Clinical trial NCT03824587: Study to Evaluate the Efficacy of Tenapanor as Adjunctive Therapy to Phosphate Binder Therapy
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Tenapanor as Adjunctive Therapy to Phosphate Binder Therapy in End-Stage Renal Disease (ESRD) Subjects With Hyperphosphatemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hyperphosphatemia
Lead sponsor: Ardelyx
Sponsor class: INDUSTRY
First posted: 2019-01-31
Enrollment: 236
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo-controlled study to evaluate the effect of tenapanor on change in s-P levels when tenapanor is administered orally, twice daily for 28 days as adjunctive therapy to ESRD subjects with hyperphosphatemia on stable phosphate binder therapy.

Detailed description: The study consists of a Screening visit; a Run-in Period of at least 2 weeks and up to 4 weeks, where existing phosphate binder treatment is maintained; and a 4-week Double-Blind Treatment Period.

At Screening, a subject must be on thrice daily phosphate binder therapy and have a serum phosphate (s-P) level ≥5.5 and ≤10.0 mg/dL to qualify for entering the study. s-P will be measured at each visit during the run-in period to enable the evaluation of the s-P randomization criteria.

Subjects who qualify to enroll in the study will be randomized in a 1:1 ratio to receive tenapanor or placebo while continuing their existing phosphate binder treatment.

During the Double-Blind Treatment Period, subjects will receive tenapanor or placebo starting at a dose of 30 mg bid

Eligibility criteria: Inclusion Criteria:

* Signed and dated informed consent prior to any study specific procedures.
* Males or females aged 18 to 80 years, inclusive, at Screening
* Females must be non-pregnant, non-lactating and either be post-menopausal for at least -2 months, have documentation of irreversible surgical sterilization, use of acceptable -contraceptive method, or sexual abstinence, or a sterile sexual partner from Screening -until 30 days after the last subject visit.
* Males must agree to avoid fathering a child (or donating sperm), and therefore be either sterile (documented) or agree to use approved methods of contraception, from the time of enrollment until 30 days after end of study.
* Chronic maintenance hemodialysis (HD) 3x/week for at least 3 months or chronic maintenance peritoneal dialysis (PD) for a minimum of 6 months.
* If receiving active vitamin D or calcimimetics, the dose should have been unchanged for the last 4 weeks prior to Screening.
* Kt/V ≥1.2 at most recent measurement prior to Screening.
* Prescribed and taking phosphate binder medication at least 3 times per day, and the prescribed dose should have been unchanged during the last 4 weeks prior to Screening.
* Serum phosphorus levels must be ≥5.5 and ≤10.0 mg/dL at Screening and the end of the run-in period, analyzed at the central laboratory used in the study.

Exclusion Criteria:

* Severe hyperphosphatemia defined as having an s-P level \>10.0 mg/dL on phosphate-binders at any time point during routine clinical monitoring for the 3 preceding months before Screening.
* Serum/plasma parathyroid hormone \>1200 pg/mL.
* Clinical signs of hypovolemia at Screening as judged by the Investigator.
* History of inflammatory bowel disease (IBD) or irritable bowel syndrome with diarrhea (IBS-D).
* Scheduled for living donor kidney transplant or plans to relocate to another center during the study period.
* Use of an investigational agent within 30 days prior to Screening.
* Involvement in the planning and/or conduct of the study (applies to both Ardelyx/Contract Research Organization (CRO) staff and/or staff at the study site).
* If, in the opinion of the Investigator, the subject is unable or unwilling to fulfill the requirements of the protocol or has a condition which would render the results uninterpretable.

Primary outcomes:
measure: Change in Serum Phosphorus (s-P) Level From Baseline to Week 4.
timeFrame: 4 Weeks (28 days randomization period; from baseline to week 4)
Secondary outcomes:
measure: s-P Response at Week 4
timeFrame: 4 Weeks (28 days randomization period)
measure: Relative Change From Baseline in iFGF23 at Week 4
timeFrame: 4 Weeks (28 days randomization period)
measure: Relative Change From Baseline in cFGF23 at Week 4
timeFrame: 4 Weeks (28 days randomization period)
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Nephrology Consultants, LLC
state: Alabama
city: Pine Bluff
country: United States
facility: US Renal Care Pine Bluff
state: Arkansas
city: Beverly Hills
country: United States
facility: Southeast Renal Research
state: California
city: Chula Vista
country: United States
facility: California Institute of Renal Research - Chula Vista
state: California
city: Lynwood
country: United States
facility: North America Research Institute
state: California
city: Montebello
country: United States
facility: DaVita Clinical Research - Santa Fe Spring
state: California
city: Salinas
country: United States
facility: Central Coast Nephrology
state: California
city: San Dimas
country: United States
facility: North America Research Institute - San Dimas
state: California
city: Union City
country: United States
facility: Chabot Nephrology Medical Group
state: California
city: Whittier
country: United States
facility: American Institute of Research
state: California
city: Bradenton
country: United States
facility: Nova Clinical Research, LLC
state: Florida
city: Coral Gables
country: United States
facility: Horizon Research Group - Coral Gables
state: Florida
city: Lauderdale Lakes
country: United States
facility: South Florida Research Institute
state: Florida
city: Miami
country: United States
facility: Total Research Group, LLC
state: Florida
city: Orlando
country: United States
facility: Omega Research Consultants, LLC
state: Florida
city: Tampa
country: United States
facility: Genesis Clinical Trials
state: Florida
city: Albany
country: United States
facility: Dialysis Clinic, Inc - Albany GA
state: Georgia
city: Caldwell
country: United States
facility: Boise Kidney & Hypertension, PLLC - Meridian
state: Idaho
city: Baton Rouge
country: United States
facility: Renal Associates of Baton Rouge
state: Louisiana
city: Boston
country: United States
facility: Dialysis Clinic, Inc - Boston/Somerville
state: Massachusetts
city: Kalamazoo
country: United States
facility: Paragon Health PC - Nephrology Center
state: Michigan
city: Minneapolis
country: United States
facility: InterMed Consultants
state: Minnesota
city: Tupelo
country: United States
facility: Nephrology and Hypertension Associates, LTD
state: Mississippi
city: Kansas City
country: United States
facility: Clinical Research Consultants, LLC
state: Missouri
city: Kansas City
country: United States
facility: Dialysis Clinic, Inc - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Polack Renal, LLC (SMO)
state: Missouri
city: Las Vegas
country: United States
facility: Kidney Specialists of Southern Nevada
state: Nevada
city: Reno
country: United States
facility: Sierra Nevada Nephrology Consultants
state: Nevada
city: North Brunswick
country: United States
facility: Dialysis Clinic, Inc - North Brunswick
state: New Jersey
city: Albuquerque
country: United States
facility: Renal Medicine Associates
state: New Mexico
city: Gallup
country: United States
facility: U.S. Renal Care - Gallup
state: New Mexico
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: Asheville
country: United States
facility: Mountain Kidney and Hypertension Associates
state: North Carolina
city: Asheville
country: United States
facility: Mountain Kidney & Hypertension Associates, P.A.
state: North Carolina
city: Durham
country: United States
facility: Durham Nephrology Associates
state: North Carolina
city: Wilmington
country: United States
facility: Southeastern Nephrology Associates - Wilmington
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati (UC) - Department of Nephrology
state: Ohio
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center
state: Pennsylvania
city: Columbia
country: United States
facility: Columbia Nephrology Associates, P.A.
state: South Carolina
city: Orangeburg
country: United States
facility: South Carolina Nephrology & Hypertension Center Inc.
state: South Carolina
city: Spartanburg
country: United States
facility: DCI - Spartanburg
state: South Carolina
city: Knoxville
country: United States
facility: Knoxville Kidney Center, PLLC
state: Tennessee
city: Houston
country: United States
facility: Med Center Dialysis
state: Texas
city: Mansfield
country: United States
facility: US Renal Care - Waxahachie
state: Texas
city: Mesquite
country: United States
facility: US Renal Care - Mesquite
state: Texas
city: San Antonio
country: United States
facility: Clinical Advancement Center, PLLC
state: Texas
city: San Antonio
country: United States
facility: US Renal Care - Pleasanton Road
state: Texas
city: San Antonio
country: United States
facility: US Renal Care - Westover Hills
state: Texas
Study officials:
affiliation: Ardelyx
name: David P Rosenbaum, PhD
role: STUDY_CHAIR
References:
citation: Pergola PE, Rosenbaum DP, Yang Y, Chertow GM. A Randomized Trial of Tenapanor and Phosphate Binders as a Dual-Mechanism Treatment for Hyperphosphatemia in Patients on Maintenance Dialysis (AMPLIFY). J Am Soc Nephrol. 2021 Jun 1;32(6):1465-1473. doi: 10.1681/ASN.2020101398. Epub 2021 Mar 25.