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

Healthy Volunteers Clinical Trial

— MAD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02136316
• Other study ID #: 7962-CL-0002
• Secondary ID: 2014-000159-95
• Status: Completed
• Phase: Phase 1
• First received: May 9, 2014
• Last updated: December 14, 2015
• Start date: May 2014
• Est. completion date: November 2015

Study information

• Verified date: December 2015
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Volunteers
• Pharmacokinetics of ASP7962

Intervention

Drug:
• ASP7962
Oral
• Placebo
Oral

Locations

Country	Name	City	State
United Kingdom	Site GB44001 Parexel Early Phase Clinical Unit	London

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Europe B.V.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety as assessed by adverse events		up to end of study visit (29 days)	Yes
Primary	Safety as assessed by vital signs		up to end of study visit (29 days)	Yes
Primary	Safety as assessed by orthostatic challenge test		Day 1 and 16	Yes
Primary	Safety as assessed by clinical laboratory tests		up to end of study visit (29 days)	Yes
Primary	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)	Yes
Primary	Safety as assessed by Bond and Lader visual analogue scale (VAS)		Day 3-19	Yes
Primary	Safety as assessed by Addiction Research Center Inventory (ARCI)-49 (49-item)		Day 3-19	Yes
Primary	Safety as assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)		Day 2-19	Yes
Primary	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	Yes
Secondary	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	No
Secondary	Pharmacokinetic profile of ASP7962 (plasma): Cmax,u, MRT, t1/2, tmax, tlag, ?z, 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 (?z), 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	No
Secondary	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	No
Secondary	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	No