A Phase I, Placebo Controlled, Randomized, Subject-And Investigator-Blind, Sponsor-Open, Multiple Ascending Dose Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-05180999 In Healthy Adult Volunteers
| Registry | NCT01981486 |
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| Status | Withdrawn |
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| Phase | Phase 1 |
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| Study type | Interventional; randomized, parallel, masking: double, basic science |
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| Sponsor | Pfizer (Industry) |
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| Conditions | Migraine |
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| Interventions | Placebo Tablets, PF-05180999 Tablets (Drug) |
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| Dates | start 2014-06-01, primary completion 2015-01-01 (estimated), completion 2015-01-01 (estimated), first posted 2013-11-11, last updated 2014-05-23 |
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Related Papers Related Patents Related Grants Related Experts
All trials for Migraine All trials of Placebo Tablets All trials of PF-05180999 Tablets
-Summary
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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+Arms and interventions
| Arm | Type | Interventions | Description |
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| Placebo | Placebo comparator | Drug: Placebo Tablets | Placebo tablets |
| PF-05180999 | Experimental | Drug: PF-05180999 Tablets | Modified-release tablets of PF-05180999 |
- Placebo Tablets (Drug): BID modified-release tablets
- PF-05180999 Tablets (Drug): BID modified-release tablets (20 to 240 mg BID)
+Outcome measures
Primary outcomes
- Maximum Observed Plasma Concentration (Cmax) [0-12 hours post-dose on Day 1]: Single dose Cmax
- Time to Reach Maximum Observed Plasma Concentration (Tmax) [0-12 hours post-dose on Day 1]: Single dose Tmax
- Area Under the Curve from Time Zero to end of dosing interval (AUCtau) [0-12 hours post-dose on Day 1]: Single dose AUCtau
- Maximum Observed Plasma Concentration at Steady-State (Cmax,ss) [0-12 hours post-dose on Day 14]: Steady-state Cmax
- Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss) [0-12 hours post-dose on Day 14]: Steady-state Tmax
- Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss) [0-12 hours post-dose on Day 14]: Steady-state Cmin
- Area Under the Curve from Time Zero to End of Dosing Interval at Steady-State (AUCtau,ss) [0-12 hours post-dose on Day 14]: Steady-state AUCtau
- Apparent Oral Clearance (CL/F) [0-48 hours post-final dose on Day 14]: 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.
- Apparent Volume of Distribution (Vz/F) [0-48 hours post-final dose on Day 14]: 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.
- Plasma Decay Half-Life (t1/2) [0-48 hours post-final dose on Day 14]: Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
- Accumulation Ratio (Racc) [0-12 hours post-dose on Days 1 and 14]: Ratio of Day 14 AUCtau to Day 1 AUCtau
- Amount Excreted in Urine (Ae) [0-12 hours post-dose on Day 14]: Amount of drug excreted in urine
- Percent of Dose Excreted in Urine (Ae%) [0-12 hours post-dose on Day 14]: Percent of total dose excreted in urine
- Renal Clearance (CLr) [0-48 hours post-dose on Day 14]: Renal clearance is a quantitative measure of the rate at which a drug substance is removed from the blood via the renal route.
Secondary outcomes
- Identification of metabolites of PF-05180999 in urine and plasma [0-12 hours post-dose on Day 14]: Metabolite identification
- Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood [Day 13 and Day 14]: Leukocyte levels in blister fluid and blood
- Change from Baseline in Cytokine Levels in Blister Fluid [Day 13 and Day 14]: Cytokine levels in blister fluid
- Time-Averaged Area Under the Effect Curve (AUEC/t) for Platelet cGMP and cAMP [0-12 hours post-dose on Day 1 and Day 14]: Time-averaged area under the effect curve
- AUEC/t Ratio [0-12 hours post-dose on Day 1 and Day 14]: Ratio of Day 14 AUEC/t to Day 1 AUEC/t
- Urinary 6beta-hydroxycortisol/cortisol ratio [Day 14]: Urinary marker of CYP3A induction
- Plasma 4beta-hydroxycholesterol/cholesterol ratio [Day 14]: Plasma marker of CYP3A induction
+Eligibility
Sex: All, ages: 18 Years to 55 Years, accepts healthy volunteers
Inclusion Criteria:
* Healthy male and/or female (of non-childbearing potential) subjects between the ages of 18 and 55 years
* Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs)
Exclusion Criteria:
* Subjects with Gilbert's disease or screening laboratory test results that deviate from the upper and/or lower limits of the reference or acceptable range. The exception is that all liver function tests must not exceed the upper limit of normal.
* Subjects with evidence of, or history of, hepatic disorder, including acute or chronic hepatitis B or hepatitis C.
* Subjects with very light skin or very dark skin (at the discretion of the investigator).
+Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer