Phase I study aiming at: * assessing the absolute bioavailability, pharmacokinetic profile, and dose proportionality of interferon beta-1a (HSA-free solution in pre-filled syringes) after i.v. and s.c. administration as well as the pharmacodynamic profile to create the link with available surrogate markers investigated with both formulations used clinically, lyophilisate with HSA (HSA+) and solution without HSA (HSA-); * gathering further information on safety and tolerability of interferon beta-1a over dose range,including local and systemic tolerance, body temperature, vital signs, and a battery of exploratory sickness behavior tests.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
12
6 MIU/0.53 mL in pre-filled glass syringe solubilized in aqueous isotonic buffered solution
Composite of interferon beta-1a PK parameters
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0-inf\]) and maximum observed concentration (Cmax) following single dose administration will be assessed. Mean residence time (MRT), half-life of elimination (t1/2), clearance (CL), and volume of distribution at steady-state (Vss) will be calculated.
Time frame: 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 [hours post-dose]
Composite of interferon beta-1a PD markers
Serum concentration of three surrogate markers (neopterin and beta2-microglobulin and 2',5' OAS) will be measured
Time frame: 0, 6, 12, 24, 48, 72, 96, 120, 168 [hours post-dose]
Number of participants with adverse events (AE)/serious adverse event (SAE) as a measure of safety and tolerability
AE/SAE will be collected from the start of study treatment and until the follow-up visit
Time frame: Up to Day 7
Composite of local reactions as a measure of local tolerance
Any local symptoms rated as moderate (grade 3 for i.v. and 2 for s.c.) or severe (grade 4 and 5 for i.v.; grade 3 for s.c.) will be reported as an adverse event. The subjective painful sensation following injection of the drug will be assessed using a visual analogue scale (VAS).
Time frame: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24 [hours post-dose] and then daily if needed until Day 5 or longer until resolution in case of local reaction
Composite of clinical laboratory tests as a measure of safety and tolerability
Clinical laboratory tests will include hematology, clinical chemistry and urinalysis
Time frame: Screening and 0, 24 [hours post-dose]
Composite of vital signs as a measure of safety and tolerability
Vital signs will include body temperature, blood pressure and heart rate
Time frame: Screening and 0, 1, 2, 4, 6, 8, 10, 12, 24 [hours post-dose]
Sickness behavior assessment
Nine parameters will be recorded (Spontaneous movement, Ambient temperature preference, Subjective feelings, Investigator's feelings, Intellectual concentration ability, Hunger/anorexia,Thirst, Paracetamol consumption, Menthol tablet consumption)
Time frame: 0, 2, 4, 6, 8, 10, 12 [hours post-dose]
Electrocardiogram (ECG) as a measure of safety and tolerability
Twelve-lead ECG will be recorded
Time frame: Screening and 0, 8 [hours post-dose]
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.