A Study To Examine Safety, Pharmacokinetics, And Pharmacodynamic Of Pf 06412562 In Healthy Males

A Randomized,Subject And Investigator Blind, Sponsor Open Placebo Controlled, Parallel Phase 1b Study To Examine The Safety, Pharmacokinetics, And Pharmacodynamic Effects Of Pf-06412562 On Cognitive And Reward/Motivation Domains In Healthy Male Volunteers Selected By Cognitive Phenotype

This study is designed to investigate the safety, tolerability pharmacokinetics and pharmacodynamic effects of PF-06412562 following multiple dose administration as MR tablets in healthy adult males.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Other: Placebo; Drug: PF-06412562 3mg BID; Drug: PF-06412562 15mg BID

Detailed Description

This study is designed to investigate the safety, tolerability pharmacokinetics and pharmacodynamic effects of PF-06412562 following multiple dose administration as MR tablets in healthy adult males. The study will be comprised of 2 analytical stages. Both analytical stages will be conducted as randomized, subject and investigator blind, sponsor open, placebo-controlled, parallel design. Study enrollment will be continuous through Stage I and Stage II. Stage I consists of approximately 45 completer subjects (approximately 15 per arm). Stage I is an exploratory hypothesis generation stage. No multiple comparison adjustment will be conducted for the Stage I analysis. The sample size in Stage I is based on operational feasibility. All endpoints including the composite scores will be tested at the end of Stage I. Each PF-06412562 dose (3 mg BID and 15 mg BID) will be compared to the placebo arm for each endpoint. Up to 5 comparisons that meet Stage I decision criteria will be treated as primary comparisons in Stage II (see Data Analysis section). Stage II is a hypothesis testing stage in which multiple comparisons will be adjusted and overall type I error rate will be controlled across all primary comparisons. Stage II will be formally powered to study those endpoints/doses most likely to demonstrate the strongest pharmacodynamic signal. Stage II will not exceed 56 completers (~21 in each PF-06412562 arm and ~14 in placebo arm). Study enrollment will be continuous through Stage I and Stage II. The three treatments in both stages include (i) PF-06412562 3 mg BID (ii) PF-06412562 15 mg BID, and (iii) placebo. Separate placebo groups, contemporaneous with the treatment groups, will be recruited for Stage I and Stage II. A total of approximately 101 subjects will be randomly assigned to one of the 3 treatments. If a subject drops out before completing the study, or withdraws for reasons unrelated to the safety of the test treatment, the subject will be replaced at the discretion of the Sponsor in consultation with the investigator. Subjects with fMRI or ERP data that does not pass imaging or ERP data QC will also be replaced.

Subjects will be randomized to a specific treatment arm according to the randomization schedule provided to the site by Pfizer. Two doses of PF-06412562 (3 mg and 15 mg), administered as MR tablets, will be given twice daily (BID) from Day 1 through Day 6. A loading dose of PF-06412562 will be administered as an IR tablet on Day 1 only to facilitate rapid attainment of concentration into the target range. For subjects assigned to the 3 mg BID group, one 3 mg MR tablet and one

1 mg PF-06412562 IR tablet will be administered. For subjects assigned to the 15 mg BID group, one 15 mg MR tablet and one 5 mg IR dose of PF-06412562 will be administered.

On Day 7 only the morning dose will be administered. Subject participation will be approximately 12 days (and 11 nights), excluding screening and follow-up. Screening activities will be completed up to 28 days prior to admission to the study on Day -3. The follow-up visit is conducted approximately 7 to 10 days after the last dose of study drug administration. Medically healthy, right-handed male subjects, aged 18-45 will be screened for working memory capacity, psychiatric disorders and other cognitive/educational constrains. Subjects who meet all entry criteria will be randomized into one of the three treatment arms.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Arcadia, California, United States, 91007
      • Arcadia MRI & Imaging Center
    • Glendale, California, United States, 91206
      • California Clinical Trials Medical Group
    • Glendale, California, United States, 91206
      • Glendale Adventist Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Medically healthy
• Male
• Right-handed aged
• 18-45 years
• BMI 17.5 to 35kg/m2.

Exclusion Criteria:

• Females
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of screening and at the time of dosing).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo BID	Other: Placebo; Placebo
Experimental: PF-06412562 3mg; PF-06412562 3mg BID	Drug: PF-06412562 3mg BID; PF-06412562; Other Names: PF-06412562 3mg
Experimental: PF-06412562 15mg; PF-06412562 15mg BID	Drug: PF-06412562 15mg BID; PF-06412562; Other Names: PF-06412562 15mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from baseline for Columbia Suicide Severity Rating Scale	Columbia Suicide Severity Rating Scale	Screening, Day 1, Day 7 and Follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cavg: Average plasma PF-06412562 and PF-06663872 concentrations at steady state	Average plasma PF-06412562 and PF-06663872 concentrations for each dose at times 0, 5, and 12 hours on days 4 and 6, as well as 0 hours on Day 8	Day 4, 6 and 8

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Balice-Gordon R, Honey GD, Chatham C, Arce E, Duvvuri S, Naylor MG, Liu W, Xie Z, DeMartinis N, Harel BT, Braley GH, Kozak R, Park L, Gray DL. A Neurofunctional Domains Approach to Evaluate D1/D5 Dopamine Receptor Partial Agonism on Cognition and Motivation in Healthy Volunteers With Low Working Memory Capacity. Int J Neuropsychopharmacol. 2020 May 27;23(5):287-299. doi: 10.1093/ijnp/pyaa007.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2015
• Primary Completion (Actual): June 14, 2016
• Study Completion (Actual): June 14, 2016

Study Registration Dates

• First Submitted: November 20, 2014
• First Submitted That Met QC Criteria: December 1, 2014
• First Posted (Estimate): December 3, 2014

Study Record Updates

• Last Update Posted (Actual): August 17, 2017
• Last Update Submitted That Met QC Criteria: August 14, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: B7441004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No