Radiolabeled [14C]PF-02341066 Study To Investigate The Absorption, Metabolism And Excretion In Healthy Male Volunteers

Healthy Volunteer Clinical Trial

Official title:

A Phase One Open-Label Single-Radiolabeled Dose Study To Investigate The Absorption, Metabolism And Excretion Of [14C]PF-02341066 In Healthy Male Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01082380
• Other study ID #: A8081009
• Status: Completed
• Phase: Phase 1
• First received: March 5, 2010
• Last updated: February 28, 2012
• Start date: March 2010
• Est. completion date: April 2010

Study information

• Verified date: February 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The rationale for this study is to investigate the absorption, metabolism and excretion of [14C]PF 02341066 and characterize plasma, fecal and urinary radioactivity, and identify any metabolites, if possible, of [14C]PF 02341066 in humans.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy male subjects between the ages of 18 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).

• Body Mass Index (BMI) of 17.5 to 30.5 kg/m^2; and a total body weight >50 kg (110 lbs).

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).

• Any condition possibly affecting drug absorption (eg, gastrectomy).

• A positive urine drug screen.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• PF-02341066
oral suspension, single 250 mg dose of PF 02341066 containing approximately 100 µCi of [14C]PF 02341066

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax)		Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours (hrs), 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax)		Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Area Under the Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast)	Area under the concentration time-curve from zero to the last measured plasma concentration (AUClast).	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Area Under the Plasma Concentration Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]	AUC (0 - 8) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Plasma Decay Half Life (t1/2)	Plasma Decay half-life is the time measured for the concentration to decrease by one half.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Apparent Oral Clearance (CL/F) of Plasma PF-02341066	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Apparent Volume of Distribution (V/F) in Plasma	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 blood concentration of a drug. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Renal Clearance (CLr) of PF-02341066	CLr is the volume of plasma from which a substance is completely removed by the kidney in a given amount of time.	Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to Infinite Time (Ae)	Ae = concentration of unchanged drug excreted in the urine multiplied by volume of unchanged drug excreted in urine.	Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Total Amount of Unchanged Drug Excreted in the Urine Expressed as Percent of Dose From Time Zero to Infinite Time [Ae(%)]		Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Maximum Observed Concentration in Plasma Radioactivity (Cmax)	Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Time to Reach Maximum Observed Plasma Radioactivity Concentration (Tmax)	Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Area Under the Curve From Time Zero to Last Quantifiable Plasma Radioactivity Concentration (AUClast)	Area under the concentration time-curve from zero to the last measured plasma concentration. Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Area Under the Plasma Radioactivity Concentration Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]	Area under the concentration curve from time zero to extrapolated infinite time [AUC (0 - 8)] in plasma. Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Decay Half Life (t1/2) of Radioactivity in Plasma	Plasma decay half-life is the time measured for the plasma radioactivity concentration to decrease by one half. Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Apparent Oral Clearance (CL/F) of Plasma Radioactivity	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Apparent Volume of Distribution (V/F) in Plasma Radioactivity	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 blood concentration of a drug. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed. Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Maximum Observed Concentration of Radioactivity in Whole Blood (Cmax)	Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Time to Reach Maximum Observed Concentration (Tmax) of Radioactivity in Whole Blood	Time to Reach Maximum Observed Concentration (Tmax) of Radioactivity in whole blood. Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Radioactivity in Whole Blood	Area under the concentration time-curve from zero to the last measured concentration (AUClast) in whole blood. Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of Radioactivity in Whole Blood	Area under the concentration curve from time zero to extrapolated infinite time [AUC (0 - 8)] in whole blood. Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Decay Half-life (t1/2) of Radioactivity in Whole Blood	Decay half life (t1/2) is the time measured for the concentration to decrease by one half in whole blood. Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Apparent Oral Clearance of Radioactivity From Whole Blood (CL/F)	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Apparent Volume of Distribution of Radioactivity in Whole Blood (V/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 blood concentration of a drug. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed. Radioactivity corresponds to 100 µCi [14C]PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Total [14C] Data in Urine	Cumulative amount excreted in urine at specified intervals after administration of a single 250-mg (100 µCi) oral dose of [14C]PF-02341066.	Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Total [14C] Data in Feces	Cumulative amount excreted in feces at specified intervals after administration of a single 250-mg (100 µCi) oral dose of [14C]PF-02341066.	From Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose	No
Primary	Overall Cumulative Percent Recovery of Radioactivity	Overall cumulative percent of radioactive dose recovered in urine, feces and toilet tissue at specified intervals after administration of a single 250-mg (100 µCi) oral dose of [14C]PF-02341066.	Pre-dose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose for urine and Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose for feces	No
Primary	Identification and Profiling of Metabolites of [14C]PF-02341066 in Plasma	Identification was done by Radio-High Performance liquid chromatography (HPLC) chromatogram. Relative abundance (profiling) of metabolites in chromatogram were determined by dividing sum of radioactive content of fractions contributing to particular peak by sum of radioactive content of all fractions constructing the radio chromatogram. Metabolites accounting for an average of greater than or equal to (>=) 10% of total recoverable radioactivity in plasma were summarized. Radioactivity corresponds to 100 µCi [14C] PF-02341066.	Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose	No
Primary	Identification and Profiling of Metabolites of [14C]PF-02341066 in Feces	In feces, metabolite abundance (profiling) was calculated by multiplying the fractional contribution of radioactive response for the peak in the Radio-HPLC chromatogram to the total radioactivity detected by the percent of administered dose recovered in the matrix. Only those metabolites that were a component of a chromatographic peak that accounted for an average of >=1% of the administered dose, were summarized. Radioactivity corresponds to 100 µCi [14C] PF-02341066.	From Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose	No
Primary	Identification and Profiling of Metabolites of [14C]PF-02341066 in Urine	In urine, metabolite abundance (profiling) was calculated by multiplying the fractional contribution of radioactive response for the peak in the Radio-HPLC chromatogram to the total radioactivity detected by the percent of administered dose recovered in the matrix. Only those metabolites that were a component of a chromatographic peak that accounted for an average of >=1% of the administered dose, were summarized. Radioactivity corresponds to 100 µCi [14C] PF-02341066.	Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose	No

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