A Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of Multiple Ascending Doses of ASP7962 in Healthy Subjects (MAD)

A Phase 1 Study to Assess the Safety, Tolerability and Pharmacokinetics of Ascending Oral Multiple Doses of ASP7962 in Healthy Male and Female Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Pharmacokinetics of ASP7962
• Intervention / Treatment: Drug: Placebo; Drug: ASP7962

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, HA13UJ
    • Site GB44001 Parexel Early Phase Clinical Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral
Experimental: ASP7962 low dose	Drug: ASP7962; Oral
Experimental: ASP7962 medium dose	Drug: ASP7962; Oral
Experimental: ASP7962 high dose	Drug: ASP7962; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by adverse events		up to end of study visit (29 days)
Safety as assessed by vital signs		up to end of study visit (29 days)
Safety as assessed by orthostatic challenge test		Day 1 and 16
Safety as assessed by clinical laboratory tests		up to end of study visit (29 days)
Safety as assessed by electrocardiogram (ECG)	Routine 12-lead ECG, continuous cardiac monitoring (Holter ECG) and real-time cardiac monitoring (ECG telemetry)	up to end of study visit (29 days)
Safety as assessed by Bond and Lader visual analogue scale (VAS)		Day 3-19
Safety as assessed by Addiction Research Center Inventory (ARCI)-49 (49-item)		Day 3-19
Safety as assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)		Day 2-19
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		Day 3-19

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profile of ASP7962 (plasma): AUC12, AUC12,u, AUCinf, AUCinf,u , AUClast, AUClast,u, CL/F, CLu/F, Cmax	Area under the concentration-time curve from the time of dosing to 12 hours postdose (AUC12), Area under the concentration-time curve from the time of dosing to 12 hours postdose for unbound study drug concentration (AUC12,u), Area under the concentration-time curve from time of dosing extrapolated to time infinity (AUCinf), Area under the concentration-time curve from time of dosing extrapolated to time infinity for unbound study drug concentration (AUCinf, u), Area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast), Area under the concentration-time curve from the time of dosing to the last measurable unbound concentration (AUClast, u), Apparent total systemic clearance after single or multiple extravascular dosing (CL/F), Apparent total systemic clearance of unbound study drug after single or multiple extravascular dosing (CLu/F), Maximum concentration (Cmax)	up to Day 19
Pharmacokinetic profile of ASP7962 (plasma): Cmax,u, MRT, t1/2, tmax, tlag, λz, fu, AUCinf,u/AUCinf , Vz/F	Maximum unbound concentration (Cmax,u), Mean residence time (MRT), Terminal elimination half-life (t1/2), Time of maximum concentration (tmax), Time prior to the time corresponding to the first measurable (nonzero) concentration (tlag), Terminal elimination rate constant (λz), Fraction of study drug available systematically unbound (= free fraction) (fu), Apparent volume of distribution during the terminal elimination phase after single or multiple extravascular dosing (Vz/F)	up to Day 19
Pharmacokinetic profile of ASP7962 (plasma): Ctrough, AUCtau, Rac(AUC), Rac(Cmax), PTR, Ratio AUCu/AUC, Vz,u/F, AUCtau,u	Concentration immediately prior to dosing at multiple dosing (Ctrough), Area under the concentration-time curve from the time of dosing to the start of the next dosing interval (AUCtau), Accumulation ratio calculated using the area under the concentration-time curve (Rac[AUC]), Accumulation ratio calculated using the maximum plasma concentration (Rac[Cmax]), Peak-trough ratio (PTR), Apparent volume of distribution during the terminal elimination phase of unbound study drug after single or multiple extravascular dosing (VZ,u/F), Area under the concentration-time curve in the dosing interval for unbound study drug concentration (AUCtau,u)	up to Day 19
Pharmacokinetic profile of ASP7962 (urine): Aeinf, Aeinf%, Aelast, Aelast%, CLR, CLR,u, Aetau, Aetau%	Cumulative amount of study drug excreted into urine from time of dosing extrapolated to time infinity (Aeinf), Percentage of study drug excreted into urine from time of dosing extrapolated to time infinity (Aeinf%), Cumulative amount of study drug excreted into urine from time of dosing up to the collection time of the last measurable concentration (Aelast), Percentage of study drug excreted into urine from the time of dosing up to the collection time of the last measurable concentration (Aelast%), Renal clearance (CLR), Renal clearance of unbound study drug (CLR,u), Cumulative amount of study drug excreted into urine from the time of dosing to the start of the next dosing interval (Aetau), Percentage of study drug dose excreted into urine over the time interval between consecutive dosing (Aetau%)	Day 1 and 16

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: May 9, 2014
• First Submitted That Met QC Criteria: May 9, 2014
• First Posted (Estimate): May 13, 2014

Study Record Updates

• Last Update Posted (Estimate): December 15, 2015
• Last Update Submitted That Met QC Criteria: December 14, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Healthy volunteers; pharmacokinetics; ASP7962
• Other Study ID Numbers: 7962-CL-0002; 2014-000159-95 (EudraCT Number)