Hypercholesterolemia
Conditions
Keywords
Cardiovascular Diseases
Brief summary
The purpose of this study is to estimate the relative bioavailability of the commercial tablet with one prototype extemporaneous preparation suspension formulation, to assist with internal decision making on formulation development.
Detailed description
Estimation of Relative Bioavailability
Interventions
DRUGAtorvastatin suspension
A single dose of 80 mg Atorvastatin suspension
DRUGLipitor
A single dose of 80 mg Lipitor tablet
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and/or female subjects * Body Mass Index (BMI) of approximately 18 to 30 kg/m2
Exclusion criteria
* Any condition possibly affecting drug absorption * A positive urine drug screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Predose (Time Zero) to 48 Hours Post-dose (AUC48) | 5 days | Geometric means of AUC48 = area under the plasma concentration-time profile from time zero (0) to 48 hours postdose of atorvastatin (test versus \[vs\] reference); measured in nanograms times hour per milliliter (ng.hr/mL). |
| Area Under the Curve From Predose (Time Zero) to Extrapolated Infinite Time (AUC Infinity) | 5 days | Geometric means of AUC infinity (AUCinf) = area under the plasma concentration-time curve from time zero (0) extrapolated to infinite time; measured in ng.hr/mL of atorvastatin (test vs reference). |
| Maximum Observed Plasma Concentration (Cmax) | 5 days | Geometric mean of Cmax = maximum observed plasma concentration of atorvastatin (test vs reference); measured in nanograms per milliliter (ng/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Predose (Time Zero) to Last Quantifiable Concentration (AUClast) | 5 days | Geometric mean of AUClast = area under the plasma concentration-time curve from time zero (0) to the last measurable concentration of atorvastatin (test vs reference); measured as ng.hr/mL |
| Terminal Phase Rate Constant (Kel) | 5 days | Geometric mean of Kel= termination phase rate constant for atorvastatin (test vs reference); measured as 1 per hour (1/hr). |
| Time to Reach Maximum Plasma Concentration (Tmax) | 5 days | Median of Tmax = time to maximum plasma concentration (Cmax) (test vs reference); measured in hours (hr). |
| Plasma Elimination Half-life (t1/2) | 5 days | Mean of t1/2 = terminal elimination half-life of atorvastatin (test vs reference); measured in hours. |
Countries
United States
Participant flow
Recruitment details
One center in the U.S.
Pre-assignment details
This study contained two sequences of 6 subjects per sequence. Each sequence received either test treatment followed by reference treatment, or reference treatment followed by test treatment. The order of administration was randomized to either of 2 sequences.
Participants by arm
| Arm | Count |
|---|---|
| All Participants | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1: First Intervention | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 34.8 years STANDARD_DEVIATION 7.7 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 12 | 1 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 |
Outcome results
Primary
Area Under the Curve From Predose (Time Zero) to 48 Hours Post-dose (AUC48)
Geometric means of AUC48 = area under the plasma concentration-time profile from time zero (0) to 48 hours postdose of atorvastatin (test versus \[vs\] reference); measured in nanograms times hour per milliliter (ng.hr/mL).
Time frame: 5 days
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Test | Area Under the Curve From Predose (Time Zero) to 48 Hours Post-dose (AUC48) | 135.05 ng.h/mL |
| Reference | Area Under the Curve From Predose (Time Zero) to 48 Hours Post-dose (AUC48) | 140.79 ng.h/mL |
Comparison: Ratio of adjusted means (test/reference), and 90% CI for ratio--for AUC48; restricted (residual) maximum likelihood (REML) method of estimation.90% CI: [85.82, 106.88]Mixed Models Analysis
Primary
Area Under the Curve From Predose (Time Zero) to Extrapolated Infinite Time (AUC Infinity)
Geometric means of AUC infinity (AUCinf) = area under the plasma concentration-time curve from time zero (0) extrapolated to infinite time; measured in ng.hr/mL of atorvastatin (test vs reference).
Time frame: 5 days
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Test | Area Under the Curve From Predose (Time Zero) to Extrapolated Infinite Time (AUC Infinity) | 135.88 ng.hr/mL |
| Reference | Area Under the Curve From Predose (Time Zero) to Extrapolated Infinite Time (AUC Infinity) | 142.86 ng.hr/mL |
Comparison: Ratio of adjusted means (test/reference), and 90% CI for ratio--for AUCinf90% CI: [84.99, 106.27]Mixed Models Analysis
Primary
Maximum Observed Plasma Concentration (Cmax)
Geometric mean of Cmax = maximum observed plasma concentration of atorvastatin (test vs reference); measured in nanograms per milliliter (ng/mL).
Time frame: 5 days
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Test | Maximum Observed Plasma Concentration (Cmax) | 38.74 ng/mL |
| Reference | Maximum Observed Plasma Concentration (Cmax) | 33.24 ng/mL |
Comparison: Ratio of adjusted means (test/reference), and 90% CI for ratio--for Cmax90% CI: [98.22, 141.53]Mixed Models Analysis
Secondary
Area Under the Curve From Predose (Time Zero) to Last Quantifiable Concentration (AUClast)
Geometric mean of AUClast = area under the plasma concentration-time curve from time zero (0) to the last measurable concentration of atorvastatin (test vs reference); measured as ng.hr/mL
Time frame: 5 days
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Test | Area Under the Curve From Predose (Time Zero) to Last Quantifiable Concentration (AUClast) | 130.21 ng.hr/mL |
| Reference | Area Under the Curve From Predose (Time Zero) to Last Quantifiable Concentration (AUClast) | 137.49 ng.hr/mL |
Comparison: Ratio of adjusted means (test/reference), and 90% CI for ratio--for AUClast90% CI: [83.86, 107.29]Mixed Models Analysis
Secondary
Plasma Elimination Half-life (t1/2)
Mean of t1/2 = terminal elimination half-life of atorvastatin (test vs reference); measured in hours.
Time frame: 5 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test | Plasma Elimination Half-life (t1/2) | 5.95 hr | Standard Deviation 1.4 |
| Reference | Plasma Elimination Half-life (t1/2) | 7.21 hr | Standard Deviation 2.23 |
Secondary
Terminal Phase Rate Constant (Kel)
Geometric mean of Kel= termination phase rate constant for atorvastatin (test vs reference); measured as 1 per hour (1/hr).
Time frame: 5 days
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Test | Terminal Phase Rate Constant (Kel) | 0.12 1/hr |
| Reference | Terminal Phase Rate Constant (Kel) | 0.10 1/hr |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax)
Median of Tmax = time to maximum plasma concentration (Cmax) (test vs reference); measured in hours (hr).
Time frame: 5 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Test | Time to Reach Maximum Plasma Concentration (Tmax) | 0.52 hr |
| Reference | Time to Reach Maximum Plasma Concentration (Tmax) | 0.50 hr |