Hepatic InsufficiencyPhase 1NCT03295266
Single-Dose Pharmacokinetics of MK-3866 in Participants With Hepatic Impairment (MK-3866-006)
A Phase 1 study testing MK-3866 in people with Hepatic Insufficiency and Antibacterial Agents, run by Merck Sharp & Dohme LLC at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Insufficiency, Antibacterial Agents
- What is being tested?
- MK-3866
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesUnited States
- Study dates
- 19 Dec 2017to 15 Mar 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body mass index ≥19 \& ≤40 kg/m^2
- Continuous non-smoker prior to screening \& enrollment
- HI Participants: Baseline health judged to be stable based on medical history (except for the HI condition), physical examination, vital signs, electrocardiograms, \& laboratory safety tests
- Healthy control participants: Is medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms
- HI Participants: Diagnosis of chronic (>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) HI with features of cirrhosis
- HI Participants - Panel A (moderate HI) only: score on the Child-Pugh scale from 7 to 9 (moderate HI). At least 3 participants must have a score of 2 or higher on at least one of the laboratory parameters (i.e., albumin, international normalized ratio, and/or bilirubin) on the Child-Pugh scale
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- HI Participants - Panel B (severe HI) only: Score on the Child-Pugh scale from 10 to 15 (severe HI)
- Is completely informed of the unknown risks of pregnancy \& agrees not to become pregnant or father a child during time in study
- For a female of childbearing potential: is either sexually inactive (abstinent) for 14 days prior to dosing \& throughout the study or is using an acceptable birth control method
- Non-vasectomized male: Participants must agree to use a condom with spermicide or abstain from sexual intercourse from dosing until 90 days after dosing
Who cannot join
- Mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study
- Has a history or presence of clinically significant medical or psychiatric condition or disease (other than HI - Panels A \& B) that might confound the results of the study or poses an additional risk to the participant. Remote history of cholecystectomy that is not an active issue may be included.
- Panels A \& B: Has a clinically significant history of cancer. Remote history with full cure or limited disease with complete resection (cure) may be included
- Has a history of drug/alcohol abuse within the past 6 months prior to dosing (Panels A \& B) or within the past 2 years prior to dosing (Panel C [Healthy controls])
- Panels A \& B: Consumes more than 3 glasses of alcoholic beverages (1 glass approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day, within 6 months of screening. Participants that consume 4 glasses of alcoholic beverages/day may be enrolled
- Panels A \& B: Consumes excessive amounts, defined as more than 6 servings (1 serving approximately equivalent to 120 mg of caffeine), of coffee, tea, cola, energy-drinks, or other caffeinated beverages/day
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- Panels A \& B: Has a history of a liver transplant
- Has a history or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds
- Has moderate or severe renal insufficiency (estimated glomerular filtration rate of ≤60 mL/min/1.73 m2 for moderate HI or healthy control participants or ≤50 mL/min/1.73 m2 for severe HI participants)
- Panel C: Has positive macroscopic urine protein at screening (trace protein by dipstick allowed)
- Is a female participant who is pregnant or lactating
- Has positive results for the urine or breath alcohol screen and/or urine drug screen at screening
- Has positive results at screening for human immunodeficiency virus (HIV) (Panels A \& B) or for HIV, HBsAg, or hepatitis C virus (HCV) (Panel C)
- Panels A \& B: Participants with active HCV infection or hepatitis B virus (HBV) infection. Participants with prior/inactive HCV infection or past HBV infection may be enrolled.
- Is unable to refrain from or anticipates use of any medication or substance prohibited in study
- Has taken amiodarone at any time in their life
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Clinical Pharmacology of Miami ( Site 0001)
Hialeah, Florida, 33014
Orlando Clinical Research Center ( Site 0002)
Orlando, Florida, 32809
About this study
Official title: An Open-Label Study to Investigate the Single-Dose Pharmacokinetics of MK-3866 When Administered to Subjects With Moderate and Severe Hepatic Impairment
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.
- Conditions
- Hepatic Insufficiency, Antibacterial Agents
- Being tested
- MK-3866
- Medical subject headings
- Hepatic Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-3866Drug
Single IV infusion of MK-3866 150 mg administered over 30 minutes at Hour 0 on Day 1 of treatment period.
| Study group | Role | What they receive |
|---|---|---|
| Moderate Hepatic Impairment (Panel A) | Experimental | 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. Receives: Drug: MK-3866 |
| Severe Hepatic Impairment (Panel B) | Experimental | 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. Receives: Drug: MK-3866 |
| Healthy Matched Controls (Panel C) | Experimental | Healthy participants receive a single IV dose of MK-3866 (150 mg) on Day 1. Receives: Drug: MK-3866 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2017
- Study start19 Dec 2017
- Primary completion15 Mar 2018
- Study completion15 Mar 2018
Why it stopped: Business and program changes
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatic InsufficiencyStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03295266
- Sponsor's protocol ID
- 3866-006
- Other IDs
- MK-3866-006
- Status last verified
- Oct 2019
- First submitted
- 25 Sep 2017
- Last updated
- 13 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Investigate the Single-Dose Pharmacokinetics of MK-3866 When Administered to Subjects With Moderate and Severe Hepatic Impairment
- ClinicalTrials.gov ID
- NCT03295266
- Acronym / sponsor ID
- 3866-006
- Conditions
- Hepatic Insufficiency, Antibacterial Agents
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business and program changes
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 19 Dec 2017 (actual)
- Primary completion
- 15 Mar 2018 (actual)
- Study completion
- 15 Mar 2018 (actual)
- First posted
- 27 Sep 2017 (actual)
- Results
- Posted 13 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Moderate Hepatic Impairment (Panel A) | Experimental | Drug: MK-3866Participants 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. |
| Severe Hepatic Impairment (Panel B) | Experimental | Drug: MK-3866Participants with severe HI (eGFR of ≤50 mL/min/1.73m^2) receive a single IV dose of MK-3866 (150 mg) on Day 1. |
| Healthy Matched Controls (Panel C) | Experimental | Drug: MK-3866Healthy participants receive a single IV dose of MK-3866 (150 mg) on Day 1. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Body mass index ≥19 \& ≤40 kg/m^2
- Continuous non-smoker prior to screening \& enrollment
- HI Participants: Baseline health judged to be stable based on medical history (except for the HI condition), physical examination, vital signs, electrocardiograms, \& laboratory safety tests
- Healthy control participants: Is medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms
- HI Participants: Diagnosis of chronic (>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) HI with features of cirrhosis
Key exclusion criteria (16 listed)
- Mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study
- Has a history or presence of clinically significant medical or psychiatric condition or disease (other than HI - Panels A \& B) that might confound the results of the study or poses an additional risk to the participant. Remote history of cholecystectomy that is not an active issue may be included.
- Panels A \& B: Has a clinically significant history of cancer. Remote history with full cure or limited disease with complete resection (cure) may be included
- Has a history of drug/alcohol abuse within the past 6 months prior to dosing (Panels A \& B) or within the past 2 years prior to dosing (Panel C [Healthy controls])
- Panels A \& B: Consumes more than 3 glasses of alcoholic beverages (1 glass approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day, within 6 months of screening. Participants that consume 4 glasses of alcoholic beverages/day may be enrolled
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-3866Single IV infusion of MK-3866 150 mg administered over 30 minutes at Hour 0 on Day 1 of treatment period. | Drug | Healthy Matched Controls (Panel C), Moderate Hepatic Impairment (Panel A), Severe Hepatic Impairment (Panel B) |
Primary outcome
Area Under the Concentration-time Curve of MK-3866 From Time 0 to Infinity (AUC0-∞)
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
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.
Area Under the Concentration-time Curve of MK-3866 From Time 0 to Last Quantifiable Concentration (AUC0-last)
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
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.
Area Under the Concentration-time Curve of MK-3866 From Time 0 to 24 Hours (AUC0-24hr)
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
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.
Concentration at the End of Infusion (Ceoi) of MK-3866
Time frame: 0.5 (end of infusion) hours postdose
The plasma sample collected at end-of-infusion (0.5 hours postdose) was used to determine Ceoi.
Time to Maximum Concentration (Tmax) of MK-3866
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
Tmax is the time at which the maximum plasma drug concentration is detected.
Apparent Terminal Half-life (t1/2) of MK-3866
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 t1/2 is the elimination half-life of MK-3866 from plasma.
Clearance (CL) of MK-3866
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
CL is the volume of plasma from which the study drug is completely removed per unit time.
Volume of Distribution (Vz) of MK-3866
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
Vz is the apparent volume of distribution during the terminal phase.
4 secondary outcomes
Fraction of Dose of MK-3866 Excreted Unchanged in Urine (Fe)
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
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)
Time frame: Up to 14 days
Number of Participants Who Discontinued the Study Due to an AE
Time frame: Up to 14 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-3866 in people with Hepatic Insufficiency and Antibacterial Agents, run by Merck Sharp & Dohme LLC at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Concentration-time Curve of MK-3866 From Time 0 to Infinity (AUC0-∞) (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). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2019; AzTrials last refreshed its copy on 8 Nov 2026.