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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02306876
• Other study ID #: B7441004
• Status: Terminated
• Phase: Phase 1
• First received: November 20, 2014
• Last updated: August 14, 2017
• Start date: January 19, 2015
• Est. completion date: June 14, 2016

Study information

• Verified date: August 2017
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 77
• Est. completion date: June 14, 2016
• Est. primary completion date: June 14, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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).

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• PF-06412562 3mg BID
PF-06412562
• PF-06412562 15mg BID
PF-06412562

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Arcadia MRI & Imaging Center	Arcadia	California
United States	California Clinical Trials Medical Group	Glendale	California
United States	Glendale Adventist Medical Center	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change from baseline for Columbia Suicide Severity Rating Scale	Columbia Suicide Severity Rating Scale	Screening, Day 1, Day 7 and Follow-up
Secondary	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

External Links

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