A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

NCT ID: NCT05342623

Last Updated: 2024-05-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

286 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-17

Study Completion Date

2024-02-29

Brief Summary

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This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of oral difelikefalin administered as a 1 mg tablet once daily compared to placebo in reducing the intensity of itch in advanced chronic kidney disease (CKD) patients with moderate-to-severe pruritus. This study is comprised of an Efficacy Assessment Phase and a Long-term Extension Phase. The Efficacy Assessment Phase includes a double-blind 12-week Treatment Period (Treatment Period 1), and the Long-term Extension Phase includes a double-blind Treatment Period (Treatment Period 2) of up to 52 weeks.

Detailed Description

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This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week double-blind Efficacy Assessment Phase (Treatment Period 1), a double-blind Long-term Extension Phase (Treatment Period 2) of up to 52 weeks, and a Follow-up Visit (7 to 10 days after the End of Treatment (EOT)/Early Termination (ET) Visit).

If patients continue to meet all inclusion and no exclusion criteria at the end of the 7-day Run-in Period, they will be randomized in a 1:1 ratio to receive once daily oral difelikefalin tablets at a dose of 1 mg or placebo for 12 weeks. Subjects will be stratified according to their use or nonuse of medications to treat pruritus prior to randomization as well as the presence or absence of specific medical conditions. During the Long-term Extension Phase, patients will be re-randomized on Day 1 of Treatment Period 2 to receive either oral difelikefalin 1 mg or placebo, once daily for up to an additional 52 weeks. A final safety Follow-up Visit will be conducted 7 to 10 days after the EOT/ET.

Informed consent will be obtained prior to performing any study-specific procedures. Screening will occur within 7 to 28 days prior to randomization to assess eligibility.

Conditions

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Chronic Kidney Diseases Pruritus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, double-blind, placebo controlled study
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Difelikefalin and placebo will be provided as enteric-coated tablets. All tablets are white in color with no markings and are identical in appearance. Difelikefalin tablets will be provided at doses of 1 mg.

Study Groups

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Difelikefalin 1 mg Oral Tablet

Patients receive oral difelikefalin 1 mg once daily

Group Type EXPERIMENTAL

Difelikefalin 1 mg Oral Tablet

Intervention Type DRUG

Difelikefalin 1 mg medication taken orally 1 time/day

Placebo Oral Tablet

Patients receive oral placebo once daily

Group Type PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type DRUG

Placebo tablet taken orally 1 time/day

Interventions

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Difelikefalin 1 mg Oral Tablet

Difelikefalin 1 mg medication taken orally 1 time/day

Intervention Type DRUG

Placebo Oral Tablet

Placebo tablet taken orally 1 time/day

Intervention Type DRUG

Other Intervention Names

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CR845

Eligibility Criteria

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Inclusion Criteria

To be eligible for inclusion into the study, a patient must meet the following criteria:

* Advanced stage 4 and 5 CKD and end stage renal disease on hemodialysis
* Subject self-reports experiencing at least near-daily (eg, most days of a week) pruritus for at least 6 months prior to screening.
* Inadequate response to current or prior treatments (including emollients/moisturizers, topical medications, or systemic treatments) for pruritus prior to screening.

Prior to randomization on Day 1 of Treatment Period 1:

1. Has recorded at least 4 WI-NRS scores during the 7-day Run-in Period; and
2. Has a mean baseline WI-NRS score ≥ 5, defined as the average of all non-missing scores reported during the 7-day Run-in Period.

Exclusion Criteria

A patient will be excluded from the study if any of the following criteria are met:

* Scheduled to receive a renal replacement therapy (dialysis or kidney transplant) during the study.
* Has a concomitant disease, significant medical condition or physical/laboratory/ECG/vital signs abnormality that, in the opinion of the investigator, puts the subject at undue risk or interferes with interpretation of study results, impedes completion of the study procedures, or compromises the validity of the study measurements.
* New or change of treatment received for itch, including antihistamines and corticosteroids (oral, intravenous, or topical), within 14 days prior to the start of run-in.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cara Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Cara Therapeutics

Role: STUDY_DIRECTOR

Cara Therapeutics

Locations

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Cara Therapeutics Study Site

Chula Vista, California, United States

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El Centro, California, United States

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Huntsville, Alabama, United States

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Phoenix, Arizona, United States

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Surprise, Arizona, United States

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Anaheim, California, United States

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Bakersfield, California, United States

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Beverly Hills, California, United States

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Garden Grove, California, United States

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La Mesa, California, United States

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Northridge, California, United States

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Ontario, California, United States

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Riverside, California, United States

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Santa Clara, California, United States

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South Gate, California, United States

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Tarzana, California, United States

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Vacaville, California, United States

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Valencia, California, United States

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Victorville, California, United States

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Arvada, Colorado, United States

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Denver, Colorado, United States

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New Haven, Connecticut, United States

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Atlantis, Florida, United States

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Cape Coral, Florida, United States

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Coral Gables, Florida, United States

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Fort Lauderdale, Florida, United States

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Hialeah, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Orange City, Florida, United States

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Cara Therapeutics Study Site 2

Orlando, Florida, United States

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Orlando, Florida, United States

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Pembroke Pines, Florida, United States

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Riverview, Florida, United States

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Tampa, Florida, United States

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West Palm Beach, Florida, United States

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Albany, Georgia, United States

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East Point, Georgia, United States

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Nampa, Idaho, United States

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Huntley, Illinois, United States

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Palos Hills, Illinois, United States

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Kansas City, Kansas, United States

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Louisville, Kentucky, United States

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Baton Rouge, Louisiana, United States

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Metairie, Louisiana, United States

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Shreveport, Louisiana, United States

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Zachary, Louisiana, United States

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Boston, Massachusetts, United States

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Flint, Michigan, United States

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Kalamazoo, Michigan, United States

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Roseville, Michigan, United States

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Saint Clair, Michigan, United States

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Saint Joseph, Michigan, United States

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Tupelo, Mississippi, United States

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Kansas City, Missouri, United States

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Las Vegas, Nevada, United States

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Laurelton, New York, United States

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The Bronx, New York, United States

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Durham, North Carolina, United States

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Columbus, Ohio, United States

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Lima, Ohio, United States

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Ardmore, Oklahoma, United States

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Bethlehem, Pennsylvania, United States

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Upland, Pennsylvania, United States

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East Providence, Rhode Island, United States

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Providence, Rhode Island, United States

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Spartanburg, South Carolina, United States

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Chattanooga, Tennessee, United States

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Jackson, Tennessee, United States

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Knoxville, Tennessee, United States

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Austin, Texas, United States

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Corsicana, Texas, United States

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El Paso, Texas, United States

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Greenville, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Cara Therapeutics Study Site 2

Houston, Texas, United States

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Lewisville, Texas, United States

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McAllen, Texas, United States

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McKinney, Texas, United States

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Pasadena, Texas, United States

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Cara Therapeutics Study Site

Sherman, Texas, United States

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Cara Therapeutics Study Site

Hampton, Virginia, United States

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Countries

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United States

References

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Didik S, Golosova D, Xu B, Staruschenko A. Opioids and the Kidney: A Compendium. Kidney360. 2023 Dec 1;4(12):1816-1823. doi: 10.34067/KID.0000000000000291. Epub 2023 Nov 6.

Reference Type DERIVED
PMID: 37927032 (View on PubMed)

Other Identifiers

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CR845-310301

Identifier Type: -

Identifier Source: org_study_id

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