Chronic Kidney DiseasesPhase 2NCT03617536

A Study to Evaluate the Safety and Efficacy of CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

A Phase 2 study testing CR845 0.25 mg Oral Tablet, CR845 0.5 mg Oral Tablet and CR845 1 mg Oral Tablet in people with Chronic Kidney Diseases and Pruritus, run by Cara Therapeutics, Inc. at 60 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Chronic Kidney Diseases, Pruritus
What is being tested?: CR845 0.25 mg Oral Tablet, CR845 0.5 mg Oral Tablet and CR845 1 mg Oral Tablet
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 269 participants
Where: 60 sitesUnited States
Study dates: 5 Jul 2018to 14 Nov 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

To be eligible for inclusion into the study, a patient must meet the following criteria:
CKD patients with stage III, IV, or V (ie, moderate renal impairment with estimated glomerular filtration rate (GFR) ≥30 and <60 mL/min/1.73 m2 or severe renal impairment with estimated GFR <30 mL/min/1.73 m2).
For severe CKD patients on hemodialysis, they must be receiving hemodialysis 3 times per week for at least 3 months prior to the start of screening;
Prior to randomization:
Has completed at least 4 Worst Itching Intensity NRS worksheets from the start of the 7-day Run-in Period;
Has a mean baseline Worst Itching Intensity NRS score ≥5, defined as the average of all non-missing scores reported from the start of the 7-day Run-in Period.

Who cannot join

A patient will be excluded from the study if any of the following criteria are met:
Patients not currently on dialysis who are likely to initiate routine dialysis during study participation;
Scheduled to receive a kidney transplant during the study;
New or change of treatment received for itch including antihistamines and corticosteroids (oral, intravenous [IV], or topical) within 14 days prior to screening;
Received another investigational drug within 30 days prior to the start of screening or is planning to participate in another clinical study while enrolled in this study;
Received ultraviolet B treatment within 30 days prior to the start of screening or anticipates receiving such treatment during the study;
Participated in a previous clinical study with CR845.

Trial locations and contacts

60 sites in 1 country.

City, postcode or hospital

60 sites in 1 country

United States60 sites

Cara Therapeutics Study Site
Alexandria, Virginia, 22304
Cara Therapeutics Study Site
Augusta, Georgia, 30909
Cara Therapeutics Study Site
Bakersfield, California, 93309
Cara Therapeutics Study Site 2
Bakersfield, California, 99309
Cara Therapeutics Study Site
Baltimore, Maryland, 21287
Cara Therapeutics Study Site
Birmingham, Alabama, 35233
Cara Therapeutics Study Site
Brooklyn, New York, 11229
Cara Therapeutics Study Site
Camp Hill, Pennsylvania, 17011
Cara Therapeutics Study Site
Canyon Country, California, 91351
Cara Therapeutics Study Site
Columbus, Ohio, 43215
Cara Therapeutics Study Site
Corsicana, Texas, 75110
Cara Therapeutics Study Site
Crystal Lake, Illinois, 60012
Cara Therapeutics Study Site
Denver, Colorado, 80230
Cara Therapeutics Study Site
Edgewater, Florida, 32132
Cara Therapeutics Study Site
Escondido, California, 92025
Cara Therapeutics Study Site
Evanston, Illinois, 60201
Cara Therapeutics Study Site
Flint, Michigan, 48503
Cara Therapeutics Study Site 2
Flint, Michigan, 48532
Cara Therapeutics Study Site
Florence, Alabama, 35630
Cara Therapeutics Study Site
Gonzales, Texas, 78629
Cara Therapeutics Study Site
Greenville, South Carolina, 29605
Cara Therapeutics Study Site
Harrisburg, Arkansas, 72432
Cara Therapeutics Study Site
Hialeah, Florida, 33016
Cara Therapeutics Study Site
Hollywood, Florida, 33024
Cara Therapeutics Study Site
Houston, Texas, 77074
Cara Therapeutics Study Site
Houston, Texas, 77081
Cara Therapeutics Study Site
Iowa City, Iowa, 52242
Cara Therapeutics Study Site
Kansas City, Missouri, 64111
Cara Therapeutics Study Site
Lake Worth, Florida, 33467
Cara Therapeutics Study Site
Lomita, California, 90717
Cara Therapeutics Study Site
Metairie, Louisiana, 70006
Cara Therapeutics Study Site 1
Miami, Florida, 33125
Cara Therapeutics Study Site 2
Miami, Florida, 33155
Cara Therapeutics Study Site
Mineola, New York, 11501
Cara Therapeutics Study Site
New Orleans, Louisiana, 70115
Cara Therapeutics Study Site
Norman, Oklahoma, 73071
Cara Therapeutics Study Site
Northridge, California, 91324
Cara Therapeutics Study Site
Ocala, Florida, 34471
Cara Therapeutics Study Site
Orlando, Florida, 32810
Cara Therapeutics Study Site
Phoenix, Arizona, 85016
Cara Therapeutics Study Site
Plano, Texas, 75093
Cara Therapeutics Study Site
Prescott, Arizona, 86401
Cara Therapeutics Study Site
Providence, Rhode Island, 02903
Cara Therapeutics Study Site
Rapid City, South Dakota, 57702
Cara Therapeutics Study Site
Riverside, California, 92505
Cara Therapeutics Study Site
Rocky Mount, North Carolina, 27804
Cara Therapeutics Study Site
Roseville, Michigan, 48066
Cara Therapeutics Study Site
Sacramento, California, 95831
Cara Therapeutics Study Site
Saint Clair, Michigan, 48081
Cara Therapeutics Study Site
San Antonio, Texas, 78207
Cara Therapeutics Study Site
San Antonio, Texas, 78224
Cara Therapeutics Study Site
Sandy Springs, Georgia, 30328
Cara Therapeutics Study Site
Sun City, Arizona, 85351
Cara Therapeutics Study Site
Takoma Park, Maryland, 20912
Cara Therapeutics Study Site
Tampa, Florida, 33614
Cara Therapeutics Study Site
Temple Terrace, Florida, 33637
Cara Therapeutics Study Site
Warwick, Rhode Island, 02886
Cara Therapeutics Study Site
Washington D.C., District of Columbia, 20037
Cara Therapeutics Study Site
Whittier, California, 90602
Cara Therapeutics Study Site
Zachary, Louisiana, 70791

Other trials in United States

About this study

Official title: A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Oral CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of 3 dose levels of oral CR845 compared to placebo in reducing the intensity of itch in chronic kidney disease (CKD) patients with moderate-to-severe pruritus. This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week Treatment Period, and a Follow-up Visit (approximately 7 days after the last dose of study drug).

Read the detailed description

This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week Treatment Period, and a Follow-up Visit (approximately 7 to 10 days after the last dose of study drug). Informed consent will be obtained prior to performing any study-specific procedures. Screening will occur within 7 to 28 days prior to randomization to assess eligibility.

If patients continue to meet all inclusion and no exclusion criteria at the end of the 7-day Run-in Period, they will be randomized in a 1:1:1:1 ratio to receive orally once daily either placebo or CR845 tablets at doses of 0.25, 0.5 or 1 mg. Randomization will be stratified according to the patient's renal disease status: moderate CKD; severe CKD non-dialysis; severe CKD on dialysis (ie, 3 categories). A final safety Follow-up Visit will be conducted 7 to 10 days after the last dose of study drug.

Conditions: Chronic Kidney Diseases, Pruritus
Being tested: CR845 0.25 mg Oral Tablet, CR845 0.5 mg Oral Tablet, CR845 1 mg Oral Tablet, Placebo Oral Tablet
Keywords: difelikefalin, CR845, Pruritus, Chronic Itch, Itch, Itching, uremic pruritus, CKD, CKD-aP, CKD-associated pruritus, Chronic Kidney Disease, Kidney dysfunction, Generalized pruritus, Hemodialysis, Dialysis, ESRD (end stage renal disease), Kidney failure, chronic
Medical subject headings: Renal Insufficiency, Chronic, Pruritus, Kidney Failure, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CR845 0.25 mg Oral TabletDrug
Also called Difelikefalin
CR845 0.25 mg medication taken orally 1 time/day
CR845 0.5 mg Oral TabletDrug
Also called Difelikefalin
CR845 0.5 mg medication taken orally 1 time/day
CR845 1 mg Oral TabletDrug
Also called Difelikefalin
CR845 1 mg medication taken orally 1 time/day
Placebo Oral TabletDrug
Placebo tablet taken orally 1 time/day

Study groups in NCT03617536
Study group	Role	What they receive
CR845 0.25 mg Oral Tablet	Experimental	Oral CR845 0.25 mg to be taken orally once daily for 12 weeks Receives: Drug: CR845 0.25 mg Oral Tablet
CR845 0.5 mg Oral Tablet	Experimental	Oral CR845 0.5 mg to be taken orally once daily for 12 weeks Receives: Drug: CR845 0.5 mg Oral Tablet
CR845 1 mg Oral Tablet	Experimental	Oral CR845 1 mg to be taken orally once daily for 12 weeks Receives: Drug: CR845 1 mg Oral Tablet
Placebo Oral Tablet	Placebo comparator	Oral Placebo to be taken orally once daily Receives: Drug: Placebo Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score During Week 12
Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable". Higher scores meant worse itch intensity.
Measured: Baseline, Week 12

Secondary outcomes (3)

Change From Baseline in Total Skindex-10 Scale Score at the End of Week 12
The Skindex-10 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. The Skindex-10 has 10 questions; the total Skindex-10 score ranges from 0 to 60. A lower total score represents better quality of life.
Measured: Baseline, Week 12
Change From Baseline in 5-D Itch Scale Score at the End of Week 12
The 5-D Itch Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past 2 weeks. The questions cover five dimensions of itch including the degree, duration of itch/day, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. The 5-D Itch Scale has 5 questions; the total 5-D Itch Scale score ranges from 5 to 25, with higher scores indicating worse responses.
Measured: Baseline, Week 12
Reduction of Itch Intensity as Assessed by the Proportion of Patients Achieving an Improvement From Baseline ≥3 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score at Week 12
Measured: Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Jul 201814 Nov 2019

First posted6 Aug 2018
Study start5 Jul 2018
Primary completion24 Oct 2019
Study completion14 Nov 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Kidney DiseasesStudies 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
Model description: Randomized, double-blind, placebo controlled study
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 269 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03617536
Sponsor's protocol ID: CR845 210301
Status last verified: Jan 2024
First submitted: 11 Jul 2018
Last updated: 24 Jan 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 24 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Oral CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus
ClinicalTrials.gov ID: NCT03617536
Acronym / sponsor ID: CR845 210301
Conditions: Chronic Kidney Diseases, Pruritus
Keywords: difelikefalin, CR845, Pruritus, Chronic Itch, Itch, Itching, uremic pruritus, CKD
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 269 participants (actual)
Lead sponsor: Cara Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 5 Jul 2018 (actual)
Primary completion: 24 Oct 2019 (actual)
Study completion: 14 Nov 2019 (actual)
First posted: 6 Aug 2018 (actual)
Results: Posted 24 Jan 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4
Model description: Randomized, double-blind, placebo controlled study

Arm	Type	Receives
CR845 0.25 mg Oral Tablet	Experimental	Drug: CR845 0.25 mg Oral TabletOral CR845 0.25 mg to be taken orally once daily for 12 weeks
CR845 0.5 mg Oral Tablet	Experimental	Drug: CR845 0.5 mg Oral TabletOral CR845 0.5 mg to be taken orally once daily for 12 weeks
CR845 1 mg Oral Tablet	Experimental	Drug: CR845 1 mg Oral TabletOral CR845 1 mg to be taken orally once daily for 12 weeks
Placebo Oral Tablet	Placebo comparator	Drug: Placebo Oral TabletOral Placebo to be taken orally once daily

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

CKD patients with stage III, IV, or V (ie, moderate renal impairment with estimated glomerular filtration rate (GFR) ≥30 and <60 mL/min/1.73 m2 or severe renal impairment with estimated GFR <30 mL/min/1.73 m2).
For severe CKD patients on hemodialysis, they must be receiving hemodialysis 3 times per week for at least 3 months prior to the start of screening;
Prior to randomization:

Key exclusion criteria (7 listed)

Patients not currently on dialysis who are likely to initiate routine dialysis during study participation;
Scheduled to receive a kidney transplant during the study;
New or change of treatment received for itch including antihistamines and corticosteroids (oral, intravenous [IV], or topical) within 14 days prior to screening;
Received another investigational drug within 30 days prior to the start of screening or is planning to participate in another clinical study while enrolled in this study;
Received ultraviolet B treatment within 30 days prior to the start of screening or anticipates receiving such treatment during the study;

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
CR845 0.25 mg Oral TabletAlso: DifelikefalinCR845 0.25 mg medication taken orally 1 time/day	Drug	CR845 0.25 mg Oral Tablet
CR845 0.5 mg Oral TabletAlso: DifelikefalinCR845 0.5 mg medication taken orally 1 time/day	Drug	CR845 0.5 mg Oral Tablet
CR845 1 mg Oral TabletAlso: DifelikefalinCR845 1 mg medication taken orally 1 time/day	Drug	CR845 1 mg Oral Tablet
Placebo Oral TabletPlacebo tablet taken orally 1 time/day	Drug	Placebo Oral Tablet

Primary outcome

Change From Baseline in Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score During Week 12
Time frame: Baseline, Week 12
Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable". Higher scores meant worse itch intensity.

3 secondary outcomes

Change From Baseline in Total Skindex-10 Scale Score at the End of Week 12
Time frame: Baseline, Week 12
Change From Baseline in 5-D Itch Scale Score at the End of Week 12
Time frame: Baseline, Week 12
Reduction of Itch Intensity as Assessed by the Proportion of Patients Achieving an Improvement From Baseline ≥3 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score at Week 12
Time frame: Week 12

Results and safety

Results posted to the registry on 24 Jan 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CR845 0.25 mg Oral Tablet	69	60
CR845 0.5 mg Oral Tablet	66	57
CR845 1 mg Oral Tablet	67	54
Placebo Oral Tablet	67	57

Primary outcome: Change From Baseline in Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score During Week 12

Time frame: Baseline, Week 12. Least squares mean (95% Confidence Interval). Unit: score on a scale

Measure	CR845 0.25 mg Oral Tablet n = 69	CR845 0.5 mg Oral Tablet n = 66	CR845 1 mg Oral Tablet n = 67	Placebo Oral Tablet n = 67
Value	-3.99 (-4.62 to -3.36)	-3.84 (-4.50 to -3.18)	-4.42 (-5.08 to -3.76)	-3.32 (-3.97 to -2.68)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were recorded starting at the Screening Visit and continuing through the Follow-up Visit (7 to 10 days after the last dose of study drug).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CR845 0.25 mg Oral Tablet	9 of 69 (13%)	12 of 69 (17.4%)	0 of 69
CR845 0.5 mg Oral Tablet	9 of 66 (13.6%)	10 of 66 (15.2%)	0 of 66
CR845 1 mg Oral Tablet	9 of 67 (13.4%)	15 of 67 (22.4%)	1 of 67
Placebo Oral Tablet	5 of 67 (7.5%)	8 of 67 (11.9%)	3 of 67

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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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.

Frédérique Menzaghi, PhD study director

Cara Therapeutics

60 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 6 inclusion and 7 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 24 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 60 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?

Yes. Results are posted in the registry (first posted 24 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change From Baseline in Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score During Week 12 (time frame: Baseline, Week 12). 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 NCT03617536.

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 24 Jan 2024.