Clinical trial NCT01815684: A Study to Assess the Safety, Tolerability and Effects of Single Ascending Doses of ASP3652 in Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Pharmacodynamics
Healthy Subjects
Safety
Keywords: Phase I
ASP3652
Dose escalation
Maximum Tolerated Dose (MTD)
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2013-03-21
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability of single ascending doses of ASP3652 assessed through vital signs, adverse events, electrocardiogram and clinical laboratory assessments
timeFrame: Day -22 to ESV (7-14 days after (early) discharge)
measure: Safety and tolerability of single ascending doses of ASP3652 assessed through electrocardiogram
timeFrame: Day -22 to ESV (7-14 days after (early) discharge)
Secondary outcomes:
measure: Pharmacokinetic profile of single ascending doses of ASP3652
timeFrame: Days 1- 4 (Investigational period 1 - 4)
measure: Effect of single ascending doses of ASP3652 on CNS Pharmacodynamics
timeFrame: Days 1 - 4 (Investigational period 1 - 4)
measure: Effect of single ascending doses of ASP3652 on plasma levels of enzyme substrates
timeFrame: Days 1 - 4 (Investigational period 1 - 4)
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Study Manager
role: STUDY_CHAIR
References:
citation: Takizawa M, Cerneus D, Michon I, Rijnders S, Meijer J, Someya A, Sato Y. Investigation of Safety and Tolerability of ASP3652 Based on Clinical Studies of Cerebrospinal Fluid Transfer After Multiple Doses and Exposure After Single Doses at High Dose Levels. Adv Ther. 2020 Sep;37(9):3967-3984. doi: 10.1007/s12325-020-01451-6. Epub 2020 Jul 26.