A Study Of The Safety, Tolerability, And Pharmacokinetics Of Multiple Doses Of PF-05180999 In Healthy Adults

Migraine Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01981486
• Other study ID #: B3441008
• Status: Withdrawn
• Phase: Phase 1
• First received: November 5, 2013
• Last updated: May 22, 2014
• Start date: June 2014
• Est. completion date: January 2015

Study information

• Verified date: May 2014
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Migraine

Intervention

Drug:
• Placebo Tablets
BID modified-release tablets
• PF-05180999 Tablets
BID modified-release tablets (20 to 240 mg BID)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax)	Single dose Cmax	0-12 hours post-dose on Day 1	No
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax)	Single dose Tmax	0-12 hours post-dose on Day 1	No
Primary	Area Under the Curve from Time Zero to end of dosing interval (AUCtau)	Single dose AUCtau	0-12 hours post-dose on Day 1	No
Primary	Maximum Observed Plasma Concentration at Steady-State (Cmax,ss)	Steady-state Cmax	0-12 hours post-dose on Day 14	No
Primary	Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss)	Steady-state Tmax	0-12 hours post-dose on Day 14	No
Primary	Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss)	Steady-state Cmin	0-12 hours post-dose on Day 14	No
Primary	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	No
Primary	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.	0-48 hours post-final dose on Day 14	No
Primary	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	No
Primary	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	No
Primary	Accumulation Ratio (Racc)	Ratio of Day 14 AUCtau to Day 1 AUCtau	0-12 hours post-dose on Days 1 and 14	No
Primary	Amount Excreted in Urine (Ae)	Amount of drug excreted in urine	0-12 hours post-dose on Day 14	No
Primary	Percent of Dose Excreted in Urine (Ae%)	Percent of total dose excreted in urine	0-12 hours post-dose on Day 14	No
Primary	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	No
Secondary	Identification of metabolites of PF-05180999 in urine and plasma	Metabolite identification	0-12 hours post-dose on Day 14	No
Secondary	Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood	Leukocyte levels in blister fluid and blood	Day 13 and Day 14	No
Secondary	Change from Baseline in Cytokine Levels in Blister Fluid	Cytokine levels in blister fluid	Day 13 and Day 14	No
Secondary	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	No
Secondary	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	No
Secondary	Urinary 6beta-hydroxycortisol/cortisol ratio	Urinary marker of CYP3A induction	Day 14	No
Secondary	Plasma 4beta-hydroxycholesterol/cholesterol ratio	Plasma marker of CYP3A induction	Day 14	No

External Links

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