Healthy
Conditions
Keywords
pharmacokinetic, eletriptan, Korean, crossover
Brief summary
The hypothesis of this study is that Korean subjects have similar Pharmacokinetics (PK) characteristics to those seen in other populations.
Interventions
DRUGEletriptan commercial tablet
20 mg tablet, single dose
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy male subjects, 18-55 years old * Body Mass Index (BMI) of 17.5 to 30.5 kg/m2 * provide informed consent
Exclusion criteria
* blood pressure \>140/90 mm Hg * any condition possibly affecting drug absorption * positive urine drug screen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | Pre-dosing, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hrs post dose (A,B,C) and additional 2.5,2.75,3.5,5,14,18 and 26 hrs post dose(D) | 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-∞). |
| AUC From Time Zero to Last Quantifiable Concentration (AUClast) | Pre-dosing, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hrs post dose (A,B,C) and additional 2.5,2.75,3.5,5,14,18 and 26 hrs post dose (D) | 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) | Pre-dosing, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hrs post dose (A,B,C) and additional 2.5,2.75,3.5,5,14,18 and 26 hrs post dose (D) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Pre-dosing, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hrs post dose (A,B,C) and additional 2.5,2.75,3.5,5,14,18 and 26 hrs post dose (D) | — |
| Plasma Decay Half Life (t1/2) | Pre-dosing, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hrs post dose (A,B,C) and additional 2.5,2.75,3.5,5,14,18 and 26 hrs post dose (D) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population All participants randomized to any treatment (Eletriptan 20 mg tablet first, eletriptan 40 mg tablet first, eletriptan 80 mg tablet first, and eletriptan 40 mg 2 hrs apart repeated dose (80 mg in total). | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 24.8 Years STANDARD_DEVIATION 2.9 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 16 | 1 / 16 | 4 / 16 | 3 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
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: Pre-dosing, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hrs post dose (A,B,C) and additional 2.5,2.75,3.5,5,14,18 and 26 hrs post dose(D)
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) |
|---|---|---|
| Eletriptan 20 mg Tablet | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 291.3 ng* hr/mL |
| Eletriptan 40 mg Tablet | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 575.6 ng* hr/mL |
| Eletriptan 80 mg Tablet | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 1282.0 ng* hr/mL |
| Eletriptan 40 mg Tablet 2 Hrs Apart Repeated Dose | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 1278.0 ng* hr/mL |
Comparison: Natural log transformed, dose-normalized AUC\[0- ∞\] of eletriptan 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: [92.17, 105.7]
Comparison: Natural log transformed, dose-normalized AUC\[0- ∞\] of eletriptan 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: [102.23, 117.24]
Comparison: Natural log transformed, dose-normalized AUC\[0- ∞\] of eletriptan 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: [102.65, 117.72]
Primary
AUC 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: Pre-dosing, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hrs post dose (A,B,C) and additional 2.5,2.75,3.5,5,14,18 and 26 hrs post dose (D)
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) |
|---|---|---|
| Eletriptan 20 mg Tablet | AUC From Time Zero to Last Quantifiable Concentration (AUClast) | 281.2 ng*hr/mL |
| Eletriptan 40 mg Tablet | AUC From Time Zero to Last Quantifiable Concentration (AUClast) | 558.7 ng*hr/mL |
| Eletriptan 80 mg Tablet | AUC From Time Zero to Last Quantifiable Concentration (AUClast) | 1243.0 ng*hr/mL |
| Eletriptan 40 mg Tablet 2 Hrs Apart Repeated Dose | AUC From Time Zero to Last Quantifiable Concentration (AUClast) | 1244.0 ng*hr/mL |
Comparison: Natural log transformed, dose-normalized AUClast of eletriptan 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: [92.97, 106.31]
Comparison: Natural log transformed, dose-normalized AUClast of eletriptan 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: [103.36, 118.18]
Comparison: Natural log transformed, dose-normalized AUClast of eletriptan 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: [103.28, 118.09]
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dosing, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hrs post dose (A,B,C) and additional 2.5,2.75,3.5,5,14,18 and 26 hrs post dose (D)
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) |
|---|---|---|
| Eletriptan 20 mg Tablet | Maximum Observed Plasma Concentration (Cmax) | 46.50 ng/mL |
| Eletriptan 40 mg Tablet | Maximum Observed Plasma Concentration (Cmax) | 94.72 ng/mL |
| Eletriptan 80 mg Tablet | Maximum Observed Plasma Concentration (Cmax) | 200.10 ng/mL |
| Eletriptan 40 mg Tablet 2 Hrs Apart Repeated Dose | Maximum Observed Plasma Concentration (Cmax) | 183.60 ng/mL |
Comparison: Natural log transformed, dose-normalized Cmax of eletriptan 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: [85.97, 120.58]
Comparison: Natural log transformed, dose-normalized Cmax of eletriptan 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: [83.23, 116.73]
Comparison: Natural log transformed, dose-normalized Cmax of eletriptan 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: [90.72, 127.25]
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: Pre-dosing, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hrs post dose (A,B,C) and additional 2.5,2.75,3.5,5,14,18 and 26 hrs post dose (D)
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 |
|---|---|---|---|
| Eletriptan 20 mg Tablet | Plasma Decay Half Life (t1/2) | 4.924 Hr | Standard Deviation 0.685 |
| Eletriptan 40 mg Tablet | Plasma Decay Half Life (t1/2) | 4.630 Hr | Standard Deviation 0.447 |
| Eletriptan 80 mg Tablet | Plasma Decay Half Life (t1/2) | 4.576 Hr | Standard Deviation 0.531 |
| Eletriptan 40 mg Tablet 2 Hrs Apart Repeated Dose | Plasma Decay Half Life (t1/2) | 4.753 Hr | Standard Deviation 0.623 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Pre-dosing, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hrs post dose (A,B,C) and additional 2.5,2.75,3.5,5,14,18 and 26 hrs post dose (D)
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) |
|---|---|---|
| Eletriptan 20 mg Tablet | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0.750 Hr |
| Eletriptan 40 mg Tablet | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0.750 Hr |
| Eletriptan 80 mg Tablet | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0.750 Hr |
| Eletriptan 40 mg Tablet 2 Hrs Apart Repeated Dose | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 5.000 Hr |