Safety, Tolerability, and Pharmacokinetics of Raltegravir (MK-0518) in Healthy Japanese Male Participants (MK-0518-851)

• Raltegravir (Drug), also known as MK-0518, ISENTRESS®: Raltegravir 600 mg tablet

Primary outcomes

• 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 outcomes

• 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.
• 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.
• 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.
• 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.
• 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.

Sex: Male, ages: 20 Years to 45 Years, accepts healthy volunteers

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.

Participant flow

Outcome results

• Number of Participants With an Adverse Event (AE) (Primary), Count of participants, Participants: Raltegravir 0
• Number of Participants Discontinued From the Study Due to an AE (Primary), Count of participants, Participants: Raltegravir 0
• Number of Participants With a Serious Adverse Event (SAE) (Primary), Count of participants, Participants: Raltegravir 0
• Number of Participants With a Drug-related AE (Primary), Count of participants, Participants: Raltegravir 0
• Area Under the Concentration-Time Curve Up to Infinity (AUC0-∞) of Plasma Raltegravir (Secondary), Geometric mean, (μM•hr): Raltegravir 62.8 (41.8 to 94.4)
• Maximum Plasma Concentration (Cmax) of Raltegravir (Secondary), Geometric mean, nM: Raltegravir 20163 (12211 to 33291)
• Plasma Concentration of Raltegravir at 24 Hours After Dosing (C24) (Secondary), Geometric mean, nM: Raltegravir 74.5 (53.9 to 103)
• Time of Maximum Plasma Concentration (Tmax) of Raltegravir (Secondary), Median, Hours: Raltegravir 1.75 (0.5 to 4.0)
• Apparent Plasma Half-life (t1/2) of Raltegravir (Secondary), Geometric mean, Hours: Raltegravir 7.50 +/- 34.6
• Apparent Total Plasma Clearance (CL/F) of Raltegravir (Secondary), Geometric mean, L/hr: Raltegravir 39.6 +/- 71.3
• Apparent Volume of Distribution (Vz/F) of Raltegravir (Secondary), Geometric mean, Liters: Raltegravir 429 +/- 81.1

Adverse events

Time frame: Up to 14 days after treatment with study drug

• Study Protocol and Statistical Analysis Plan (PDF, 2018-07-10)

• Medical Director, Study director, Merck Sharp & Dohme LLC