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

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03667547
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Actual Duration (Days): 26
• Patients Per Site Per Month: 14

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Human Immunodeficiency Virus (HIV) Infection	Drug: Raltegravir	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Sep 27, 2018
• Actual Primary Completion Date: Oct 23, 2018
• Actual Study Completion Date: Oct 23, 2018

Arms and Interventions

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®

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Corporation Houeikai Sekino Clinical Pharmacology Clinic ( Site 0001)	Tokyo		Japan	171-0014

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 10, 2018

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03667547
• Other Study ID Numbers: 0518-851; MK-0518-851
• First Posted: Sep 12, 2018
• Last Update Posted: Oct 2, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Raltegravir Potassium

Study Results

Participant Flow

Arm/Group Title	Raltegravir
Arm/Group Description	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
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Raltegravir
Arm/Group Description	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
Overall Participants	12
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	28.17 (4.86)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	12 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	12 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	12 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With an Adverse Event (AE)
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of the study drug

Arm/Group Title	Raltegravir
Arm/Group Description	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
Measure Participants	12
Count of Participants [Participants]	0 0%

2. Primary Outcome

Title	Number of Participants Discontinued From the Study Due to an AE
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of the study drug

Arm/Group Title	Raltegravir
Arm/Group Description	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
Measure Participants	12
Count of Participants [Participants]	0 0%

3. Primary Outcome

Title	Number of Participants With a Serious Adverse Event (SAE)
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of the study drug

Arm/Group Title	Raltegravir
Arm/Group Description	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
Measure Participants	12
Count of Participants [Participants]	0 0%

4. Primary Outcome

Title	Number of Participants With a Drug-related AE
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of the study drug

Arm/Group Title	Raltegravir
Arm/Group Description	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
Measure Participants	12
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Area Under the Concentration-Time Curve Up to Infinity (AUC0-∞) of Plasma Raltegravir
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Raltegravir
Arm/Group Description	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
Measure Participants	12
Geometric Mean (95% Confidence Interval) [(μM•hr)]	62.8

6. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of Raltegravir
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Raltegravir
Arm/Group Description	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
Measure Participants	12
Geometric Mean (95% Confidence Interval) [nM]	20163

7. Secondary Outcome

Title	Plasma Concentration of Raltegravir at 24 Hours After Dosing (C24)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Raltegravir
Arm/Group Description	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
Measure Participants	12
Geometric Mean (95% Confidence Interval) [nM]	74.5

8. Secondary Outcome

Title	Time of Maximum Plasma Concentration (Tmax) of Raltegravir
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Raltegravir
Arm/Group Description	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
Measure Participants	12
Median (Full Range) [Hours]	1.75

9. Secondary Outcome

Title	Apparent Plasma Half-life (t1/2) of Raltegravir
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Raltegravir
Arm/Group Description	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
Measure Participants	12
Geometric Mean (Geometric Coefficient of Variation) [Hours]	7.50 (34.6)

10. Secondary Outcome

Title	Apparent Total Plasma Clearance (CL/F) of Raltegravir
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Raltegravir
Arm/Group Description	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
Measure Participants	12
Geometric Mean (Geometric Coefficient of Variation) [L/hr]	39.6 (71.3)

11. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/F) of Raltegravir
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Raltegravir
Arm/Group Description	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
Measure Participants	12
Geometric Mean (Geometric Coefficient of Variation) [Liters]	429 (81.1)

Adverse Events

Time Frame	Up to 14 days after treatment with study drug
Adverse Event Reporting Description	All participants who received at least one dose of the study drug.
Arm/Group Title	Raltegravir
Arm/Group Description	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
All Cause Mortality
	Raltegravir
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Serious Adverse Events
	Raltegravir
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	Raltegravir
	Affected / at Risk (%)	# Events
Total	0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If publication activity is not directed by the Sponsor, investigators agree to provide all manuscripts or abstracts to the Sponsor before submission.