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Trial Outcomes & Findings for Single-Dose Pharmacokinetics of MK-3866 in Participants With Hepatic Impairment (MK-3866-006) (NCT NCT03295266)

NCT ID: NCT03295266

Last Updated: 2019-11-13

Results Overview

AUC0-∞ is determined for the period up to 72 hours post-single dose. AUC0-∞ is an estimate of total plasma exposure from dosing to (extrapolated) infinity.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

9 participants

Primary outcome timeframe

Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

Results posted on

2019-11-13

Participant Flow

The study terminated prior to enrollment of any healthy control participants.

Participants with moderate or severe hepatic impairment (HI) based on estimated glomerular filtration rate (eGFR) were enrolled at 2 study centers in the US.

Participant milestones

Participant milestones
Measure
Moderate Hepatic Impairment (Panel A)
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Overall Study
STARTED
5
4
Overall Study
COMPLETED
5
4
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Single-Dose Pharmacokinetics of MK-3866 in Participants With Hepatic Impairment (MK-3866-006)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Moderate Hepatic Impairment (Panel A)
n=5 Participants
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
n=4 Participants
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Total
n=9 Participants
Total of all reporting groups
Age, Continuous
60.0 Years
STANDARD_DEVIATION 5.96 • n=5 Participants
56.0 Years
STANDARD_DEVIATION 8.98 • n=7 Participants
58.2 Years
STANDARD_DEVIATION 7.24 • n=5 Participants
Sex: Female, Male
Female
1 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
Sex: Female, Male
Male
4 Participants
n=5 Participants
3 Participants
n=7 Participants
7 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
3 Participants
n=5 Participants
2 Participants
n=7 Participants
5 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
White
4 Participants
n=5 Participants
3 Participants
n=7 Participants
7 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

Population: All treated participants with data available are included.

AUC0-∞ is determined for the period up to 72 hours post-single dose. AUC0-∞ is an estimate of total plasma exposure from dosing to (extrapolated) infinity.

Outcome measures

Outcome measures
Measure
Moderate Hepatic Impairment (Panel A)
n=5 Participants
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
n=4 Participants
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Area Under the Concentration-time Curve of MK-3866 From Time 0 to Infinity (AUC0-∞)
71.4 hour*µM
Geometric Coefficient of Variation 7.3
58.6 hour*µM
Geometric Coefficient of Variation 41.4

PRIMARY outcome

Timeframe: Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

Population: All treated participants with data available are included.

AUC0-last is determined for the period up to 72 hours post-single dose. AUC0-last is an estimate of total plasma exposure from dosing to the time of last measurable sample.

Outcome measures

Outcome measures
Measure
Moderate Hepatic Impairment (Panel A)
n=5 Participants
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
n=4 Participants
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Area Under the Concentration-time Curve of MK-3866 From Time 0 to Last Quantifiable Concentration (AUC0-last)
70.7 hour*µM
Geometric Coefficient of Variation 7.4
57.9 hour*µM
Geometric Coefficient of Variation 42.2

PRIMARY outcome

Timeframe: Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours postdose

Population: All treated participants with data available are included.

AUC0-24 is determined for the period up to 24 hours post-single dose. AUC0-24 is an estimate of total daily plasma exposure from dosing to 24 hours postdose.

Outcome measures

Outcome measures
Measure
Moderate Hepatic Impairment (Panel A)
n=5 Participants
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
n=3 Participants
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Area Under the Concentration-time Curve of MK-3866 From Time 0 to 24 Hours (AUC0-24hr)
67.6 hour*µM
Geometric Coefficient of Variation 7.5
54.6 hour*µM
Geometric Coefficient of Variation 34.5

PRIMARY outcome

Timeframe: 0.5 (end of infusion) hours postdose

Population: All treated participants with data available are included.

The plasma sample collected at end-of-infusion (0.5 hours postdose) was used to determine Ceoi.

Outcome measures

Outcome measures
Measure
Moderate Hepatic Impairment (Panel A)
n=5 Participants
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
n=4 Participants
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Concentration at the End of Infusion (Ceoi) of MK-3866
19.2 µM
Geometric Coefficient of Variation 22.0
11.0 µM
Geometric Coefficient of Variation 30.4

PRIMARY outcome

Timeframe: Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

Population: All treated participants with data available are included.

Tmax is the time at which the maximum plasma drug concentration is detected.

Outcome measures

Outcome measures
Measure
Moderate Hepatic Impairment (Panel A)
n=5 Participants
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
n=4 Participants
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Time to Maximum Concentration (Tmax) of MK-3866
0.47 hours
Interval 0.47 to 0.53
0.50 hours
Interval 0.47 to 1.0

PRIMARY outcome

Timeframe: Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

Population: All treated participants with data available are included.

Apparent t1/2 is the elimination half-life of MK-3866 from plasma.

Outcome measures

Outcome measures
Measure
Moderate Hepatic Impairment (Panel A)
n=5 Participants
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
n=4 Participants
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Apparent Terminal Half-life (t1/2) of MK-3866
6.54 hours
Geometric Coefficient of Variation 13.3
6.02 hours
Geometric Coefficient of Variation 4.16

PRIMARY outcome

Timeframe: Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

Population: All treated participants with data available are included.

CL is the volume of plasma from which the study drug is completely removed per unit time.

Outcome measures

Outcome measures
Measure
Moderate Hepatic Impairment (Panel A)
n=5 Participants
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
n=4 Participants
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Clearance (CL) of MK-3866
4.16 Liters/hour
Geometric Coefficient of Variation 7.3
5.07 Liters/hour
Geometric Coefficient of Variation 41.3

PRIMARY outcome

Timeframe: Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

Population: All treated participants with data available are included.

Vz is the apparent volume of distribution during the terminal phase.

Outcome measures

Outcome measures
Measure
Moderate Hepatic Impairment (Panel A)
n=5 Participants
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
n=4 Participants
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Volume of Distribution (Vz) of MK-3866
39.3 Liters
Geometric Coefficient of Variation 15.8
44.0 Liters
Geometric Coefficient of Variation 27.4

SECONDARY outcome

Timeframe: Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose

Population: Urine samples were collected but were not analyzed.

Fe is the amount of drug excreted unchanged in urine. Urine samples were collected in 4-hour intervals up to 24 hours post-dose. The study terminated prior to analysis of urine samples and therefore no data are available.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose

Population: Urine samples were collected but were not analyzed.

CLr is the volume of plasma from which the study drug is completely removed per unit time by the kidney (i.e., excreted into the urine). Urine samples are collected in 4-hour intervals up to 24 hours post-dose. The study terminated prior to analysis of urine samples and therefore no data are available.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 14 days

Population: All treated participants are included.

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure
Moderate Hepatic Impairment (Panel A)
n=5 Participants
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
n=4 Participants
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Number of Participants With at Least One Adverse Event (AE)
2 Participants
1 Participants

SECONDARY outcome

Timeframe: Up to 14 days

Population: All treated participants are included.

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure
Moderate Hepatic Impairment (Panel A)
n=5 Participants
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
n=4 Participants
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Number of Participants Who Discontinued the Study Due to an AE
0 Participants
0 Participants

Adverse Events

Moderate Hepatic Impairment (Panel A)

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Severe Hepatic Impairment (Panel B)

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Moderate Hepatic Impairment (Panel A)
n=5 participants at risk
Participants with moderate HI (eGFR of ≤60mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Severe Hepatic Impairment (Panel B)
n=4 participants at risk
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) received a single IV dose of MK-3866 (150 mg infused over 30 minutes) on Day 1.
Gastrointestinal disorders
Abdominal pain
20.0%
1/5 • Number of events 1 • Up to 14 days
All treated participants are included.
0.00%
0/4 • Up to 14 days
All treated participants are included.
Gastrointestinal disorders
Diarrhoea
20.0%
1/5 • Number of events 1 • Up to 14 days
All treated participants are included.
0.00%
0/4 • Up to 14 days
All treated participants are included.
Injury, poisoning and procedural complications
Skin abrasion
0.00%
0/5 • Up to 14 days
All treated participants are included.
25.0%
1/4 • Number of events 1 • Up to 14 days
All treated participants are included.
Nervous system disorders
Dysgeusia
20.0%
1/5 • Number of events 1 • Up to 14 days
All treated participants are included.
0.00%
0/4 • Up to 14 days
All treated participants are included.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Results disclosure agreements

  • Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation.
  • Publication restrictions are in place

Restriction type: OTHER