Back to resultsA Study to Evaluate the Safety and Efficacy of CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus
Primary Purpose
Chronic Kidney Diseases, Pruritus
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CR845 0.25 mg Oral Tablet
CR845 0.5 mg Oral Tablet
CR845 1 mg Oral Tablet
Placebo Oral Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Kidney Diseases focused on measuring difelikefalin, CR845, Pruritus, Chronic Itch, Itch, Itching, uremic pruritus, CKD, CKD-aP, CKD-associated pruritus, Chronic Kidney Disease, Kidney dysfunction, Generalized pruritus, Hemodialysis, Dialysis, ESRD (end stage renal disease), Kidney failure, chronic
Eligibility Criteria
Inclusion Criteria:
To be eligible for inclusion into the study, a patient must meet the following criteria:
- CKD patients with stage III, IV, or V (ie, moderate renal impairment with estimated glomerular filtration rate (GFR) ≥30 and <60 mL/min/1.73 m2 or severe renal impairment with estimated GFR <30 mL/min/1.73 m2).
- For severe CKD patients on hemodialysis, they must be receiving hemodialysis 3 times per week for at least 3 months prior to the start of screening;
Prior to randomization:
- Has completed at least 4 Worst Itching Intensity NRS worksheets from the start of the 7-day Run-in Period;
- Has a mean baseline Worst Itching Intensity NRS score ≥5, defined as the average of all non-missing scores reported from the start of the 7-day Run-in Period.
Exclusion Criteria:
A patient will be excluded from the study if any of the following criteria are met:
- Patients not currently on dialysis who are likely to initiate routine dialysis during study participation;
- Scheduled to receive a kidney transplant during the study;
- New or change of treatment received for itch including antihistamines and corticosteroids (oral, intravenous [IV], or topical) within 14 days prior to screening;
- Received another investigational drug within 30 days prior to the start of screening or is planning to participate in another clinical study while enrolled in this study;
- Received ultraviolet B treatment within 30 days prior to the start of screening or anticipates receiving such treatment during the study;
- Participated in a previous clinical study with CR845.
Sites / Locations
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site 2
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site 1
- Cara Therapeutics Study Site 2
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site 2
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
- Cara Therapeutics Study Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
CR845 0.25 mg Oral Tablet
CR845 0.5 mg Oral Tablet
CR845 1 mg Oral Tablet
Placebo Oral Tablet
Arm Description
Oral CR845 0.25 mg to be taken orally once daily for 12 weeks
Oral CR845 0.5 mg to be taken orally once daily for 12 weeks
Oral CR845 1 mg to be taken orally once daily for 12 weeks
Oral Placebo to be taken orally once daily
Outcomes
Primary Outcome Measures
Reduction of itch-intensity as assessed by the change from baseline in weekly mean of the daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) score during Week 12
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".
Secondary Outcome Measures
Improvement in itch-related quality of life as assessed by the change from baseline in total Skindex-10 Scale score at the end of Week 12
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 in 5-D Itch Scale score at the end of Week 12
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 Worst Itching Intensity NRS score at Week 12
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".
Full Information
NCT ID
NCT03617536
First Posted
July 11, 2018
Last Updated
October 22, 2020
Sponsor
Cara Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03617536
Brief Title
A Study to Evaluate the Safety and Efficacy of CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus
Official Title
A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Oral CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
July 5, 2018 (Actual)
Primary Completion Date
October 24, 2019 (Actual)
Study Completion Date
November 14, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cara Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of 3 dose levels of oral CR845 compared to placebo in reducing the intensity of itch in chronic kidney disease (CKD) patients with moderate-to-severe pruritus. This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week Treatment Period, and a Follow-up Visit (approximately 7 days after the last dose of study drug).
Detailed Description
This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week Treatment Period, and a Follow-up Visit (approximately 7 to 10 days after the last dose of study drug). 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.
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 1:1:1:1 ratio to receive orally once daily either placebo or CR845 tablets at doses of 0.25, 0.5 or 1 mg. Randomization will be stratified according to the patient's renal disease status: moderate CKD; severe CKD non-dialysis; severe CKD on dialysis (ie, 3 categories). A final safety Follow-up Visit will be conducted 7 to 10 days after the last dose of study drug.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Diseases, Pruritus
Keywords
difelikefalin, CR845, Pruritus, Chronic Itch, Itch, Itching, uremic pruritus, CKD, CKD-aP, CKD-associated pruritus, Chronic Kidney Disease, Kidney dysfunction, Generalized pruritus, Hemodialysis, Dialysis, ESRD (end stage renal disease), Kidney failure, chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind, placebo controlled study
Masking
ParticipantInvestigator
Masking Description
CR845 will be provided as enteric-coated tablets. All tablets are white in color with no markings and are identical in appearance, regardless of dose.
CR845 tablets will be provided at doses of 0.25, 0.5, and 1 mg.
Allocation
Randomized
Enrollment
271 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CR845 0.25 mg Oral Tablet
Arm Type
Experimental
Arm Description
Oral CR845 0.25 mg to be taken orally once daily for 12 weeks
Arm Title
CR845 0.5 mg Oral Tablet
Arm Type
Experimental
Arm Description
Oral CR845 0.5 mg to be taken orally once daily for 12 weeks
Arm Title
CR845 1 mg Oral Tablet
Arm Type
Experimental
Arm Description
Oral CR845 1 mg to be taken orally once daily for 12 weeks
Arm Title
Placebo Oral Tablet
Arm Type
Placebo Comparator
Arm Description
Oral Placebo to be taken orally once daily
Intervention Type
Drug
Intervention Name(s)
CR845 0.25 mg Oral Tablet
Other Intervention Name(s)
Difelikefalin
Intervention Description
CR845 0.25 mg medication taken orally 1 time/day
Intervention Type
Drug
Intervention Name(s)
CR845 0.5 mg Oral Tablet
Other Intervention Name(s)
Difelikefalin
Intervention Description
CR845 0.5 mg medication taken orally 1 time/day
Intervention Type
Drug
Intervention Name(s)
CR845 1 mg Oral Tablet
Other Intervention Name(s)
Difelikefalin
Intervention Description
CR845 1 mg medication taken orally 1 time/day
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Placebo tablet taken orally 1 time/day
Primary Outcome Measure Information:
Title
Reduction of itch-intensity as assessed by the change from baseline in weekly mean of the daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) score during Week 12
Description
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".
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Improvement in itch-related quality of life as assessed by the change from baseline in total Skindex-10 Scale score at the end of Week 12
Description
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.
Time Frame
Baseline, Week 12
Title
Improvement in itch-related quality of life as assessed by the change from baseline in 5-D Itch Scale score at the end of Week 12
Description
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.
Time Frame
Baseline, Week 12
Title
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 Worst Itching Intensity NRS score at Week 12
Description
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".
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
To be eligible for inclusion into the study, a patient must meet the following criteria:
CKD patients with stage III, IV, or V (ie, moderate renal impairment with estimated glomerular filtration rate (GFR) ≥30 and <60 mL/min/1.73 m2 or severe renal impairment with estimated GFR <30 mL/min/1.73 m2).
For severe CKD patients on hemodialysis, they must be receiving hemodialysis 3 times per week for at least 3 months prior to the start of screening;
Prior to randomization:
Has completed at least 4 Worst Itching Intensity NRS worksheets from the start of the 7-day Run-in Period;
Has a mean baseline Worst Itching Intensity NRS score ≥5, defined as the average of all non-missing scores reported from the start of the 7-day Run-in Period.
Exclusion Criteria:
A patient will be excluded from the study if any of the following criteria are met:
Patients not currently on dialysis who are likely to initiate routine dialysis during study participation;
Scheduled to receive a kidney transplant during the study;
New or change of treatment received for itch including antihistamines and corticosteroids (oral, intravenous [IV], or topical) within 14 days prior to screening;
Received another investigational drug within 30 days prior to the start of screening or is planning to participate in another clinical study while enrolled in this study;
Received ultraviolet B treatment within 30 days prior to the start of screening or anticipates receiving such treatment during the study;
Participated in a previous clinical study with CR845.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frédérique Menzaghi, PhD
Organizational Affiliation
Cara Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Cara Therapeutics Study Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Florence
State/Province
Alabama
ZIP/Postal Code
35630
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Prescott
State/Province
Arizona
ZIP/Postal Code
86401
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Sun City
State/Province
Arizona
ZIP/Postal Code
85351
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Harrisburg
State/Province
Arkansas
ZIP/Postal Code
72432
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309
Country
United States
Facility Name
Cara Therapeutics Study Site 2
City
Bakersfield
State/Province
California
ZIP/Postal Code
99309
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Canyon Country
State/Province
California
ZIP/Postal Code
91351
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Escondido
State/Province
California
ZIP/Postal Code
92025
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Lomita
State/Province
California
ZIP/Postal Code
90717
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Northridge
State/Province
California
ZIP/Postal Code
91324
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Riverside
State/Province
California
ZIP/Postal Code
92505
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95831
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Whittier
State/Province
California
ZIP/Postal Code
90602
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Edgewater
State/Province
Florida
ZIP/Postal Code
32132
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33024
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Lake Worth
State/Province
Florida
ZIP/Postal Code
33467
Country
United States
Facility Name
Cara Therapeutics Study Site 1
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
Cara Therapeutics Study Site 2
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32810
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Temple Terrace
State/Province
Florida
ZIP/Postal Code
33637
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30909
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Sandy Springs
State/Province
Georgia
ZIP/Postal Code
30328
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Crystal Lake
State/Province
Illinois
ZIP/Postal Code
60012
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
Cara Therapeutics Study Site
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70115
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Zachary
State/Province
Louisiana
ZIP/Postal Code
70791
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Takoma Park
State/Province
Maryland
ZIP/Postal Code
20912
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Flint
State/Province
Michigan
ZIP/Postal Code
48503
Country
United States
Facility Name
Cara Therapeutics Study Site 2
City
Flint
State/Province
Michigan
ZIP/Postal Code
48532
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Roseville
State/Province
Michigan
ZIP/Postal Code
48066
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Saint Clair
State/Province
Michigan
ZIP/Postal Code
48081
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11229
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Rocky Mount
State/Province
North Carolina
ZIP/Postal Code
27804
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43215
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Norman
State/Province
Oklahoma
ZIP/Postal Code
73071
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Camp Hill
State/Province
Pennsylvania
ZIP/Postal Code
17011
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Warwick
State/Province
Rhode Island
ZIP/Postal Code
02886
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57702
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Corsicana
State/Province
Texas
ZIP/Postal Code
75110
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Gonzales
State/Province
Texas
ZIP/Postal Code
78629
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77081
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Plano
State/Province
Texas
ZIP/Postal Code
75093
Country
United States
Facility Name
Cara Therapeutics Study Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78207
Country
United States
Facility Name
Cara Therapeutics Study Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78224
Country
United States
Facility Name
Cara Therapeutics Study Site
City
Alexandria
State/Province
Virginia
ZIP/Postal Code
22304
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study to Evaluate the Safety and Efficacy of CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus
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