Trial Outcomes & Findings for Safety, Tolerability, and Pharmacokinetics of Raltegravir (MK-0518) in Healthy Japanese Male Participants (MK-0518-851) (NCT NCT03667547)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

12 participants

Primary outcome timeframe

Up to Day 14 after dosing

Results posted on

2019-10-02

Participant Flow

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Raltegravir n=12 Participants 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
Age, Continuous	28.17 Years STANDARD_DEVIATION 4.86 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	12 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 14 after dosing

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

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.

Outcome measures

Outcome measures
Measure	Raltegravir n=12 Participants 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
Number of Participants With an Adverse Event (AE)	0 Participants

PRIMARY outcome

Timeframe: Up to Day 14 after dosing

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

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.

Outcome measures

Outcome measures
Measure	Raltegravir n=12 Participants 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
Number of Participants Discontinued From the Study Due to an AE	0 Participants

PRIMARY outcome

Timeframe: Up to Day 14 after dosing

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

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.

Outcome measures

Outcome measures
Measure	Raltegravir n=12 Participants 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
Number of Participants With a Serious Adverse Event (SAE)	0 Participants

PRIMARY outcome

Timeframe: Up to Day 14 after dosing

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

The number of participants with a drug-related AE was reported. Causality was be determined by the investigator.

Outcome measures

Outcome measures
Measure	Raltegravir n=12 Participants 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
Number of Participants With a Drug-related AE	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Raltegravir n=12 Participants 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
Area Under the Concentration-Time Curve Up to Infinity (AUC0-∞) of Plasma Raltegravir	62.8 (μM•hr) Interval 41.8 to 94.4

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Raltegravir n=12 Participants 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
Maximum Plasma Concentration (Cmax) of Raltegravir	20163 nM Interval 12211.0 to 33291.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Raltegravir n=12 Participants 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
Plasma Concentration of Raltegravir at 24 Hours After Dosing (C24)	74.5 nM Interval 53.9 to 103.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Raltegravir n=12 Participants 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
Time of Maximum Plasma Concentration (Tmax) of Raltegravir	1.75 Hours Interval 0.5 to 4.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Raltegravir n=12 Participants 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
Apparent Plasma Half-life (t1/2) of Raltegravir	7.50 Hours Geometric Coefficient of Variation 34.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Raltegravir n=12 Participants 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
Apparent Total Plasma Clearance (CL/F) of Raltegravir	39.6 L/hr Geometric Coefficient of Variation 71.3

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Raltegravir n=12 Participants 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
Apparent Volume of Distribution (Vz/F) of Raltegravir	429 Liters Geometric Coefficient of Variation 81.1

Adverse Events

Raltegravir

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, investigators agree to provide all manuscripts or abstracts to the Sponsor before submission.
Publication restrictions are in place

Restriction type: OTHER