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

Phase 2
Completed
Conditions
Atopic Dermatitis
Pruritus
Interventions
Drug: Placebo
Registration Number
NCT02475447
Lead Sponsor
Tioga Pharmaceuticals
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
249
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo-matched tablets twice daily for 4 weeks.
AsimadolineAsimadolineAsimadoline tablets twice daily (5 mg total daily dose) for 8 weeks.
Primary Outcome Measures
NameTimeMethod
Number of participants with adverse eventsParticipants will be followed for the duration of the study, an expected 12 weeks
Secondary Outcome Measures
NameTimeMethod
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
Change from Baseline in Worst Itching Severity using a Visual Analog Scale4 weeks
Area under the plasma concentration-versus-time curve (AUC) from the time of the dose to the end of the 12-hour dosing interval0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing

Trial Locations

Locations (22)

Park Avenue Dermatology

🇺🇸

Orange Park, Florida, United States

Tory Sullivan, MD PA

🇺🇸

North Miami Beach, Florida, United States

Sneeze, Wheeze and Itch Associates, LLC

🇺🇸

Normal, Illinois, United States

Corning Center for Clinical Research

🇺🇸

Corning, New York, United States

UNC Dermatology and Skin Cancer Center

🇺🇸

Chapel Hill, North Carolina, United States

Wake Forest Baptist Health

🇺🇸

Winston-Salem, North Carolina, United States

Medical Research South

🇺🇸

Charleston, South Carolina, United States

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Axis Clinical Research

🇺🇸

Los Angeles, California, United States

Northwest Clinical Trials

🇺🇸

Boise, Idaho, United States

Forefront Dermatology

🇺🇸

Carmel, Indiana, United States

MediSearch Clinical Trials

🇺🇸

Saint Joseph, Missouri, United States

University of Pennsylvania, Department of Dermatology

🇺🇸

Philadelphia, Pennsylvania, United States

Temple Itch Center

🇺🇸

Philadelphia, Pennsylvania, United States

National Allergy and Asthma Research, LLC

🇺🇸

North Charleston, South Carolina, United States

Dermatology Treatment and Research Center, PA

🇺🇸

Dallas, Texas, United States

Sylvana Research Associates

🇺🇸

San Antonio, Texas, United States

The Dermatology Group

🇺🇸

Verona, New Jersey, United States

Radiant Research, Inc.

🇺🇸

Anderson, South Carolina, United States

Clinical Research Center of Alabama

🇺🇸

Birmingham, Alabama, United States

Olympian Clinical Research

🇺🇸

Tampa, Florida, United States

Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

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