Human Immunodeficiency Virus (HIV) Infection
Conditions
Brief summary
This study is designed to evaluate safety, tolerability, and pharmacokinetics of a single 1200-mg dose of raltegravir (MK-0518, ISENTRESS®) in healthy Japanese male participants.
Interventions
DRUGRaltegravir
Raltegravir 600 mg tablet
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Japanese male in good health * Body mass index (BMI) between 18.5 and 32.0 kg/m\^2 * Nonsmoker and has not used nicotine-containing products for over 3 months at the time of screening test.
Exclusion criteria
* History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or neurological (including cerebrovascular stroke and epilepsy) abnormalities or diseases * Significant emotional problem at the time of screening test or suspected to occur during the conduct of the study, or has a history of clinically significant psychiatric disorder within the last 5 years * History of malignancy * History of clinically significant allergies to multiple antigens or severe allergies (e.g., food, drug, and latex \[natural rubber\] allergies), or has had an anaphylactic reaction or significant intolerability (e.g., systemic allergic reaction) to prescription or non-prescription drugs or food * Positive for hepatitis B virus surface antigen, hepatitis C virus antibodies, syphilis, or HIV antigen or antibody on the screening test * Had surgery or donated or lost blood within 4 weeks prior to the screening test * Participated in another study (clinical trial) within 4 months prior to the screening test * Consumes greater than 3 glasses of alcoholic beverages (definition of 1 glass: 354 mL for beer, 118 mL for wine, 29.5 mL for distilled spirits) per day * Consumes greater than 6 servings (definition of 1 serving: equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day * Regular user of cannabis, any illicit drugs, or has a history of drug or alcohol abuse within 2 years at the time of the screening test. Participants must have a negative predose urine drug screen * Unable to consent to refrain from the consumption of citrus beverages and foods (e.g., grapefruits) beginning 2 weeks prior to administration of the study drug until the end of post-study examination, and the consumption of all fruit beverages and foods for 24 hours predose and after dosing * Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is study site or Sponsor staff directly involved with this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Adverse Event (AE) | Up to Day 14 after dosing | An AE is any untoward medical occurrence in a participant, temporally associated with the use of a study drug, whether or not considered related to the study drug. The number of participants with an AE was reported. |
| Number of Participants Discontinued From the Study Due to an AE | Up to Day 14 after dosing | An AE is any untoward medical occurrence in a participant, temporally associated with the use of a study drug, whether or not considered related to the study drug. The number of participants discontinued from the study due to an AE was reported. |
| Number of Participants With a Serious Adverse Event (SAE) | Up to Day 14 after dosing | A SAE is an AE that results in death, is life-threatening, requires or prolongs an existing hospitalization, results in significant disability or incapacity, is a congenital anomaly or birth defect, is another medically important event, is a new cancer, or is an overdose. The number of participants with an SAE was reported. |
| Number of Participants With a Drug-related AE | Up to Day 14 after dosing | The number of participants with a drug-related AE was reported. Causality was be determined by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Plasma Half-life (t1/2) of Raltegravir | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing | Blood samples were collected from pre-dose up to 48 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. The apparent plasma half-life (t1/2) of raltegravir was reported. |
| Area Under the Concentration-Time Curve Up to Infinity (AUC0-∞) of Plasma Raltegravir | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing | Blood samples were collected from pre-dose up to 48 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. Area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of plasma raltegravir was calculated based on natural log-transformed values. |
| Apparent Volume of Distribution (Vz/F) of Raltegravir | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing | Blood samples were collected from pre-dose up to 48 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. The apparent volume of distribution of raltegravir during the terminal phase (Vz/F) was reported. |
| Apparent Total Plasma Clearance (CL/F) of Raltegravir | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing | Blood samples were collected from pre-dose up to 48 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. The apparent total plasma clearance of raltegravir after oral dosing (CL/F) was reported. |
| Maximum Plasma Concentration (Cmax) of Raltegravir | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing | Blood samples were collected from pre-dose up to 48 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. Maximum plasma concentration (Cmax) of raltegravir was calculated based on natural log-transformed values. |
| Plasma Concentration of Raltegravir at 24 Hours After Dosing (C24) | 24 hours after dosing | Blood samples were collected at 24 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. The plasma concentration of raltegravir at 24 hours after dosing (C24) was calculated based on natural log-transformed values. |
| Time of Maximum Plasma Concentration (Tmax) of Raltegravir | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing | Blood samples were collected from pre-dose up to 48 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. The time at which Cmax of plasma raltegravir is achieved (Tmax) was reported. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Raltegravir Participants received a single oral dose of raltegravir 1200 mg (600 mg tablet X 2) in a fasted state on Day 0 and were followed up to 2 weeks | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Raltegravir |
|---|---|
| Age, Continuous | 28.17 Years STANDARD_DEVIATION 4.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Number of Participants Discontinued From the Study Due to an AE
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a study drug, whether or not considered related to the study drug. The number of participants discontinued from the study due to an AE was reported.
Time frame: Up to Day 14 after dosing
Population: All participants who received at least one dose of the study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Raltegravir | Number of Participants Discontinued From the Study Due to an AE | 0 Participants |
Primary
Number of Participants With a Drug-related AE
The number of participants with a drug-related AE was reported. Causality was be determined by the investigator.
Time frame: Up to Day 14 after dosing
Population: All participants who received at least one dose of the study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Raltegravir | Number of Participants With a Drug-related AE | 0 Participants |
Primary
Number of Participants With an Adverse Event (AE)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a study drug, whether or not considered related to the study drug. The number of participants with an AE was reported.
Time frame: Up to Day 14 after dosing
Population: All participants who received at least one dose of the study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Raltegravir | Number of Participants With an Adverse Event (AE) | 0 Participants |
Primary
Number of Participants With a Serious Adverse Event (SAE)
A SAE is an AE that results in death, is life-threatening, requires or prolongs an existing hospitalization, results in significant disability or incapacity, is a congenital anomaly or birth defect, is another medically important event, is a new cancer, or is an overdose. The number of participants with an SAE was reported.
Time frame: Up to Day 14 after dosing
Population: All participants who received at least one dose of the study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Raltegravir | Number of Participants With a Serious Adverse Event (SAE) | 0 Participants |
Secondary
Apparent Plasma Half-life (t1/2) of Raltegravir
Blood samples were collected from pre-dose up to 48 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. The apparent plasma half-life (t1/2) of raltegravir was reported.
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing
Population: Participants meeting the protocol criteria likely to provide data that sufficiently reflects the effect of treatment under the scientific model. These included measures such as the exposure to study drug, the availability of measurements, and the absence of significant protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Raltegravir | Apparent Plasma Half-life (t1/2) of Raltegravir | 7.50 Hours | Geometric Coefficient of Variation 34.6 |
Secondary
Apparent Total Plasma Clearance (CL/F) of Raltegravir
Blood samples were collected from pre-dose up to 48 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. The apparent total plasma clearance of raltegravir after oral dosing (CL/F) was reported.
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing
Population: Participants meeting the protocol criteria likely to provide data that sufficiently reflects the effect of treatment under the scientific model. These included measures such as the exposure to study drug, the availability of measurements, and the absence of significant protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Raltegravir | Apparent Total Plasma Clearance (CL/F) of Raltegravir | 39.6 L/hr | Geometric Coefficient of Variation 71.3 |
Secondary
Apparent Volume of Distribution (Vz/F) of Raltegravir
Blood samples were collected from pre-dose up to 48 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. The apparent volume of distribution of raltegravir during the terminal phase (Vz/F) was reported.
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing
Population: Participants meeting the protocol criteria likely to provide data that sufficiently reflects the effect of treatment under the scientific model. These included measures such as the exposure to study drug, the availability of measurements, and the absence of significant protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Raltegravir | Apparent Volume of Distribution (Vz/F) of Raltegravir | 429 Liters | Geometric Coefficient of Variation 81.1 |
Secondary
Area Under the Concentration-Time Curve Up to Infinity (AUC0-∞) of Plasma Raltegravir
Blood samples were collected from pre-dose up to 48 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. Area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of plasma raltegravir was calculated based on natural log-transformed values.
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing
Population: Participants meeting the protocol criteria likely to provide data that sufficiently reflects the effect of treatment under the scientific model. These included measures such as the exposure to study drug, the availability of measurements, and the absence of significant protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Raltegravir | Area Under the Concentration-Time Curve Up to Infinity (AUC0-∞) of Plasma Raltegravir | 62.8 (μM•hr) |
Secondary
Maximum Plasma Concentration (Cmax) of Raltegravir
Blood samples were collected from pre-dose up to 48 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. Maximum plasma concentration (Cmax) of raltegravir was calculated based on natural log-transformed values.
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing
Population: Participants meeting the protocol criteria likely to provide data that sufficiently reflects the effect of treatment under the scientific model. These included measures such as the exposure to study drug, the availability of measurements, and the absence of significant protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Raltegravir | Maximum Plasma Concentration (Cmax) of Raltegravir | 20163 nM |
Secondary
Plasma Concentration of Raltegravir at 24 Hours After Dosing (C24)
Blood samples were collected at 24 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. The plasma concentration of raltegravir at 24 hours after dosing (C24) was calculated based on natural log-transformed values.
Time frame: 24 hours after dosing
Population: Participants meeting the protocol criteria likely to provide data that sufficiently reflects the effect of treatment under the scientific model. These included measures such as the exposure to study drug, the availability of measurements, and the absence of significant protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Raltegravir | Plasma Concentration of Raltegravir at 24 Hours After Dosing (C24) | 74.5 nM |
Secondary
Time of Maximum Plasma Concentration (Tmax) of Raltegravir
Blood samples were collected from pre-dose up to 48 hours post-dose in order to measure the concentration of plasma raltegravir. Values below the lower limit of quantitation were replaced with 0. The time at which Cmax of plasma raltegravir is achieved (Tmax) was reported.
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing
Population: Participants meeting the protocol criteria likely to provide data that sufficiently reflects the effect of treatment under the scientific model. These included measures such as the exposure to study drug, the availability of measurements, and the absence of significant protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Raltegravir | Time of Maximum Plasma Concentration (Tmax) of Raltegravir | 1.75 Hours |