A Study to Evaluate the Safety and Efficacy of CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

Sponsor

Cara Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03617536

Collaborator

(none)

271

Enrollment

Locations

Arms

16.3

Actual Duration (Months)

4.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Diseases Pruritus	Drug: CR845 0.25 mg Oral Tablet Drug: CR845 0.5 mg Oral Tablet Drug: CR845 1 mg Oral Tablet Drug: Placebo Oral Tablet	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

271 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, double-blind, placebo controlled studyRandomized, double-blind, placebo controlled study

Masking:

Double (Participant, Investigator)

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.

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 5, 2018

Actual Primary Completion Date :

Oct 24, 2019

Actual Study Completion Date :

Nov 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CR845 0.25 mg Oral Tablet Oral CR845 0.25 mg to be taken orally once daily for 12 weeks	Drug: CR845 0.25 mg Oral Tablet CR845 0.25 mg medication taken orally 1 time/day Other Names: Difelikefalin
Experimental: CR845 0.5 mg Oral Tablet Oral CR845 0.5 mg to be taken orally once daily for 12 weeks	Drug: CR845 0.5 mg Oral Tablet CR845 0.5 mg medication taken orally 1 time/day Other Names: Difelikefalin
Experimental: CR845 1 mg Oral Tablet Oral CR845 1 mg to be taken orally once daily for 12 weeks	Drug: CR845 1 mg Oral Tablet CR845 1 mg medication taken orally 1 time/day Other Names: Difelikefalin
Placebo Comparator: Placebo Oral Tablet Oral Placebo to be taken orally once daily	Drug: Placebo Oral Tablet Placebo tablet taken orally 1 time/day

Outcome Measures

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 [Baseline, 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 [Baseline, 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 [Baseline, 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 [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".

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cara Therapeutics Study Site	Birmingham	Alabama	United States	35233
2	Cara Therapeutics Study Site	Florence	Alabama	United States	35630
3	Cara Therapeutics Study Site	Phoenix	Arizona	United States	85016
4	Cara Therapeutics Study Site	Prescott	Arizona	United States	86401
5	Cara Therapeutics Study Site	Sun City	Arizona	United States	85351
6	Cara Therapeutics Study Site	Harrisburg	Arkansas	United States	72432
7	Cara Therapeutics Study Site	Bakersfield	California	United States	93309
8	Cara Therapeutics Study Site 2	Bakersfield	California	United States	99309
9	Cara Therapeutics Study Site	Canyon Country	California	United States	91351
10	Cara Therapeutics Study Site	Escondido	California	United States	92025
11	Cara Therapeutics Study Site	Lomita	California	United States	90717
12	Cara Therapeutics Study Site	Northridge	California	United States	91324
13	Cara Therapeutics Study Site	Riverside	California	United States	92505
14	Cara Therapeutics Study Site	Sacramento	California	United States	95831
15	Cara Therapeutics Study Site	Whittier	California	United States	90602
16	Cara Therapeutics Study Site	Denver	Colorado	United States	80230
17	Cara Therapeutics Study Site	Washington	District of Columbia	United States	20037
18	Cara Therapeutics Study Site	Edgewater	Florida	United States	32132
19	Cara Therapeutics Study Site	Hialeah	Florida	United States	33016
20	Cara Therapeutics Study Site	Hollywood	Florida	United States	33024
21	Cara Therapeutics Study Site	Lake Worth	Florida	United States	33467
22	Cara Therapeutics Study Site 1	Miami	Florida	United States	33125
23	Cara Therapeutics Study Site 2	Miami	Florida	United States	33155
24	Cara Therapeutics Study Site	Ocala	Florida	United States	34471
25	Cara Therapeutics Study Site	Orlando	Florida	United States	32810
26	Cara Therapeutics Study Site	Tampa	Florida	United States	33614
27	Cara Therapeutics Study Site	Temple Terrace	Florida	United States	33637
28	Cara Therapeutics Study Site	Augusta	Georgia	United States	30909
29	Cara Therapeutics Study Site	Sandy Springs	Georgia	United States	30328
30	Cara Therapeutics Study Site	Crystal Lake	Illinois	United States	60012
31	Cara Therapeutics Study Site	Evanston	Illinois	United States	60201
32	Cara Therapeutics Study Site	Iowa City	Iowa	United States	52242
33	Cara Therapeutics Study Site	Metairie	Louisiana	United States	70006
34	Cara Therapeutics Study Site	New Orleans	Louisiana	United States	70115
35	Cara Therapeutics Study Site	Zachary	Louisiana	United States	70791
36	Cara Therapeutics Study Site	Baltimore	Maryland	United States	21287
37	Cara Therapeutics Study Site	Takoma Park	Maryland	United States	20912
38	Cara Therapeutics Study Site	Flint	Michigan	United States	48503
39	Cara Therapeutics Study Site 2	Flint	Michigan	United States	48532
40	Cara Therapeutics Study Site	Roseville	Michigan	United States	48066
41	Cara Therapeutics Study Site	Saint Clair	Michigan	United States	48081
42	Cara Therapeutics Study Site	Kansas City	Missouri	United States	64111
43	Cara Therapeutics Study Site	Brooklyn	New York	United States	11229
44	Cara Therapeutics Study Site	Mineola	New York	United States	11501
45	Cara Therapeutics Study Site	Rocky Mount	North Carolina	United States	27804
46	Cara Therapeutics Study Site	Columbus	Ohio	United States	43215
47	Cara Therapeutics Study Site	Norman	Oklahoma	United States	73071
48	Cara Therapeutics Study Site	Camp Hill	Pennsylvania	United States	17011
49	Cara Therapeutics Study Site	Providence	Rhode Island	United States	02903
50	Cara Therapeutics Study Site	Warwick	Rhode Island	United States	02886
51	Cara Therapeutics Study Site	Greenville	South Carolina	United States	29605
52	Cara Therapeutics Study Site	Rapid City	South Dakota	United States	57702
53	Cara Therapeutics Study Site	Corsicana	Texas	United States	75110
54	Cara Therapeutics Study Site	Gonzales	Texas	United States	78629
55	Cara Therapeutics Study Site	Houston	Texas	United States	77074
56	Cara Therapeutics Study Site	Houston	Texas	United States	77081
57	Cara Therapeutics Study Site	Plano	Texas	United States	75093
58	Cara Therapeutics Study Site	San Antonio	Texas	United States	78207
59	Cara Therapeutics Study Site	San Antonio	Texas	United States	78224
60	Cara Therapeutics Study Site	Alexandria	Virginia	United States	22304