A STUDY COMPARING VLY-686 AND PLACEBO IN SUBJECTS WHO DO NOT RECEIVE RELIEF FROM CURRENT TREATMENT OPTIONS FOR ITCH ASSOCIATED WITH ATOPIC DERMATITIS.

Phase 1

Conditions: Males or females with treatment resistant pruritus associated with atopic dermatitis.
MedDRA version: 17.1Level: PTClassification code 10037087Term: PruritusSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: EUCTR2013-002931-25-DE

Lead Sponsor: Vanda Pharmaceuticals Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 68

Inclusion Criteria

Men and women ages 18 – 65 years, inclusive;
a. Suffering from atopic dermatitis with a SCORAD index at inclusion =80;
b. With atopic lesions on arms, legs, trunk and neck;
2. Chronic pruritus with pruritus being actively present for at least 6 weeks prior to screening;
3. Subjects who have treatment-resistant pruritus; pruritus duration of > 6 weeks despite the use of antihistamines or corticosteroids;
4. Pruritus VAS intensity =70 mm (mean intensity during one of the two days preceding inclusion into the study / Baseline Visit);
5. Patient assessment of pruritus (PGA Likert scale item pruritus”) at inclusion =3;
6. Subjects with Body Mass Index (BMI) of =18 and =35 kg/m2 (BMI = weight (kg)/ [height (m)]2);
7. Males, non-fecund females (i.e., surgically sterilized, if procedure was done 6 months before screening or subject is postmenopausal, without menses for 1 year before screening), or females of child-bearing potential using 2 independent barrier methods of birth control (i.e., condoms, diaphragm, spermicidal agents, cervical cap) for a period of 35 days before the first dosing, during the study and for one month after the last dose and must have a negative pregnancy test at the screening and baseline visits;
a. Note: Abstinence is considered a reliable method of birth control in this study
b. Note: Hormonal contraception is not considered a reliable method of birth control in this study.
c. Note: For subjects over 55 years of age at the screening visit absence of menses for 1 year before screening is sufficient to establish the postmenopausal status. The postmenopausal status of a patient under 55 years of age at the screening visit will be confirmed by measuring the following hormones:
i.Follicle-stimulating hormone (FSH) = 40 mIU/mL;
ii.Estradiol = 30 pg/mL (110.1 pmol/L).
8. Vital signs (after 3 minutes resting in a sitting or semi-supine position) which are within the ranges shown below:
a. Body temperature between 35.5-37.8 °C;
b. Systolic blood pressure between 91-130 mmHg;
c. Diastolic blood pressure between 51-90 mmHg;
d. Pulse rate between 50-100 bpm.
9. Ability and acceptance to provide written informed consent;
10. Willing and able to comply with study requirements and restrictions including the discontinuation of all current therapies for pruritus;
11. Willing to not participate in any other clinical trials for the duration of the VLY-686 trial;
12. Subjects must be in good health as determined by past medical history, physical examination, electrocardiogram, clinical laboratory tests and urinalysis.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1. Chronic pruritus due to conditions other than atopic dermatitis (AD) including the following conditions:
a. Prurigo nodularis;
b. Lichen simplex chronicus;
c. Bullous pemphigoid;
2. Other non-AD subjects (notalgia paresthetica, brachioradial pruritus, somatoform prurigo, dilusional parasitosis, depression associated prurigo);
3. Acute superinfection of AD;
4. Current and past systematic use of:
a. topical or systemic antihistamines (2 weeks prior to the Baseline Visit);
b. topical steroids (2 weeks prior to Baseline Visit);
c. systemic steroids (6 weeks prior to the Baseline Visit);
d. cytotoxic treatment (4 weeks prior to the Baseline Visit);
e. cyclosporin A and other immunosuppressants (8 weeks prior to the Baseline Visit);
f. naltrexone, paroxetine, fluvoxamine, amitriptyline, gabapentin, pregabalin (prescribed for the pruritus treatment, 4 weeks prior to the Baseline Visit);
g. topical calcineurin inhibitors, topical antibiotics, antiseptic bathes and cleansing lotions (8 weeks prior to the Baseline Visit);
5. Under actual medical treatment for a skin disease with a therapy listed in the prohibited medications section that may influence the results of the study;
6. History of recent (within six months) drug or alcohol abuse as defined in DSM V, Diagnostic Criteria for Drug and Alcohol Abuse or evidence of such abuse as indicated by the laboratory assays conducted during the Screening or Baseline Visits;
7. Subjects who are currently considered a suicide risk, any subject who has ever made a suicide attempt, or those who are currently demonstrating active (within the past 6 months) suicidal ideation of type 4 or 5 as deemed by the Columbia Suicide Severity Rating Scale (C-SSRS);
8. Any major surgery within three months of the Baseline Visit or any minor surgery within one month;
9. Current clinically significant cardiovascular, respiratory, neurologic, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction unless currently controlled and stable;
a. Uncontrolled diabetes mellitus defined as HbA1c >7% or fasting glucose levels >130 mg/dL;
b. Positive hepatitis C antibody test (anti-HCF);
c. Positive hepatitis B surface antigen (HBsAg);
10. History (including family history) or current evidence of congenital long QT syndrome or known acquired QT interval prolongation;
11. Exposure to any investigational medication, including placebo, within 60 days of the Baseline Visit;
12. Exposure (within 2 weeks of the Baseline Visit) to any over-the-counter medications including melatonin, dietary supplements and/or herbal remedies;
13. Treatment with any medication known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 days preceding the Screening visit;
14. History of intolerance and/or hypersensitivity to medications similar toVLY-686 and its accompanying excipients;
15. Significant illness within the two weeks prior to the Baseline visit;
16. Pregnant or lactating females;
17. Participation in a previous LY686017 or VLY-686 trial;
18. Have a history of cirrhosis or laboratory evidence of hepatocellular injury, as evidenced by elevated levels of serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) greater than 2 times the upper limit of normal (2X ULN);
19. Not willing to accept information-transfer concerning participation in the study, or information regarding his/her health (e.g. laboratory results or medical history);
20. Anyone affiliated with the site o