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

Sponsor

Cara Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02229929

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

4.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Pruritus Uremic Pruritus	Drug: Part A: Placebo Drug: Part A: CR845 0.5 mcg/kg Drug: Part A: CR845 1.0 mcg/kg Drug: Part A: CR845 2.5 mcg/kg Drug: Part B: Placebo Drug: Part B: CR845 1.0 mcg/kg	Phase 2

Detailed Description

Placebo-controlled

Study Design

Study Type:

Interventional

Actual Enrollment :

89 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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 Start Date :

Jul 1, 2014

Actual Primary Completion Date :

Jul 1, 2015

Actual Study Completion Date :

Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Part A: Placebo Intravenous matched placebo	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) Other Names: Matched Placebo
Experimental: Part A: CR845 0.5 mcg/kg Intravenous CR845, 0.5 mcg/kg	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) Other Names: CR845 0.5 mcg/kg
Experimental: Part A: CR845 1.0 mcg/kg Intravenous CR845, 1.0 mcg/kg	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) Other Names: CR845 1.0 mcg/kg
Experimental: Part A: CR845 2.5 mcg/kg Intravenous CR845, 2.5 mcg/kg	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) Other Names: CR845 2.5 mcg/kg
Placebo Comparator: Part B: Placebo Intravenous matched placebo	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) Other Names: Matched Placebo
Experimental: Part B: CR845 1.0 mcg/kg Intravenous CR845, 1.0 mcg/kg	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) Other Names: CR845 1.0 mcg/kg

Outcome Measures

Primary Outcome Measures

Part A: Determine the Pharmacokinetics of Repeated Doses of CR845 in Hemodialysis Patients (half-life, Cmax, Tmax, AUC, Vd) [1 week]
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 [2 weeks]
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 [2 weeks]
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 [2 weeks]
Change from baseline to Day 15 in itch-related sleep disturbance based on the Itch MOS sleep problems index II (SLP-9)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	US Renal Care	Pine Bluff	Arkansas	United States	71603
2	US Renal Care	Chula Vista	California	United States	91915
3	US Renal Care	Long Beach	California	United States	90806
4	Valley Renal Medical Group	Northridge	California	United States	91324
5	Nephrology Specialists Medical Group, Inc	Orange	California	United States	92868
6	North American Research Institute	San Dimas	California	United States	91773
7	University of Florida College of Medicine Jacksonville	Jacksonville	Florida	United States	32209
8	Orlando Clinical Research Center	Orlando	Florida	United States	32809
9	Pines Clinical Research, Inc.	Pembroke Pines	Florida	United States	33028
10	Emory Dialysis Center at Northside	Atlanta	Georgia	United States	30318
11	Western New England Renal & Transplant Associates, PC	Springfield	Massachusetts	United States	01107
12	US Renal Care	Gallup	New Mexico	United States	87301
13	Trude Weishaupt Memorial Dialysis Center	Fresh Meadows	New York	United States	11365
14	Winthrop University Hospital	Mineola	New York	United States	11501
15	Brookview Hills Research Associates, LLC	Winston Salem	North Carolina	United States	27103
16	US Renal Care	Aiken	South Carolina	United States	29803
17	Southeast Renal Research Institute	Chattanooga	Tennessee	United States	37408
18	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
19	US Renal Care	Grand Prairie	Texas	United States	75050
20	US Renal Care	San Antonio	Texas	United States	78202