Healthy
Conditions
Keywords
bioavailability, capsule, tablet, healthy volunteer
Brief summary
The study will be an open-label, randomized, 2-period, 2-treatment, 2-sequence, cross-over, single-dose study employing administration of two PF-02341066 formulations in the fasted state to healthy adult volunteers.
Interventions
DRUGPF-02341066
A 250-mg single dose of PF-02341066 administered as 1 x 50-mg Powder-in-Capsule and 2 x 100-mg Powder-in-Capsules
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and/or female of non-childbearing potential 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 electrocardiogram(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). * Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication. * Pregnant or nursing females; females of childbearing potential, including those with tubal ligation. To be considered for enrollment, women of 45 to 55 years of age who are postmenopausal (defined as being amenorrheic for at least 2 years) must have confirmatory Follicle-stimulating hormone(FSH) test results at Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hours (hrs) post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2 | Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hrs post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2 | AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞). |
| Maximum Observed Plasma Concentration (Cmax) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hrs post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hrs post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2 | — |
| Apparent Volume of Distribution (Vz/F) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hrs post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2 | 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 (Vz/F) is influenced by the fraction absorbed. |
| Plasma Decay Half Life (t1/2) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hrs post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Apparent Oral Clearance (CL/F) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hrs post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes participants randomized to receive PF-02341066 250 mg IRT first and PF-02341066 250 mg PIC first. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 32.1 years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 24 | 8 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞])
AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hrs post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg PIC | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) | 2945.5 ng*hr/mL | Standard Deviation 955.2 |
| PF-02341066 250 mg IRT | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) | 2722.5 ng*hr/mL | Standard Deviation 939.2 |
Comparison: Natural log transformed AUC (0-∞) of PF-02341066 was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [84.86, 100.68]
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast).
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hours (hrs) post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2
Population: Pharmacokinetic (PK) parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg PIC | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 2804.5 ng*hr/mL | Standard Deviation 941.4 |
| PF-02341066 250 mg IRT | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 2597.3 ng*hr/mL | Standard Deviation 924.1 |
Comparison: Natural log transformed AUClast of PF-02341066 was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [84.84, 101.09]
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hrs post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg PIC | Maximum Observed Plasma Concentration (Cmax) | 113.35 ng/mL | Standard Deviation 34.22 |
| PF-02341066 250 mg IRT | Maximum Observed Plasma Concentration (Cmax) | 112.11 ng/mL | Standard Deviation 34.87 |
Comparison: Natural log transformed Cmax of PF-02341066 was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CI for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [90.18, 108.48]
Secondary
Apparent Oral Clearance (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.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hrs post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg PIC | Apparent Oral Clearance (CL/F) | 84.9 L/hr | Standard Deviation 31.6 |
| PF-02341066 250 mg IRT | Apparent Oral Clearance (CL/F) | 91.8 L/hr | Standard Deviation 35.8 |
Secondary
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 blood concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hrs post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg PIC | Apparent Volume of Distribution (Vz/F) | 3566.8 L | Standard Deviation 1820.5 |
| PF-02341066 250 mg IRT | Apparent Volume of Distribution (Vz/F) | 3809.3 L | Standard Deviation 1784.4 |
Secondary
Plasma Decay Half Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hrs post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg PIC | Plasma Decay Half Life (t1/2) | 29.48 hr | Standard Deviation 4.62 |
| PF-02341066 250 mg IRT | Plasma Decay Half Life (t1/2) | 29.10 hr | Standard Deviation 4.66 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72, 84 and 96 hrs post PF-02341066 dose in period 1 and additional 168 hrs post PF-02341066 dose in period 2
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-02341066 250 mg PIC | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 6.00 hr |
| PF-02341066 250 mg IRT | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 6.00 hr |