Safety, Pharmacokinetics and Preliminary Efficacy of Asimadoline in Pruritus Associated With Atopic Dermatitis

A Phase 2 Multicenter Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of Asimadoline in Adult Subjects With Pruritus Associated With Atopic Dermatitis

Kappa-opioid receptors mediate the sensation of itch in animals and humans. Asimadoline is an orally active, selective kappa-opioid receptor agonist and has demonstrated efficacy in several preclinical pruritus models. The purpose of this Phase 2 study is to evaluate the safety, tolerability and clinical efficacy of asimadoline in patients with pruritus associated with atopic dermatitis.

Study Overview

• Status: Completed
• Conditions: Pruritus; Atopic Dermatitis
• Intervention / Treatment: Drug: Placebo; Drug: Asimadoline

Detailed Description

Asimadoline has been administered to over 1900 human subjects or patients in clinical trials and exhibits an acceptable safety profile. Due to its high selectivity for the kappa-opioid receptor, asimadoline does not produce mu-opioid like side-effects. Results from preclinical models indicate asimadoline significantly reduces the frequency of scratching induced by pruritic agents. This double-blind placebo-controlled clinical study is designed to evaluate the safety, tolerability and clinical efficacy of asimadoline in patients with pruritus associated with atopic dermatitis.

• Study Type: Interventional
• Enrollment (Actual): 249
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35244
      • Clinical Research Center of Alabama
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Los Angeles, California, United States, 90036
      • Axis Clinical Research
  • Florida
    • North Miami Beach, Florida, United States, 33162
      • Tory Sullivan, Md Pa
    • Orange Park, Florida, United States, 32073
      • Park Avenue Dermatology
    • Tampa, Florida, United States, 33609
      • Olympian Clinical Research
  • Idaho
    • Boise, Idaho, United States, 83704
      • Northwest Clinical Trials
  • Illinois
    • Normal, Illinois, United States, 61761
      • Sneeze, Wheeze and Itch Associates, LLC
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Forefront Dermatology
  • Missouri
    • Saint Joseph, Missouri, United States, 64506
      • MediSearch Clinical Trials
  • New Jersey
    • Verona, New Jersey, United States, 07044
      • The Dermatology Group
  • New York
    • Corning, New York, United States, 14830
      • Corning Center for Clinical Research
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27516
      • UNC Dermatology and Skin Cancer Center
    • Winston-Salem, North Carolina, United States, 27104
      • Wake Forest Baptist Health
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania, Department of Dermatology
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple Itch Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Radiant Research, Inc.
    • Charleston, South Carolina, United States, 29407
      • Medical Research South
    • North Charleston, South Carolina, United States, 29420
      • National Allergy and Asthma Research, LLC
  • Texas
    • Dallas, Texas, United States, 75230
      • Dermatology Treatment and Research Center, PA
    • San Antonio, Texas, United States, 78229
      • Sylvana Research Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

1. Signed informed consent and must be able and willing to follow study procedures and instructions
2. Male or female subject aged 18 years or older (no upper age limit)
3. Established clinical diagnosis of atopic dermatitis for at least 6 months
4. Itching Visual Analog Scale (VAS) average worst itching score of at least 40 mm on a 100 mm scale
5. Female subject of childbearing potential and male subject of procreative capacity agree to use an effective method of contraception for the duration of the study

Main Exclusion Criteria:

1. Pregnant, attempting to conceive, or nursing
2. Received phototherapy (ultraviolet B, psoralen plus ultraviolet A) within the previous 4 weeks

3. Received treatment with any of the following within the previous 2 weeks:

   - Topical or oral immunosuppressants or calcineurin inhibitors, sedating anti-histamines or anti-histamines taken for pruritus treatment, prescription topical corticosteroid creams or ointments, any other oral or topical steroids, aprepitant, naltrexone, pregabalin, gabapentin, or tricyclic antidepressants, or any other medications that, in the investigator's judgement, could affect the subject's pruritus or atopic dermatitis, and that are not specified below

   OR taking any of the following and has not been on stable use for at least the previous 4 weeks:

   - Non-prescription topical hydrocortisone creams or ointments, lotions, moisturizers, emollients, bath oil treatments, non-sedating oral anti-histamines being taken for allergy treatment, selective serotonin reuptake inhibitor (SSRI) antidepressants.

4. Currently participating in other investigational clinical studies or having received investigational drugs in a clinical research study within the previous 3 months. Subjects currently enrolled in an observational study are eligible for participation in this study, however subjects must not enroll in a new observational study during the course of their participation in this study
5. Pruritus due to conditions other than atopic dermatitis (e.g., hepatitis, biliary cirrhosis, scabies) or due to medications known to cause pruritus
6. Acute illnesses, uncontrolled or unmanaged diabetes or thyroid disease, decompensated heart failure, cirrhosis or liver failure, chronic kidney disease, or uncontrolled psychiatric disease
7. Evidence or treatment of malignancy (other than localized basal cell cancer, squamous cell skin cancer, or cancer in situ that has been resected) within the previous 5 years
8. History of HIV infection
9. History of alcohol or drug abuse within the past 3 years
10. Diseases or conditions that could, in the opinion of the investigator, interfere with the assessment of safety and efficacy of the study drug and compliance of the subject with study visits/procedures (e.g. exacerbation of multiple sclerosis or other comorbid conditions)
11. Use of any product that acts as an inhibitor of P-glycoprotein (P-gp) or as a P-gp substrate (with the exception of topical ketoconazole product for skin or scalp) within the previous 4 weeks
12. Known allergy to asimadoline or its drug components.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo-matched tablets twice daily for 4 weeks.	Drug: Placebo; placebo-matched control; Other Names: No brand name, serial number and code name
Experimental: Asimadoline; Asimadoline tablets twice daily (5 mg total daily dose) for 8 weeks.	Drug: Asimadoline; kappa-opioid receptor agonist; Other Names: No brand name, serial number and code name

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events	Participants will be followed for the duration of the study, an expected 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Worst Itching Severity using a Visual Analog Scale	4 weeks
Maximum observed plasma drug concentration (Cmax)	0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing
Time to reach Cmax in plasma (Tmax)	0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing
Area under the plasma concentration-versus-time curve (AUC) from the time of the dose to the end of the 12-hour dosing interval	0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing

Collaborators and Investigators

• Sponsor: Tioga Pharmaceuticals
• Investigators: Study Director: Dawn McGuire, MD FAAN, Tioga Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: February 10, 2015
• First Submitted That Met QC Criteria: June 15, 2015
• First Posted (Estimate): June 18, 2015

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: December 11, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Manifestations; Skin Diseases, Eczematous; Dermatitis; Eczema; Pruritus; Dermatitis, Atopic
• Other Study ID Numbers: ASMP2006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No