A Phase 1, Within Cohort, Randomized, Double Blind, Third-Party Open, Placebo-Controlled, Single- And Multiple Dose Escalation, Parallel Group Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-04965842 In Healthy Western and Japanese Subjects

PF-04965842

Placebo

PF-04965842

Placebo

PF-04965842

Placebo

PF-04965842

Placebo

PF-04965842

Placebo

Changes from baseline vital signs (blood pressure, pulse rate, oral temperature and respiration rate) and physical examinations

Changes from baseline in 12 lead ECG parameters

Incidence and severity of treatment emergent adverse events and withdrawals due to treatment emergent adverse events

Incidence and magnitude of treatment emergent clinical laboratory abnormalities including hematology (with white blood cell count differentials, platelets, PT and aPTT), chemistry, fasting glucose, urinalysis

Change from baseline in immunoglobulin levels

24-hour urine creatinine clearance (Single Ascending Dose Period)

24-hour urine creatinine clearance (Multiple Ascending Dose Period)

Complement Level: C3

Complement Level: C4

Complement Level: C3A

Complement Level: Bb

Single Ascending Dose: Dose-normalized Area Under the Curve From Time Zero to Infinity (AUCinf(dn))

Multiple Ascending Dose: Accumulation Ratio based on Cmax (Rac(Cmax))

Urinary Pharmacokinetics; for twice-a-day dosing, amount of PF-0496842 excreted unchanged in 12 hours (AE12)

Urinary Pharmacokinetics; for twice-a-day dosing, percent of PF-0496842 excreted unchanged in 12 hours (AE12%)

Multiple Ascending Dose: Apparent Volume of Distribution at Steady State (Vz/F)

Multiple Ascending Dose: Apparent Total Body Clearance (CL/F)

Urinary Pharmacokinetics; for once-a-day dosing, amount of PF-0496842 excreted unchanged in 24 hours (AE24)

Urinary Pharmacokinetics; for once-a-day dosing, percent of PF-0496842 excreted unchanged in 24 hours (AE24%)

Renal Clearance (CLr)

High-Sensitivity C-Reactive Protein (hsCRP)

Neutrophil counts

Reticulocyte counts

Complement Level: CH50

Single Ascending Dose: Apparent Total Body Clearance (CL/F)

Multiple Ascending Dose: Maximum Observed Plasma Concentration (Cmax)

Multiple Ascending Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax)

Multiple Ascending Dose: Dose-normalized Maximum Observed Plasma Concentration (Cmax(dn))

Multiple Ascending Dose: Area Under the Curve to the end of the dosing period (AUCtau(dn))

Multiple Ascending Dose: Accumulation Ratio based on AUC predicted (Rss)

Multiple Ascending Dose: Accumulation Ration based on AUC observed (Rac)

Multiple Ascending Dose: Plasma Decay Half-Life (t1/2)

Multiple Ascending Dose: Peak to Trough Fluctuation (PTF)

Single Ascending Dose: Dose-normalized Area Under the Curve to the end of the dosing period (AUCtau(dn))

Single Ascending Dose: Area Under the Curve From Time Zero to Infinity (AUCinf)

Single Ascending Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)

Single Ascending Dose: Dose-normalized Maximum Observed Plasma Concentration (Cmax(dn))

Single Ascending Dose: Area Under the Curve to the end of the dosing period (AUCtau)

Single Ascending Dose: Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn))

Single Ascending Dose: Plasma Decay Half-Life (t1/2)

Multiple Ascending Dose: Area Under the Curve to the end of the dosing period (AUCtau)

Single Ascending Dose: Apparent Volume of Distribution (Vz/F)

Single Ascending Dose: Maximum Observed Plasma Concentration (Cmax)