Safety and Pharmacokinetics of IV CR845 in Hemodialysis Patients, and Its Efficacy in Patients With Uremic Pruritus

NCT ID: NCT02229929

Last Updated: 2016-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2015-07-31

Brief Summary

The primary purpose of this study is to:

• Evaluate the safety and pharmacokinetic profile of repeated doses IV CR845 over one week in patients who are undergoing hemodialysis. (Part A)
• This study is also investigating whether repeated doses of IV CR845 over two weeks is safe and effective in reducing the intensity of itching in hemodialysis patients with uremic pruritus (Part B).

Detailed Description

Placebo-controlled

Conditions

Pruritus; Uremic Pruritus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part A: Placebo

Intravenous matched placebo

Group Type: PLACEBO_COMPARATOR

Part A: Placebo

Intervention Type: DRUG

Part A: Single i.v. dose of Placebo administered after each dialysis session over a 1 week treatment period (3 times per week)

Part A: CR845 0.5 mcg/kg

Intravenous CR845, 0.5 mcg/kg

Group Type: EXPERIMENTAL

Part A: CR845 0.5 mcg/kg

Intervention Type: DRUG

Part A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week)

Part A: CR845 1.0 mcg/kg

Intravenous CR845, 1.0 mcg/kg

Group Type: EXPERIMENTAL

Part A: CR845 1.0 mcg/kg

Intervention Type: DRUG

Part A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week)

Part A: CR845 2.5 mcg/kg

Intravenous CR845, 2.5 mcg/kg

Group Type: EXPERIMENTAL

Part A: CR845 2.5 mcg/kg

Intervention Type: DRUG

Part A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week)

Part B: Placebo

Intravenous matched placebo

Group Type: PLACEBO_COMPARATOR

Part B: Placebo

Intervention Type: DRUG

Part B: Single i.v. dose of Placebo administered after each dialysis session over a 2 week treatment period (3 times per week)

Part B: CR845 1.0 mcg/kg

Intravenous CR845, 1.0 mcg/kg

Group Type: EXPERIMENTAL

Part B: CR845 1.0 mcg/kg

Intervention Type: DRUG

Part B: Single i.v. dose of CR845 administered after each dialysis session over a 2 week treatment period (3 times per week)

Interventions

Part A: Placebo

Part A: Single i.v. dose of Placebo administered after each dialysis session over a 1 week treatment period (3 times per week)

Intervention Type: DRUG

Part A: CR845 0.5 mcg/kg

Part A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week)

Intervention Type: DRUG

Part A: CR845 1.0 mcg/kg

Part A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week)

Intervention Type: DRUG

Part A: CR845 2.5 mcg/kg

Part A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week)

Intervention Type: DRUG

Part B: Placebo

Part B: Single i.v. dose of Placebo administered after each dialysis session over a 2 week treatment period (3 times per week)

Intervention Type: DRUG

Part B: CR845 1.0 mcg/kg

Part B: Single i.v. dose of CR845 administered after each dialysis session over a 2 week treatment period (3 times per week)

Intervention Type: DRUG

Other Intervention Names

Matched Placebo; CR845 0.5 mcg/kg; CR845 1.0 mcg/kg; CR845 2.5 mcg/kg; Matched Placebo; CR845 1.0 mcg/kg

Eligibility Criteria

Inclusion Criteria

• Able to provide written informed consent prior to any study procedures;
• Able to communicate clearly with the Investigator and staff, able to read and understand the study procedures;
• Males or females 18 years of age or older;
• End stage renal disease (ESRD) patients who have been on hemodialysis for at least three months and are currently on hemodialysis:

• At least three times per week (Part A)
• Three times per week (Part B)
• Has a body weight ≤ 135 kg
• Part B: Patient who self-reports daily or near daily pruritus during the 6 weeks prior to Screening;
• Part B: Patient who reports a Patient B or Patient C profile on the Patient Self-categorization of Pruritus Disease Severity questionnaire at Screening;
• Part B: At the end of the Run-in Period:

• Patient who completed ratings of worst itching intensity [visual analog scale (VAS)] at least 8 times out of 14 VAS assessments;
• Patient who has a mean value of >40 mm on the worst itching VAS over the one week Run-in Period.

Exclusion Criteria

• Known to be non-compliant with dialysis treatment (i.e., has a history of missed dialysis sessions due to non-compliance in the past 2 months);
• Anticipated to receive a kidney transplant during the study;
• Known history of allergic reaction to opiates such as hives (Note: side effects related to the use of opioids such as constipation or nausea would not exclude the patients from the study);
• Known or suspected history of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)-diagnosed alcohol, narcotic, or other drug abuse or dependence within 12 months prior to Screening;
• Acute or unstable medical condition(s) such as congestive heart failure [New York Heart Association (NYHA) class IV], which in the opinion of the Investigator would pose undue risk to the patient or would impede complete collection of the data or its evaluability;
• Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) greater than 2.5X the reference upper limit of normal (ULN), or bilirubin greater than 4X the ULN at Screening;
• Received another investigational drug within 30 days prior to the start of the Run-in Period or has planned to participate in another clinical trial while enrolled in this study
• Part B: 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);
• Part B: Has localized itch restricted to the palms of the hands as determined from the Brief Itch Inventory diagram, completed during the Screening Period;
• Part B: Has pruritus only during the dialysis session (by patient report);
• Part B: Has used gabapentin, calcineurin inhibitors, opioids; antipsychotics; systemic or topical corticosteroids (other than otic or ophthalmic preparations); sedatives; hypnotics; anti-anxiety agents selective serotonin reuptake inhibitors (SSRIs); or tricyclic antidepressants for < 4 weeks prior to the start of the Run-In Period or had a dose change within the previous 30 days;
• Part B: Is not willing to abstain from use of antihistamines (oral, IV, or topical) for 3 weeks (from the start of the Run-In Period through the end of Week 2);
• Part B: Not willing to abstain from making changes to topical non-drug treatments (e.g., emollients, creams, oils) for pruritus for 3 weeks (from the start of the Run-In Period through the end of Week 2);
• Part B: Received ultraviolet B treatment within 30 days prior to the start of the Run-in Period.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cara Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frederique Menzaghi, PhD

Role: STUDY_DIRECTOR

Cara Therapeutics, Inc.

Locations

US Renal Care

Pine Bluff, Arkansas, United States

US Renal Care

Chula Vista, California, United States

US Renal Care

Long Beach, California, United States

Valley Renal Medical Group

Northridge, California, United States

Nephrology Specialists Medical Group, Inc

Orange, California, United States

North American Research Institute

San Dimas, California, United States

University of Florida College of Medicine Jacksonville

Jacksonville, Florida, United States

Orlando Clinical Research Center

Orlando, Florida, United States

Pines Clinical Research, Inc.

Pembroke Pines, Florida, United States

Emory Dialysis Center at Northside

Atlanta, Georgia, United States

Western New England Renal & Transplant Associates, PC

Springfield, Massachusetts, United States

US Renal Care

Gallup, New Mexico, United States

Trude Weishaupt Memorial Dialysis Center

Fresh Meadows, New York, United States

Winthrop University Hospital

Mineola, New York, United States

Brookview Hills Research Associates, LLC

Winston-Salem, North Carolina, United States

US Renal Care

Aiken, South Carolina, United States

Southeast Renal Research Institute

Chattanooga, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

US Renal Care

Grand Prairie, Texas, United States

US Renal Care

San Antonio, Texas, United States

Countries

United States

References

Spencer RH, Noonan PK, Marbury T, Menzaghi F. Impact of renal impairment on the pharmacokinetic profile of intravenous difelikefalin, a kappa opioid receptor agonist for the treatment of pruritus. BMC Nephrol. 2024 Oct 14;25(1):351. doi: 10.1186/s12882-024-03790-w.

Reference Type: DERIVED

PMID: 39402448 (View on PubMed)

Other Identifiers

CR845-CLIN2005

Identifier Type: -

Identifier Source: org_study_id