The purpose of this study is to evaluate the safety and tolerability of single ascending intravenous doses and single subcutaneous (sc) doses of ASP6294 in healthy young male and female subjects. This study will also evaluate the pharmacokinetics (pk) of single ascending intravenous doses and single ascending sc doses of ASP6294; determine the effect of ASP6294 administered intravenously and sc on the serum levels of circulating total Nerve Growth Factor (NGF); explore a potential gender difference in safety, tolerability and pk of single intravenous dose and single sc doses administrations of ASP6294 as well as determine the maximum tolerated dose (MTD) of single intravenous doses and single sc doses of ASP6294. Part 2 will also evaluate the relative bioavailability of ASP6294 when administered sc.
The study consists of two parts: Part 1 (ascending intravenous dose) and Part 2 (ascending subcutaneous dose). Subjects will participate in either Part 1 or Part 2. Subjects in Part 1 and Part 2 will have a residential period of 6 days followed by outpatient visits.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
74
Intravenous (IV)
Subcutaneous (SC)
Intravenous (IV)
Subcutaneous (SC)
Site GB44001
Harrow, United Kingdom
Safety of ASP6294 as assessed by Nature, frequency and severity of Adverse Events (AEs)
Time frame: Up to 120 Days
Safety of ASP6294 as assessed by Vital signs
Vital signs include blood pressure, pulse and oral body temperature
Time frame: Up to 120 Days
Safety of ASP6294 as assessed by Neurological examination
Neurological Assessment will be measured on a scale for the following Neurological examinations: Gait; Coordination; Speech; Cranial Nerves; Sensations; Muscle Strength; Muscle Tone; Muscle Movement and Reflexes and will be rated as "Normal" or "Abnormal".
Time frame: Up to 120 Days
Safety of ASP6294 as assessed by laboratory tests
Laboratory tests include hematology, biochemistry and urinalysis
Time frame: Up to 120 Days
Safety of ASP6294 as assessed by routine 12-lead Electrocardiogram (ECG)
Time frame: Up to 120 Days
Safety of ASP6294 as assessed by continuous cardiac monitoring (Holter ECG) (part 1 only)
ECGs are to be collected using a 12-lead ECG continuous monitoring and recording system.
Time frame: Days 1 and 2
Safety of ASP6294 as assessed by Sensory assessments
Sensory Assessment will be measured on a scale for Lower Limbs and Hands. The following categories: Touch Pressure; Pinprick; Vibration and Joint Position will be rated as Normal (=0 points), Decreased (= 1 point) or Absent (=2 points). A total score for the left and right side of lower limbs and hands will be calculated.
Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: AUClast
Area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)
Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: AUC168h
Area under the concentration-time curve from the time of dosing to 168 hours postdose (AUC168h)
Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: AUCinf
Area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf)
Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: Cmax
Maximum concentration (Cmax)
Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: CL (part 1 only)
Total systemic clearance after intravenous dosing (CL)
Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: CL/F (part 2 only)
Apparent total systemic clearance after extravascular dosing (CL/F)
Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: λz
Terminal elimination rate constant (λz)
Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: MRT
Mean residence time (MRT)
Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: tmax
Time of maximum concentration (tmax)
Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: t1/2
Terminal elimination half-life (t1/2)
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Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: Vss (part 1 only)
Volume of distribution at steady state determined after intravenous dosing (Vss)
Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: Vz (part 1 only)
Volume of distribution during terminal elimination phase after intravenous dosing (Vz)
Time frame: Up to 120 Days
Pharmacokinetics of ASP6294: Vz/F (part 2 only)
Apparent volume of distribution during the terminal elimination phase after extravascular dosing (Vz/F)
Time frame: Up to 120 Days
Pharmacodynamics of ASP6294 Nerve growth factor (NGF) total serum concentration: Cmax
Time frame: Up to 120 Days
Pharmacodynamics of ASP6294 NGF total serum concentration: tmax
Time frame: Up to 120 Days