This study will be a Proof of Mechanism (POM) study to establish evidence of central pharmacodynamic activity for PF 04455242, and will be a parallel group, randomized, double blind, sponsor open study conducted in healthy male subjects. Once subjects achieve steady state of PF 04455242, they will undergo PF 00345768 (spiradoline) challenge. Data will be analyzed to determine whether PF-04455242 blocks spiradoline induced prolactin release.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
24
Single oral 18 mg dose of PF-04455242.
Spiradoline 3.2 mcg/kg to be administered intramuscularly once on the morning of the spiradoline challenge day.
Oral placebo.
Pfizer Investigational Site
Singapore, Singapore
Change from baseline area under the serum PRL concentration time curve from 0 to 120 minutes after intramuscular administration of PF 00345768 (spiradoline).
Time frame: 1 week
Change from baseline to peak of serum PRL concentration.
Time frame: 1 week
Change from baseline to peak of plasma ACTH concentration.
Time frame: 1 week
Change from baseline area under the plasma ACTH concentration time curve from 0-120 minutes after intramuscular administration of PF 00345768 (spiradoline).
Time frame: 1 week
Plasma concentrations of PF 04455242.
Time frame: 1 week
Clinical monitoring of safety and tolerability will include physical exam and neurological assessment, clinical safety laboratory results, 12 lead ECGs, vital signs, suicidality assessment, and adverse event monitoring
Time frame: 1 week
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Spiradoline 3.2 mcg/kg to be administered intramuscularly once on the morning of the spiradoline challenge day.
Single 30 mg oral dose of PF-04455242.
Spiradoline 3.2 mcg/kg to be administered intramuscularly once on the morning of the spiradoline challenge day.