Chemotherapy-Induced Nausea and Vomiting
Conditions
Brief summary
This study will assess the bioequivalence of single oral doses of aprepitant (MK0869) to a single intravenous infusion of fosaprepitant (MK0517) and also determine the effect of food on the bioavailability of oral aprepitant.
Interventions
Single dose of aprepitant 165 mg tablet in the fasted state during treatment period 1,2, or 3.
DRUGComparator: aprepitant 185 mg
Single dose of aprepitant 185 mg tablet in the fasted state during treatment period 1, 2, or 3.
DRUGComparator: fosaprepitant 150 mg
Single dose of fosaprepitant 150 mg intravenous infusion in the fasted state during treatment period 1,2, or 3.
DRUGComparator: aprepitant with food
Single dose of aprepitant 165 mg or 185 mg tablet in the fed state during treatment period 4.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is in good health * Subject is a nonsmoker * Subject is willing to comply with the study restrictions
Exclusion criteria
* Subject has a history of any illness that might confound the results of the study or might make participation in the study unsafe * Subject has a history of stroke, seizures, or major neurological disorder * Subject has a history of cancer * Subject consumes more than two alcoholic drinks per day * Subject consumes more than three caffeinated beverages daily
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Curve (AUC(0 to Infinity)) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg | Through 72 Hours Postdose |
| Peak Plasma Concentration (Cmax) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg. | Through 72 Hours Postdose |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All randomized patients. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
| Period 4 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 27.8 years |
| Height | 172.9 Centimeters |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 32 Participants |
| Weight | 74.2 Kilograms |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 41 | 13 / 42 | 15 / 41 | 6 / 21 | 3 / 20 |
| serious Total, serious adverse events | 0 / 41 | 1 / 42 | 0 / 41 | 0 / 21 | 0 / 20 |
Outcome results
Primary
Area Under the Curve (AUC(0 to Infinity)) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg
Time frame: Through 72 Hours Postdose
Population: All subjects excluding one subject who dropped from the study after Period 1 due to accidental overdose were included in the pharmacokinetic (PK) analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 165 mg Aprepitant (Fasted State) | Area Under the Curve (AUC(0 to Infinity)) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg | 34589 ng•hr/mL | Standard Deviation 39.7 |
| 185 mg Aprepitant (Fasted State) | Area Under the Curve (AUC(0 to Infinity)) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg | 39053 ng•hr/mL | Standard Deviation 37.5 |
| 150 mg Fosaprepitant Dimeglumine (Fasted State) | Area Under the Curve (AUC(0 to Infinity)) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg | 37375 ng•hr/mL | Standard Deviation 39.5 |
| 165 mg Aprepitant (Light) | Area Under the Curve (AUC(0 to Infinity)) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg | 37795 ng•hr/mL | Standard Deviation 48.4 |
| 165 mg Aprepitant (High-Fat) | Area Under the Curve (AUC(0 to Infinity)) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg | 50172 ng•hr/mL | Standard Deviation 22 |
| 185 mg Aprepitant (Light) | Area Under the Curve (AUC(0 to Infinity)) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg | 51146 ng•hr/mL | Standard Deviation 27.2 |
| 185 mg Aprepitant (High-Fat) | Area Under the Curve (AUC(0 to Infinity)) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg | 60578 ng•hr/mL | Standard Deviation 57.5 |
p-value: 0.00195% CI: [0.84, 1.02]two one-sided tests
p-value: <0.00195% CI: [0.96, 1.15]two one-sided tests
Comparison: The effect of a standard high-fat breakfast and a standard light breakfast on aprepitant plasma pharmacokinetics (AUC0-∞ and Cmax) following a single 165 mg oral dose of aprepitant and following a single 185 mg oral dose of aprepitant will be estimated in healthy young adult subjects90% CI: [1.23, 1.76]
Comparison: The effect of a standard high-fat breakfast and a standard light breakfast on aprepitant plasma pharmacokinetics (AUC0-∞ and Cmax) following a single 165 mg oral dose of aprepitant and following a single 185 mg oral dose of aprepitant will be estimated in healthy young adult subjects90% CI: [0.88, 1.32]
Comparison: The effect of a standard high-fat breakfast and a standard light breakfast on aprepitant plasma pharmacokinetics (AUC0-∞ and Cmax) following a single 165 mg oral dose of aprepitant and following a single 185 mg oral dose of aprepitant will be estimated in healthy young adult subjects90% CI: [1.01, 1.46]
Comparison: The effect of a standard high-fat breakfast and a standard light breakfast on aprepitant plasma pharmacokinetics (AUC0-∞ and Cmax) following a single 165 mg oral dose of aprepitant and following a single 185 mg oral dose of aprepitant will be estimated in healthy young adult subjects90% CI: [1.16, 1.75]
Primary
Peak Plasma Concentration (Cmax) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg.
Time frame: Through 72 Hours Postdose
Population: All subjects excluding one subject who dropped from the study after Period 1 due to accidental overdose were included in the pharmacokinetic (PK) analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 165 mg Aprepitant (Fasted State) | Peak Plasma Concentration (Cmax) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg. | 1738 ng/mL | Standard Error 30.8 |
| 185 mg Aprepitant (Fasted State) | Peak Plasma Concentration (Cmax) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg. | 1636 ng/mL | Standard Error 31.2 |
| 150 mg Fosaprepitant Dimeglumine (Fasted State) | Peak Plasma Concentration (Cmax) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg. | 1870 ng/mL | Standard Error 33.3 |
| 165 mg Aprepitant (Light) | Peak Plasma Concentration (Cmax) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg. | 2362 ng/mL | Standard Error 38.5 |
| 165 mg Aprepitant (High-Fat) | Peak Plasma Concentration (Cmax) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg. | 2116 ng/mL | Standard Error 14.8 |
| 185 mg Aprepitant (Light) | Peak Plasma Concentration (Cmax) Following Single Dose Administration of Aprepitant 165 mg or 185 mg and Fosaprepitant 150 mg. | 1995 ng/mL | Standard Error 35.2 |
Comparison: The effect of a standard high-fat breakfast and a standard light breakfast on aprepitant plasma pharmacokinetics (AUC0-∞ and Cmax) following a single 165 mg oral dose of aprepitant and following a single 185 mg oral dose of aprepitant will be estimated in healthy young adult subjects90% CI: [1.13, 1.56]
Comparison: The effect of a standard high-fat breakfast and a standard light breakfast on aprepitant plasma pharmacokinetics (AUC0-∞ and Cmax) following a single 165 mg oral dose of aprepitant and following a single 185 mg oral dose of aprepitant will be estimated in healthy young adult subjects95% CI: [0.86, 1.25]
Comparison: The effect of a standard high-fat breakfast and a standard light breakfast on aprepitant plasma pharmacokinetics (AUC0-∞ and Cmax) following a single 165 mg oral dose of aprepitant and following a single 185 mg oral dose of aprepitant will be estimated in healthy young adult subjects90% CI: [0.96, 1.34]
Comparison: The effect of a standard high-fat breakfast and a standard light breakfast on aprepitant plasma pharmacokinetics (AUC0-∞ and Cmax) following a single 165 mg oral dose of aprepitant and following a single 185 mg oral dose of aprepitant will be estimated in healthy young adult subjects90% CI: [1.16, 1.68]