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Study to Evaluate the Safety and Efficacy of Oral CR845 (Difelikefalin) in Patients With Primary Biliary Cholangitis (PBC) and Moderate-to-Severe Pruritus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03995212
Recruitment Status : Recruiting
First Posted : June 21, 2019
Last Update Posted : February 10, 2020
Sponsor:
Information provided by (Responsible Party):
Cara Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE June 19, 2019
First Posted Date  ICMJE June 21, 2019
Last Update Posted Date February 10, 2020
Actual Study Start Date  ICMJE June 25, 2019
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2019)
Change from baseline to Week 16 with respect to the weekly mean of the daily 24-hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) score. [ Time Frame: Baseline, Week 16 ]
Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable".
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2019)
  • Improvement in itch-related quality of life as assessed by the change from baseline to Week 16 in total Skindex-10 Scale score [ Time Frame: Baseline, Week 16 ]
    The Skindex-10 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. A lower total score represents better quality of life.
  • Improvement in itch-related quality of life as assessed by the change from baseline to Week 16 in 5-D Itch Scale score [ Time Frame: Baseline, Week 16 ]
    The 5-D Itch Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past 2 weeks. The questions cover five dimensions of itch including the degree, duration of itch/day, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. A lower total score represents better quality of life.
  • Reduction of itch intensity as assessed by the proportion of patients achieving an improvement from baseline ≥3 points with respect to the weekly mean of the daily 24-hour WI-NRS score at Week 16 [ Time Frame: Week 16 ]
    Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable".
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Safety and Efficacy of Oral CR845 (Difelikefalin) in Patients With Primary Biliary Cholangitis (PBC) and Moderate-to-Severe Pruritus
Official Title  ICMJE A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Oral CR845 in Patients With Primary Biliary Cholangitis (PBC) and Moderate-to-Severe Pruritus
Brief Summary This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of twice-daily (BID) oral CR845 1.0 mg in patients with PBC with moderate-to-severe pruritus. The study includes a 16-week Treatment Period.
Detailed Description

This study will consist of a Screening Visit, a 7-day Run-in Period, a 16-week Treatment Period, and a Follow-up Visit (approximately 7-10 days after the last dose of study drug). Informed consent will be obtained prior to performing any study-specific procedures.

The Screening Visit will occur within 7 to 28 days prior to randomization to assess eligibility.

Day 1 of the Treatment Period will be defined as the day of the administration of the first dose of study drug. 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 either placebo or CR845 tablets at a dose of 1.0 mg orally BID for 16 weeks.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Cholestatic Pruritus
Intervention  ICMJE
  • Drug: CR845 1.0 mg
    Oral CR845 1.0 mg administered twice daily
    Other Names:
    • CR845
    • Difelikefalin
  • Drug: Placebo
    Oral Placebo administered twice daily
Study Arms  ICMJE
  • Active Comparator: CR845 1.0 mg
    Oral CR845 1.0 mg tablet administered twice daily
    Intervention: Drug: CR845 1.0 mg
  • Placebo Comparator: Placebo
    Oral placebo tablet administered twice daily
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 19, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

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

  • Confirmed diagnosis of PBC;
  • If currently taking ursodeoxycholic acid (UDCA), should be on stable dose for >12 weeks prior to screening and plan on continuing to take UDCA throughout the study;
  • If previously taking UDCA, should have discontinued its use >12 weeks prior to screening;
  • Self-reports experiencing daily or near-daily pruritus during the month prior to screening;
  • Prior to randomization has a mean baseline WI-NRS score indicative of moderate to severe pruritus.

Key Exclusion Criteria:

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

  • Presence of Child-Pugh Class C decompensated cirrhosis at screening;
  • Itching secondary to biliary obstruction;
  • History or presence of hepatocellular carcinoma, hepatic abscess, or acute portal vein thrombosis;
  • Current placement on liver transplantation list with anticipated liver transplant during the course of the study or current Model for End-stage Liver Disease (MELD) score ≥15;
  • Alanine aminotransferase or aspartate aminotransferase >5 × upper limit of normal at screening, or within 2 months prior to screening;
  • Anticipates receiving an opioid antagonist (eg, naloxone, naltrexone) or opioid-mixed agonist-antagonist (eg, buprenorphine, nalbuphine) from the start of screening through the end of the Treatment Period;
  • New or change of treatment with antihistamines and corticosteroids (oral, intravenous, or topical), opioids, gabapentin, pregabalin, cholestyramine, rifampicin or fibrates within 14 days prior to screening.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Georgine Ragsdale, PharmD 203-406-3700 clinicaltrials.gov@caratherapeutics.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03995212
Other Study ID Numbers  ICMJE CR845-210401
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Cara Therapeutics, Inc.
Study Sponsor  ICMJE Cara Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Frédérique Menzaghi, PhD Cara Therapeutics
PRS Account Cara Therapeutics, Inc.
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP