The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of single and multiple ascending doses of LAD603 in healthy adult participants in both Part 1 and 2.
This is a 2-part study. Part 1 will comprise up to 8 cohorts of healthy adult participants and investigate single ascending doses of LAD603. Part 2 will comprise up to 4 cohorts of healthy adult subjects and will investigate multiple ascending doses of LAD603. Each ascending dose level will be investigated by a sequential cohort, with dose escalation based on satisfactory safety, tolerability, PK, and pharmacodynamics (PD) (biomarker) data from the previous cohort(s). Dose levels evaluated in Part 2 of this study will not exceed dose levels that were safe and well tolerated in the single-dose study, and may be changed, depending on emerging safety and tolerability, PK, and PD (biomarker) data. Each participant will participate for about 8 weeks in Part 1 and for about 14 weeks in Part 2 of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
92
ICON Phase 1 unit Lenexa
Lenexa, Kansas, United States
Part 1: Number of Participants with Adverse Events (AEs) and Severity of AEs
Time frame: Baseline up to Day 31
Part 1: Number of Participants with Clinically Significant Changes from Baseline in Vital Sign Parameter
Time frame: Baseline up to Day 31
Part 1: Number of Participants with Clinically Significant Changes from Baseline in Electrocardiograms (ECGs) Parameters
Time frame: Baseline up to Day 31
Part 1: Number of Participants with Clinically Significant Changes from Baseline in Clinical Laboratory Parameters
Time frame: Baseline up to Day 31
Part 2: Number of Participants with AEs and Severity of AEs
Time frame: Baseline up to Day 64
Part 2: Number of Participants with Clinically Significant Changes from Baseline in Vital Sign Parameter
Time frame: Baseline up to Day 64
Part 2: Number of Participants with Clinically Significant Changes from Baseline in ECGs Parameters
Time frame: Baseline up to Day 64
Part 2: Number of Participants with Clinically Significant Changes from Baseline in Clinical Laboratory Parameters
Time frame: Baseline up to Day 64
Part 1: Maximum Serum Concentration (Cmax) of LAD603
Time frame: Pre-dose, 2, 6, 12 hours (Day 1); Post-dose: at 24 and 36 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), 120 hours (Day 6), 168 hours (Day 8), 240 hours (Day 11); 336 hours (Day 15), 504 hours (Day 22), 672 hours (Day 29)
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Part 1: Minimum Serum Concentration (Cmin) of LAD603
Time frame: Pre-dose, 2, 6, 12 hours (Day 1); Post-dose: at 24 and 36 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), 120 hours (Day 6), 168 hours (Day 8), 240 hours (Day 11); 336 hours (Day 15), 504 hours (Day 22), 672 hours (Day 29)
Part 1: Time to Reach Maximum Serum Concentration (Tmax) of LAD603
Time frame: Pre-dose, 2, 6, 12 hours (Day 1); Post-dose: at 24 and 36 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), 120 hours (Day 6), 168 hours (Day 8), 240 hours (Day 11); 336 hours (Day 15), 504 hours (Day 22), 672 hours (Day 29)
Part 1: Area Under the Serum Concentration-time Curve (AUC) from Zero to Time of the Last Concentration (AUC0-t) of LAD603
Time frame: Pre-dose, 2, 6, 12 hours (Day 1); Post-dose: at 24 and 36 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), 120 hours (Day 6), 168 hours (Day 8), 240 hours (Day 11); 336 hours (Day 15), 504 hours (Day 22), 672 hours (Day 29)
Part 1: Area Under the Serum Concentration-time Curve (AUC) from Zero to infinity (AUC0-inf) of LAD603
Time frame: Pre-dose, 2, 6, 12 hours (Day 1); Post-dose: at 24 and 36 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), 120 hours (Day 6), 168 hours (Day 8), 240 hours (Day 11); 336 hours (Day 15), 504 hours (Day 22), 672 hours (Day 29)
Part 1: Area Under the Serum Concentration-time Curve (AUC) from Zero to 1 Week After Investigational Medicinal Product (IMP) Administration (AUC0-1w) of LAD603
Time frame: Pre-dose, 2, 6, 12 hours (Day 1); Post-dose: at 24 and 36 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), 120 hours (Day 6), 168 hours (Day 8), 240 hours (Day 11); 336 hours (Day 15), 504 hours (Day 22), 672 hours (Day 29)
Part 1: Elimination Half-life (t½) of LAD603
Time frame: Pre-dose, 2, 6, 12 hours (Day 1); Post-dose: at 24 and 36 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), 120 hours (Day 6), 168 hours (Day 8), 240 hours (Day 11); 336 hours (Day 15), 504 hours (Day 22), 672 hours (Day 29)
Part 1: Smallest Terminal Elimination Rate Constant (λz) of LAD603
Time frame: Pre-dose, 2, 6, 12 hours (Day 1); Post-dose: at 24 and 36 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), 120 hours (Day 6), 168 hours (Day 8), 240 hours (Day 11); 336 hours (Day 15), 504 hours (Day 22), 672 hours (Day 29)
Part 1: Apparent Total Serum Clearance (CL/F) of LAD603
Time frame: Pre-dose, 2, 6, 12 hours (Day 1); Post-dose: at 24 and 36 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), 120 hours (Day 6), 168 hours (Day 8), 240 hours (Day 11); 336 hours (Day 15), 504 hours (Day 22), 672 hours (Day 29)
Part 1: Mean Residence Time (MRT) of LAD603
Time frame: Pre-dose, 2, 6, 12 hours (Day 1); Post-dose: at 24 and 36 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), 120 hours (Day 6), 168 hours (Day 8), 240 hours (Day 11); 336 hours (Day 15), 504 hours (Day 22), 672 hours (Day 29)
Part 1: Apparent Volume of Distribution Associated with the Terminal Phase (Vz/F) of LAD603
Time frame: Pre-dose, 2, 6, 12 hours (Day 1); Post-dose: at 24 and 36 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), 120 hours (Day 6), 168 hours (Day 8), 240 hours (Day 11); 336 hours (Day 15), 504 hours (Day 22), 672 hours (Day 29)
Part 2: Area Under the Concentration-time Curve within a Dosing Interval (AUCτ) of LAD603
Time frame: Pre-dose, 2, 6, and 12 hours post-dose (Day 1)
Part 2: Maximum Serum Concentration (Cmax) of LAD603
Time frame: Pre-dose, 2, 6, and 12 hours post-dose (Day 1)
Part 2: Time to Reach Maximum Serum Concentration (Tmax) of LAD603
Time frame: Pre-dose, 2, 6, and 12 hours post-dose (Day 22)
Part 2: Area Under the Concentration-time Curve within a Dosing Interval (AUCτ) at Steady State of LAD603
Time frame: Pre-dose, 2, 6, and 12 hours post-dose (Day 22)
Part 2: Average Steady State Serum Drug Concentration (Cav,ss)
Time frame: Pre-dose, 2, 6, and 12 hours post-dose (Day 22)
Part 2: Elimination Half-life (t½) of LAD603
Time frame: Pre-dose, 2, 6, and 12 hours post-dose (Day 22)
Part 2: Smallest Terminal Elimination Rate Constant (λz) of LAD603
Time frame: Pre-dose, 2, 6, and 12 hours post-dose (Day 22)
Part 2: Accumulation Ratios (RA) at Steady State Based on AUCτ (RA[AUC]) of LAD603
Time frame: Pre-dose, 2, 6, and 12 hours post-dose (Day 22)
Part 2: Accumulation Ratios (RA) at Steady State Based on Cmax (RA[Cmax]) of LAD603
Time frame: Pre-dose, 2, 6, and 12 hours post-dose (Day 22)
Part 2: Serum Concentration Observed at the Last Planned Sampling Timepoint Prior to Dosing (Ctrough; RA[Ctrough]) of LAD603
Time frame: Pre-dose, 2, 6, and 12 hours post-dose (Day 22)
Part 2: Serum Concentration Observed at the Last Planned Sampling Timepoint Prior to Dosing (Ctrough) of LAD603
Time frame: Pre-dose, 2, 6, 12 hours (Day 1); Post-dose: 24 and 36 hours (Day 2), 48 hours (Day 3), 96 hours (Day 5), 168 hours (Day 8); Pre-dose (Day 15); Pre-dose, 2, 6, and 12 hours post-dose (Day 22)