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

• Sponsor: Tioga Pharmaceuticals
• Information provided by (Responsible Party): Tioga Pharmaceuticals

Tracking Information

• First Submitted Date: February 10, 2015
• First Posted Date: June 18, 2015
• Last Update Posted Date: December 13, 2017
• Actual Study Start Date: July 2015
• Actual Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 15, 2015): Number of participants with adverse events [ Time Frame: Participants will be followed for the duration of the study, an expected 12 weeks ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02475447 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: June 15, 2015)

• Change from Baseline in Worst Itching Severity using a Visual Analog Scale [ Time Frame: 4 weeks ]
• Maximum observed plasma drug concentration (Cmax) [ Time Frame: 0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing ]
• Time to reach Cmax in plasma (Tmax) [ Time Frame: 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 [ Time Frame: 0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Pruritus
• Atopic Dermatitis

Intervention

• Drug: Asimadoline
  kappa-opioid receptor agonist
  Other Name: No brand name, serial number and code name
• Drug: Placebo
  placebo-matched control
  Other Name: No brand name, serial number and code name

Study Arms

• Placebo Comparator: Placebo
  Placebo-matched tablets twice daily for 4 weeks.
  Intervention: Drug: Placebo
• Experimental: Asimadoline
  Asimadoline tablets twice daily (5 mg total daily dose) for 8 weeks.
  Intervention: Drug: Asimadoline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 11, 2017): 249
• Original Estimated Enrollment (submitted: June 15, 2015): 200
• Actual Study Completion Date: June 2017
• Actual Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02475447
• Other Study ID Numbers: ASMP2006
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Tioga Pharmaceuticals
• Study Sponsor: Tioga Pharmaceuticals
• Collaborators: Not Provided

Investigators

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

• PRS Account: Tioga Pharmaceuticals
• Verification Date: December 2017