Study to Evaluate the Efficacy and Safety of Oral Difelikefalin for Moderate to Severe Pruritus in Subjects With Notalgia Paresthetica

Study Overview
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Brief Summary
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This is a 2-part, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of twice-daily (BID) oral difelikefalin for moderate-to-severe pruritus in adult subjects with NP.

Detailed Description
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Part A of this study will evaluate the benefit-risk of 3 doses of difelikefalin compared to placebo. The dose with the best benefit-risk profile will be further evaluated in Part B. Part A of this study comprises a 28-day Screening Period, a 7-day Run-in Period, an 8-week Double-blind Treatment Period, a 2-week Treatment Discontinuation Period, and a Safety Follow-up Visit (14 days after the last dose of study treatment). Part B of this study will evaluate the efficacy, safety, and tolerability of oral difelikefalin. The dose of oral difelikefalin to be assessed in Part B will depend on the results of Part A. Part B of this study comprises a 28-day Screening Period, a 7-day Run-in Period, an 8-week Double-blind Treatment Period, up to a 52-week OLE Period, and a Safety Follow-up Visit. Subjects who participated in Part A of the study may not participate in Part B. All subjects will sign an informed consent form (ICF) and undergo screening for study eligibility.

Official Title
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A 2-part, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Oral Difelikefalin for Moderate-to-Severe Pruritus in Adult Subjects With Notalgia Paresthetica

Conditions
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Pruritus, Notalgia Paresthetica

Intervention / Treatment
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* Drug: difelikefalin 2.0 mg tablets
* Drug: difelikefalin 1.0 mg tablets
* Drug: difelikefalin 0.25 mg tablets
* Drug: Placebo tablets


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: To be eligible for inclusion into the study, a patient must meet the following criteria: Subject has clinically confirmed diagnosis of active Notalgia Paresthetica; Subject has a history of chronic pruritus due to Notalgia Paresthetica; Subject has moderate to severe pruritus; Female subject is not pregnant or nursing during any period of the study. Key Exclusion Criteria: A patient will be excluded from the study if any of the following criteria are met: Subject has pruritus attributed to a cause other than Notalgia Paresthetica; Subject has any clinically significant medical condition or physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere with interpretation of study results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part A includes 4 arms and Part B includes 2 arms.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Difelikefalin 2.0 mg tablets<br>Oral difelikefalin 2.0 mg tablet administered twice daily | Drug: difelikefalin 2.0 mg tablets<br>* Oral difelikefalin 2.0 mg administered twice daily<br>* Other names: CR845;|
| Active Comparator: Difelikefalin 1.0 mg tablets<br>Oral difelikefalin 1.0 mg tablet administered twice daily | Drug: difelikefalin 1.0 mg tablets<br>* Oral difelikefalin 1.0 mg administered twice daily<br>* Other names: CR845;|
| Active Comparator: Difelikefalin 0.25 mg tablets<br>Oral difelikefalin 0.25 mg tablet administered twice daily | Drug: difelikefalin 0.25 mg tablets<br>* Oral difelikefalin 0.25 mg administered twice daily<br>* Other names: CR845;|
| Placebo Comparator: Placebo tablets<br>Oral placebo tablet administered twice daily | Drug: Placebo tablets<br>* Oral Placebo administered twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving ≥4-point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score |  | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving ≥4-point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 4 in Part B |  | Baseline, Week 4 | 
| Proportion of subjects achieving ≥4-point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 2 in Part B |  | Baseline, Week 2 | 
| Proportion of subjects achieving ≥4-point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 1 in Part B |  | Baseline, Week 1 | 
| Change from Baseline in the Numeric Rating Scale of Burning Sensation and Skin Tingling at Week 8 in Part B |  | Baseline, Week 8 | 
| Proportion of Subjects with H-IGA of Clear or Almost Clear at Week 8 in Part B |  | Week 8 | 
| Proportion of ≥4-point Improvement in Daily I-NRS at Day 2 in Part B |  | Day 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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difelikefalin, Itch, Notalgia Paresthetica, Pruritus, CR845, Chronic Itch, Itching, Generalized pruritus, NP, Neuropathic itch