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

Sponsor

Cara Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05978063

Collaborator

(none)

440

Enrollment

Location

Arms

Anticipated Duration (Months)

13.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pruritus Notalgia Paresthetica	Drug: difelikefalin 2.0 mg tablets Drug: difelikefalin 1.0 mg tablets Drug: difelikefalin 0.25 mg tablets Drug: Placebo tablets	Phase 2/Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

440 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Part A includes 4 arms and Part B includes 2 arms.Part A includes 4 arms and Part B includes 2 arms.

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2026

Anticipated Study Completion Date :

May 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Difelikefalin 2.0 mg tablets Oral difelikefalin 2.0 mg tablet administered twice daily	Drug: difelikefalin 2.0 mg tablets Oral difelikefalin 2.0 mg administered twice daily Other Names: CR845
Active Comparator: Difelikefalin 1.0 mg tablets Oral difelikefalin 1.0 mg tablet administered twice daily	Drug: difelikefalin 1.0 mg tablets Oral difelikefalin 1.0 mg administered twice daily Other Names: CR845
Active Comparator: Difelikefalin 0.25 mg tablets Oral difelikefalin 0.25 mg tablet administered twice daily	Drug: difelikefalin 0.25 mg tablets Oral difelikefalin 0.25 mg administered twice daily Other Names: CR845
Placebo Comparator: Placebo tablets Oral placebo tablet administered twice daily	Drug: Placebo tablets Oral Placebo administered twice daily

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.