Clinical trial NCT02136316: A Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of Multiple Ascending Doses of ASP7962 in Healthy Subjects
Official title: A Phase 1 Study to Assess the Safety, Tolerability and Pharmacokinetics of Ascending Oral Multiple Doses of ASP7962 in Healthy Male and Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Pharmacokinetics of ASP7962
Keywords: Healthy volunteers
ASP7962
pharmacokinetics
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-05-13
Enrollment: 48
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 and tolerability as well as the pharmacokinetics of increasing oral multiple doses of ASP7962 in healthy young male and female subjects.

Detailed description: Subjects will be admitted to the clinical unit and will stay residential for a total of 20 days/19 nights, to be discharged from the clinical unit on day 19.

Eligibility criteria: Inclusion Criteria:

* Subject has a body mass index of 18.5 - 30.0 kg/m2, inclusive. Subject weighs at least 50 kg.
* Female subject must be of non-childbearing potential:

  * Postmenopausal (defined as at least 1 year without any menses and confirmation of FSH levels) prior to screening, or
  * Documented surgically sterile or status post-hysterectomy (at least 1 month prior to screening).
* Male subject and their female spouse/partner who are of childbearing potential must be using 2 highly effective forms of birth control (1 of which must be a barrier method) starting at screening and continued throughout the clinical study period, and for 90 days after the final study drug administration.
* Male subject must not donate sperm starting at screening, throughout the clinical study period, and for 90 days after the final study drug administration.
* Subject agrees not to participate in another interventional study while participating in the present clinical study, defined as signing the informed consent form until completion of the last study visit.

Exclusion Criteria:

* Subject has a known or suspected hypersensitivity to ASP7962 or any components of the formulation used.
* Subject has a history of suicide attempt or suicidal behavior. Any suicidal ideation within the last 3 months.
* Subject has any of the liver function tests (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase, gamma glutamyl transferase, total bilirubin \[TBL\]) above the upper limit of normal \[ULN\]. In such a case the assessment may be repeated once \[day -1\].
* Subject has any clinically significant history of allergic conditions.
* Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to admission to the clinical unit on day -1.
* Subject has a mean pulse rate \< 40 or \> 90 bpm; mean systolic blood pressure (SBP) \> 140 mmHg; mean diastolic blood pressure (DPB) \> 90 mmHg (vital sign measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse rate will be measured automatically) \[day -1\]. If the mean pulse rate, mean SBP or mean DBP is out of the range as specified above, 1 additional triplicate measurement may be taken on day -1.
* Subject has a mean corrected QT interval using Fridericia's formula (QTcF) interval \> 430 ms (for male subjects) and \> 450 ms (for female subjects) on admission to the clinical unit on day 1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken \[day -1\].
* Subject uses any prescribed or non-prescribed drugs (including 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.
* Subject has a history of drinking more than 21 units of alcohol per week for male subjects or 14 units of alcohol per week 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.
* Subject uses any drugs of abuse within 3 months prior to admission to the clinical unit.
* Subject uses any inducer of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to admission to the clinical unit.
* 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.
* Subject has a positive serology test for hepatitis B surface antigen, hepatitis A virus antibodies (immunoglobulin M), hepatitis C virus antibodies, 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 28 days or 5 half-lives, whichever is longer, prior to screening.
* Subject is an employee of the Astellas Group or Contract Research Organization involved in the clinical study.

Primary outcomes:
measure: Safety as assessed by adverse events
timeFrame: up to end of study visit (29 days)
measure: Safety as assessed by vital signs
timeFrame: up to end of study visit (29 days)
measure: Safety as assessed by orthostatic challenge test
timeFrame: Day 1 and 16
measure: Safety as assessed by clinical laboratory tests
timeFrame: up to end of study visit (29 days)
measure: Safety as assessed by electrocardiogram (ECG)
timeFrame: up to end of study visit (29 days)
measure: Safety as assessed by Bond and Lader visual analogue scale (VAS)
timeFrame: Day 3-19
measure: Safety as assessed by Addiction Research Center Inventory (ARCI)-49 (49-item)
timeFrame: Day 3-19
measure: Safety as assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)
timeFrame: Day 2-19
measure: Safety as assessed by CogState cognitive test battery: Groton Maze Learning Task, Groton Maze Learning Task-Delayed Recall, Detection Task, Identification Task, One Card Learning Task, One Back Task
timeFrame: Day 3-19
Secondary outcomes:
measure: Pharmacokinetic profile of ASP7962 (plasma): AUC12, AUC12,u, AUCinf, AUCinf,u , AUClast, AUClast,u, CL/F, CLu/F, Cmax
timeFrame: up to Day 19
measure: Pharmacokinetic profile of ASP7962 (plasma): Cmax,u, MRT, t1/2, tmax, tlag, λz, fu, AUCinf,u/AUCinf , Vz/F
timeFrame: up to Day 19
measure: Pharmacokinetic profile of ASP7962 (plasma): Ctrough, AUCtau, Rac(AUC), Rac(Cmax), PTR, Ratio AUCu/AUC, Vz,u/F, AUCtau,u
timeFrame: up to Day 19
measure: Pharmacokinetic profile of ASP7962 (urine): Aeinf, Aeinf%, Aelast, Aelast%, CLR, CLR,u, Aetau, Aetau%
timeFrame: Day 1 and 16
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Site GB44001 Parexel Early Phase Clinical Unit
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Medical Monitor
role: STUDY_DIRECTOR
References: