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

Pruritus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02229929
• Other study ID #: CR845-CLIN2005
• Status: Completed
• Phase: Phase 2
• First received: August 27, 2014
• Last updated: August 8, 2016
• Start date: July 2014
• Est. completion date: July 2015

Study information

• Verified date: August 2016
• Source: Cara Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Description:

Placebo-controlled

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pruritus
• Uremic Pruritus

Intervention

Drug:
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)

Locations

Country	Name	City	State
United States	US Renal Care	Aiken	South Carolina
United States	Emory Dialysis Center at Northside	Atlanta	Georgia
United States	Southeast Renal Research Institute	Chattanooga	Tennessee
United States	US Renal Care	Chula Vista	California
United States	Trude Weishaupt Memorial Dialysis Center	Fresh Meadows	New York
United States	US Renal Care	Gallup	New Mexico
United States	US Renal Care	Grand Prairie	Texas
United States	University of Florida College of Medicine Jacksonville	Jacksonville	Florida
United States	US Renal Care	Long Beach	California
United States	Winthrop University Hospital	Mineola	New York
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Valley Renal Medical Group	Northridge	California
United States	Nephrology Specialists Medical Group, Inc	Orange	California
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Pines Clinical Research, Inc.	Pembroke Pines	Florida
United States	US Renal Care	Pine Bluff	Arkansas
United States	US Renal Care	San Antonio	Texas
United States	North American Research Institute	San Dimas	California
United States	Western New England Renal & Transplant Associates, PC	Springfield	Massachusetts
United States	Brookview Hills Research Associates, LLC	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Cara Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Determine the Pharmacokinetics of Repeated Doses of CR845 in Hemodialysis Patients (half-life, Cmax, Tmax, AUC, Vd)	To evaluate the pharmacokinetics of repeated doses of CR845 in hemodialysis patients over a one-week treatment period.	1 week	No
Primary	Part B: Change in Worst Itching Intensity using a 100-mm Visual Analog Scale	Change from baseline to the average of Week 2 worst itching (daytime and nighttime) VAS where 0 mm represents "No Itch" and 100 mm represents the "Worst Itch You Can Imagine".	2 weeks	No
Secondary	Part B: Change in quality-of-life assessed using the Skindex-10 survey	Change from baseline to Day 15 in itch-related quality of life as assessed by the total Skindex-10 scores	2 weeks	No
Secondary	Part B: Sleep disturbance assessed using Itch Medical Outcomes Study (MOS) survey	Change from baseline to Day 15 in itch-related sleep disturbance based on the Itch MOS sleep problems index II (SLP-9)	2 weeks	No