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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-06372865 or Placebo; Drug: PF-06372865 or Placebo or Lorazepam

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • CL
    • Leiden, CL, Netherlands, 2333
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Single ascending doses of PF-06372865 or placebo to investigate the safety/tolerability PK and PD of PF-06372865.	Drug: PF-06372865 or Placebo; 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.
Experimental: Cohort 2: Single ascending doses of PF-06372865 or placebo to investigate the safety/tolerability PK and PD of PF-06372865.	Drug: PF-06372865 or Placebo; 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.
Experimental: Cohort 3: Single ascending doses of PF-06372865 or placebo to investigate the safety/tolerability PK and PD of PF-06372865.	Drug: PF-06372865 or Placebo; 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.
Experimental: Cohort 4 (optional cohort): 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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: September 13, 2013
• First Submitted That Met QC Criteria: September 23, 2013
• First Posted (Estimate): September 26, 2013

Study Record Updates

• Last Update Posted (Estimate): August 18, 2014
• Last Update Submitted That Met QC Criteria: August 15, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Phase 1; Pharmacodynamics; Single Dose; Toleration
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anticonvulsants; Lorazepam; PF-06372865
• Other Study ID Numbers: B7431001