% of patients taking Tenapanor experienced COVID-19, with no placebo comparison available.
• Hypotension (Vascular disorders): 6.4% of patients taking Tenapanor experienced hypotension, with no placebo comparison available.
• Vomiting (Gastrointestinal disorders): 5.8% of patients taking Tenapanor experienced vomiting, with no placebo comparison available.
• Cellulitis (Infections and infestations): 5.8% of patients taking Tenapanor experienced cellulitis, with no placebo comparison available.
• Hypertension (Vascular disorders): 5.8% of patients taking Tenapanor experienced hypertension, with no placebo comparison available.
• Nasopharyngitis (Infections and infestations): 5.8% of patients taking Tenapanor experienced nasopharyngitis, with no placebo comparison available.
• Nausea (Gastrointestinal disorders): 5.8% of patients taking Tenapanor experienced nausea, with no placebo comparison available.
• Pain in Extremity (Musculoskeletal and connective tissue disorders): 5.8% of patients taking Tenapanor experienced pain in extremity, with no placebo comparison available.
• Pneumonia (Infections and infestations): 5.2% of patients taking Tenapanor experienced pneumonia, with no placebo comparison available.
• Anaemia (Blood and lymphatic system disorders): 5.2% of patients taking Tenapanor experienced anaemia, with no placebo comparison available.
• Arteriovenous Fistula Site Complication (Injury, poisoning and procedural complications): 4.7% of patients taking Tenapanor experienced arteriovenous fistula site complication, with no placebo comparison available.

Clinical Trial Results

Clinical trials have evaluated the efficacy and safety of Tenapanor across its studied conditions. Here are some key findings from completed studies:

• For Irritable Bowel Syndrome with Constipation (IBS-C):

  • In a 12-week study (NCT02621892), Tenapanor 50 mg BID showed improvements in abdominal pain and bowel movements:
    • For the 6 of 12 Week Overall Abdominal Pain Responder Rate, 135 participants on Tenapanor 50 mg BID responded, compared to 99 participants on placebo.
    • For the 6 of 12 Week Overall Complete Spontaneous Bowel Movement (CSBM) Responder Rate, 104 participants on Tenapanor 50 mg BID responded, compared to 88 participants on placebo.
    • For the 9 of 12 Week Overall CSBM Responder Rate, 52 participants on Tenapanor 50 mg BID responded, compared to 15 participants on placebo.
  • A 26-week study (NCT02686138) also demonstrated positive results with Tenapanor 50 mg BID:
    • For the Percentage of Subjects With Overall Abdominal Pain Response for 6 Out of 12 Weeks, 146 participants on Tenapanor 50 mg BID responded, compared to 115 participants on placebo.
    • For the Percentage of Subjects With Overall Complete Spontaneous Bowel Movement (CSBM) Response for 6 Out of 12 Weeks, 139 participants on Tenapanor 50 mg BID responded, compared to 100 participants on placebo.
    • For the Percentage of Subjects With Overall Response for 6 Out of 12 Weeks, 107 participants on Tenapanor 50 mg BID responded, compared to 71 participants on placebo.

• For Hyperphosphatemia in End-Stage Renal Disease (ESRD) Patients on Dialysis:

  • An 8-week study (NCT02675998) showed a reduction in serum phosphate levels:
    • The 10 mg BID, 30 mg Dose Titration, and 3 mg BID Tenapanor arms all showed a change in serum phosphate of -1.1 mg/dL during the 8-week treatment period.
    • During the randomized withdrawal period, the placebo-adjusted change in serum phosphate from pooled Tenapanor arms was 1.4 mg/dL for the 30 mg Dose Titration group, compared to 0.6 mg/dL for placebo.
  • A Phase 3 study (NCT03427125) further evaluated Tenapanor for hyperphosphatemia:
    • The change in serum phosphorus levels during the placebo-controlled randomized withdrawal period was 0.22 mg/dL for the Tenapanor 10 mg, 20 mg, 30 mg BID group, compared to 0.88 mg/dL for placebo in the ITT population.
    • In the responder population, the change was 0.43 mg/dL for the Tenapanor group, compared to 1.80 mg/dL for placebo.
    • Baseline serum phosphorus was 7.44 mg/dL for the Tenapanor group, which decreased to 5.88 mg/dL.

Currently Recruiting Trials

Tenapanor continues to be investigated in several ongoing clinical trials. These studies aim to further understand its safety and efficacy in new populations and conditions:

• NCT07382167: "A 26-Wk Study to Assess Safety & Efficacy of Tenapanor for T/t of Chronic Idiopathic Constipation in Adults"

  • Status: RECRUITING
  • Phase: PHASE3
  • Conditions: Chronic Idiopathic Constipation (CIC)
  • Summary: This 26-week study is evaluating the safety and efficacy of Tenapanor at 5 mg, 25 mg, and 50 mg doses, administered twice daily, in adults with CIC.
  • Sponsor: Ardelyx

• NCT06810167: "Assessing Tenapanor as a Treatment of CF-related Constipation."

  • Status: RECRUITING
  • Phase: PHASE3
  • Conditions: Cystic Fibrosis, Constipation
  • Summary: This study is investigating Tenapanor as a treatment for cystic fibrosis-related constipation (CFrC). Participants will take one 50 mg tablet of Tenapanor twice daily for 4 weeks.
  • Sponsor: Massachusetts General Hospital

• NCT06460038: "Tenapanor in Synucleinopathy-Related Constipation"

  • Status: RECRUITING
  • Phase: PHASE2
  • Conditions: Synucleinopathy, Parkinson's Disease
  • Summary: This trial is exploring Tenapanor as a potential treatment for constipation associated with synucleinopathy, such as in Parkinson's Disease.
  • Sponsor: Cedar Valley Digestive Health Center

• NCT06553547: "4-Week, Multi-center Dose-Ranging Study for the IBS-C in Pts. 6 to <12 Yrs"

  • Status: RECRUITING
  • Phase: PHASE2
  • Conditions: Irritable Bowel Syndrome With Constipation (IBS-C)
  • Summary: A randomized, double-blind, placebo-controlled study to assess the safety and efficacy of a Tenapanor 5 mg/mL solution for treating IBS-C in pediatric patients aged 6 to less than 12 years old.
  • Sponsor: Ardelyx

• NCT05905926: "Safety Study of Tenapanor for the Treatment of Pediatric Patients (6 to Less Than 18 Years Old) With IBS-C"

  • Status: ENROLLING_BY_INVITATION
  • Phase: PHASE3
  • Conditions: Irritable Bowel Syndrome With Constipation (IBS-C)
  • Summary: This is an open-label, long-term safety study for pediatric patients with IBS-C. Eligible patients will continue Tenapanor at doses of either 50 mg BID or 25 mg BID.
  • Sponsor: Ardelyx

• NCT05643534: "Study to Assess Safety and Efficacy of Tenapanor for Treatment of IBS-C in Pediatric Patients 12 to Less Than 18 Years"

  • Status: RECRUITING
  • Phase: PHASE3
  • Conditions: Irritable Bowel Syndrome With Constipation (IBS-C)
  • Summary: This study is assessing the efficacy, safety, and tolerability of Tenapanor at 25 mg and 50 mg doses, administered twice daily, in pediatric patients aged 12 to less than 18 years old with IBS-C.
  • Sponsor: Ardelyx

Where to Participate

Individuals interested in participating in Tenapanor clinical trials can find recruiting sites across 39 states in the United States. There are 125 research sites across 108 cities. Some of the top locations for recruiting trials include:

• Miami, Florida (7 sites)
• El Paso, Texas (6 sites)
• Brooklyn, New York (3 sites)
• Boys Town, Nebraska (3 sites)
• Greenville, South Carolina (3 sites)
• Peoria, Illinois (3 sites)
• Sugar Land, Texas (3 sites)
• San Antonio, Texas (3 sites)
• South Miami, Florida (3 sites)
• Charlotte, North Carolina (3 sites)

Eligibility criteria for these studies generally include individuals between 6 and 89 years of age. Both males and females are eligible, and children can participate in age-appropriate studies. Healthy volunteers are typically not sought for these trials.

Development Timeline

The development of Tenapanor began with the first clinical trial posted on December 4, 2015. Since then, there have been a total of 17 clinical trials investigating Tenapanor, with a cumulative enrollment of 5,240 participants. The most recent trial was posted on February 2, 2026, indicating ongoing research and future studies.

The majority of these trials (13 out of 17) have been sponsored by Ardelyx, an industry leader in drug development, with additional contributions from academic and other research centers. The drug has progressed through various phases of clinical development:

• Phase 3: 9 trials
• Phase 4: 4 trials
• Phase 2: 2 trials
• Phase 1: 1 trial
• Phase 2/Phase 3: 1 trial

Tenapanor's research initially focused on conditions like Irritable Bowel Syndrome with Constipation and hyperphosphatemia. Over time, its potential has expanded to include other conditions such as cystic fibrosis-related constipation, hyperoxaluria, and synucleinopathy-related constipation, demonstrating a broad and evolving pipeline for this medication.