Biological Availability
Conditions
Keywords
Single dose bioavailability study of methylprednisolone powder for oral suspension (4mg/mL) versus methylprednisolone tablet (32 mg)
Brief summary
A new formulation of methylprednisolone is being developed. A study is needed to determine the drug availability using the new formulation, a powder for reconstitution into a suspension, versus the current commercially available tablet formulation in healthy volunteers.
Interventions
DRUGmethylprednisolone
powder for oral suspension 4 mg/mL single dose (8 mL)
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; * a total body weight \>45 kg (99 lbs).
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease; * Any condition possibly affecting drug absorption (eg, gastrectomy).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hours (hrs) 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 - ∞). |
| Maximum Observed Plasma Concentration (Cmax) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose | — |
| Plasma Decay Half-life (t1/2) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
Countries
Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes all participants randomized to receive methylprednisolone 32 mg tablet first, formulation 1: methylprednisolone oral suspension 4 mg/mL at 32 mg (Micronized API) first and formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) first. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| First Intervention Period | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
| Second Intervention Period | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 32.5 Years STANDARD_DEVIATION 7.9 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 24 | 0 / 22 | 1 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 22 | 0 / 23 |
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, 5, 6, 12, 16 and 24 hours (hrs) post-dose
Population: Pharmacokinetic (PK) parameter analysis population included all randomized participants who were treated and had at least 1 of the PK parameters of interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Methylprednisolone 32 mg Tablet | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 1286.00 ng*hr/mL | Standard Deviation 385.27 |
| Methylprednisolone 32 mg Micronized API | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 1204.00 ng*hr/mL | Standard Deviation 394.65 |
| Methylprednisolone 32 mg Sieve Cut API | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 1180.00 ng*hr/mL | Standard Deviation 355.26 |
Comparison: Natural log transformed AUC (0 - ∞) of methylprednisolone was analyzed using 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: [88.23, 96.15]
Comparison: Natural log transformed AUC (0 - ∞) of methylprednisolone was analyzed using 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: [86.49, 94.11]
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose
Population: PK parameter analysis population included all randomized participants who were treated and had at least 1 of the PK parameters of interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Methylprednisolone 32 mg Tablet | Maximum Observed Plasma Concentration (Cmax) | 289.00 ng/mL | Standard Deviation 60.42 |
| Methylprednisolone 32 mg Micronized API | Maximum Observed Plasma Concentration (Cmax) | 279.10 ng/mL | Standard Deviation 82.91 |
| Methylprednisolone 32 mg Sieve Cut API | Maximum Observed Plasma Concentration (Cmax) | 246.20 ng/mL | Standard Deviation 66.05 |
Comparison: Natural log transformed Cmax of methylprednisolone was analyzed using 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: [88.06, 101.98]
Comparison: Natural log transformed Cmax of methylprednisolone was analyzed using 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: [78.06, 90.17]
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, 5, 6, 12, 16 and 24 hrs post-dose
Population: PK parameter analysis population included all randomized participants who were treated and had at least 1 of the PK parameters of interest in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylprednisolone 32 mg Tablet | Plasma Decay Half-life (t1/2) | 2.43 hr | Standard Deviation 0.39 |
| Methylprednisolone 32 mg Micronized API | Plasma Decay Half-life (t1/2) | 2.42 hr | Standard Deviation 0.37 |
| Methylprednisolone 32 mg Sieve Cut API | Plasma Decay Half-life (t1/2) | 2.45 hr | Standard Deviation 0.35 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose
Population: PK parameter analysis population included all randomized participants who were treated and had at least 1 of the PK parameters of interest in at least 1 treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Methylprednisolone 32 mg Tablet | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 2.00 hr |
| Methylprednisolone 32 mg Micronized API | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 1.00 hr |
| Methylprednisolone 32 mg Sieve Cut API | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 2.00 hr |