A First In Human Study In Healthy People To Evaluate Safety, Toleration, Pharmacokinetics and Pharmacodynamics of Single Oral Doses Of PF-06372865

Study Overview
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Brief Summary
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The purpose of this study in healthy people is to evaluate safety, toleration and time course of plasma concentration of single oral doses of PF-06372865. The pharmacodynamic activity of PF-06372865 will also be assessed. The effect of food on PK and the PK of PF-06372865 administered as a tablet formulation may also be investigated. Pharmacodynamic interaction between PF-06372865 and lorazepam will be evaluated.

Official Title
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A Double Blind (3rd Party Open) Randomized, Placebo Controlled, Crossover Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06372865 in Healthy Male and Female Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-06372865 or Placebo
* Drug: PF-06372865 or Placebo
* Drug: PF-06372865 or Placebo
* Drug: PF-06372865 or Placebo or Lorazepam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects or female subjects of non-child bearing potential between the ages of 18 and 55 years, inclusive. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). An informed consent document signed and dated by the subject Subjects who are willing and able to comply with 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 (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Any condition possibly affecting drug absorption (e.g., gastrectomy). A positive urine drug screen.

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1:<br>Single ascending doses of PF-06372865 or placebo to investigate the safety/tolerability PK and PD of PF-06372865. | Drug: PF-06372865 or Placebo<br>* PF-06372865 will be administered as an extemporaneously prepared solution for all doses unless the tablet formulation need to be evaluated. Correspondingly, placebo doses will be administered as solution or tablet.<br>|
| Experimental: Cohort 2:<br>Single ascending doses of PF-06372865 or placebo to investigate the safety/tolerability PK and PD of PF-06372865. | Drug: PF-06372865 or Placebo<br>* PF-06372865 will be administered as an extemporaneously prepared solution for all doses unless the tablet formulation need to be evaluated. Correspondingly, placebo doses will be administered as solution or tablet.<br>|
| Experimental: Cohort 3:<br>Single ascending doses of PF-06372865 or placebo to investigate the safety/tolerability PK and PD of PF-06372865. | Drug: PF-06372865 or Placebo<br>* PF-06372865 will be administered as an extemporaneously prepared solution for all doses unless the tablet formulation need to be evaluated. Correspondingly, placebo doses will be administered as solution or tablet.<br>|
| Experimental: Cohort 4 (optional cohort):<br>Two single doses of PF-06372865 or placebo or lorazepam to further investigate the pharmacodynamics of PF-06372865. | Drug: PF-06372865 or Placebo or Lorazepam<br>* Lorazepam 2 mg dose, PF-06372865 Dose 1, PF-06372865 Dose 2, PF-06372865 Dose 1 and Dose 2 in combination with lorazepam, placebo administered as tablet formulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) |  | 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) |  | 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time |  | 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-dose | 
| Apparent Oral Clearance (CL/F) |  | 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-dose | 
| Apparent Volume of Distribution (Vz/F) |  | 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-dose | 
| Plasma Decay Half-Life (t1/2) |  | 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-dose | 
| Area Under the Curve From Time Zero to 24 hours |  | 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-dose | 
| Change in Saccadic Eye Movements (saccadic reaction time, saccadic peak velocity and saccadic inaccuracy) |  | 0, 0.5, 1, 1.5, 2, 4, 6, 12 hours post-dose | 
| Change in Body Sway |  | 0, 0.5, 1, 1.5, 2, 4, 6, 12 hours post-dose | 
| Change in Smooth Pursuit |  | 0, 0.5, 1, 1.5, 2, 4, 6, 12 hours post-dose | 
| Change in Bond and Lader VAS |  | 0, 0.5, 1, 1.5, 2, 4, 6, 12 hours post-dose | 
| Change in Adaptive Tracking |  | 0, 0.5, 1, 1.5, 2, 4, 6, 12 hours post-dose | 
| Change in Visual Verbal Learning Test |  | 1 and 6 hours post dose | 
| Change in Pharmaco-EEG |  | 0, 0.5, 1, 1.5, 2, 4, 6, 12 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Single Dose, Pharmacokinetics, Safety, Toleration, Pharmacodynamics