A Phase 1 interventional study of MK-3866 in Hepatic Insufficiency and Antibacterial Agents, sponsored by Merck Sharp & Dohme LLC. Terminated at 2 sites in United States. Open to participants aged 18 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-11-13.
Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment
This is an open-label, single-dose, Phase 1 study to evaluate the pharmacokinetics (PK) of intravenous (IV) MK-3866 in participants with moderate and severe hepatic impairment (HI) compared to that of matched healthy participants. The primary purpose of this study is to understand the effect of HI on the plasma PK of MK-3866 in order to guide dosing recommendations for participants with HI. This study will also evaluate the safety and tolerability of MK-3866 in participants with moderate and severe HI.
Exclusion Criteria:
Participants with moderate HI (estimated glomerular filtration rate \[eGFR\] of ≤60mL/min/1.73m\^2) receive a single IV dose of MK-3866 (150 mg) on Day 1.
Drug: MK-3866
Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) receive a single IV dose of MK-3866 (150 mg) on Day 1.
Drug: MK-3866
Healthy participants receive a single IV dose of MK-3866 (150 mg) on Day 1.
Drug: MK-3866
Single IV infusion of MK-3866 150 mg administered over 30 minutes at Hour 0 on Day 1 of treatment period.
Area Under the Concentration-time Curve of MK-3866 From Time 0 to Infinity (AUC0-∞)
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.
Time frame: 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
Area Under the Concentration-time Curve of MK-3866 From Time 0 to Last Quantifiable Concentration (AUC0-last)
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.
Time frame: 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
Area Under the Concentration-time Curve of MK-3866 From Time 0 to 24 Hours (AUC0-24hr)
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.
Time frame: Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours postdose
Concentration at the End of Infusion (Ceoi) of MK-3866
The plasma sample collected at end-of-infusion (0.5 hours postdose) was used to determine Ceoi.
Time frame: 0.5 (end of infusion) hours postdose
Time to Maximum Concentration (Tmax) of MK-3866
Tmax is the time at which the maximum plasma drug concentration is detected.
Time frame: 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
Apparent Terminal Half-life (t1/2) of MK-3866
Apparent t1/2 is the elimination half-life of MK-3866 from plasma.
Time frame: 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
Clearance (CL) of MK-3866
CL is the volume of plasma from which the study drug is completely removed per unit time.
Time frame: 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
Volume of Distribution (Vz) of MK-3866
Vz is the apparent volume of distribution during the terminal phase.
Time frame: 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
Fraction of Dose of MK-3866 Excreted Unchanged in Urine (Fe)
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.
Time frame: Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose
Renal Clearance (CLr) of MK-3866
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.
Time frame: Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose
Number of Participants With at Least One Adverse Event (AE)
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.
Time frame: Up to 14 days
Number of Participants Who Discontinued the Study Due to an AE
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.
Time frame: Up to 14 days
The study terminated prior to enrollment of any healthy control participants.
| Milestone | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) |
|---|---|---|
| Started | 5 | 4 |
| Completed | 5 | 4 |
| Not completed | 0 | 0 |
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.
| hour*µM | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) |
|---|---|---|
| Area Under the Concentration-time Curve of MK-3866 From Time 0 to Infinity (AUC0-∞) | 71.4 ± 7.3 | 58.6 ± 41.4 |
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.
| hour*µM | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) |
|---|---|---|
| Area Under the Concentration-time Curve of MK-3866 From Time 0 to Last Quantifiable Concentration (AUC0-last) | 70.7 ± 7.4 | 57.9 ± 42.2 |
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.
| hour*µM | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) |
|---|---|---|
| Area Under the Concentration-time Curve of MK-3866 From Time 0 to 24 Hours (AUC0-24hr) | 67.6 ± 7.5 | 54.6 ± 34.5 |
The plasma sample collected at end-of-infusion (0.5 hours postdose) was used to determine Ceoi.
| µM | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) |
|---|---|---|
| Concentration at the End of Infusion (Ceoi) of MK-3866 | 19.2 ± 22.0 | 11.0 ± 30.4 |
Tmax is the time at which the maximum plasma drug concentration is detected.
| hours | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) |
|---|---|---|
| Time to Maximum Concentration (Tmax) of MK-3866 | 0.47 (0.47 to 0.53) | 0.50 (0.47 to 1.00) |
Apparent t1/2 is the elimination half-life of MK-3866 from plasma.
| hours | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) |
|---|---|---|
| Apparent Terminal Half-life (t1/2) of MK-3866 | 6.54 ± 13.3 | 6.02 ± 4.16 |
CL is the volume of plasma from which the study drug is completely removed per unit time.
| Liters/hour | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) |
|---|---|---|
| Clearance (CL) of MK-3866 | 4.16 ± 7.3 | 5.07 ± 41.3 |
Vz is the apparent volume of distribution during the terminal phase.
| Liters | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) |
|---|---|---|
| Volume of Distribution (Vz) of MK-3866 | 39.3 ± 15.8 | 44.0 ± 27.4 |
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
| Participants | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) |
|---|---|---|
| Number of Participants With at Least One Adverse Event (AE) | 2 | 1 |
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.
| Participants | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) |
|---|---|---|
| Number of Participants Who Discontinued the Study Due to an AE | 0 | 0 |
Collected over Up to 14 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Moderate Hepatic Impairment (Panel A) | 0/5 (0%) | 0/5 (0%) | 2/5 (40%) |
| Severe Hepatic Impairment (Panel B) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) |
| Event | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) |
|---|---|---|
| Skin abrasionInjury, poisoning and procedural complications | 0/5 | 1/4 |
| Abdominal painGastrointestinal disorders | 1/5 | 0/4 |
| DiarrhoeaGastrointestinal disorders | 1/5 | 0/4 |
| DysgeusiaNervous system disorders | 1/5 | 0/4 |
| Age, Continuous(Years) | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) | Total |
|---|---|---|---|
| Mean | 60.0 ± 5.96 | 56.0 ± 8.98 | 58.2 ± 7.24 |
| Sex: Female, Male(Participants) | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) | Total |
|---|---|---|---|
| Female | 1 | 1 | 2 |
| Male | 4 | 3 | 7 |
| Ethnicity (NIH/OMB)(Participants) | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) | Total |
|---|---|---|---|
| Hispanic or Latino | 2 | 2 | 4 |
| Not Hispanic or Latino | 3 | 2 | 5 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Moderate Hepatic Impairment (Panel A) | Severe Hepatic Impairment (Panel B) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 1 |
| White | 4 | 3 | 7 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
This study is terminated, as verified in Oct 2019. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Merck Sharp & Dohme LLC