Clinical trial NCT02229929: Safety and Pharmacokinetics of IV CR845 in Hemodialysis Patients, and Its Efficacy in Patients With Uremic Pruritus
Official title: A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Pharmacokinetics of Intravenous CR845 in Hemodialysis Patients, and Its Safety and Efficacy in Hemodialysis Patients With Uremic Pruritus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pruritus
Uremic Pruritus
Keywords: Pruritus
uremic pruritus
kappa opioid
CR845
Lead sponsor: Cara Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2014-09-03
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Part A: Determine the Pharmacokinetics of Repeated Doses of CR845 in Hemodialysis Patients (half-life, Cmax, Tmax, AUC, Vd)
timeFrame: 1 week
measure: Part B: Change in Worst Itching Intensity using a 100-mm Visual Analog Scale
timeFrame: 2 weeks
Secondary outcomes:
measure: Part B: Change in quality-of-life assessed using the Skindex-10 survey
timeFrame: 2 weeks
measure: Part B: Sleep disturbance assessed using Itch Medical Outcomes Study (MOS) survey
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Pine Bluff
country: United States
facility: US Renal Care
state: Arkansas
city: Chula Vista
country: United States
facility: US Renal Care
state: California
city: Long Beach
country: United States
facility: US Renal Care
state: California
city: Northridge
country: United States
facility: Valley Renal Medical Group
state: California
city: Orange
country: United States
facility: Nephrology Specialists Medical Group, Inc
state: California
city: San Dimas
country: United States
facility: North American Research Institute
state: California
city: Jacksonville
country: United States
facility: University of Florida College of Medicine Jacksonville
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Clinical Research, Inc.
state: Florida
city: Atlanta
country: United States
facility: Emory Dialysis Center at Northside
state: Georgia
city: Springfield
country: United States
facility: Western New England Renal & Transplant Associates, PC
state: Massachusetts
city: Gallup
country: United States
facility: US Renal Care
state: New Mexico
city: Fresh Meadows
country: United States
facility: Trude Weishaupt Memorial Dialysis Center
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: Winston Salem
country: United States
facility: Brookview Hills Research Associates, LLC
state: North Carolina
city: Aiken
country: United States
facility: US Renal Care
state: South Carolina
city: Chattanooga
country: United States
facility: Southeast Renal Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Grand Prairie
country: United States
facility: US Renal Care
state: Texas
city: San Antonio
country: United States
facility: US Renal Care
state: Texas
Study officials:
affiliation: Cara Therapeutics, Inc.
name: Frederique Menzaghi, PhD
role: STUDY_DIRECTOR
References: