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

Atopic Dermatitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02475447
• Other study ID #: ASMP2006
• Status: Completed
• Phase: Phase 2
• First received: February 10, 2015
• Last updated: December 11, 2017
• Start date: July 2015
• Est. completion date: June 2017

Study information

• Verified date: December 2017
• Source: Tioga Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 249
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema
• Pruritus

Intervention

Drug:
• Asimadoline
kappa-opioid receptor agonist
• Placebo
placebo-matched control

Locations

Country	Name	City	State
United States	Radiant Research, Inc.	Anderson	South Carolina
United States	Clinical Research Center of Alabama	Birmingham	Alabama
United States	Northwest Clinical Trials	Boise	Idaho
United States	Forefront Dermatology	Carmel	Indiana
United States	UNC Dermatology and Skin Cancer Center	Chapel Hill	North Carolina
United States	Medical Research South	Charleston	South Carolina
United States	Corning Center for Clinical Research	Corning	New York
United States	Dermatology Treatment and Research Center, PA	Dallas	Texas
United States	Axis Clinical Research	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Sneeze, Wheeze and Itch Associates, LLC	Normal	Illinois
United States	National Allergy and Asthma Research, LLC	North Charleston	South Carolina
United States	Tory Sullivan, MD PA	North Miami Beach	Florida
United States	Park Avenue Dermatology	Orange Park	Florida
United States	Temple Itch Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania, Department of Dermatology	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	MediSearch Clinical Trials	Saint Joseph	Missouri
United States	Sylvana Research Associates	San Antonio	Texas
United States	Olympian Clinical Research	Tampa	Florida
United States	The Dermatology Group	Verona	New Jersey
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Tioga Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events		Participants will be followed for the duration of the study, an expected 12 weeks
Secondary	Change from Baseline in Worst Itching Severity using a Visual Analog Scale		4 weeks
Secondary	Maximum observed plasma drug concentration (Cmax)		0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing
Secondary	Time to reach Cmax in plasma (Tmax)		0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing
Secondary	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