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

An Open-label Single Oral Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-0518 1200 mg (600 mg Tablet × 2) in Healthy Japanese Male Participants

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.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus (HIV) Infection
• Intervention / Treatment: Drug: Raltegravir

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 171-0014
    • Medical Corporation Houeikai Sekino Clinical Pharmacology Clinic ( Site 0001)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Raltegravir; Participants will receive a single oral dose of raltegravir 1200 mg (600 mg tablet X 2) in a fasted state on Day 0 and will be followed up to 2 weeks	Drug: Raltegravir; Raltegravir 600 mg tablet; Other Names: MK-0518; ISENTRESS®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to Day 14 after dosing
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.	Up to Day 14 after dosing
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.	Up to Day 14 after dosing
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.	Up to Day 14 after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing
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.	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing
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.	24 hours after dosing
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.	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing
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.	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing
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.	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing
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.	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 48 hours after dosing

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2018
• Primary Completion (Actual): October 23, 2018
• Study Completion (Actual): October 23, 2018

Study Registration Dates

• First Submitted: September 10, 2018
• First Submitted That Met QC Criteria: September 10, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Actual): October 2, 2019
• Last Update Submitted That Met QC Criteria: September 9, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium
• Other Study ID Numbers: 0518-851; MK-0518-851 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No