This is a 6-part first-in-human study in up to approximately 184 participants. Parts 1 to 5 is in health volunteers and part 6 is in subjects with atopic dermatitis. The purpose of this first-in-human study is to assess the safety and tolerability and pharmacokinetics (PK) of single and multiple doses of LOU064 both as once and twice daily oral administration in healthy volunteers and those with atopic diathesis or atopic dermatitis. This study will also explore the effect of food intake and different drug substance particle sizes on the in vivo disposition of LOU064 in healthy volunteers to guide dosing and formulation development for future clinical trials. The study is registered on CT.Gov with the initiation of part 6 in patients (FPFV in April 2019).
The study is composed of the following parts: Part 1 is a double-blind, placebo-controlled single ascending dose (SAD) escalation study of up to 10 cohorts (N = approximately 80) in healthy volunteers Part 2 is a double-blind, placebo-controlled multiple ascending dose (MAD) escalation study in up to 6 cohorts in healthy volunteers with asymptomatic atopic diathesis with a 12-day treatment period (daily dosing) and 4-day follow-up period (N = approximately 48) Part 3 is a single cohort, single dose, open-label crossover food effect study (N = approximately 12) in healthy volunteers Part 4 is a double-blind, placebo-controlled multiple dose study in up to 2 cohorts of healthy volunteers with asymptomatic atopic diathesis with a 12-day treatment period (twice daily dosing) and 4-day follow-up period (N = approximately 16) Part 5 is a double-blind, single dose, crossover formulation effect study (N = approximately 12) in healthy volunteers Part 6 is a double-blind, placebo-controlled multiple dose study in subjects with atopic dermatitis with a 4-week treatment period (twice daily dosing of LOU064) and 3-week follow-up period in approximately 16 subjects
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
185
Novartis Investigative Site
Berlin, Germany
Novartis Investigative Site
Leiden, Netherlands
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Clinically significant changes in physical examination and anamnesis, vital signs, ECG, safety laboratory will be reported under (S)AEs.
Time frame: Part 1: 22 days, Part 2: 33 days, Part 3: 40 days, Part 4: 33 days, Part 5: 26 days, Part 6: 50 days
LOU064 pharmacokinetics Cmax
Cmax:The observed maximum plasma (or serum or blood) concentration following drug administration \[mass / volume\]
Time frame: Part 1: Day 1, 2, 3, 4, 5 and 8, Part 2: Day 1, 2, 3, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 3: Day 1, 2, 3, 4 and 5, Part 4: Day 1, 2, 3, 4, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 5: Day 1, 2, 3, 5 and 8 Part 6: Day 1, 2, 8, 15, 22, 29, and day 30
LOU064 pharmacokinetics Tmax
Tmax: The time to reach the maximum concentration after drug administration \[time\]
Time frame: Part 1: Day 1, 2, 3, 4, 5 and 8, Part 2: Day 1, 2, 3, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 3: Day 1, 2, 3, 4 and 5, Part 4: Day 1, 2, 3, 4, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 5: Day 1, 2, 3, 5 and 8 Part 6: Day 1, 2, 8, 15, 22, 29, and day 30
LOU064 pharmacokinetics AUCinf
AUCinf: The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity \[mass x time / volume\]
Time frame: Part 1: Day 1, 2, 3, 4, 5 and 8, Part 2: Day 1, 2, 3, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 3: Day 1, 2, 3, 4 and 5, Part 4: Day 1, 2, 3, 4, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 5: Day 1, 2, 3, 5 and 8 Part 6: Day 1, 2, 8, 15, 22, 29, and day 30
LOU064 pharmacokinetics AUClast
AUClast: The area under the plasma (or serum or blood) concentration-time curve from time zero to the time of the last quantifiable concentration \[mass x time / volume\]
Time frame: Part 1: Day 1, 2, 3, 4, 5 and 8, Part 2: Day 1, 2, 3, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 3: Day 1, 2, 3, 4 and 5, Part 4: Day 1, 2, 3, 4, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 5: Day 1, 2, 3, 5 and 8 Part 6: Day 1, 2, 8, 15, 22, 29, and day 30
LOU064 pharmacokinetics AUCtau
AUCtau: The area under the plasma (or serum or blood) concentration-time curve from time zero to the end of the dosing interval tau \[mass x time / volume\]
Time frame: Part 1: Day 1, 2, 3, 4, 5 and 8, Part 2: Day 1, 2, 3, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 3: Day 1, 2, 3, 4 and 5, Part 4: Day 1, 2, 3, 4, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 5: Day 1, 2, 3, 5 and 8 Part 6: Day 1, 2, 8, 15, 22, 29, and day 30
LOU064 pharmacokinetics T1/2
T1/2: The terminal elimination half-life \[time\]
Time frame: Part 1: Day 1, 2, 3, 4, 5 and 8, Part 2: Day 1, 2, 3, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 3: Day 1, 2, 3, 4 and 5, Part 4: Day 1, 2, 3, 4, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 5: Day 1, 2, 3, 5 and 8 Part 6: Day 1, 2, 8, 15, 22, 29, and day 30
LOU064 pharmacokinetics CL/F
CL/F: The apparent systemic (or total body) clearance from plasma (or serum or blood) following extravascular administration \[volume / time\]
Time frame: Part 1: Day 1, 2, 3, 4, 5 and 8, Part 2: Day 1, 2, 3, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 3: Day 1, 2, 3, 4 and 5, Part 4: Day 1, 2, 3, 4, 5, 7, 9, 12, 13, 14, 15, 16 and 19, Part 5: Day 1, 2, 3, 5 and 8 Part 6: Day 1, 2, 8, 15, 22, 29, and day 30
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