Clinical trial NCT02475447: Safety, Pharmacokinetics and Preliminary Efficacy of Asimadoline in Pruritus Associated With Atopic Dermatitis
Official title: A Phase 2 Multicenter Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of Asimadoline in Adult Subjects With Pruritus Associated With Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pruritus
Atopic Dermatitis
Lead sponsor: Tioga Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-06-18
Enrollment: 249
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: Participants will be followed for the duration of the study, an expected 12 weeks
Secondary outcomes:
measure: Change from Baseline in Worst Itching Severity using a Visual Analog Scale
timeFrame: 4 weeks
measure: Maximum observed plasma drug concentration (Cmax)
timeFrame: 0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing
measure: Time to reach Cmax in plasma (Tmax)
timeFrame: 0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing
measure: Area under the plasma concentration-versus-time curve (AUC) from the time of the dose to the end of the 12-hour dosing interval
timeFrame: 0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Axis Clinical Research
state: California
city: North Miami Beach
country: United States
facility: Tory Sullivan, MD PA
state: Florida
city: Orange Park
country: United States
facility: Park Avenue Dermatology
state: Florida
city: Tampa
country: United States
facility: Olympian Clinical Research
state: Florida
city: Boise
country: United States
facility: Northwest Clinical Trials
state: Idaho
city: Normal
country: United States
facility: Sneeze, Wheeze and Itch Associates, LLC
state: Illinois
city: Carmel
country: United States
facility: Forefront Dermatology
state: Indiana
city: Saint Joseph
country: United States
facility: MediSearch Clinical Trials
state: Missouri
city: Verona
country: United States
facility: The Dermatology Group
state: New Jersey
city: Corning
country: United States
facility: Corning Center for Clinical Research
state: New York
city: Chapel Hill
country: United States
facility: UNC Dermatology and Skin Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania, Department of Dermatology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple Itch Center
state: Pennsylvania
city: Anderson
country: United States
facility: Radiant Research, Inc.
state: South Carolina
city: Charleston
country: United States
facility: Medical Research South
state: South Carolina
city: North Charleston
country: United States
facility: National Allergy and Asthma Research, LLC
state: South Carolina
city: Dallas
country: United States
facility: Dermatology Treatment and Research Center, PA
state: Texas
city: San Antonio
country: United States
facility: Sylvana Research Associates
state: Texas
Study officials:
affiliation: Tioga Pharmaceuticals, Inc.
name: Dawn McGuire, MD FAAN
role: STUDY_DIRECTOR
References: