Safety and Pharmacokinetics of IV CR845 in Hemodialysis Patients, and Its Efficacy in Patients With Uremic Pruritus
Primary Purpose
Pruritus, Uremic Pruritus
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Part A: Placebo
Part A: CR845 0.5 mcg/kg
Part A: CR845 1.0 mcg/kg
Part A: CR845 2.5 mcg/kg
Part B: Placebo
Part B: CR845 1.0 mcg/kg
Sponsored by
About this trial
This is an interventional treatment trial for Pruritus focused on measuring Pruritus, uremic pruritus, kappa opioid, CR845
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.
Sites / Locations
- US Renal Care
- US Renal Care
- US Renal Care
- Valley Renal Medical Group
- Nephrology Specialists Medical Group, Inc
- North American Research Institute
- University of Florida College of Medicine Jacksonville
- Orlando Clinical Research Center
- Pines Clinical Research, Inc.
- Emory Dialysis Center at Northside
- Western New England Renal & Transplant Associates, PC
- US Renal Care
- Trude Weishaupt Memorial Dialysis Center
- Winthrop University Hospital
- Brookview Hills Research Associates, LLC
- US Renal Care
- Southeast Renal Research Institute
- Vanderbilt University Medical Center
- US Renal Care
- US Renal Care
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Arm Label
Part A: Placebo
Part A: CR845 0.5 mcg/kg
Part A: CR845 1.0 mcg/kg
Part A: CR845 2.5 mcg/kg
Part B: Placebo
Part B: CR845 1.0 mcg/kg
Arm Description
Intravenous matched placebo
Intravenous CR845, 0.5 mcg/kg
Intravenous CR845, 1.0 mcg/kg
Intravenous CR845, 2.5 mcg/kg
Intravenous matched placebo
Intravenous CR845, 1.0 mcg/kg
Outcomes
Primary Outcome Measures
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.
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".
Secondary Outcome Measures
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
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)
Full Information
NCT ID
NCT02229929
First Posted
August 27, 2014
Last Updated
August 8, 2016
Sponsor
Cara Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02229929
Brief Title
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
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cara Therapeutics, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pruritus, Uremic Pruritus
Keywords
Pruritus, uremic pruritus, kappa opioid, CR845
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
89 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A: Placebo
Arm Type
Placebo Comparator
Arm Description
Intravenous matched placebo
Arm Title
Part A: CR845 0.5 mcg/kg
Arm Type
Experimental
Arm Description
Intravenous CR845, 0.5 mcg/kg
Arm Title
Part A: CR845 1.0 mcg/kg
Arm Type
Experimental
Arm Description
Intravenous CR845, 1.0 mcg/kg
Arm Title
Part A: CR845 2.5 mcg/kg
Arm Type
Experimental
Arm Description
Intravenous CR845, 2.5 mcg/kg
Arm Title
Part B: Placebo
Arm Type
Placebo Comparator
Arm Description
Intravenous matched placebo
Arm Title
Part B: CR845 1.0 mcg/kg
Arm Type
Experimental
Arm Description
Intravenous CR845, 1.0 mcg/kg
Intervention Type
Drug
Intervention Name(s)
Part A: Placebo
Other Intervention Name(s)
Matched Placebo
Intervention Description
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
Intervention Name(s)
Part A: CR845 0.5 mcg/kg
Other Intervention Name(s)
CR845 0.5 mcg/kg
Intervention Description
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
Intervention Name(s)
Part A: CR845 1.0 mcg/kg
Other Intervention Name(s)
CR845 1.0 mcg/kg
Intervention Description
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
Intervention Name(s)
Part A: CR845 2.5 mcg/kg
Other Intervention Name(s)
CR845 2.5 mcg/kg
Intervention Description
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
Intervention Name(s)
Part B: Placebo
Other Intervention Name(s)
Matched Placebo
Intervention Description
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
Intervention Name(s)
Part B: CR845 1.0 mcg/kg
Other Intervention Name(s)
CR845 1.0 mcg/kg
Intervention Description
Part B: Single i.v. dose of CR845 administered after each dialysis session over a 2 week treatment period (3 times per week)
Primary Outcome Measure Information:
Title
Part A: Determine the Pharmacokinetics of Repeated Doses of CR845 in Hemodialysis Patients (half-life, Cmax, Tmax, AUC, Vd)
Description
To evaluate the pharmacokinetics of repeated doses of CR845 in hemodialysis patients over a one-week treatment period.
Time Frame
1 week
Title
Part B: Change in Worst Itching Intensity using a 100-mm Visual Analog Scale
Description
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".
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
Part B: Change in quality-of-life assessed using the Skindex-10 survey
Description
Change from baseline to Day 15 in itch-related quality of life as assessed by the total Skindex-10 scores
Time Frame
2 weeks
Title
Part B: Sleep disturbance assessed using Itch Medical Outcomes Study (MOS) survey
Description
Change from baseline to Day 15 in itch-related sleep disturbance based on the Itch MOS sleep problems index II (SLP-9)
Time Frame
2 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frederique Menzaghi, PhD
Organizational Affiliation
Cara Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
US Renal Care
City
Pine Bluff
State/Province
Arkansas
ZIP/Postal Code
71603
Country
United States
Facility Name
US Renal Care
City
Chula Vista
State/Province
California
ZIP/Postal Code
91915
Country
United States
Facility Name
US Renal Care
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Valley Renal Medical Group
City
Northridge
State/Province
California
ZIP/Postal Code
91324
Country
United States
Facility Name
Nephrology Specialists Medical Group, Inc
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
North American Research Institute
City
San Dimas
State/Province
California
ZIP/Postal Code
91773
Country
United States
Facility Name
University of Florida College of Medicine Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Facility Name
Pines Clinical Research, Inc.
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33028
Country
United States
Facility Name
Emory Dialysis Center at Northside
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
Western New England Renal & Transplant Associates, PC
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01107
Country
United States
Facility Name
US Renal Care
City
Gallup
State/Province
New Mexico
ZIP/Postal Code
87301
Country
United States
Facility Name
Trude Weishaupt Memorial Dialysis Center
City
Fresh Meadows
State/Province
New York
ZIP/Postal Code
11365
Country
United States
Facility Name
Winthrop University Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Brookview Hills Research Associates, LLC
City
Winston Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
US Renal Care
City
Aiken
State/Province
South Carolina
ZIP/Postal Code
29803
Country
United States
Facility Name
Southeast Renal Research Institute
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37408
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
US Renal Care
City
Grand Prairie
State/Province
Texas
ZIP/Postal Code
75050
Country
United States
Facility Name
US Renal Care
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78202
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety and Pharmacokinetics of IV CR845 in Hemodialysis Patients, and Its Efficacy in Patients With Uremic Pruritus
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