This Phase 1b/2a clinical development plan is focused on the use of NP-201 acetate injection to investigate the pharmacokinetics (PK), safety, efficacy, PD (pharmacodynamic) markers (Phase 1b) and tolerability of NP-201 acetate injection after subcutaneous (SC) injection of multiple doses in healthy adults and in the ulcerative colitis (UC) patient population.
This Phase 1b/2a randomized, double-blinded study will be conducted in two parts - Phase 1b (Part A) in healthy volunteers and Phase 2a (Part B) in UC patients. This record relates only to Part A/Phase 1b study. This will be updated once Part A is complete. Part A (Multiple Ascending Doses-MAD): Up to a total of 32 healthy participants will be enrolled into four sequential cohorts (MAD1, MAD2, MAD3 and MAD4) and randomized 6:2 to receive either two dosing regimens of NP-201 acetate injection or placebo daily for 5 days or for MAD cohort 4 will be randomized 6:2 to receive 4 weekly doses of NP-201 acetate injection or placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
35
Route of administration- Sub cutaneous. Dosage interval and frequency: MAD1-200mg daily for 5 days; MAD2- 300mg daily for 5 days, MAD3- 400mg daily for 5 days, MAD4- 400mg administered 4 weekly doses.
Matching placebo administered across Part A and Part B
CMAX Clinical Research Pty Ltd
Adelaide, South Australia, Australia
Safety of NP-201 acetate injection in Healthy Volunteers. To evaluate the safety of NP-201 acetate injection by incidence, relationship and severity of adverse events (AE), serious adverse events and Treatment emergent AE
Time frame: Part A-Screening to Day 12 post first dose administration
Safety of NP-201 acetate injection in Healthy Volunteers. To evaluate the safety of NP-201 acetate injection by changes in baseline Laboratory values
Time frame: Part A-Screening to Day 12 post first dose administration
Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- AUC from time 0 to 24 (AUC24)
Time frame: Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- AUC over the dosing interval (AUCtau)
Time frame: Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- Area under curve from 0 to last AUC(0-last)
Time frame: Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- Maximum plasma concentration at steadystate (Cmax,ss)
Time frame: Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- time to Cmax,ss (tmax,ss)
Time frame: Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- Apparent oral body clearance at steady-state (CL/Fss)
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Time frame: Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection- Apparent volume of distribution at steady-state (Vd/Fss)
Time frame: Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A-Plasma PK parameters following multiple doses of NP-201 acetate injection-Terminal half life (t1/2)
Time frame: Part A-Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A-Urine PK parameters of NP-201 acetate injection after multiple doses- cumulative amount of drug excreted in urine (Ae)
Time frame: Part A-Samples collected on Day 1 and Day 5 post first dose administration
Part A-Urine PK parameters of NP-201 acetate injection after multiple doses- percent fraction of drug recovered in urine (Fe)
Time frame: Part A-Samples collected on Day 1 and Day 5 post first dose adminstration
Part A-Urine PK parameters of NP-201 acetate injection after multiple doses- Renal clearance (CLr)
Time frame: Part A-Samples collected on Day 1 and Day 5 post first dose adminstration
Area Under the Plasma Concentration-Time Curve (AUC)
Area under the plasma concentration-time curve (AUC) of NP-201 following subcutaneous administration at multiple dose levels.
Time frame: Day 1, Day 8, Day 15, Day 22, Day 29, Day 30 (24 hours post-dose), Day 43
Peak Plasma Concentration (Cmax)
Maximum observed plasma concentration (Cmax) of NP-201 following subcutaneous administration at multiple dose levels.
Time frame: Day 1, Day 8, Day 15, Day 22, Day 29, Day 30 (24 hours post-dose), Day 43
Time to Reach Maximum Plasma Concentration (Tmax)
Time to reach maximum plasma concentration (Tmax) of NP-201 following subcutaneous administration at multiple dose levels
Time frame: Day 1, Day 8, Day 15, Day 22, Day 29
Apparent Clearance (CL/F)
Apparent clearance (CL/F) of NP-201 following subcutaneous administration at multiple dose levels.
Time frame: Day 30, Day 43
Apparent Volume of Distribution (Vd/F)
Apparent volume of distribution (Vd/F) of NP-201 following subcutaneous administration at multiple dose levels
Time frame: Day 30, Day 43
Terminal Half-life (t½)
Terminal elimination half-life (t½) of NP-201 following subcutaneous administration at multiple dose levels.
Time frame: Day 30, Day 43
Renal Clearance (Clr)
Renal clearance (Clr) of NP-201 following subcutaneous administration at multiple dose levels.
Time frame: Day 1 and Day 29
Amount Excreted in Urine (Ae)
Total amount of NP-201 excreted in urine following subcutaneous administration at multiple dose levels.
Time frame: Day 1 and Day 29
Fraction of Dose Excreted in Urine (Fe)
Fraction of administered dose excreted in urine (Fe) following subcutaneous administration at multiple dose levels.
Time frame: Day 1 and Day 29
Part A-Immunogenicity (ADA) in Cohort MAD4
To assess presence of anti-drug antibodies following repeated weekly SC injections.
Time frame: Day 1 (pre-dose), Day 15, Day 29, and Day 43
Part A- PK of NP-201 acetate injection metabolite- AUC from time 0 to 24 (AUC24)
Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite Area under the concentration- time curve from 0 to 24hrs (AUC24)
Time frame: Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A- PK of NP-201 acetate injection metabolite- AUC over the dosing interval (AUCtau)
Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite Area under the concentration- time curve over the dosing interval (AUCtau)
Time frame: Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A-PK of NP-201 acetate injection metabolite- Maximum plasma concentration at steady state (Cmax,ss)
Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite maximum plasma concentration at steady state (CMAX, ss)
Time frame: Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A- PK of NP-201 acetate Injection metabolite- Time to Cmax,ss (tmax,ss)
Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite time to CMAX, ss (tmax, ss)
Time frame: Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A-PK of NP-201 acetate injection metabolite- Apparent oral body clearance at steady state (CL/Fss)
Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite apparent oral body clearance at steady state (CL/Fss)
Time frame: Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A- PK of NP-201 acetate injection metabolite- Apparent volume of distribution at steady-state (Vd/Fss),
Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite apparent volume distribution at steady state (Vd/Fss)
Time frame: Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A-PK of NP-201 acetate Injection metabolite- terminal half-life (T1/2)
Plasma Pharmacokinetics in Healthy Volunteers following administration of multiple doses of NP-201 acetate injection by measuring the NP-201 acetate injection metabolite terminal half-life (t1/2)
Time frame: Part A- Samples collected on Day 1, Day 2, Day 5 and Day 6 post first dose administration
Part A-Metabolite PK parameters in Cohort MAD4-t½
To evaluate metabolite t½ (Apparent terminal half-life)
Time frame: Part A-Day 1, Day 8, Day 15, Day 22, Day 29, Day 30, Day 43
Part A-Metabolite PK parameters in Cohort MAD4-AUC
To evaluate metabolite AUC (Area under the plasma concentration versus time curve)
Time frame: Part A-Day 1, Day 8, Day 15, Day 22, Day 29, Day 30, Day 43
Part A-Metabolite PK parameters in Cohort MAD4- Cmax
To evaluate metabolite Cmax (Peak Plasma Concentration)
Time frame: Part A-Day 1, Day 8, Day 15, Day 22, Day 29, Day 30, Day 43
Part A-Metabolite PK parameters in Cohort MAD4- Tmax
To evaluate metabolite Tmax (Time to maximum concentration)
Time frame: Part A-Day 1, Day 8, Day 15, Day 22, Day 29, Day 30, Day 43
Part A-Metabolite PK parameters in Cohort MAD4- CL/Fss
To evaluate metabolite CL/Fss (Apparent clearance)
Time frame: Part A-Day 1, Day 8, Day 15, Day 22, Day 29, Day 30, Day 43
Part A-Metabolite PK parameters in Cohort MAD4- Vd/Fss
To evaluate metabolite Vd/Fss (Apparent terminal volume of distribution)
Time frame: Part A-Day 1, Day 8, Day 15, Day 22, Day 29, Day 30, Day 43