A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP3700 in Healthy Subjects

Inclusion Criteria:

• Subject has a skin type I, II or III (Fitzpatrick classification).
• Subject has a body mass index (BMI) of 18.5 to 30.0 kg/m2, inclusive. The subject weighs at least 50 kg at screening.

Exclusion Criteria:

• Female subject who has been pregnant within 6 months prior to screening assessment or breast feeding within 3 months prior to screening.
• Subject has a known or suspected hypersensitivity to ASP3700 or any components of the formulation used.
• Subject does not respond to the capsaicin challenge at screening or day -1. A nonresponder is defined by a dermal blood flow (DBF) of ≤ 100% increase from baseline (normal skin) compared to DBF 30 minutes after application of 0.4 mL (approximately 300 µg) of capsaicin cream (Axsain®, 0.075% capsaicin w/w).
• Subject does not respond to the histamine challenge at screening or day -1. A nonresponder is defined by an insufficient wheal (mean diameter < 0.5 cm) and/or flare (mean diameter < 2 cm) reaction (visually assessed and measured by trained staff member) after 10 minutes of the histamine intradermal injection.
• Subject has a history of suicide attempt or suicidal behavior. Any suicidal ideation within the last 3 months (a level of 4 or 5 for any 1 item on the scale), or who are at significant risk to commit suicide, as judged by the investigator using the C-SSRS at screening and on admission to the clinical unit on day -1.
• Subject has any of the liver function tests (aspartate aminotransferase [AST], Alanine aminotransferase [ALT], alkaline phosphatase [ALP], gamma glutamyl transferase, total bilirubin [TBL]) above the upper limit of normal (ULN). In such a case the assessment may be repeated once on day -1.
• Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
• Subject has a history of clinically significant reaction to cannabis or synthetic cannabinoids as judged by the investigator.
• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy, as judged by the investigator.
• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (noncutaneous) infection within 1 week prior to admission to the clinical unit.
• Subject has any clinically significant abnormality following the investigator's review of the physical examination, electrocardiogram (ECG) and protocol defined clinical laboratory tests at screening or day -1.
• Subject has a mean pulse < 40 or > 90 bpm; mean systolic blood pressure (SBP) > 140 mmHg; mean diastolic blood pressure (DBP) > 90 mmHg (vital sign measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically) on day -1. If the mean pulse, mean SBP or mean DBP is out of the range as specified above, 1 additional triplicate measurement may be taken.
• Subject has a mean QTc(F) interval of > 430 ms (for males) and > 450 ms (for females) at day -1. If the mean QTc(F) exceeds the limits above, 1 additional triplicate ECG can be taken.
• Subject uses any prescribed or nonprescribed drugs (including antihistamines, vitamins, natural and herbal remedies, e.g., St. John's wort) in the 2 weeks prior to study drug administration, except for occasional use of paracetamol (up to 2 g/day).
• Subject has used nicotine-containing products within 6 months prior to admission to the clinical unit on day -1.
• Subject has a history of drinking > 21 units of alcohol per week for male subjects or > 14 units of alcohol for female subjects (1 unit = 10 g pure alcohol = 250 mL of beer [5%] or 35 mL of spirits [35%] or 100 mL of wine [12%]) within 3 months prior to admission to the clinical unit on day -1.
• Subject has used any drugs of abuse within 3 months prior to admission to the clinical unit on day -1.
• Subject has used any inducer of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to admission to the clinical unit on day -1.
• Subject has consumed grapefruit, grapefruit-containing products, Seville orange-containing products, caffeine, xanthine, quinidine or theobromine containing products within 72 hours prior to admission to the clinical unit on day -1.
• Subject has had a significant blood loss, donated 1 unit (500 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to admission to the clinical unit on day -1.
• Subject has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (immunoglobulin M) (antiHAV [IgM]), hepatitis C virus antibodies (antiHCV), or antibodies to human immunodeficiency virus type 1 (HIV-1) and/or type 2 (HIV-2) at screening.
• Subject has participated in any clinical study or has been treated with any investigational drugs within 3 months or 5 half-lives, whichever is longer, prior to screening.
• Subject has a skin disease, acute or chronic (e.g., atopic dermatitis) or any active dermatological conditions, local pigmentary disorders, or body art (e.g., tattoos) that might interfere with the clinical study assessments.
• Subject has any condition which, in the investigator's opinion, makes the subject unsuitable for clinical study participation.
• Subject is an employee of the Astellas Group or Contract Research Organization (CRO) involved in the clinical study.