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PF-05180999 is a novel phosphodiesterase-2 (PDE2) inhibitor. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple doses of PF-05180999 administered twice daily over 14 days. Exploratory measures of PDE2 inhibition will also be evaluated in blood and blister fluid.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo tablets |
|
| PF-05180999 | Experimental | Modified-release tablets of PF-05180999 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo Tablets | Drug | BID modified-release tablets |
| |
| PF-05180999 Tablets |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Single dose Cmax | 0-12 hours post-dose on Day 1 |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Single dose Tmax | 0-12 hours post-dose on Day 1 |
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) | Single dose AUCtau | 0-12 hours post-dose on Day 1 |
| Maximum Observed Plasma Concentration at Steady-State (Cmax,ss) | Steady-state Cmax | 0-12 hours post-dose on Day 14 |
| Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss) | Steady-state Tmax | 0-12 hours post-dose on Day 14 |
| Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss) | Steady-state Cmin | 0-12 hours post-dose on Day 14 |
| Area Under the Curve from Time Zero to End of Dosing Interval at Steady-State (AUCtau,ss) | Steady-state AUCtau | 0-12 hours post-dose on Day 14 |
| Apparent Oral Clearance (CL/F) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Measure | Description | Time Frame |
|---|---|---|
| Identification of metabolites of PF-05180999 in urine and plasma | Metabolite identification | 0-12 hours post-dose on Day 14 |
| Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| D001768 | Blister |
| ID | Term |
|---|---|
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| Drug |
BID modified-release tablets (20 to 240 mg BID) |
|
| 0-48 hours post-final dose on Day 14 |
| Apparent Volume of Distribution (Vz/F) | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | 0-48 hours post-final dose on Day 14 |
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0-48 hours post-final dose on Day 14 |
| Accumulation Ratio (Racc) | Ratio of Day 14 AUCtau to Day 1 AUCtau | 0-12 hours post-dose on Days 1 and 14 |
| Amount Excreted in Urine (Ae) | Amount of drug excreted in urine | 0-12 hours post-dose on Day 14 |
| Percent of Dose Excreted in Urine (Ae%) | Percent of total dose excreted in urine | 0-12 hours post-dose on Day 14 |
| Renal Clearance (CLr) | Renal clearance is a quantitative measure of the rate at which a drug substance is removed from the blood via the renal route. | 0-48 hours post-dose on Day 14 |
Leukocyte levels in blister fluid and blood
| Day 13 and Day 14 |
| Change from Baseline in Cytokine Levels in Blister Fluid | Cytokine levels in blister fluid | Day 13 and Day 14 |
| Time-Averaged Area Under the Effect Curve (AUEC/t) for Platelet cGMP and cAMP | Time-averaged area under the effect curve | 0-12 hours post-dose on Day 1 and Day 14 |
| AUEC/t Ratio | Ratio of Day 14 AUEC/t to Day 1 AUEC/t | 0-12 hours post-dose on Day 1 and Day 14 |
| Urinary 6beta-hydroxycortisol/cortisol ratio | Urinary marker of CYP3A induction | Day 14 |
| Plasma 4beta-hydroxycholesterol/cholesterol ratio | Plasma marker of CYP3A induction | Day 14 |
| D009422 | Nervous System Diseases |
| D012872 | Skin Diseases, Vesiculobullous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |