Healthy Volunteers
Conditions
Keywords
Bio-equivalence, Linezolid OS, Linezolid tablet
Brief summary
The purpose of this study is to estimate the bioequivalence comparing Linezolid 600 MG Oral Suspension with 600 MG tablet in Chinese healthy male subjects. This study data will be used to support Linezolid OS NDA in China.
Detailed description
To support Linezolid NDA in China.
Interventions
DRUGLinezolid
1. Linezolid OS 600 MG 2. Linezolid Tablet 600 MG
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers. * 18-40 years old, male. * BMI 19-24kg/m2.
Exclusion criteria
* Alcohol, drug, smoke user. * Sensitive to oxazolidinones antibiotics class drug or heparin. * Severe medical or psychiatric condition or laboratory abnormality. * Blood donation. * 12-ECG abnormal. * Treatment with study drug; clinically significant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 0, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose | Area under the plasma concentration-time curve from time zero (pre-dose) to the time of the last measurable concentration (AUClast). |
| Maximum Observed Plasma Concentration (Cmax) | 0, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose | Maximum observed plasma concentration within the dosing interval was directly obtained from the concentration-time data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 0, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose | 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 to Reach Maximum Observed Plasma Concentration (Tmax) | 0, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose | The time of the first occurrence of peak concentration observed directly from data. |
| Terminal Half-Life (t1/2) | 0, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose | Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half. |
Countries
China
Participant flow
Recruitment details
Participants were enrolled at a single site in China.
Participants by arm
| Arm | Count |
|---|---|
| Linezolid Linezolid 600 mg once (oral suspension or tablet) in morning (at approximately 8:00 AM) on Day 1 after fasting overnight. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Linezolid |
|---|---|
| Age Continuous | 25.4 Years STANDARD_DEVIATION 2.1 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 1 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration-time curve from time zero (pre-dose) to the time of the last measurable concentration (AUClast).
Time frame: 0, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose
Population: Pharmacokinetic concentration population: all randomized and treated participants who had at least 1 concentration in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linezolid 600 mg Oral Suspension | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 108.90 microgram*hour/milliliter (mcg*h/mL) | Standard Deviation 21.66 |
| Linezolid 600 mg Tablet | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 112.00 microgram*hour/milliliter (mcg*h/mL) | Standard Deviation 24.74 |
Comparison: Natural log transformed AUClast of linezolid was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect.90% CI: [93.11, 102.75]
Primary
Maximum Observed Plasma Concentration (Cmax)
Maximum observed plasma concentration within the dosing interval was directly obtained from the concentration-time data.
Time frame: 0, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose
Population: Pharmacokinetic concentration population: all randomized and treated participants who had at least 1 concentration in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linezolid 600 mg Oral Suspension | Maximum Observed Plasma Concentration (Cmax) | 15.51 microgram/milliliter (mcg/mL) | Standard Deviation 3.53 |
| Linezolid 600 mg Tablet | Maximum Observed Plasma Concentration (Cmax) | 13.68 microgram/milliliter (mcg/mL) | Standard Deviation 3.53 |
Comparison: Natural log transformed Cmax of linezolid was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect.90% CI: [105.26, 122.75]
Secondary
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, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose
Population: Pharmacokinetic concentration population: all randomized and treated participants who had at least 1 concentration in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linezolid 600 mg Oral Suspension | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 109.20 mcg*h/mL | Standard Deviation 21.72 |
| Linezolid 600 mg Tablet | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 112.60 mcg*h/mL | Standard Deviation 24.94 |
Comparison: Natural log transformed AUCinf of linezolid was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect.90% CI: [92.92, 102.63]
Secondary
Terminal Half-Life (t1/2)
Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 0, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose
Population: Pharmacokinetic concentration population: all randomized and treated participants who had at least 1 concentration in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Linezolid 600 mg Oral Suspension | Terminal Half-Life (t1/2) | 5.08 hours | Standard Deviation 0.7 |
| Linezolid 600 mg Tablet | Terminal Half-Life (t1/2) | 5.13 hours | Standard Deviation 0.92 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
The time of the first occurrence of peak concentration observed directly from data.
Time frame: 0, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose
Population: Pharmacokinetic concentration population: all randomized and treated participants who had at least 1 concentration in at least 1 treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Linezolid 600 mg Oral Suspension | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0.63 hours |
| Linezolid 600 mg Tablet | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 1.50 hours |