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

NCT02285465 | Withdrawn Phase 1

• 2 other identifiers: 3700-CL-00022014-003226-41
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Healthy Volunteers; Pharmacokinetics of ASP3700

Keywords

Healthy volunteers; Pharmacokinetics; Pharmacodynamics; ASP3700

Outcome Measures

Primary Outcomes (4)

• Safety as assessed by adverse events

  up to end of study visit (up to 26 days)

• Safety as assessed by vital signs

  up to end of study visit (up to 26 days)

• Safety as assessed by orthostatic evaluation

  Days 1 and 14

• Safety as assessed by laboratory tests

  Laboratory tests include hematology, biochemistry and urinalysis.

  up to end of study visit (up to 26 days)

Secondary Outcomes (6)

• 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

  up to end of study visit (up to 26 days)

• Pharmacokinetics profile of ASP3700 (plasma): Cmax, tmax, tlag

  Cmax, tmax = Days 1 and 14; tlag = Day 1

• Pharmacokinetics profile of ASP3700 (plasma): AUCtau, CL/F, λz, MRT, t1/2, Vz/F, Rac (AUC), Rac (Cmax), PTR

  Day 14

• Pharmacokinetics parameter of ASP3700 (plasma): Ctrough

  Days 4, 6, 8, 10, 14 and 15

• Pharmacokinetics profile of ASP3700 (urine): Ae24, Ae24%, Aetau, Aetau%

  Ae24, Ae24% = Day 1; Aetau, Aetau% = Day14

Study Arms (2)

ASP3700 multiple ascending dose cohort

EXPERIMENTAL

Drug: ASP3700

Placebo cohort

PLACEBO COMPARATOR

Drug: Placebo

Interventions

ASP3700 DRUG

Oral

ASP3700 multiple ascending dose cohort

Placebo DRUG

Oral

Placebo cohort

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Officials

• Medical Director

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 5, 2014
• First Posted: November 7, 2014
• Study Start: November 1, 2014
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: January 12, 2015

Record last verified: 2015-01