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Randomized. double blind, placebo controlled, parallel arms dose finding study with a 4 weeks treatment period
The study consists of a screening period of approximately 1 week, a wash out period of up to 3 weeks, where existing phosphate lowering medication is withheld, a 4-week treatment period and a follow-up period of up to 2 weeks, during which patients are put back on their pre washout phosphate lowering medication.
The wash out period will be either 1 week, 2 weeks or 3 weeks depending on the increase in s-phosphate levels.
There are 7 parallel treatment arms in the study with bid and od treatment regimens.
Laboratory efficacy endpoints and safety assessments will be evaluated at various times throughout the study.
The target population of the study is: male or female patients, above18 years of age with End Stage Renal Disease (ESRD) on chronic maintenance hemodialysis (HD) 3 times a week for a minimum of 3 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 mg bid | Experimental | 1 mg AZD1722 bid |
|
| 3 mg bid | Experimental | 3 mg AZD1722 bid |
|
| 10 mg bid | Experimental | 10 mg AZD1722 bid |
|
| 30 mg bid | Experimental | 30 mg AZD1722 bid |
|
| 3 mg od | Experimental | 3 mg AZD1722 od |
|
| 30 mg od | Experimental | 30 mg AZD1722 od |
|
| Placebo | Placebo Comparator |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD1722 | Drug | AZD1722, oral tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Serum Phosphate Levels | Change in serum phosphate levels from the end of wash out (pre randomization value) to end of treatment | End of wash out (pre randomization value) to end of treatment (Day 29) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Calcium x Phosphorus Product | Change from baseline (end of wash out) in calcium x phosphorus product | End of wash out (pre randomization value) to end of treatment (Day 29) |
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Inclusion Criteria:
Exclusion Criteria:
Severe hyperphosphatemia defined as >10 mg/dL on Phosphate-binders at all time points during clinical routine monitoring for the 3 preceding months before screening visit.
Serum parathyroid hormone >1200 pg/mL
Significant metabolic acidosis
Clinical signs of hypovolemia at randomization
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| Name | Affiliation | Role |
|---|---|---|
| Geoffrey A Block, MD | Denver Nephrology PC, Denver, CO 80230 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Downey | California | United States | |||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38323855 | Derived | Sprague SM, Weiner DE, Tietjen DP, Pergola PE, Fishbane S, Block GA, Silva AL, Fadem SZ, Lynn RI, Fadda G, Pagliaro L, Zhao S, Edelstein S, Spiegel DM, Rosenbaum DP. Tenapanor as Therapy for Hyperphosphatemia in Maintenance Dialysis Patients: Results from the OPTIMIZE Study. Kidney360. 2024 May 1;5(5):732-742. doi: 10.34067/KID.0000000000000387. Epub 2024 Feb 7. | |
| 29617976 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 1 mg Bid | 1 mg AZD1722 bid AZD1722: tenapanor, oral tablet |
| FG001 | 3 mg Bid | 3 mg AZD1722 bid AZD1722: tenapanor, oral tablet |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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Placebo (double dummy technique) |
|
| Placebo | Drug | Placebo bid, double dummy technique |
|
| Los Angeles |
| California |
| United States |
| Research Site | Sacramento | California | United States |
| Research Site | Whittier | California | United States |
| Research Site | Denver | Colorado | United States |
| Research Site | Pembroke Pines | Florida | United States |
| Research Site | Tampa | Florida | United States |
| Research Site | Winter Park | Florida | United States |
| Research Site | Springfield | Massachusetts | United States |
| Research Site | Detroit | Michigan | United States |
| Research Site | Voorhees Township | New Jersey | United States |
| Research Site | Flushing | New York | United States |
| Research Site | Maspeth | New York | United States |
| Research Site | Charlotte | North Carolina | United States |
| Research Site | Cincinnati | Ohio | United States |
| Research Site | San Antonio | Texas | United States |
| Research Site | Bialystok | Poland |
| Research Site | Częstochowa | Poland |
| Research Site | Działdowo | Poland |
| Research Site | Legnica | Poland |
| Research Site | Lublin | Poland |
| Research Site | Radom | Poland |
| Research Site | Szczecin | Poland |
| Research Site | Warsaw | Poland |
| Research Site | Wroclaw | Poland |
| Research Site | Zamość | Poland |
| Research Site | Zgierz | Poland |
| Research Site | Żary | Poland |
| Research Site | Banská Bystrica | Slovakia |
| Research Site | Bratislava | Slovakia |
| Research Site | Hlohovec | Slovakia |
| Research Site | Košice | Slovakia |
| Research Site | Piešťany | Slovakia |
| Research Site | Púchov | Slovakia |
| Research Site | Senica | Slovakia |
| Research Site | Birmingham | United Kingdom |
| Research Site | Doncaster | United Kingdom |
| Research Site | Exeter | United Kingdom |
| Research Site | Hull | United Kingdom |
| Research Site | Leicester | United Kingdom |
| Research Site | London | United Kingdom |
| Block GA, Rosenbaum DP, Yan A, Greasley PJ, Chertow GM, Wolf M. The effects of tenapanor on serum fibroblast growth factor 23 in patients receiving hemodialysis with hyperphosphatemia. Nephrol Dial Transplant. 2019 Feb 1;34(2):339-346. doi: 10.1093/ndt/gfy061. |
| FG002 | 10 mg Bid | 10 mg AZD1722 bid AZD1722: tenapanor, oral tablet |
| FG003 | 30 mg Bid | 30 mg AZD1722 bid AZD1722: tenapanor, oral tablet |
| FG004 | 3 mg od | 3 mg AZD1722 od AZD1722: tenapanor, oral tablet |
| FG005 | 30 mg od | 30 mg AZD1722 od AZD1722: tenapanor, oral tablet |
| FG006 | Placebo | Placebo (double dummy technique) Placebo: Placebo bid, double dummy technique |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 1 mg Bid | 1 mg AZD1722 bid AZD1722: tenapanor, oral tablet |
| BG001 | 3 mg Bid | 3 mg AZD1722 bid AZD1722: tenapanor, oral tablet |
| BG002 | 10 mg Bid | 10 mg AZD1722 bid AZD1722: tenapanor, oral tablet |
| BG003 | 30 mg Bid | 30 mg AZD1722 bid AZD1722: tenapanor, oral tablet |
| BG004 | 3 mg od | 3 mg AZD1722 od AZD1722: tenapanor, oral tablet |
| BG005 | 30 mg od | 30 mg AZD1722 od AZD1722: tenapanor, oral tablet |
| BG006 | Placebo | Placebo (double dummy technique) Placebo: Placebo bid, double dummy technique |
| BG007 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| serum phosphorus | Mean | Standard Deviation | mg/dL |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Serum Phosphate Levels | Change in serum phosphate levels from the end of wash out (pre randomization value) to end of treatment | two patients in the 30 mg bid group are not included in the analysis since they had no post randomization serum phosphorus measurements | Posted | Least Squares Mean | Standard Deviation | mg/dL | End of wash out (pre randomization value) to end of treatment (Day 29) |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Calcium x Phosphorus Product | Change from baseline (end of wash out) in calcium x phosphorus product | The number of patients analyzed are less than the randomized number since the data to accomplish the analysis was not available. | Posted | Mean | Standard Deviation | mg/dL * mg/dL | End of wash out (pre randomization value) to end of treatment (Day 29) |
|
Adverse events were collected for a total of 5 weeks; 4-weeks of treatment and 1 treatment-free week
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1 mg Bid | 1 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 1 | 23 | 2 | 23 | 6 | 23 |
| EG001 | 3 mg Bid | 3 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 0 | 21 | 2 | 21 | 6 | 21 |
| EG002 | 10 mg Bid | 10 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 0 | 23 | 3 | 23 | 11 | 23 |
| EG003 | 30 mg Bid | 30 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 0 | 26 | 2 | 26 | 17 | 26 |
| EG004 | 3 mg od | 3 mg AZD1722 od AZD1722: tenapanor, oral tablet | 0 | 22 | 1 | 22 | 4 | 22 |
| EG005 | 30 mg od | 30 mg AZD1722 od AZD1722: tenapanor, oral tablet | 0 | 21 | 0 | 21 | 11 | 21 |
| EG006 | Placebo | Placebo (double dummy technique) Placebo: Placebo bid, double dummy technique | 0 | 26 | 4 | 26 | 3 | 26 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chest pain | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| pneumonia | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
| |
| osteomyelitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Fluid overload | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Rectal prolapse | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Lacunar infarction | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| diarrhea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Acute Myocardial Infarction | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Development Officer | Ardelyx | 6175134929 | drosenbaum@ardelyx.com |
| ID | Term |
|---|---|
| D054559 | Hyperphosphatemia |
| D007676 | Kidney Failure, Chronic |
| ID | Term |
|---|---|
| D010760 | Phosphorus Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000599417 | tenapanor |
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| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
3 mg AZD1722 od
AZD1722: tenapanor, oral tablet
| OG005 | 30 mg od | 30 mg AZD1722 od AZD1722: tenapanor, oral tablet |
| OG006 | Placebo | Placebo (double dummy technique) Placebo: Placebo bid, double dummy technique |
|
|