A Phase Ib/IIa, Double-Blind, Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of S-777469 in Subjects With Atopic Dermatitis

NCT00697710 | Completed Phase 1

• 1 other identifier: 0710D1416
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this randomized, double-blind, placebo-controlled, sequential-cohort, dose-escalation study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of S-777469, a CB2 cannabinoid receptor agonist, in subjects with mild to moderate atopic dermatitis.

Conditions

Atopic Dermatitis

Keywords

Atopic Dermatitis

Outcome Measures

Primary Outcomes (2)

• Safety Assessments

  Safety assessments included adverse event monitoring, vital sign measurements, physical examination measurements, 12-lead electrocardiograms assessments, and standard clinical laboratory safety tests (hematology, blood chemistry, and urinalysis).

  Throughout the study period

• Pharmacokinetic Assessments

  Pharmacokinetic endpoints included Cmax, Tmax, T1/2,12hr, T1/2,z, and AUC0-12h for each dose level of S-777469 based on the sampling schedule. Time to achieve steady state was determined for each dose level. Serum protein binding of S-777469 was determined for all cohorts. Plasma and urine concentrations of S-777469 was determined for single dose and multiple doses for all cohorts. The plasma and urine samples were used for determination of concentrations of metabolites of S-777469. Plasma and urine samples for single dose and multiple doses for Cohort B was used for metabolite profiling.

  Days 1, 7, and 14

Secondary Outcomes (1)

• Efficacy assessment: To assess the potential anti-pruritic and anti-inflammatory efficacy of S-777469 after single-dose administration and twice daily administration in subjects with mild-to-moderate Atopic Dermatitis

  Change from baseline to Day 14

Study Arms (3)

Cohort A

EXPERIMENTAL

50 mg S-777469 or Placebo, BID

Drug: 50 mg S-777469; Drug: Placebo

Cohort B

EXPERIMENTAL

200 mg S-777469 or Placebo, BID

Drug: 200 mg S-777469; Drug: Placebo

Cohort C

EXPERIMENTAL

800 mg S-777469 or Placebo, BID

Drug: 800 mg S-777469; Drug: Placebo

Interventions

50 mg S-777469 DRUG

S-777469, 50 mg BID

Cohort A

200 mg S-777469 DRUG

S-777469, 200 mg BID

Cohort B

800 mg S-777469 DRUG

S-777469, 800 mg BID

Cohort C

Placebo DRUG

Matching Placebo

Cohort A; Cohort B; Cohort C

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Otherwise healthy males and females between 18 and 65 years of age at the time of obtaining the written informed consent
• Subject understands the study procedures and agrees to participate in the study by giving written informed consent
• Subject satisfies the diagnostic criteria for mild to moderate atopic dermatitis (AD) as judged by the Physician's Global Assessment Score and modified criteria
• All of these features must be present:
• Pruritus
• Eczema (acute, subacute, chronic) with the following characteristics:current or prior flexural lesions, lesions on the face, neck, and extensor surfaces, sparing of groin and axillary regions (no lesions)
• History of a chronic and relapsing course of eczema
• Personal or family history of atopy
• Subject is judged to be in general good health based on medical history, physical examination, and routine laboratory tests performed at screen and baseline, with the exception of diagnosis of mild to moderate AD
• Subject has a negative laboratory results for hepatitis B surface antigen, hepatitis C virus (anti-HCV antibodies), and Human Immunodeficiency Virus antibody screens
• Female subjects have a negative pregnancy test at screen and baseline
• Serum creatinine in the normal range \[0.5 to 1.5 mg/dl\]
• Liver function tests (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], and gamma glutamyl transpeptidase \[GGT\]) within normal range
• Negative screen for drugs of abuse at screen and baseline
• Subject agrees to refrain from smoking for the duration of the trial

You may not qualify if:

• Subjects will not be eligible if they meet any of the following criteria:
• Active dermatologic conditions which may confound the diagnosis of AD, such as scabies, allergic contact dermatitis, seborrheic dermatitis, cutaneous lymphoma, ichthyosis, or psoriasis
• History of malignancy not in remission for \>5 years
• Presence of comorbid conditions that would preclude participation in the study, including:
• Subject has any acute or chronic condition or prior therapy that, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in this clinical study or otherwise would make the subject unsuitable for this study
• Subject has a history of drug abuse within 1 year prior to Day 1
• Subject consumes excess amounts of alcohol, defined as exceeding an average of 14 drinks/week (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor, or any combination of them) within 2 months prior to Study Entry, or is unwilling to comply with the restricted use of alcohol from screening, throughout the study, and until study completion (post-study visit)
• Subject has used any systemic antibiotics for 3 weeks prior to the Day 1 visit (washout period)
• Subject is pregnant or lactating or intends to become pregnant or, in the case of a male subject, intends to father a child during the study period and for 1 month after the last dose of study medication
• Subject requires use of immunosuppressive drugs such as oral corticosteroids or inhaled corticosteroids
• Subject has donated blood within 6 weeks prior to Day 1 or plasma within 2 weeks prior to screening, or received blood products within 2 months prior to Day 1
• Subject has poor peripheral venous access
• Subject has participated in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days prior to Day 1
• Any reason which, in the opinion of the investigator, interferes with the ability of the subject to participate to, or complete, the trial

Sponsors & Collaborators

• Shionogi: lead

Study Sites (1)

Comprehensive Phase One

Miramar, Florida, 33025, United States

Location

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

S-777469

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Shionogi Clinical Trials Administrator Clinical Support Help Line

  Shionogi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2008
• First Posted: June 16, 2008
• Study Start: July 1, 2007
• Primary Completion: February 1, 2008
• Study Completion: September 1, 2008
• Last Updated: May 1, 2018

Record last verified: 2018-04

Locations

US (1)