PruritusPhase 2NCT02229929
Safety and Pharmacokinetics of IV CR845 in Hemodialysis Patients, and Its Efficacy in Patients With Uremic Pruritus
A Phase 2 study testing Part A: CR845 0.5 mcg/kg, Part A: CR845 1.0 mcg/kg and Part A: CR845 2.5 mcg/kg in people with Pruritus and Uremic Pruritus, run by Cara Therapeutics, Inc. at 20 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pruritus, Uremic Pruritus
- What is being tested?
- Part A: CR845 0.5 mcg/kg, Part A: CR845 1.0 mcg/kg and Part A: CR845 2.5 mcg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 89 participants
- Where
- 20 sitesUnited States
- Study dates
- Jul 2014to Jul 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
United States20 sites
US Renal Care
Aiken, South Carolina, 29803
Emory Dialysis Center at Northside
Atlanta, Georgia, 30318
Southeast Renal Research Institute
Chattanooga, Tennessee, 37408
US Renal Care
Chula Vista, California, 91915
Trude Weishaupt Memorial Dialysis Center
Fresh Meadows, New York, 11365
US Renal Care
Gallup, New Mexico, 87301
US Renal Care
Grand Prairie, Texas, 75050
University of Florida College of Medicine Jacksonville
Jacksonville, Florida, 32209
US Renal Care
Long Beach, California, 90806
Winthrop University Hospital
Mineola, New York, 11501
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Valley Renal Medical Group
Northridge, California, 91324
Nephrology Specialists Medical Group, Inc
Orange, California, 92868
Orlando Clinical Research Center
Orlando, Florida, 32809
Pines Clinical Research, Inc.
Pembroke Pines, Florida, 33028
US Renal Care
Pine Bluff, Arkansas, 71603
US Renal Care
San Antonio, Texas, 78202
North American Research Institute
San Dimas, California, 91773
Western New England Renal & Transplant Associates, PC
Springfield, Massachusetts, 01107
Brookview Hills Research Associates, LLC
Winston-Salem, North Carolina, 27103
About this study
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
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).
Read the detailed description
Placebo-controlled
- Conditions
- Pruritus, Uremic Pruritus
- Being tested
- 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
- Keywords
- Pruritus, uremic pruritus, kappa opioid, CR845
- Medical subject headings
- Pruritus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part A: PlaceboDrug
Also called Matched 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/kgDrug
Also called 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/kgDrug
Also called 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/kgDrug
Also called 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: PlaceboDrug
Also called Matched 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/kgDrug
Also called 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)
| Study group | Role | What they receive |
|---|---|---|
| Part A: Placebo | Placebo comparator | Intravenous matched placebo Receives: Drug: Part A: Placebo |
| Part A: CR845 0.5 mcg/kg | Experimental | Intravenous CR845, 0.5 mcg/kg Receives: Drug: Part A: CR845 0.5 mcg/kg |
| Part A: CR845 1.0 mcg/kg | Experimental | Intravenous CR845, 1.0 mcg/kg Receives: Drug: Part A: CR845 1.0 mcg/kg |
| Part A: CR845 2.5 mcg/kg | Experimental | Intravenous CR845, 2.5 mcg/kg Receives: Drug: Part A: CR845 2.5 mcg/kg |
| Part B: Placebo | Placebo comparator | Intravenous matched placebo Receives: Drug: Part B: Placebo |
| Part B: CR845 1.0 mcg/kg | Experimental | Intravenous CR845, 1.0 mcg/kg Receives: Drug: Part B: CR845 1.0 mcg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 week
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".
Measured: 2 weeks
Secondary outcomes (2)
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
Measured: 2 weeks
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)
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2014 (estimated)
- Study startJul 2014
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PruritusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cara Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Frederique Menzaghi, PhD, Study director, Cara Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02229929
- Sponsor's protocol ID
- CR845-CLIN2005
- Status last verified
- Aug 2016
- First submitted
- 27 Aug 2014
- Last updated
- 10 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Mourani C, Kaur A, Jaoudeh PA, Reynolds B, Morin I, Enoiu M. The pharmacokinetics of a single intravenous dose of difelikefalin in adolescents aged 12 to 17 years on hemodialysis. Pediatr Nephrol. 2026 Oct 19. doi: 10.1007/s00467-026-07561-7. Online ahead of print.
PubMed 42895571Spencer 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.
PubMed 39402448
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02229929
- Acronym / sponsor ID
- CR845-CLIN2005
- Conditions
- Pruritus, Uremic Pruritus
- Keywords
- Pruritus, uremic pruritus, kappa opioid, CR845
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- Cara Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2014
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 3 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part A: Placebo | Placebo comparator | Drug: Part A: PlaceboIntravenous matched placebo |
| Part A: CR845 0.5 mcg/kg | Experimental | Drug: Part A: CR845 0.5 mcg/kgIntravenous CR845, 0.5 mcg/kg |
| Part A: CR845 1.0 mcg/kg | Experimental | Drug: Part A: CR845 1.0 mcg/kgIntravenous CR845, 1.0 mcg/kg |
| Part A: CR845 2.5 mcg/kg | Experimental | Drug: Part A: CR845 2.5 mcg/kgIntravenous CR845, 2.5 mcg/kg |
| Part B: Placebo | Placebo comparator | Drug: Part B: PlaceboIntravenous matched placebo |
| Part B: CR845 1.0 mcg/kg | Experimental | Drug: Part B: CR845 1.0 mcg/kgIntravenous CR845, 1.0 mcg/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- Has a body weight ≤ 135 kg
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Part A: PlaceboAlso: Matched PlaceboPart A: Single i.v. dose of Placebo administered after each dialysis session over a 1 week treatment period (3 times per week) | Drug | Part A: Placebo |
| Part A: CR845 0.5 mcg/kgAlso: CR845 0.5 mcg/kgPart A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week) | Drug | Part A: CR845 0.5 mcg/kg |
| Part A: CR845 1.0 mcg/kgAlso: CR845 1.0 mcg/kgPart A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week) | Drug | Part A: CR845 1.0 mcg/kg |
| Part A: CR845 2.5 mcg/kgAlso: CR845 2.5 mcg/kgPart A: Single i.v. dose of CR845 administered after each dialysis session over a 1 week treatment period (3 times per week) | Drug | Part A: CR845 2.5 mcg/kg |
| Part B: PlaceboAlso: Matched PlaceboPart B: Single i.v. dose of Placebo administered after each dialysis session over a 2 week treatment period (3 times per week) | Drug | Part B: Placebo |
| Part B: CR845 1.0 mcg/kgAlso: CR845 1.0 mcg/kgPart B: Single i.v. dose of CR845 administered after each dialysis session over a 2 week treatment period (3 times per week) | Drug | Part B: CR845 1.0 mcg/kg |
Primary outcome
Part A: Determine the Pharmacokinetics of Repeated Doses of CR845 in Hemodialysis Patients (half-life, Cmax, Tmax, AUC, Vd)
Time frame: 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
Time frame: 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".
2 secondary outcomes
Part B: Change in quality-of-life assessed using the Skindex-10 survey
Time frame: 2 weeks
Part B: Sleep disturbance assessed using Itch Medical Outcomes Study (MOS) survey
Time frame: 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2016.
- Derived from this study: PubMed 42895571Mourani C, Kaur A, Jaoudeh PA, Reynolds B, Morin I, Enoiu M. The pharmacokinetics of a single intravenous dose of difelikefalin in adolescents aged 12 to 17 years on hemodialysis. Pediatr Nephrol. 2026 Oct 19. doi: 10.1007/s00467-026-07561-7. Online ahead of print.
- Derived from this study: PubMed 39402448Spencer 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frederique Menzaghi, PhD study director
Cara Therapeutics, Inc.
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Part A: CR845 0.5 mcg/kg, Part A: CR845 1.0 mcg/kg and Part A: CR845 2.5 mcg/kg in people with Pruritus and Uremic Pruritus, run by Cara Therapeutics, Inc. at 20 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Determine the Pharmacokinetics of Repeated Doses of CR845 in Hemodialysis Patients (half-life, Cmax, Tmax, AUC, Vd) (time frame: 1 week). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02229929, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2016.