NCT03295266

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

Terminated Phase 1 Results posted Last updated 13 November 2019

What this trial tests

Phase 1 trial testing MK-3866 in Hepatic Insufficiency in 9 participants. Terminated before completion.

Timeline

19 December 2017

Primary endpoint
15 March 2018

15 March 2018

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	9
Start date	19 December 2017
Primary completion	15 March 2018
Estimated completion	15 March 2018
Sites	2 locations across United States

Drugs / interventions tested

• MK-3866 — full drug profile →

Conditions studied

• Hepatic Insufficiency — all drugs for Hepatic Insufficiency →
• Antibacterial Agents — all drugs for Antibacterial Agents →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 75, any sex, with Hepatic Insufficiency or Antibacterial Agents. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Area Under the Concentration-time Curve of MK-3866 From Time 0 to Infinity (AUC0-∞) Primary · 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

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.

Group	Value	95% CI
Moderate Hepatic Impairment (Panel A)	71.4	± 7.3
Severe Hepatic Impairment (Panel B)	58.6	± 41.4

Area Under the Concentration-time Curve of MK-3866 From Time 0 to Last Quantifiable Concentration (AUC0-last) Primary · 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

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.

Group	Value	95% CI
Moderate Hepatic Impairment (Panel A)	70.7	± 7.4
Severe Hepatic Impairment (Panel B)	57.9	± 42.2

Area Under the Concentration-time Curve of MK-3866 From Time 0 to 24 Hours (AUC0-24hr) Primary · Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours postdose

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.

Group	Value	95% CI
Moderate Hepatic Impairment (Panel A)	67.6	± 7.5
Severe Hepatic Impairment (Panel B)	54.6	± 34.5

Concentration at the End of Infusion (Ceoi) of MK-3866 Primary · 0.5 (end of infusion) hours postdose

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

Group	Value	95% CI
Moderate Hepatic Impairment (Panel A)	19.2	± 22.0
Severe Hepatic Impairment (Panel B)	11.0	± 30.4

Time to Maximum Concentration (Tmax) of MK-3866 Primary · 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

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

Group	Value	95% CI
Moderate Hepatic Impairment (Panel A)	0.47	0.47 – 0.53
Severe Hepatic Impairment (Panel B)	0.50	0.47 – 1.00

Apparent Terminal Half-life (t1/2) of MK-3866 Primary · 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 t1/2 is the elimination half-life of MK-3866 from plasma.

Group	Value	95% CI
Moderate Hepatic Impairment (Panel A)	6.54	± 13.3
Severe Hepatic Impairment (Panel B)	6.02	± 4.16

Clearance (CL) of MK-3866 Primary · 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

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

Group	Value	95% CI
Moderate Hepatic Impairment (Panel A)	4.16	± 7.3
Severe Hepatic Impairment (Panel B)	5.07	± 41.3

Volume of Distribution (Vz) of MK-3866 Primary · 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

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

Group	Value	95% CI
Moderate Hepatic Impairment (Panel A)	39.3	± 15.8
Severe Hepatic Impairment (Panel B)	44.0	± 27.4

Number of Participants With at Least One Adverse Event (AE) Secondary · Up to 14 days

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.

Group	Value	95% CI
Moderate Hepatic Impairment (Panel A)	2
Severe Hepatic Impairment (Panel B)	1

Number of Participants Who Discontinued the Study Due to an AE Secondary · Up to 14 days

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.

Group	Value	95% CI
Moderate Hepatic Impairment (Panel A)	0
Severe Hepatic Impairment (Panel B)	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 14 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Moderate Hepatic Impairment (Panel A)

Serious: 0/5 (0%)

Deaths: 0/5

Severe Hepatic Impairment (Panel B)

Serious: 0/4 (0%)

Deaths: 0/4

Other adverse events (4 terms — click to expand)

Reaction	System	Moderate Hepatic Impairmen…	Severe Hepatic Impairment …
Abdominal pain	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Skin abrasion	Injury, poisoning and procedural complications	—	—
Dysgeusia	Nervous system disorders	—	—

Data from ClinicalTrials.gov NCT03295266 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Antibiotics in the clinical pipeline in October 2019.
   Butler MS, Paterson DL. · · 2020 · cited 174× · PMID 32152527 · DOI 10.1038/s41429-020-0291-8