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

• Sponsor: Tioga Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02475447
• Collaborator: (none)
• Enrollment: 249
• Locations: 22
• Arms: 2
• Actual Duration (Months): 23
• Patients Per Site: 11.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pruritus; Atopic Dermatitis	Drug: Asimadoline; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 249 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of participants with adverse events [Participants will be followed for the duration of the study, an expected 12 weeks]

Secondary Outcome Measures

1. Change from Baseline in Worst Itching Severity using a Visual Analog Scale [4 weeks]

2. Maximum observed plasma drug concentration (Cmax) [0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing]

3. Time to reach Cmax in plasma (Tmax) [0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing]

4. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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

2. Pruritus due to conditions other than atopic dermatitis (e.g., hepatitis, biliary cirrhosis, scabies) or due to medications known to cause pruritus

3. Acute illnesses, uncontrolled or unmanaged diabetes or thyroid disease, decompensated heart failure, cirrhosis or liver failure, chronic kidney disease, or uncontrolled psychiatric disease

4. 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

5. History of HIV infection

6. History of alcohol or drug abuse within the past 3 years

7. 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)

8. 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

9. Known allergy to asimadoline or its drug components.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Center of Alabama	Birmingham	Alabama	United States	35244
2	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
3	Axis Clinical Research	Los Angeles	California	United States	90036
4	Tory Sullivan, MD PA	North Miami Beach	Florida	United States	33162
5	Park Avenue Dermatology	Orange Park	Florida	United States	32073
6	Olympian Clinical Research	Tampa	Florida	United States	33609
7	Northwest Clinical Trials	Boise	Idaho	United States	83704
8	Sneeze, Wheeze and Itch Associates, LLC	Normal	Illinois	United States	61761
9	Forefront Dermatology	Carmel	Indiana	United States	46032
10	MediSearch Clinical Trials	Saint Joseph	Missouri	United States	64506
11	The Dermatology Group	Verona	New Jersey	United States	07044
12	Corning Center for Clinical Research	Corning	New York	United States	14830
13	UNC Dermatology and Skin Cancer Center	Chapel Hill	North Carolina	United States	27516
14	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27104
15	Oregon Health and Science University	Portland	Oregon	United States	97239
16	University of Pennsylvania, Department of Dermatology	Philadelphia	Pennsylvania	United States	19104
17	Temple Itch Center	Philadelphia	Pennsylvania	United States	19140
18	Radiant Research, Inc.	Anderson	South Carolina	United States	29621
19	Medical Research South	Charleston	South Carolina	United States	29407
20	National Allergy and Asthma Research, LLC	North Charleston	South Carolina	United States	29420
21	Dermatology Treatment and Research Center, PA	Dallas	Texas	United States	75230
22	Sylvana Research Associates	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Tioga Pharmaceuticals

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tioga Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02475447
• Other Study ID Numbers: ASMP2006
• First Posted: Jun 18, 2015
• Last Update Posted: Dec 13, 2017
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema; Pruritus

Study Results

No Results Posted as of Dec 13, 2017