Proof Of Mechanism Study To Determine Efficacy Of PF-04455242 In Blocking Spiradoline (PF-00345768) Stimulated Prolactin Release

Study Overview
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Brief Summary
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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.

Official Title
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Phase I, Randomized, Placebo Controlled Proof Of Mechanism Study To Determine Efficacy Of PF-04455242 In Blocking Spiradoline (PF-00345768) Stimulated Prolactin Release In Healthy Male Adult Subjects

Conditions
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Bipolar Depression

Intervention / Treatment
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* Drug: PF-04455242
* Drug: spiradoline
* Other: Placebo
* Drug: spiradoline
* Drug: PF-04455242
* Drug: spiradoline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects between the ages of 21 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests. 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).

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04455242 18 mg<br>Subjects in this arm will receive a single 18 mg oral dose of PF-04455242 prior to spiradoline challenge | Drug: PF-04455242<br>* Single oral 18 mg dose of PF-04455242.<br>Drug: spiradoline<br>* Spiradoline 3.2 mcg/kg to be administered intramuscularly once on the morning of the spiradoline challenge day.<br>|
| Placebo Comparator: Placebo<br>Subjects in this arm will receive placebo prior to spiradoline challenge. | Other: Placebo<br>* Oral placebo.<br>Drug: spiradoline<br>* Spiradoline 3.2 mcg/kg to be administered intramuscularly once on the morning of the spiradoline challenge day.<br>|
| Experimental: PF-04455242 30 mg<br>Subjects in this arm will receive a single 30 mg oral dose of PF-04455242 prior to spiradoline challenge. | Drug: PF-04455242<br>* Single 30 mg oral dose of PF-04455242.<br>Drug: spiradoline<br>* Spiradoline 3.2 mcg/kg to be administered intramuscularly once on the morning of the spiradoline challenge day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline area under the serum PRL concentration time curve from 0 to 120 minutes after intramuscular administration of PF 00345768 (spiradoline). |  | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to peak of serum PRL concentration. |  | 1 week | 
| Change from baseline to peak of plasma ACTH concentration. |  | 1 week | 
| Change from baseline area under the plasma ACTH concentration time curve from 0-120 minutes after intramuscular administration of PF 00345768 (spiradoline). |  | 1 week | 
| Plasma concentrations of PF 04455242. |  | 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 |  | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proof of mechanism study