Clinical trial NCT02285465: A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP3700 in Healthy Subjects
Official title: A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ascending Multiple Oral Doses of ASP3700 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Healthy Volunteers
Pharmacokinetics of ASP3700
Keywords: Healthy volunteers
Pharmacokinetics
Pharmacodynamics
ASP3700
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-11-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of ascending multiple oral doses of ASP3700 in healthy subjects.

Detailed description: Subjects will be confined in the clinic for 18 days.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety as assessed by adverse events
timeFrame: up to end of study visit (up to 26 days)
measure: Safety as assessed by vital signs
timeFrame: up to end of study visit (up to 26 days)
measure: Safety as assessed by orthostatic evaluation
timeFrame: Days 1 and 14
measure: Safety as assessed by laboratory tests
timeFrame: up to end of study visit (up to 26 days)
Secondary outcomes:
measure: Safety profile: Routine 12-lead ECG, C-SSRS, ARCI-49, Bond and Lader VAS, continuous cardiac monitoring (12-lead Holter ECG), exploratory sex hormone-related and renal biomarkers
timeFrame: up to end of study visit (up to 26 days)
measure: Pharmacokinetics profile of ASP3700 (plasma): Cmax, tmax, tlag
timeFrame: Cmax, tmax = Days 1 and 14; tlag = Day 1
measure: Pharmacokinetics profile of ASP3700 (plasma): AUCtau, CL/F, λz, MRT, t1/2, Vz/F, Rac (AUC), Rac (Cmax), PTR
timeFrame: Day 14
measure: Pharmacokinetics parameter of ASP3700 (plasma): Ctrough
timeFrame: Days 4, 6, 8, 10, 14 and 15
measure: Pharmacokinetics profile of ASP3700 (urine): Ae24, Ae24%, Aetau, Aetau%
timeFrame: Ae24, Ae24% = Day 1; Aetau, Aetau% = Day14
measure: Pharmacokinetics parameter of ASP3700 (urine): CLR
timeFrame: Days 1 and 14
Other outcomes:
Locations:
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Medical Director
role: STUDY_DIRECTOR
References: