Tenapanor for Kidney Stones

Overseen By Jonathan M Whittamore, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: OATP2B1 substrates, ACE inhibitors

Disqualifiers: Kidney stones, Pregnancy, GI disease, 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: 1

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Tenapanor, a drug approved for kidney issues, can reduce the absorption of dietary oxalate in the intestines. Since oxalate can contribute to kidney stones, reducing it might lower the risk of stone formation. Participants will receive either Tenapanor or a placebo (a non-active pill) to compare effects. Healthy adults who have never had kidney stones and don't have certain medical conditions are suitable for this trial. As a Phase 4 trial, Tenapanor is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, especially if you use drugs like enalapril or others listed in the exclusion criteria. It's best to discuss your current medications with the trial team to see if any changes are needed.

What is the safety track record for Tenapanor?

Research has shown that Tenapanor is generally well-tolerated. It has undergone testing in many individuals. In studies involving patients with chronic kidney disease, Tenapanor effectively lowered phosphorus levels. Some participants experienced side effects, with diarrhea being the most common. Other side effects included nausea and bloating, typically mild to moderate.

The FDA has approved Tenapanor for certain kidney-related conditions, indicating its safety for humans. However, discussing any concerns with a doctor is important. They can help determine if joining a trial is the right choice. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for kidney stones focus on pain relief or helping stones pass, like alpha-blockers or hydration therapy. However, Tenapanor is unique because it targets the absorption of sodium in the gut, which can reduce calcium levels in urine, a key factor in kidney stone formation. This new mechanism of action sets it apart from existing options that don't directly address this root cause. Researchers are excited about Tenapanor because it could offer a preventative approach to kidney stones, potentially reducing the frequency and formation of stones altogether.

What evidence suggests that Tenapanor might be an effective treatment for kidney stones?

Research has shown that Tenapanor effectively lowers phosphate levels in the body. For individuals with chronic kidney disease, it manages these levels by preventing phosphate absorption in the intestines. Since phosphate and oxalate absorb similarly, Tenapanor might also reduce oxalate levels. High oxalate levels can lead to kidney stones, so the drug could potentially help prevent them. While Tenapanor has proven effective in controlling phosphate, its effects on oxalate and kidney stones remain under investigation in this trial, where participants will receive either Tenapanor or a placebo. ^{6 7 8 9 10}

Who Is on the Research Team?

Jonathan M Whittamore, Ph.D.

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with high urinary oxalate levels (hyperoxaluria) and those at risk of kidney stones. Participants should be adults who have not been diagnosed with chronic kidney disease but are experiencing these conditions.

Inclusion Criteria

I am a healthy adult.

Exclusion Criteria

Lithogenic urine chemistry at baseline (oxalate > 45 mg/24 h, urine calcium > 300 mg/24 h)

Pregnant or nursing

Intestinal inflammation (Fecal calprotectin > 120 mcg/g)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Phase 1 Treatment

Participants consume a pre-prepared oxalate-rich metabolic diet for 5 days while taking 30 mg Tenapanor or Placebo twice a day. Urine samples are collected on days 4 and 5.

5 days

Daily visits for monitoring

Washout

Participants undergo a 9-day washout period between treatment phases.

9 days

Phase 2 Treatment

Participants consume a pre-prepared oxalate-rich metabolic diet for 5 days while taking 30 mg Tenapanor or Placebo twice a day. Urine samples are collected on days 4 and 5.

5 days

Daily visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tenapanor

Trial Overview The study tests Tenapanor, a drug approved for another kidney condition, to see if it can also reduce the absorption of oxalate from food and lower the risk of kidney stones. A placebo group will serve as a comparison to measure Tenapanor's effectiveness.

How Is the Trial Designed?

Group I: Tenapanor Experimental Treatment 1 Intervention

30 mg Tenapanor twice a day

Group II: Placebo Placebo Group 1 Intervention

30 mg Placebo twice a day

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?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Published Research Related to This Trial

The study successfully created ibuprofen-loaded mesoporous hydroxyapatite (IBU-MHA) particles, achieving a high drug loading efficiency of 34.5% under optimized conditions, which included a specific ibuprofen to MHANPs ratio and a 24-hour impregnation period.

In vitro tests showed that IBU-MHA particles provide a sustained and controlled release of ibuprofen, suggesting they could be effective as drug delivery systems for localized treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facile Synthesis and Characterization of Ibuprofen-mesoporous Hydroxyapatite Nanohybrid as a Sustained Drug Delivery System. Namazi, Z., Jafarzadeh Kashi, TS., Erfan, M., et al.[2020]

The study demonstrates that an injectable calcium phosphate cement containing tetracycline can effectively fill bone defects while providing local antibiotic treatment, although the tetracycline must be treated with calcium sulfate to allow proper cement maturation.

While the treated tetracycline enables the cement to mature into hydroxyapatite, it results in a longer setting time and reduced mechanical properties, but still allows for a sustained release of 60% of the antibiotic over 6 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behaviour of an injectable calcium phosphate cement with added tetracycline. Ratier, A., Freche, M., Lacout, JL., et al.[2013]

Type I calcium phosphate hydraulic cements (CPHC) show excellent biocompatibility and resorbability in in-vivo experiments on dogs, indicating their potential for safe use in medical applications.

The setting time and tensile strength of these cements can be adjusted based on their composition, with strengths ranging from 1.2 to 3.5 MPa and porosity between 38% and 55%, allowing for tailored applications in bone repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Setting, hardening and resorption of calcium phosphate hydraulic cements. Lemaitre, J., Munting, E., Mirtchi, AA.[2013]

A new drug delivery device using bioactive cement made from tetracalcium phosphate and dicalcium phosphate effectively releases indomethacin over more than 3 weeks, demonstrating its potential for sustained drug delivery.

Indomethacin transforms into an amorphous form within the cement matrix, and the drug release follows the Higuchi model, indicating a consistent release profile that is not affected by the thickness of the cement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel skeletal drug delivery system using self-setting calcium phosphate cement. 2. Physicochemical properties and drug release rate of the cement-containing indomethacin. Otsuka, M., Matsuda, Y., Suwa, Y., et al.[2019]

Hydroxyapatite (HAP) treatment significantly reduced hypersensitivity symptoms in patients, showing effectiveness at 1 day and up to 4 weeks after treatment, compared to control groups.

Scanning electron microscopy revealed that HAP completely occluded dentinal tubules, indicating its potential as a permanent desensitizer, although effects diminished by 8 weeks, suggesting the need for further long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydroxyapatite as an in-office agent for tooth hypersensitivity: a clinical and scanning electron microscopic study. Shetty, S., Kohad, R., Yeltiwar, R.[2022]

Citations

1. ajkd.org ajkd.org/article/S0272-6386(25)00937-0/fulltext

Tenapanor: An Update on Evidence of Effectiveness and ... Because the medication is not absorbed, no effects on renal tubular NHE3 activity are expected in patients with residual kidney function.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10695649/

Tenapanor Improves Long-Term Control of ... - PubMed Central Tenapanor alone or with phosphate binders led to 35%–49% of patients achieving serum phosphate ≤4.5 mg/dl over an 18-month period versus 22% at baseline.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0272638625009370

Tenapanor: An Update on Evidence of Effectiveness and ... Tenapanor, a novel therapy that targets intestinal phosphate absorption, has shown promise in reducing serum phosphate as monotherapy and in combination with ...

4. rrtjournal.biomedcentral.com rrtjournal.biomedcentral.com/articles/10.1186/s41100-025-00648-1

Efficacy of tenapanor hydrochloride for hyperphosphatemia in ... Well-controlled studies have reported the effective control of serum phosphorus levels (phosphorus) by tenapanor hydrochloride (tenapanor) in hemodialysis ...

5. pharmacytimes.com pharmacytimes.com/view/tenapanor-in-hyperphosphatemia-is-effective-but-has-cost-market-barriers

Tenapanor in Hyperphosphatemia Is Effective but Has Cost ... The AMPLIFY trial showed tenapanor's superior efficacy when combined with phosphate binders compared to placebo. ... kidney stones and ...

6. xphozah-hcp.com xphozah-hcp.com/safety/

XPHOZAH (tenapanor) Tablets | Clinical Safety Data XPHOZAH (tenapanor) 30 mg BID is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy.

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

IBSRELA® (tenapanor) Clinical Safety Data | For US HCPs See IBSRELA® safety data from two phase 3 clinical trials. See Important Safety Information, including Boxed Warning, and full Prescribing Information.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/213931s000lbl.pdf

XPHOZAH (tenapanor) - accessdata.fda.gov The safety data described below reflect data from 754 adults with CKD on dialysis taking XPHOZAH in clinical trials as monotherapy and in combination with ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/211801s004lbl.pdf

IBSRELA (tenapanor) tablets, for oral use - accessdata.fda.gov The safety data described below reflect data from 1203 adult patients with IBS-C in two randomized, double-blind, placebo-controlled clinical trials (Trial ...

10. ir.ardelyx.com ir.ardelyx.com/news-releases/news-release-details/ardelyx-shares-additional-data-supporting-first-class-xphozahr

Ardelyx Shares Additional Data Supporting First-In-Class ... XPHOZAH (tenapanor), 30 mg BID, is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy.