MODERATE-TO-SEVERE PRURITUS IN HEMODIALYSIS PATIENTS
Conditions
Interventions
Product Name: Difelikefalin
Product Code: CR845
Pharmaceutical Form: Solution for injection
Pharmaceutical form of the placebo: Solution for solution fo
Sponsors
Cara Therapeutics INC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: To be eligible for inclusion into the Double-blind Phase of the study, a patient must meet the following criteria: 1.Willing and able to provide written informed consent prior to participating in this study; 2.Able to communicate clearly with the Investigator and staff, able to understand the study procedures, and able and willing to comply with the study requirements, including providing written responses to questionnaires; 3.Male or female between 18 and 85 years of age inclusive; Note: Subjects in Korea, must be male or female between 19 and 85 years of age, inclusive. 4.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; Note 1: Patients who require an occasional additional dialysis treatment to manage fluid overload or electrolyte excesses may be enrolled as long as it is anticipated that no more than 1 such treatment will be required in any given week and no More than 4 occasions during the 12-week double-blind period. Patients routinely on 4 dialyses a week will not be eligible. Note 2: Patients receiving in-home hemodialysis may participate as long as they have switched to in-center hemodialysis at least 2 weeks prior to screening and plan to remain on in-center hemodialysis for the duration of the study. Note 3: Patients receiving alternate dialysis modalities such as nocturnal dialysis will not be eligible. 5.If female, is not pregnant or nursing during any period of the study; 6.If female: a.Is surgically sterile; or b.Has been amenorrhoeic for at least 1 year and is over the age of 55 years; or c.Has a negative serum pregnancy test at screening and agrees to use acceptable contraceptive measures (eg, hormonal contraceptives, barrier with spermicide, intrauterine device, vasectomized partner, or abstinence) from the time of informed consent until 7 days after the last dose of study drug; 7.If male, agrees not to donate sperm after the first dose of study drug until 7 days after the last dose of study drug, and agrees to use a condom with spermicide or abstain from heterosexual intercourse during the study until 7 days after the last dose of study drug. (Note: No restrictions are required for a vasectomized male provided his vasectomy was performed =4 months prior to screening); 8.Has a prescription dry body weight between 40.0 and 135.0 kg, inclusive; 9.Has at least 2 single-pool Kt/V measurements =1.2, or at least 2 urea reduction ratio measurements =65%, or 1 single-pool Kt/V measurement =1.2 and 1 urea reduction ratio measurement =65% on different dialysis days during the 3 months period prior to screening; 10.Prior to randomization: a.Has completed at least four out of eight Worst Itching Intensity Numerical Rating Scale (NRS) worksheets fromhe start of the 7-day Run-in Period up to and including the pre-randomization assessment on Day 1; b.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-d
Exclusion criteria
Exclusion criteria: Exclusion Criteria: A patient will be excluded from the Double-blind Phase of the study if any of the following criteria are met: 1. Known noncompliance with dialysis treatment that in the opinion of the Investigator would impede completion or validity of the study; 2. Scheduled to receive a kidney transplant during the study; 3. 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 patients from the study). 4. Has a concomitant disease or a history of any medical condition that, in the opinion of the Investigator, could pose undue risk to the patient, impede completion of the study procedures, or would compromise the validity of the study measurements, including, but not limited to: a. Known or suspected history of alcohol, narcotic, or other drug abuse, or substance dependence within 12 months prior to screening; b. Significant systolic or diastolic heart failure (eg, New York Heart Association Class IV congestive heart failure [Appendix 1, Section 14.1]); c. Severe mental illness or cognitive impairment (eg, dementia); d. Any other relevant acute or chronic medical or neuropsychiatric condition within 3 months prior to screening (eg, diagnosis of encephalopathy, coma, delirium); 5. New or change of treatment received for itch including antihistamines and corticosteroids (oral, IV, or topical) within 14 days prior to screening; 6. New or change of prescription for opioids, gabapentin, or pregabalin within 14 days prior to screening; 7. 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; 8. In the opinion of the Investigator, has pruritus attributed to a cause other than ESRD or its complications (eg, patients with concomitant pruritic dermatological disease or cholestatic liver disease) (Note: Patients whose pruritus is attributed to ESRD complications, such as hyperparathyroidism, hyperphosphatemia, anemia, or the dialysis procedure or prescription may be enrolled); 9. Has localized itch restricted to the palms of the hands; 10. Has pruritus only during the dialysis session (by patient report); 11. Is receiving ongoing ultraviolet B treatment and anticipates receiving such treatment during the study; 12. Participated in a previous clinical study with CR845.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of IV CR845 at a dose of 0.5 mcg/kg compared to placebo in reducing the intensity of itch in hemodialysis patients with moderate-to-severe pruritus. ; Secondary Objective: To evaluate the efficacy of IV CR845 at a dose of 0.5 mcg/kg compared to placebo in improving itch-related quality-of-life measures in hemodialysis patients with moderate-to-severe pruritus. To evaluate the safety of IV CR845 at a dose of 0.5 mcg/kg in hemodialysis patients with moderate-to-severe pruritus. ; Primary end point(s): Primary Efficacy Endpoint • Proportion of patients achieving at least a 3-point improvement from baseline with respect to the weekly mean of the daily 24- hour Worst Itching Intensity NRS score at Week 12 of the Double-blind Treatment Period ;Timepoint(s) of evaluation of this end point: week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints • Change from baseline in itch-related quality of life at the end of Week 12 of the Double-blind Treatment Period, as assessed by the 5-D Itch Scale total score • Change from baseline in itch-related quality of life at the end of Week 12 of the Double-blind Treatment Period, as assessed by the Skindex-10 Scale total score • Proportion of patients achieving =4-point improvement from baseline with respect to the weekly mean of the daily 24-hour Worst Itching Intensity NRS at Week 12 of the Double-blind Treatment Period. Additional efficacy endpoints are described in Section 8.7.4. of the protocol Safety Endpoints The safety endpoints used to evaluate the overall safety and tolerability of CR845 will be adverse events, ECG, vital signs, and clinical safety laboratory evaluations. ;Timepoint(s) of evaluation of this end point: week 12 | — |
Countries
Australia, Canada, Czech Republic, Germany, Hungary, Korea, Republic of, New Zealand, Poland, Romania, Taiwan, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs
Icon clinical Research Ltd
Outcome results
None listed