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CR845 /kg

Phase 3

Uremic Pruritus | Small molecule | Nephrology |Cara Therapeutics, Inc.|Last Updated: Apr 26, 2022

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials5
Total Enrollment1,587

FDA Designations

No designations recorded

Clinical trial landscape

CR845 /kg · 7 trials · 3 indications

Phase 3 4Phase 2 2Phase 1 1
NCT03998163CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe PruritusUremic Pruritus
COMPLETED222 Analytics
NCT03636269CR845-CLIN3103: A Global Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe PruritusUremic Pruritus
COMPLETED473 Analytics
NCT03422653A Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-1)Uremic Pruritus
COMPLETED378 Analytics
NCT03281538Extension Study to Evaluate IV CR845 in Hemodialysis Patients With Moderate-to-Severe PruritusUremic Pruritus
COMPLETED288 Analytics
PHASE3COMPLETED
CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
Uremic PruritusUnlock trial analytics
PHASE3COMPLETED
CR845-CLIN3103: A Global Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
Uremic PruritusUnlock trial analytics
PHASE3COMPLETED
A Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-1)
Uremic PruritusUnlock trial analytics
PHASE3COMPLETED
Extension Study to Evaluate IV CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
Uremic PruritusUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Participants With AEs.
Up to Follow-Up Visit (Week 13-14)

Assessed by monitoring of adverse events.

Reduction of Itch Intensity as Assessed by the Percentage of Patients Achieving an Improvement From Baseline ≥3 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score at Week 12
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". LS means estimated percent, odds ratio and P value used a logistic regression model.

Number of Participants With AEs
Up to 52 weeks

Assessed by physical examination, monitoring of adverse events, vital signs and laboratory assessments

Change From Baseline in the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score During Week 8
Baseline, Week 8

Intensity of itch was measured using a numerical rating scale (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.

A comparison of the change in Pain Intensity over time using the Numeric Rating Scale
24 hours

Using the Numeric Rating Scale (NRS) to quantify the difference between CR845-treated patients and placebo-treated patients.

QTc change from baseline following CR845 treatment.
Baseline, Day 1

Secondary Endpoints

Reduction of Itch Intensity as Assessed by the Percentage of Patients Achieving an Improvement From Baseline ≥4 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score at Week 12
Week 12
Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in Total Skindex-10 Scale Score at the End of Week 12
Baseline, Week 12
Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in 5-D Itch Scale Score at the End of Week 12
Baseline, Week 12
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
CR845 0.5mcg/kgEXPERIMENTALIV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)
PlaceboPLACEBO_COMPARATORIV Placebo administered after each dialysis session (3 times/week)
CR845 1 mcg/kgEXPERIMENTALPart A of study: IV CR845 1 mcg/kg administered after each dialysis session (3 times/week)
CR845 1.5mcg/kgEXPERIMENTALPart A of study: IV CR845 1.5 mcg/kg administered after each dialysis session (3 times/week)
CR845 IV 1 mcg/kgACTIVE_COMPARATORCR845 IV solution will be supplied in 2 mL glass vials.Study drug will be administered as an IV bolus into an infusion line, the volume is dependent upon the patient's body weight.
CR845 IV 0.5 mcg/kgACTIVE_COMPARATORCR845 solution will be supplied in 2 mL glass vials. Study drug will be administered as an IV bolus into an infusion line, the volume is dependent upon the patient's body weight.
Placebo IVPLACEBO_COMPARATORPlacebo will be supplied in matched vials containing the same volume of buffer but with no active drug. It will be administered as an IV bolus into an infusion line, the volume is dependent upon the patient's body weight.
CR845 0.5 mcg/kg IV (Therapeutic Dose)EXPERIMENTAL -
CR845 3 mcg/kg IV (Supratherapeutic Dose)EXPERIMENTAL -
Moxifloxacin 400 mgACTIVE_COMPARATOR -

Interventions

NameTypeDescription
CR845 0.5 mcg/kgDRUGIV CR845 0.5 mcg/kg administered three times/week
PlaceboDRUGIV placebo administered three times/week
CR845DRUGIV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)
CR845 1 mcg/kgDRUGIV medication delivered three times/week
CR845 1.5mcg/kgDRUGIV medication delivered three times/week
CR845 IV 1 mcg/kgDRUGCR845 IV 1 mcg/kg will be administered as an IV bolus 2x loading dose one hour prior to anesthetic induction for surgery, then a dose within 30 minutes of the patient being considered stable in the post operative recovery room. Subsequent dosing will be administered at 6, 12 and 18 hours. Antinausea rescue medication (ondansetron 4 mg IV) may be requested, as well as analgesic rescue medication (morphine 5mg IV), post surgery, as needed. Saline infusion (IV 0.45%) for fluid replenishment will be provided.
CR845 IV 0.5 mcg/kgDRUGCR845 IV 0.5 mcg/kg will be administered as an IV bolus 2x loading dose one hour prior to anesthetic induction for surgery, then a dose within 30 minutes of the patient being considered stable in the post operative recovery room. Subsequent dosing will be administered at 6, 12 and 18 hours. Antinausea rescue medication (ondansetron 4 mg IV) may be requested, as well as analgesic rescue medication (morphine 5mg IV), post surgery, as needed. Saline infusion (IV 0.45%) for fluid replenishment will be provided.
Placebo IVDRUGPlacebo IV will be administered as an IV bolus 2x loading dose one hour prior to anesthetic induction for surgery, then a dose within 30 minutes of the patient being considered stable in the post operative recovery room. Subsequent dosing will be administered at 6, 12 and 18 hours. Antinausea rescue medication (ondansetron 4 mg IV) may be requested, as well as analgesic rescue medication (morphine 5mg IV), post surgery, as needed. Saline infusion (IV 0.45%) for fluid replenishment will be provided.
CR845 0.5 mcg/kg IVDRUG0.5 mcg/kg IV CR845
CR845 3 mcg/kg IVDRUG3 mcg/kg IV CR845
Moxifloxacin 400 mg Oral TabletDRUG400 mg Oral Moxifloxacin
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Eligibility Criteria

Age Range18 Years to 85 Years
SexALL
Healthy VolunteersNo
Study Sites47

Key Inclusion Criteria: To be eligible for inclusion into the study, a patient must meet the following criteria: * Has end-stage renal disease (ESRD) and has been on hemodialysis 3 times per week for at least 3 months prior to the start of screening; * Has at least 2 single-pool Kt/V measurements ...

Countries:United StatesCzechiaHungaryPolandAustraliaCanadaGermanyNew ZealandSouth KoreaTaiwanUnited KingdomPuerto Rico
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Frequently asked questions about CR845 /kg

What is CR845 used for?

CR845 is an investigational small molecule being studied for pain and uremic pruritus. It has been evaluated in clinical trials for osteoarthritis of the hip or knee, acute pain, and conditions related to chronic kidney disease, including uremic pruritus in patients on hemodialysis. It is not approved and remains in clinical development.

Who makes CR845?

CR845 is being developed by Cara Therapeutics, Inc., a biopharmaceutical company traded on NASDAQ under the ticker CARA. The company has sponsored multiple clinical trials of CR845, including Phase 1 and Phase 2 studies in the United States.

What phase is CR845 in?

CR845 has completed Phase 2 clinical trials for osteoarthritis and related pain conditions. It has also completed Phase 1 studies in healthy subjects and patients with end stage renal disease on hemodialysis. The drug is investigational and has not been approved by regulatory authorities.

What clinical trials is CR845 in?

CR845 has been studied in several completed trials, including NCT02524197 and NCT02944448 for osteoarthritis of the hip or knee, NCT03947970 for pharmacokinetics in hemodialysis patients and healthy subjects, and NCT04019574 for effects on the QTc interval in healthy subjects. All trials are completed.

Is CR845 the same as difelikefalin?

Yes, CR845 is also known as difelikefalin. Clinical trial records refer to the drug as both CR845 and difelikefalin, including studies evaluating its pharmacokinetics and metabolism in patients with end stage renal disease on hemodialysis and in healthy subjects.