A Study to Investigate the Appearance and Disappearance of ASP3652 in Blood and Spinal Fluid in Healthy Male Subjects

Healthy Subjects Clinical Trial

Official title:

A Phase I, Open-label Study to Investigate the Safety, Tolerability and Plasma and Cerebrospinal Fluid Pharmacokinetics and Pharmacodynamics of Multiple Doses of ASP3652 in Healthy Young Caucasian Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02034734
• Other study ID #: 3652-CL-0048
• Secondary ID: 2011-004226-97
• Status: Completed
• Phase: Phase 1
• First received: January 10, 2014
• Last updated: January 10, 2014
• Start date: September 2012
• Est. completion date: December 2012

Study information

• Verified date: January 2014
• 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 plasma and cerebrospinal fluid (CSF) pharmacokinetics (PK) of multiple doses of ASP3652 in healthy young Caucasian male subjects. Also to evaluate the plasma and CSF pharmacodynamics (PD) of multiple doses of ASP3652 in healthy young Caucasian male subjects and to assess the safety and tolerability of multiple doses of ASP3652 in healthy young Caucasian male subjects.

Description:

Screening takes place between Day -22 to Day -2. Subjects are admitted to the clinical on Day -1 and remain until Day 12.

On Days 5 to 9, subjects receive twice-daily doses of ASP3652, and a single dose on the morning of Day 10. Subjects fast for 10h before the morning dose on Days 5 to 9 and they are served the first standard meal 1h after the morning dose.

A spinal tap is used to collect cerebrospinal fluid (CSF) on Day 1 and Day 10. A plasma sample for PK sample is obtained before first dosing on Day 5. To confirm steady-state concentrations of ASP3652 in plasma, blood samples are obtained before the morning dose on Days 7, 9 and 10, and before the evening dose on Days 5, 7 and 9. On Day 10, a PK profile of ASP3652 in plasma is obtained for up to 48h after the morning dose and for up to 24h in CSF.

Profiles of several enzyme substrates in plasma and seminal fluid (exploratory) are obtained on Day 1 and Day 10 up to 24h in CSF and up to 48h in plasma, before the morning and evening dose on Days 5, 7 and 9 in plasma.

Vital signs, 12-lead electrocardiograms (ECGs), safety laboratory assessments, adverse events (AEs) and concomitant medication are monitored throughout the investigational period until the ESV.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Subject is white and of Caucasian origin.

• Body Mass Index more than or equal to 18.5 and less than 30.0 kg/m2.

• Male subject must agree to practice an adequate contraceptive method with female sexual partners to prevent pregnancy.

Exclusion Criteria:

• Known or suspected hypersensitivity to ASP3652 or any components of the formulation used.

• History of excessive bleeding or bruising.

• Abnormalities of coagulation screen including platelet count, prothrombin time (PT) and activated partial thromboplastin time (aPTT).

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Subjects
• Pharmacodynamics of ASP3652
• Pharmacokinetics of ASP3652

Intervention

Drug:
• ASP3652
oral

Locations

Country	Name	City	State
United Kingdom	PAREXEL Early Phase Clinical Unit	Harrow

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	Pharmacokinetics (PK) of ASP3652 in plasma measured by area under the plasma concentration-time curve in the dosing interval (AUCtau)		Days 5, 7 and 9, and Days 10 - 12	No
Primary	PK of ASP3652 in plasma measured by maximum observed plasma concentration (Cmax)		Days 5, 7 and 9, and Days 10 - 12	No
Primary	PK parameter of ASP3652 in cerebrospinal fluid (CSF) measured by area under the plasma concentration-time curve in the dosing interval (AUCtau)		Days 10 -11	No
Primary	PK parameter of ASP3652 in cerebrospinal fluid (CSF) measured by maximum observed plasma concentration (Cmax)		Days 10 -11	No
Secondary	Additional PK of multiple doses of ASP3652 in plasma and cerebrospinal fluid (CSF)	plasma concentration immediately before the next dose (Ctrough), time to attain Cmax (tmax), apparent terminal elimination half-life (t½), volume of terminal phase distribution at steady state (Vz/F), apparent clearance after oral administration at steady state (CL/F) and peak trough ratio (PTR)	Plasma: Days 5, 7 and 9, and Days 10 - 12 / CSF: Days 10 -11	No
Secondary	Pharmacodynamics (PD) of multiple doses of ASP3652 in plasma and CSF	response immediately prior to dosing (Rtrough), time of the maximum response (tmaxR), maximum response (Rmax), area under the response-time curve from 0 to 12h (AURC0-12h), percentage change in maximum response (Rmax%), percentage change in AURC from 0 to 12h (AUR0-12h%)	Plasma: Days 1-3 and Days 5-12 / CSF: Days 1-2 and Days 10-11	No
Secondary	Safety and tolerability of multiple doses of ASP3652		Screening (Day -22 to Day -2) to End-of-Study Visit (7 to 14 days after (early) discharge)	No