This is a Phase 1, randomized, double-blinded, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NH280105 in healthy volunteers. In addition, this study will evaluate the effects of food on NH280105 under a two-period study setting.
This study will be conducted in 2 parts: Part 1 (SAD) and Part 2 (MAD). Approximately 48 participants will be enrolled. * Part 1 (Cohorts 1, 2, and 4): The study design includes a double-blind, placebo-controlled setting for SAD cohorts. * Part 1 (Cohort 3): This cohort will be a double-blind, placebo-controlled, two-conditions (ie, fed vs. fasted), two-period, crossover setting for the Food-effect Cohort. * Part 2: The study design includes a double-blind, placebo-controlled setting for MAD cohorts. Oversight will be provided by a Safety Review Committee (SRC). Safety, tolerability, and PK/PD data (if available) of the preceding dose levels in both Part 1 (SAD) and Part 2 (MAD) will be reviewed by the SRC for dose escalation and the actual doses to be administered may be adjusted accordingly.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
32
Dose formulation: Capsule Route of administration: oral
Dose formulation: Capsule Route of administration: oral
Matching placebo comparator
CMAX Clinical Research Pty Ltd
Adelaide, South Australia, Australia
Number of participants with adverse events following single and multiple adminstration of NH280105
Time frame: SAD- Up to Day 8; SAD FE- Up to Day 22; MAD- Up to Day 21 post first dose administration
Number of participants with change in laboratory parameters following treatment administration.
Hematology, clinical chemistry, coagulation and urinalysis will be assessed.
Time frame: SAD- Up to Day 8; SAD FE- Up to Day 22; MAD- Up to Day 21 post first dose administration
Number of participants with change in vital sign measurements following treatment adminstration
Blood pressure, heart rate, body temperature and respiratory rate will be assessed
Time frame: SAD- Up to Day 8; SAD FE- Up to Day 22; MAD- Up to Day 21 post first dose administration
Number of participants with change in physical examination following treatment administration
Time frame: SAD- Up to Day 8; SAD FE- Up to Day 22; MAD- Up to Day 21 post first dose administration
Plasma PK Parameters- Maximum plasma concentration (Cmax) for SAD and MAD cohorts
Time frame: SAD- From Day 1 to Day 5; SAD FE- Day 1 to Day 5 and Day 15 to day 19; MAD- Day 1, Day2, Day3, Day 5, day 8, day 12, day 14, day 15, day 16, day 17and Day 18 post dose adminstration
Plasma PK Parameters-Time for maximum plasma concentration (Tmax) for SAD and MAD cohorts
Time frame: SAD- From Day 1 to Day 5; SAD FE- Day 1 to Day 5 and Day 15 to day 19; MAD- Day 1, Day2, Day3, Day 5, day 8, day 12, day 14, day 15, day 16, day 17and Day 18 post dose adminstration
Plasma PK Parameters-Delay between the time of dosing and time of appearance of concentration (Tlag) for SAD and MAD cohorts
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Time frame: SAD- From Day 1 to Day 5; SAD FE- Day 1 to Day 5 and Day 15 to day 19; MAD- Day 1, Day2, Day3, Day 5, day 8, day 12, day 14, day 15, day 16, day 17and Day 18 post dose adminstration
Plasma PK Parameters-Area Under Curve for SAD and MAD cohorts
Time frame: SAD- From Day 1 to Day 5; SAD FE- Day 1 to Day 5 and Day 15 to day 19; MAD- Day 1, Day2, Day3, Day 5, day 8, day 12, day 14, day 15, day 16, day 17and Day 18 post dose adminstration
Plasma PK Parameters-Elimination half-life (t1/2) for SAD and MAD cohorts
Time frame: SAD- From Day 1 to Day 5; SAD FE- Day 1 to Day 5 and Day 15 to day 19; MAD- Day 1, Day2, Day3, Day 5, day 8, day 12, day 14, day 15, day 16, day 17and Day 18 post dose adminstration
Plasma PK Parameters- Elimination rate constant (Kel) for SAD and MAD cohorts
Time frame: SAD- From Day 1 to Day 5; SAD FE- Day 1 to Day 5 and Day 15 to day 19; MAD- Day 1, Day2, Day3, Day 5, day 8, day 12, day 14, day 15, day 16, day 17and Day 18 post dose adminstration
Plasma PK Parameters-Volume of distribution (Vz/F) for SAD and MAD cohorts
Time frame: SAD- From Day 1 to Day 5; SAD FE- Day 1 to Day 5 and Day 15 to day 19; MAD- Day 1, Day2, Day3, Day 5, day 8, day 12, day 14, day 15, day 16, day 17and Day 18 post dose adminstration
Plasma PK Parameters- Clearance per bioavailability (CL/F) for SAD and MAD cohorts
Time frame: SAD- From Day 1 to Day 5; SAD FE- Day 1 to Day 5 and Day 15 to day 19; MAD- Day 1, Day2, Day3, Day 5, day 8, day 12, day 14, day 15, day 16, day 17and Day 18 post dose adminstration
Plasma PK Parameters- Mean Residence time (MRT) for SAD and MAD cohorts
Time frame: SAD- From Day 1 to Day 5; SAD FE- Day 1 to Day 5 and Day 15 to day 19; MAD- Day 1, Day2, Day3, Day 5, day 8, day 12, day 14, day 15, day 16, day 17and Day 18 post dose adminstration
To evaluate the PD effect of repeated oral doses of NH280105 on the plasma Lp-PLA2 inhibition from baseline
Time frame: SAD- From Day 1 to Day 5; SAD FE- Day 1 to Day 5 and Day 15 to day 19; MAD- Day 1, Day2, Day3, Day 5, day 8, day 12, day 14, day 15, day 16, day 17and Day 18 post dose adminstration
Plasma PK: The ratio of fed/fasted on Cmax- Maximum plasma concentration
Time frame: Part 1 - Food effect Cohort (Cohort 3) From Day 1 to Day 19 except Day 14.
Plasma PK: The ratio of fed/fasted on AUC(0-t)- Area under curve from 0 to timepoint
Time frame: Part 1 - Food effect Cohort (Cohort 3) From Day 1 to Day 19 except Day 14.
Plasma PK: The ratio of fed/fasted on AUC(0-inf)- Area under curve from 0 to infinity
Time frame: Part 1 - Food effect Cohort (Cohort 3) From Day 1 to Day 19 except Day 14.