A Study to Assess the Safety, Tolerability and Effects of Single Ascending Doses of ASP3652 in Healthy Subjects

Healthy Subjects Clinical Trial

Official title:

A Phase I, Double Blind, Placebo-controlled, Randomized 4-way Alternating Cross-over Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of Single Ascending Doses of ASP3652 in Healthy Young Caucasian Male and Female Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01815684
• Other study ID #: 3652-CL-0049
• Secondary ID: 2011-004247-41
• Status: Completed
• Phase: Phase 1
• First received: March 19, 2013
• Last updated: March 19, 2013
• Start date: August 2012
• Est. completion date: December 2012

Study information

• Verified date: March 2013
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to explore the safety (including the effect on cardiac intervals), tolerability, the effects on the Central Nervous System (CNS), as well as the CNS side effect profile of single ascending doses of ASP3652 in healthy, Caucasian male and female subjects.

Description:

Each subject receives 3 single ascending doses of ASP3652 and a single dose of matching placebo during one randomly selected investigational period. Randomization is conducted separately for males and females.

The washout period between dosing occasions is at least 7 days. Screening takes place from Day -22 to Day -2. Subjects are admitted to the clinic in the afternoon of Day -1 of investigational period 1, 2, 3 and 4 for pre-dose assessments.

On Day -1 of all investigational periods, subjects do not take any food or drink for at least 10 hours before the anticipated dosing time on Day 1. For the duration of their stay in the clinic, subjects are not allowed to consume caffeine or other xanthine-containing drinks.

The subjects are discharged on Day 4 of each investigational period. The End of Study Visit (ESV) is planned to take place 7-14 days after early discharge or after Day 4 of investigational period 4.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• 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 30.0kg/m2.

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

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

Exclusion Criteria:

• Pregnancy within 6 months before screening assessment or breast feeding within 3 months before screening (for females subjects only).

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

• A mean QTc(F) interval of >430 ms (for males) and >450 ms (for females) after triplicate measurements, a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS). In case of an abnormal QTc(F) interval, the assessment may be repeated once (in triplicate). If the QTc(F) interval exceeds the limits, two additional Electrocardiogram (ECG)s can be recorded and the average of the three QTc(F) values should be used to determine the subject's eligibility.

Study Design

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

Related Conditions & MeSH terms

• Healthy Subjects
• Pharmacodynamics
• Pharmacokinetics
• Safety

Intervention

Drug:
• ASP3652
Oral
• Placebo
Oral

Locations

Country	Name	City	State
Netherlands	Centre for Human Drug Research	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Europe B.V.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of single ascending doses of ASP3652 assessed through vital signs, adverse events, electrocardiogram and clinical laboratory assessments		Day -22 to ESV (7-14 days after (early) discharge)	Yes
Primary	Safety and tolerability of single ascending doses of ASP3652 assessed through electrocardiogram	QT (Q wave to T wave)/QTc interval (QT interval corrected for heart rate), QT interval, RR (R wave to R wave) interval, HR (Heart Rate), PR interval, QRS interval, QTcB, QTcF	Day -22 to ESV (7-14 days after (early) discharge)	Yes
Secondary	Pharmacokinetic profile of single ascending doses of ASP3652	Plasma: Cmax (Maximum concentration), AUClast (AUC until last sample taken), AUCinf (AUC extrapolated until infinity), tmax (Time to attain Cmax), tlag (Absorption lag time), t1/2 (Apparent terminal elimination half-life), Vz/F (Apparent volume of distribution), CL/F (Apparent total body plasma clearance)/ Urine: Aelast (Amount excreted in urine until last sample), Aeinf (Cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose), Aelast% (Percentage of unchanged drug excreted into the urine from time of last measurable concentration), Aeinf% (Percentage of unchanged drug excreted into the urine from time zero to infinity after single dose), CLR (Renal clearance)	Days 1- 4 (Investigational period 1 - 4)	No
Secondary	Effect of single ascending doses of ASP3652 on CNS Pharmacodynamics	Body sway, alertness, perception, mood, learning, memory, distraction, adaptive tracking, eye movements, addiction, neuro-endocrine parameters	Days 1 - 4 (Investigational period 1 - 4)	No
Secondary	Effect of single ascending doses of ASP3652 on plasma levels of enzyme substrates	Rmax, tmax R, AUR	Days 1 - 4 (Investigational period 1 - 4)	No