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

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Cara Therapeutics

Status and phase

Phase 3


Chronic Kidney Diseases


Drug: Difelikefalin 1 mg Oral Tablet
Drug: Placebo Oral Tablet

Study type


Funder types




Details and patient eligibility


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.

Full description

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.


286 patients




18 to 85 years old


No Healthy Volunteers

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:

  • Has recorded at least 4 WI-NRS scores during the 7-day Run-in Period; and
  • 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.

Trial design

Primary purpose




Interventional model

Parallel Assignment


Double Blind

286 participants in 2 patient groups, including a placebo group

Difelikefalin 1 mg Oral Tablet
Experimental group
Patients receive oral difelikefalin 1 mg once daily
Drug: Difelikefalin 1 mg Oral Tablet
Placebo Oral Tablet
Placebo Comparator group
Patients receive oral placebo once daily
Drug: Placebo Oral Tablet

Trial contacts and locations



Central trial contact

Cara Therapeutics

Data sourced from clinicaltrials.gov

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