To Evaluate Safety, Tolerability, Plasma Drug Levels And Other Biological Effects In Healthy Volunteers

A Phase 1, First-Into-Human, Escalating Dose Trial To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of PF-03382792 After Administration Of Single Oral Doses To Healthy Adult Subjects

The purpose of this study is to evaluate safety and tolerability after a single administration of PF-03382792 in healthy volunteers.; and to evaluate plasma drug levels and biological activity.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-03382792 Cohort 1; Drug: PF-03382792 Cohort 2; Drug: PF-03382792; Drug: Food Effect cohort; Drug: CSF cohort

Detailed Description

Evaluate the safety, tolerability, plasma concentrations of PF-03382792 and other biological activity following a single dose of PF-03382792. Three ascending single doses of PF-03382792 were administered in this study (0.05 mg, 0.15mg and 0.5 mg). The decision to terminate the study was made on June 4, 2010 due to safety findings and limitations regarding the levels of the metabolite projected for doses above 0.5 mg.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For all cohorts, healthy male and/or female subjects of nonchildbearing potential between the ages of 18 and 55 years, inclusive.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
• 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.
• Signs or symptoms of adrenal insufficiency.
• Ocular lens (eye) abnormalities.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PART A: Ascending Cohorts; Single ascending dose cross-over. (0.05, 0.15, 0.5, 1.5, 5, 15 mg)	Drug: PF-03382792 Cohort 1; First cohort for: Single oral ascending dose of PF-03382792, formulated in solution.; Drug: PF-03382792 Cohort 2; Second cohort for: Single oral ascending dose of PF-03382792, formulated in solution.; Drug: PF-03382792; Optional cohort 3: Single oral ascending dose of PF-03382792, formulated in solution.
Experimental: PART B: Food effect; Food effect on PF-03382792 PK	Drug: Food Effect cohort; Single oral dose, cross-over to determine effect of food on PF-03382792 pharmacokinetics. Dose will be decided after reviewing data from the ascending dose portion.
Experimental: PART C: CSF Cohort; Optional CSF Cohort	Drug: CSF cohort; Single oral dose of PF-03382792 formulated in solution. Dose will be decided after reviewing data from the ascending dose portion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety endpoints include evaluation: adverse events, change from baseline in vital signs, triplicate ECG (Part A only), singlet ECG for Parts B and C. 8 hours of cardiac telemetry postdose (Part A only).	For cohorts in Part A, up to 24 days; for Cohorts in Part B, up to 17; for Part C, up to 10 days
Additional Safety endpoints: clinical safety laboratory endpoints, plasma cortisol and ACTH, clinical examinations, slit lamp examination.	For cohorts in Part A, up to 24 days; for Cohorts in Part B, up to 17; for Part C, up to 10 days
Pharmacokinetic endpoints: plasma concentration of PF 03382792 over time (eg, AUC, Cmax, Tmax, t1/2), plasma concentration of PF 03227077 over time (eg, AUC, Cmax, Tmax, t1/2).	up to 72 hours post the final dose for each cohort

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma aldosterone concentrations.	For Part A and C; up to 24 hours post final dose
Change and percent change from baseline in average CSF sAPP fragment concentrations over all postdose collection time points up to 8 hours. • CSF sAPP fragment concentrations over time. • CSF concentration of PF 03382792 and PF	Part C only, up to 8 hours post dose
03227077 over time (eg, AUC, Cmax, Tmax).	Part C only, up to 8 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: February 1, 2010
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: January 8, 2010
• First Submitted That Met QC Criteria: January 8, 2010
• First Posted (Estimate): January 11, 2010

Study Record Updates

• Last Update Posted (Estimate): August 4, 2010
• Last Update Submitted That Met QC Criteria: August 3, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: volunteer
• Other Study ID Numbers: B1651001