Study to Evaluate IV CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

• ClinicalTrials.gov Identifier: NCT02858726
• Recruitment Status: Completed
• First Posted: August 8, 2016
• Last Update Posted: May 31, 2019
• Sponsor: Cara Therapeutics, Inc.
• Information provided by (Responsible Party): Cara Therapeutics, Inc.

Study Description

Brief Summary:

2 Part Study: Part A will assess 3 different dosing levels of IV CR845 versus placebo in patient on hemodialysis who have moderate-to-severe itching due to uremic pruritus. Patients will receive either CR845 or placebo after each dialysis session for eight weeks. The safety and efficacy of CR845 will be monitored throughout the study. A sub-group of patients will also have pharmacokinetic assessments completed. Part B of the study will assess one dose of IVCR845 versus placebo for 12 weeks in patients on hemodialysis who have moderate-to-severe itching. The dose of CR845 used in Part B will be based on safety and efficacy found in Part A.

Condition or disease	Intervention/treatment	Phase
Uremic Pruritus	Drug: CR845 0.5 mcg/kg; Drug: CR845 1 mcg/kg; Drug: CR845 1.5mcg/kg; Drug: Placebo	Phase 2; Phase 3

Detailed Description:

This is a two-part study. Patients participating in Part A will be consented and trained on the completion of questionnaires about the severity of itching and overall health. Patients will be required to complete questionnaires during their visits to the dialysis center and also while at home on other days. Results of the screening questionnaires will assess eligibility for the study. Additional laboratory tests and measurements for safety will also be completed during the screening period. Patients meeting all criteria for entry into Part A of the study will be randomized to receive either one of three different doses of CR845 or a placebo. Patients will receive the study drug for eight weeks IV after each hemodialysis treatment (i.e. 3 times per week). Assessments for intensity of itch and safety will also be completed during the 8 week treatment period. When patients have completed treatment, a Follow-up visit will be completed 7 days later.

Patients participating in Part B will be consented and trained on the completion of questionnaires about itching and overall health. Patients will be required to complete questionnaires during their visits to the dialysis center and also while at home on other days. Laboratory tests and measurements for safety will also be completed during the screening period to determine study eligibility. Patients meeting all criteria for entry into Part B of the study will be randomized to receive either CR845 or a placebo. The dose of CR845 used will have been determined based on the safety and efficacy from Part A. Patients will be dosed with either CR845 or placebo for twelve weeks after each hemodialysis treatment (i.e. 3 times per week). Assessments for intensity of itch and safety will be completed during the treatment period also. When patients have completed treatment, a Follow-up visit will be completed 7 days later.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 175 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Two-Part, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
• Study Start Date: June 2016
• Actual Primary Completion Date: March 14, 2017
• Actual Study Completion Date: March 14, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: CR845 0.5mcg/kg; Part A of study: IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)	Drug: CR845 0.5 mcg/kg; IV medication delivered three times/week; Other Name: CR845
Experimental: CR845 1 mcg/kg; Part A of study: IV CR845 1 mcg/kg administered after each dialysis session (3 times/week)	Drug: CR845 1 mcg/kg; IV medication delivered three times/week; Other Name: CR845
Experimental: CR845 1.5mcg/kg; Part A of study: IV CR845 1.5 mcg/kg administered after each dialysis session (3 times/week)	Drug: CR845 1.5mcg/kg; IV medication delivered three times/week; Other Name: CR845
Placebo Comparator: Placebo; Part A of study: IV Placebo administered after each dialysis session (3 times/week)	Drug: Placebo; IV medication delivered three times/week

Outcome Measures

Primary Outcome Measures :

1. Part A: An assessment of 3 dose levels of CR845 and placebo in reducing the intensity of itch in hemodialysis patients [ Time Frame: 8 weeks ]
   Patient reported intensity of itch using the Worst Itching Intensity Numerical Rating Scale
2. Part B: An assessment of CR845 compared to placebo in reducing the intensity of itch in hemodialysis patients [ Time Frame: 12 weeks ]
   Patient reported intensity of itch using the Worst Itching Intensity Numerical Rating Scale

Secondary Outcome Measures :

1. Part A and Part B: Safety of IV CR845 will be assessed by physical examination, monitoring of adverse events, vital signs and laboratory assessments [ Time Frame: up to 12 weeks ]
   The safety of CR845 will be assessed in this patient population by physical examination, monitoring of adverse events, vital signs and laboratory assessments at specified times. Participants with clinically significant laboratory values or abnormal exam findings, as well as those with adverse events related to study drug,will be compared to those receiving placebo.
2. Part A: The pharmacokinetic profile of CR845 will be determined between Week 1 and Week 8. The calculation of the accumulation ratio between the first and last doses with respect to Cmax will be reported. [ Time Frame: 8 weeks ]
   To evaluate the pharmacokinetics of 3 dose levels of CR845 given 3 times a week for 8 weeks.
3. Part A: The pharmacokinetic profile of CR845 will be determined between Week 1 and Week 8. The calculation of the accumulation ratio between the first and last doses with respect to AUC will be reported. [ Time Frame: 8 weeks ]
   To evaluate the pharmacokinetics of 3 dose levels of CR845 given 3 times a week for 8 weeks.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Willing and able to provide written informed consent prior to participating in this study;
2. Able to communicate clearly with the Investigator and staff, able to read, complete questionnaires, and understand the study procedures;
3. Males or females 18 years of age or older;
4. ESRD patients who have been on hemodialysis 3 times per week for at least 3 months prior to the start of Screening;
5. Women of child-bearing potential must have a negative serum pregnancy test and agree to practice an acceptable form of birth control for the duration of the study
6. Male patients that are not biologically or surgically sterile must agree to practice an acceptable from of birth control for the duration of the study
7. Weigh between 88.2 lb (40.0 kg) and 297.6 lb (135.0 kg).
8. Patient must self-report pruritus in the month prior to screening.
9. If patient is receiving treatment for itch, this treatment must be stable prior to screening and during treatment period.
10. At least 2 single-pool Kt/V measurements ≥ 1.2, or at least 2 urea reduction ratio measurements ≥ 65%, or 1 single-pool Kt/V measurement ≥ 1.2 and 1 urea reduction ratio measurement ≥ 65% on different dialysis days during the 3 months period prior to Screening;
11. Patient who self-categorize as moderate-to-severe itch.

Exclusion Criteria:

1. Known to be non-compliant with dialysis treatment (i.e., has missed more than 2 dialysis sessions in the past 2 months because of non-compliance);
2. Anticipated to receive a kidney transplant during the study;
3. Known history of allergic reaction to opiates, such as hives
4. Known or suspected history of alcohol, narcotic, or other drug abuse or dependence within 12 months prior to Screening;
5. Patient has any clinically relevant acute or chronic medical or neuropsychiatric condition which, in the opinion of the Investigator, would pose undue risk to the patient, would impede completion of the study procedures, or would compromise the validity of the study measurements;
6. Serum alanine aminotransferase or aspartate aminotransferase greater than 2.5 times the reference upper limit of normal (ULN), or total bilirubin greater than 2 times ULN at Screening;
7. Received another investigational drug within 30 days prior to the start of Screening or has planned to participate in another clinical trial while enrolled in this study;
8. Has pruritus probably or definitely attributed to a cause other than ESRD or its complications (e.g., patients with concomitant pruritic dermatological disease or cholestatic liver disease would be excluded). (Note: Patients whose pruritus is attributed to ESRD complications such as hyperparathyroidism, hyperphosphatemia, anemia, or the dialysis procedure or prescription may be enrolled);
9. Has localized itch restricted to the palms of the hands;
10. Has pruritus only during the dialysis session (by patient report);
11. Anticipated to receive opioid antagonists (e.g., naloxone, naltrexone), or opioid mixed agonist-antagonist (e.g., buprenorphine, nalbuphine) from the start of Screening through the end of the Treatment Period;
12. Used Salvia divinorum or Salvinorin A within 30 days prior to the start of Screening or is anticipated to use it during the study;
13. Received ultraviolet B treatment within 30 days prior to the start of Screening or anticipated to receive such treatment during the study;
14. Participated in a previous clinical trial with CR845.

Contacts and Locations

  Show 29 Study Locations

Sponsors and Collaborators

Cara Therapeutics, Inc.

Investigators

• Study Director: Frederique Menzaghi, PhD; Cara Therapeutics

More Information

• Responsible Party: Cara Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02858726 History of Changes
• Other Study ID Numbers: CR845-CLIN2101
• First Posted: August 8, 2016
• Last Update Posted: May 31, 2019
• Last Verified: May 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Cara Therapeutics, Inc.:

Hemodialysis; CR845; Kappa opioid; Anti-itch; difelikefalin

Additional relevant MeSH terms:

Pruritus; Skin Diseases; Skin Manifestations; Signs and Symptoms