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
Overview
- Phase
- Phase 1
- Intervention
- PF-06372865 or Placebo
- Conditions
- Healthy
- Sponsor
- Pfizer
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Apparent Volume of Distribution (Vz/F)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
Cohort 1:
Single ascending doses of PF-06372865 or placebo to investigate the safety/tolerability PK and PD of PF-06372865.
Intervention: PF-06372865 or Placebo
Cohort 2:
Single ascending doses of PF-06372865 or placebo to investigate the safety/tolerability PK and PD of PF-06372865.
Intervention: PF-06372865 or Placebo
Cohort 3:
Single ascending doses of PF-06372865 or placebo to investigate the safety/tolerability PK and PD of PF-06372865.
Intervention: PF-06372865 or Placebo
Cohort 4 (optional cohort):
Two single doses of PF-06372865 or placebo or lorazepam to further investigate the pharmacodynamics of PF-06372865.
Intervention: PF-06372865 or Placebo or Lorazepam
Outcomes
Primary Outcomes
Apparent Volume of Distribution (Vz/F)
Time Frame: 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)
Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-dose
Maximum Observed Plasma Concentration (Cmax)
Time Frame: 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)
Time Frame: 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
Time Frame: 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)
Time Frame: 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
Time Frame: 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)
Time Frame: 0, 0.5, 1, 1.5, 2, 4, 6, 12 hours post-dose
Change in Body Sway
Time Frame: 0, 0.5, 1, 1.5, 2, 4, 6, 12 hours post-dose
Change in Smooth Pursuit
Time Frame: 0, 0.5, 1, 1.5, 2, 4, 6, 12 hours post-dose
Change in Bond and Lader VAS
Time Frame: 0, 0.5, 1, 1.5, 2, 4, 6, 12 hours post-dose
Change in Adaptive Tracking
Time Frame: 0, 0.5, 1, 1.5, 2, 4, 6, 12 hours post-dose
Change in Visual Verbal Learning Test
Time Frame: 1 and 6 hours post dose
Change in Pharmaco-EEG
Time Frame: 0, 0.5, 1, 1.5, 2, 4, 6, 12 hours post-dose