Safety and Tolerability of PF-06818883 in Healthy Subjects

Study Overview
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Brief Summary
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Safety, Tolerability and Pharmacokinetics of PF-06818883

Official Title
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A Phase 1, Randomized, Double-blind, Sponsor-open, Placebo-controlled, Single-ascending Dose Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of Pf-06818883 Following Single Intravenous Administration In Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Placebo
* Drug: PF-06818883


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy female subjects of nonchildbearing potential and/or male subjects Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease Any condition possibly affecting the placement of an intravenous drug administration line. A confirmed positive urine drug screen History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening Use of tobacco- or nicotine-containing products in excess of the equivalent of 5 cigarettes per day or 2 chews of tobacco per day Treatment with an investigational drug within 30 days (or as determined by the local requirement) Screening supine blood pressure >140 mm Hg (systolic) or <90 mm Hg (diastolic), following at least 5 minutes of supine rest Screening supine 12-lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing. History of sensitivity to heparin or heparin-induced thrombocytopenia History of human immunodeficiency virus (HIV), hepatitis B or C; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb) or hepatitis C antibody (HCVAb). Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>IV placebo | Drug: Placebo<br>* Placebo<br>|
| Experimental: PF-06818883<br>Experimental drug | Drug: PF-06818883<br>* Treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Number of Participants with Adverse Events as a Measure of Safety and Tolerability | An assessment of Adverse Events | Day 0, Day 1, Day 2, Day 3 | 
| Change in Physical examination | Safety test to check overall health | Day 0, Day 1, Day 2 and Day 3 | 
| Change in Neurological Exam | Assessment of sensory neuron and motor responses | Day 0, Day 1, Day 2 and Day 3 | 
| Change in 12-lead ECG (electrocardiogram) | heart's electrical activity recorded from electrodes on the body surface | Day 1 hr 0.25, 1, 2, 6, 8, 12, Day 2 hr 24 and 36, Day 3 hr 48 | 
| Change in Vital signs | clinical measurements, specifically pulse rate, temperature, and blood pressure, that indicate the state of a patient's essential body functions | Day 1 hr 0.25, 1, 2, 6, 8, 12, Day 2 hr 24 and 36, Day 3 hr 48 | 
| Change in Clinical laboratory tests (haematology: haemoglobin; haematocrit/erythrocytes; haemoglobin/erythroctes; Erythro-, leuco-,lympho-, mono-Cytes; Platelets) | Intended to detect, identify, or quantify one or more significant substances, evaluate organ functions, or establish the nature of a condition | Day 0, Day 2 and Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) after single dose for all periods | Cmax after a single dose | Day 1 hr 0.25, 0.5, 1, 1.5, 2, 3, 6, 8, 12, 16, Day 2 hr 24 and 36, Day 3 hr 48 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) after single dose for all periods | Tmax after single dose | Day 1 hr 0.25, 0.5, 1, 1.5, 2, 3, 6, 8, 12, 16, Day 2 hr 24 and 36, Day 3 hr 48 | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) after single dose for all periods | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) after single dose | Day 1 hr 0.25, 0.5, 1, 1.5, 2, 3, 6, 8, 12, 16, Day 2 hr 24 and 36, Day 3 hr 48 | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf)] after single dose for all periods | AUC (0 - inf)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf) after single dose | Day 1 hr 0.25, 0.5, 1, 1.5, 2, 3, 6, 8, 12, 16, Day 2 hr 24 and 36, Day 3 hr 48 | 
| Plasma Decay Half-Life (t1/2) after single dose for all periods | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half after single dose | Day 1 hr 0.25, 0.5, 1, 1.5, 2, 3, 6, 8, 12, 16, Day 2 hr 24 and 36, Day 3 hr 48 | 
| Clearance (CL) after single dose for all periods | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | Day 1 hr 0.25, 0.5, 1, 1.5, 2, 3, 6, 8, 12, 16, Day 2 hr 24 and 36, Day 3 hr 48 | 
| Volume of Distribution (Vss) after single dose for all periods | Volume of distribution is defined as the volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. | Day 1 hr 0.25, 0.5, 1, 1.5, 2, 3, 6, 8, 12, 16, Day 2 hr 24 and 36, Day 3 hr 48 | 
| Dose-Normalized Maximum Plasma Concentration (Cmax(dn)) after single dose for all period | Dose-Normalized Cmax after a single dose | Day 1 hr, 0.25, 0.5, 1, 1.5, 2, 3, 6, 8, 12, 16, Day 2 hr 24 and 36, Day 3 hr 48 | 
| Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) after single dose for all periods | Dose Normalized Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast(dn)) after single dose | Day 1 hr 0.25, 0.5, 1, 1.5, 2, 3, 6, 8, 12, 16, Day 2 hr 24 and 36, Day 3 hr 48 | 
| Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf(dn))] after single dose for all periods | AUC (0 - inf (dn)) = Dose Normalized Area under the plasma concentration versus time curve (AUC(dn)) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf) after single dose | Day 1 hr 0.25, 0.5, 1, 1.5, 2, 3, 6, 8, 12, 16, Day 2 hr 24 and 36, Day 3 hr 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute neuroinflammatory