An 8-Week Study to Evaluate Tenapanor in the Treatment of Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)
Primary Purpose
Hyperphosphatemia
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Tenapanor
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hyperphosphatemia
Eligibility Criteria
Inclusion Criteria:
- 18 to 80 years old
- Females must be non-pregnant, non-lactating, and either be post-menopausal for at least 12 months, have documentation of irreversible surgical sterilization, or confirm the use of one of the acceptable contraceptive methods.
- Males must agree to avoid fathering a child and agree to use an appropriate method of contraception
- Chronic maintenance hemodialysis 3x/week for at least 3 months
- Kt/V ≥ 1.3 at most recent measurement prior to screening
- Prescribed and taking at least 3 doses of phosphate binder per day
- Serum phosphate levels should be between 4.0 and 7.0 mg/dL (inclusive) at screening
- For randomization in the study, after 1 week wash-out of phosphate binders, subjects must have serum phosphate level of at least 9 mg/dL but below 10 mg/dL and have had an increase of at least 1.5 mg/dL versus pre-wash out value
- For randomization in the study, after 2 or 3 weeks wash-out of phosphate binders, subjects must have serum phosphate level of at least 6 mg/dL but below 10 mg/dL and have had an increase of at least 1.5 mg/dL versus pre-wash out value
Exclusion Criteria:
- Severe hyperphosphatemia defined as >10 mg/dL on Phosphate-binders at any time point during clinical routine monitoring for the 3 preceding months before screening
- Serum parathyroid hormone >1200 pg/mL
- Persistent metabolic acidosis defined as serum carbon dioxide <18 mmol/L from two consecutive measurements during screening and washout periods
- Clinical signs of hypovolemia at randomization
- History of inflammatory bowel disease (IBD) or diarrhea predominant irritable bowel syndrome (IBS-D)
- Scheduled for living donor kidney transplant, change to peritoneal dialysis, home HD or plans to relocate to another center during the study period
- Diarrhea or loose stools during the week before randomization defined as BSFS ≥ 6 and frequency ≥ 3 for 2 or more days
- Any evidence of or treatment of malignancy within one year, excluding non-melanomatous malignancies of the skin
- Positive serology with evidence of significant hepatic impairment or WBC elevation according to the Investigator
- Life expectancy < 6 months
Sites / Locations
- Ardelyx Investigative Site 429
- Ardelyx Investigative Site 425
- Ardelyx Clinical Site 403
- Ardelyx Investigative Site 410
- Ardelyx Investigative Site 430
- Ardelyx Investigative Site 427
- Ardelyx Investigative Site 432
- Ardelyx Investigative Site 415
- Ardelyx Investigative Site 402
- Ardelyx Investigative Site 424
- Ardelyx Investigative Site 409
- Ardelyx Investigative Site 417
- Ardelyx Investigative Site 431
- Ardelyx Investigative Site 423
- Ardelyx Investigative Site 416
- Ardelyx Investigative Site 419
- Ardelyx Investigative Site 408
- Ardelyx Investigative Site 411
- Ardelyx Investigative Site 420
- Ardelyx Investigative Site 426
- Ardelyx Investigative Site 412
- Ardelyx Investigative Site 414
- Ardelyx Investigative Site 404
- Ardelyx Investigative Site 421
- Ardelyx Investigative Site 428
- Ardelyx Investigative Site 413
- Ardelyx Investigative Site 418
- Ardelyx Investigative Site 406
- Ardelyx Investigative Site 405
- Ardelyx Investigative Site 422
- Ardelyx Investigative Site 407
- Ardelyx Investigative Site 401
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
3mg BID
10mg BID
Dose Titration
Placebo
Arm Description
Tenapanor, 3mg BID (6mg total)
Tenapanor, 10mg BID (20mg total)
Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question
Placebo
Outcomes
Primary Outcome Measures
Placebo Adjusted Change in Serum Phosphate During Randomized Withdrawal Period From Pooled Tenapanor Arms
Serum phosphorus difference between placebo and tenapanor in the change from the end of the 8 week treatment period to the end of the randomized withdrawal period in Efficacy Analysis Set. The efficacy analysis was pre-defined to be a pooled analysis of all tenapanor treated patients with a minimum of a 1.2 mg/dL decrease in serum phosphorus during the 8-week treatment period
Secondary Outcome Measures
Change in Serum Phosphate During 8-Week Treatment Period
Serum phosphorus difference between baseline (end of washout period) to the end of the 8 week treatment period in ITT analysis set
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02675998
Brief Title
An 8-Week Study to Evaluate Tenapanor in the Treatment of Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)
Official Title
An 8-week, Multicenter, Randomized, Double-Blind, Parallel Group Study With a 4-week, Placebo-Controlled, Randomized Withdrawal Period to Evaluate the Efficacy, Safety, and Tolerability of Tenapanor to Treat Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
January 2016 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
January 17, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ardelyx
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase 3, 8-week, randomized, double-blind, parallel group, multi-center study with a 4-week, placebo-controlled, randomized withdrawal period will evaluate the efficacy, safety and tolerability of Tenapanor to treat hyperphosphatemia in end-stage renal disease patients on hemodialysis (ESRD-HD). Subjects who qualify are randomized into the study will either receive 3 mg BID, 10 mg BID, or a titration regimen of tenapanor.
Detailed Description
The study consists of a screening visit, a wash out period of up to 3 weeks, when existing phosphate lowering medication is withheld, an 8-week treatment period, in which all groups receive tenapanor, and a 4-week placebo-controlled, randomized withdrawal period, during which patients are re-randomized 1:1 to either remain on their current tenapanor treatment or placebo.
Depending on the increase in serum phosphate levels, subjects can be randomized 1,2, or 3 weeks after being taken off their phosphate lowering medication.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperphosphatemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
219 (Actual)
8. Arms, Groups, and Interventions
Arm Title
3mg BID
Arm Type
Experimental
Arm Description
Tenapanor, 3mg BID (6mg total)
Arm Title
10mg BID
Arm Type
Experimental
Arm Description
Tenapanor, 10mg BID (20mg total)
Arm Title
Dose Titration
Arm Type
Experimental
Arm Description
Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Tenapanor
Other Intervention Name(s)
RDX5791, AZD1722
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Placebo Adjusted Change in Serum Phosphate During Randomized Withdrawal Period From Pooled Tenapanor Arms
Description
Serum phosphorus difference between placebo and tenapanor in the change from the end of the 8 week treatment period to the end of the randomized withdrawal period in Efficacy Analysis Set. The efficacy analysis was pre-defined to be a pooled analysis of all tenapanor treated patients with a minimum of a 1.2 mg/dL decrease in serum phosphorus during the 8-week treatment period
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Change in Serum Phosphate During 8-Week Treatment Period
Description
Serum phosphorus difference between baseline (end of washout period) to the end of the 8 week treatment period in ITT analysis set
Time Frame
Baseline and 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 to 80 years old
Females must be non-pregnant, non-lactating, and either be post-menopausal for at least 12 months, have documentation of irreversible surgical sterilization, or confirm the use of one of the acceptable contraceptive methods.
Males must agree to avoid fathering a child and agree to use an appropriate method of contraception
Chronic maintenance hemodialysis 3x/week for at least 3 months
Kt/V ≥ 1.3 at most recent measurement prior to screening
Prescribed and taking at least 3 doses of phosphate binder per day
Serum phosphate levels should be between 4.0 and 7.0 mg/dL (inclusive) at screening
For randomization in the study, after 1 week wash-out of phosphate binders, subjects must have serum phosphate level of at least 9 mg/dL but below 10 mg/dL and have had an increase of at least 1.5 mg/dL versus pre-wash out value
For randomization in the study, after 2 or 3 weeks wash-out of phosphate binders, subjects must have serum phosphate level of at least 6 mg/dL but below 10 mg/dL and have had an increase of at least 1.5 mg/dL versus pre-wash out value
Exclusion Criteria:
Severe hyperphosphatemia defined as >10 mg/dL on Phosphate-binders at any time point during clinical routine monitoring for the 3 preceding months before screening
Serum parathyroid hormone >1200 pg/mL
Persistent metabolic acidosis defined as serum carbon dioxide <18 mmol/L from two consecutive measurements during screening and washout periods
Clinical signs of hypovolemia at randomization
History of inflammatory bowel disease (IBD) or diarrhea predominant irritable bowel syndrome (IBS-D)
Scheduled for living donor kidney transplant, change to peritoneal dialysis, home HD or plans to relocate to another center during the study period
Diarrhea or loose stools during the week before randomization defined as BSFS ≥ 6 and frequency ≥ 3 for 2 or more days
Any evidence of or treatment of malignancy within one year, excluding non-melanomatous malignancies of the skin
Positive serology with evidence of significant hepatic impairment or WBC elevation according to the Investigator
Life expectancy < 6 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David P Rosenbaum, Ph.D.
Organizational Affiliation
Ardelyx, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Ardelyx Investigative Site 429
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35805
Country
United States
Facility Name
Ardelyx Investigative Site 425
City
Riverside
State/Province
California
ZIP/Postal Code
92505
Country
United States
Facility Name
Ardelyx Clinical Site 403
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
Facility Name
Ardelyx Investigative Site 410
City
Lauderdale Lakes
State/Province
Florida
ZIP/Postal Code
33313
Country
United States
Facility Name
Ardelyx Investigative Site 430
City
Miami
State/Province
Florida
ZIP/Postal Code
33173
Country
United States
Facility Name
Ardelyx Investigative Site 427
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
Facility Name
Ardelyx Investigative Site 432
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71101
Country
United States
Facility Name
Ardelyx Investigative Site 415
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20814
Country
United States
Facility Name
Ardelyx Investigative Site 402
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49008
Country
United States
Facility Name
Ardelyx Investigative Site 424
City
Roseville
State/Province
Michigan
ZIP/Postal Code
48066
Country
United States
Facility Name
Ardelyx Investigative Site 409
City
Brookhaven
State/Province
Mississippi
ZIP/Postal Code
39601
Country
United States
Facility Name
Ardelyx Investigative Site 417
City
Columbus
State/Province
Mississippi
ZIP/Postal Code
39705
Country
United States
Facility Name
Ardelyx Investigative Site 431
City
Tupelo
State/Province
Mississippi
ZIP/Postal Code
38801
Country
United States
Facility Name
Ardelyx Investigative Site 423
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63136
Country
United States
Facility Name
Ardelyx Investigative Site 416
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87109
Country
United States
Facility Name
Ardelyx Investigative Site 419
City
Bronx
State/Province
New York
ZIP/Postal Code
10803
Country
United States
Facility Name
Ardelyx Investigative Site 408
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28805
Country
United States
Facility Name
Ardelyx Investigative Site 411
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Ardelyx Investigative Site 420
City
New Bern
State/Province
North Carolina
ZIP/Postal Code
28562
Country
United States
Facility Name
Ardelyx Investigative Site 426
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27609
Country
United States
Facility Name
Ardelyx Investigative Site 412
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28403
Country
United States
Facility Name
Ardelyx Investigative Site 414
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18017
Country
United States
Facility Name
Ardelyx Investigative Site 404
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
Ardelyx Investigative Site 421
City
Orangeburg
State/Province
South Carolina
ZIP/Postal Code
29118
Country
United States
Facility Name
Ardelyx Investigative Site 428
City
Sumter
State/Province
South Carolina
ZIP/Postal Code
29150
Country
United States
Facility Name
Ardelyx Investigative Site 413
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37923
Country
United States
Facility Name
Ardelyx Investigative Site 418
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37205
Country
United States
Facility Name
Ardelyx Investigative Site 406
City
Austin
State/Province
Texas
ZIP/Postal Code
78758
Country
United States
Facility Name
Ardelyx Investigative Site 405
City
Bellville
State/Province
Texas
ZIP/Postal Code
77418
Country
United States
Facility Name
Ardelyx Investigative Site 422
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Ardelyx Investigative Site 407
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Ardelyx Investigative Site 401
City
Saint George
State/Province
Utah
ZIP/Postal Code
84790
Country
United States
12. IPD Sharing Statement
Learn more about this trial
An 8-Week Study to Evaluate Tenapanor in the Treatment of Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)
We'll reach out to this number within 24 hrs