Amnestic Mild Cognitive ImpairmentPhase 1NCT02910739

An Open-Label Study Investigating MK-8931 in Participants With Mild and Moderate Hepatic Insufficiency (MK-8931-016)

A Phase 1 study testing MK-8931 in people with Amnestic Mild Cognitive Impairment and Alzheimer's Disease, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 45 to 85 yearsHealthy volunteers can take part
Conditions the study is for: Amnestic Mild Cognitive Impairment, Alzheimer's Disease, Prodromal Alzheimer's Disease
What is being tested?: MK-8931
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: No sites listed yet
Study dates: 11 Oct 2016to 12 Apr 2017
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 45 to 85 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Adult male or female participants, 45-85 years of age, inclusive, at screening.
Body Mass Index (BMI) ≥ 19 and ≤ 40 kg/m^2, at screening.
Continuous non-smokers or light smokers (< 10 cigarettes/day or the equivalent).
Baseline health is judged to be stable based on medical history (except for the hepatic insufficiency condition).
Participant has a 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 due to any etiology.
Part 1 only: Participant's score on the Child-Pugh scale must range from 7 to 9 (moderate HI) at screening.

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Part 2 only: Participant's score on the Child-Pugh scale must range from 5 to 6 (mild HI) at screening.
Participants must be completely informed of the unknown risks of pregnancy and agree not to become pregnant or father a child during the time they are participating in this study.
For a female of childbearing potential: either be sexually inactive (abstinent) for 14 days prior to dosing and throughout the study or be using an acceptable birth control method.
Females of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
hysteroscopic sterilization;
bilateral tubal ligation or bilateral salpingectomy;
hysterectomy;
bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to dosing and have follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status as per Investigator or designee's judgment.
Non-vasectomized male participants must agree to use a condom with spermicide or abstain from sexual intercourse from dosing until 90 days after dosing.
Male participants must agree not to donate sperm from dosing until 90 days after dosing.
Understands the study procedures in informed consent forms (ICFs), be willing and able to comply with the protocol, and provides written informed consent for the trial, including for Future Biomedical Research. Future Biomedical Research participation is voluntary and is not required in order to participate in the trial.
Healthy adult male or female participants, 45-85 years of age, inclusive, at screening.
BMI ≥ 19 and ≤ 40 kg/m^2 at screening.
Continuous non-smokers or light smokers (< 10 cigarettes/day or the equivalent).
Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the Investigator.
Participants must be completely informed of the unknown risks of pregnancy and agree not to become pregnant or father a child during the time they are participating in this study.
For a female of childbearing potential: either be sexually inactive (abstinent) for 14 days prior to dosing and throughout the study or be using an acceptable birth control method.
Females of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
hysteroscopic sterilization;
bilateral tubal ligation or bilateral salpingectomy;
hysterectomy;
bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to dosing and have FSH serum levels consistent with postmenopausal status as per Investigator or designee's judgment.
Non-vasectomized male participants must agree to use a condom with spermicide or abstain from sexual intercourse from dosing until 90 days after dosing.
Male participants must agree not to donate sperm from dosing until 90 days after dosing.
Understands the study procedures in ICFs, be willing and able to comply with the protocol, and provides written informed consent for the trial, including for Future Biomedical Research. Future Biomedical Research participation is voluntary and is not required in order to participate in the trial.

Who cannot join

Participant is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator.
History of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
History or presence of alcoholism or drug abuse within the past 2 years prior to dosing.
History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds.
Female participants who are pregnant or lactating.

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Positive results for the urine drug and/or alcohol screen at screening or check-in, unless the positive drug screen is due to prescription drug use and is approved by the Investigator and the Sponsor Medical Monitor.
Positive results at screening for human immunodeficiency virus (HIV) or hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV; i.e., HCV antibody positive, HCV ribonucleic acid (RNA) positive) with decompensated liver disease.
Seated blood pressure is less than 90/40 mmHg or greater than 180/105 mmHg at screening.
Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.
Fridericia's correction of the QT interval (QTcF) is > 480 msec or has ECG findings deemed abnormal with clinical significance by the Investigator or designee at screening.
Abnormal hemoglobin level deemed clinically significant by the Investigator at screening.
Unable to refrain from or anticipates the use of any medication or substance (including prescription or over-the-counter, vitamin supplements, natural or herbal supplements).
Has been on a diet incompatible with the Clinical Research Unit (CRU) -provided standard meals/snacks, in the opinion of the Investigator, within the 28 days prior to dosing of study drug, and throughout the study.
Donation of blood or had significant blood loss within 56 days prior to dosing of study drug.
Plasma donation within 28 days prior to dosing of study drug.
Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or Sponsor staff directly involved with this study.
Participation in another clinical trial within 28 days prior to dosing.
Participant who dosed in one part (e.g., Part 1) will not be enrolled in the other part (e.g., Part 2).
Participant is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator.
History of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
History or presence of alcoholism or drug abuse within the past 2 years prior to dosing.
History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds.
Female participants who are pregnant or lactating.
Positive results for the urine drug and/or urine or breath alcohol screen at screening or check-in.
Positive results at screening for HIV or HBsAg or HCV with decompensated liver disease.
Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.
QTcF is > 480 msec or has ECG findings deemed abnormal with clinical significance by the Investigator or designee at screening.
Abnormal hemoglobin level deemed clinically significant by the Investigator at screening.
Unable to refrain from or anticipates the use of any medication or substance (including prescription or over-the-counter, vitamin supplements, natural or herbal supplements).
Has been on a diet incompatible with the CRU-provided standard meals/snacks, in the opinion of the Investigator, within the 28 days prior to dosing of study drug, and throughout the study.
Donation of blood or had significant blood loss within 56 days prior to dosing of study drug.
Plasma donation within 28 days prior to dosing of study drug.
Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or Sponsor staff directly involved with this study.
Participation in another clinical trial within 28 days prior to dosing.

About this study

Official title: A Two-Part, Open-Label Study to Investigate the Single-Dose Pharmacokinetics of MK-8931 When Administered to Subjects With Mild and Moderate Hepatic Insufficiency

This study consists of Part I and an optional Part II. The purpose of Part I is to compare the plasma pharmacokinetics of verubecestat (MK-8931) following administration of a single oral dose of 40 mg MK-8931 to participants with moderate hepatic insufficiency (HI) to that of healthy matched controls. An interim safety and pharmacokinetic analysis on the basis of Part I will be performed in order to support the decision to continue with the optional Part II. If a decision to continue with Part II is made, participants with mild HI will be enrolled to receive a single oral dose of 40mg MK-8931. If any healthy participants from Part I do not meet the matching criteria for Part II additional healthy participants will be enrolled.

Conditions: Amnestic Mild Cognitive Impairment, Alzheimer's Disease, Prodromal Alzheimer's Disease
Being tested: MK-8931
Medical subject headings: Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-8931Drug
Also called Verubecestat
MK-8931 40 mg

Study groups in NCT02910739
Study group	Role	What they receive
Part I: MK-8931 40 mg in Moderate HI Participants	Experimental	Single oral dose of MK-8931 40 mg tablet in participants with moderate HI in fasted state (Part I) Receives: Drug: MK-8931
Part I: MK-8931 40 mg in Healthy Participants	Active comparator	Single oral dose of MK-8931 40 mg tablet in healthy matched participants in fasted state (Part I) Receives: Drug: MK-8931
Part II: MK-8931 40 mg in Mild HI Participants	Experimental	Single oral dose of MK-8931 40 mg tablet in participants with mild HI in fasted state (Part II) Receives: Drug: MK-8931
Part II: MK-8931 40 mg in Healthy Participants	Active comparator	Single oral dose of MK-8931 40 mg tablet in healthy matched participants in fasted state (Part II) Receives: Drug: MK-8931

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Concentration Versus Time Curve of MK-8931 From 0 to Infinity (AUC0-∞)
Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine AUC0-∞, defined as the area under the MK-8931 concentration versus time curve from 0 (predose) extrapolated to infinity after a single oral dose of MK-8931 40 mg. Individual AUC0-∞ values were natural log (ln) transformed and evaluated with an analysis of covariance (ANCOVA) model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for AUC0-∞ in each arm.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose
Maximum Observed Plasma Concentration of MK-8931 (Cmax)
Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine Cmax, defined as the maximum plasma concentration of MK-8931 observed following oral dosing. Individual Cmax values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for Cmax in each arm.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after MK-8931 40 mg dose
Area Under the Concentration Versus Time Curve of MK-8931 From 0 to the Time of the Last Quantifiable (Above LLOQ) Sample (AUC0-last)
Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine AUC0-last, defined as the area under the MK-8931 concentration versus time curve from 0 (predose) to the time of the last sample with quantifiable MK-8931 (above the lower limit of quantification; LLOQ) after a single oral dose of MK-8931 40 mg. Individual AUC0-last values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for AUC0-last in each arm.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose
Area Under the Concentration Versus Time Curve of MK-8931 From 0 to 24 Hours (AUC0-24hr)
Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine AUC0-24hr, defined as the area under the MK-8931 concentration versus time curve from 0 (predose) until 24 hours after single oral dosing of MK-8931 40 mg. Individual AUC0-24hr values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for AUC0-24hr in each arm.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours after MK-8931 40 mg dose
Plasma Concentration of MK-8931 at 24 Hours (C24hr)
Blood samples were collected 24 hours following oral dosing of MK-8931 and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified to determine C24hr, defined as the plasma concentration of MK-8931 at 24 hours after single oral dosing of MK-8931 40 mg. Individual C24hr values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for C24hr in each arm.
Measured: 24 hours after MK-8931 40 mg dose
Apparent Clearance of MK-8931 After Extravascular Administration (CL/F)
Geometric mean apparent clearance of MK-8931 after extravascular administration (CL/F) was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine CL/F, defined as the rate of MK-8931 elimination normalized to the bioavailability of MK-8931 in the plasma following oral MK-8931 administration.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose
Time to Maximum Observed MK-8931 Plasma Drug Concentration (Tmax)
Median time to maximum observed MK-8931 plasma drug concentration (Tmax) was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine Tmax, defined as the amount of time required following MK-8931 administration for the plasma concentration of MK-8931 to reach maximum observed concentration.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after MK-8931 40 mg dose
Apparent Terminal Half-Life of MK-8931 (t1/2)
Geometric mean apparent terminal half-life (t1/2) of MK-8931 was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine t1/2, defined as the time required for the plasma MK-8931 concentration to decrease to 50% of maximum.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose
Apparent Volume of Distribution of MK-8931 During the Terminal Phase After Extravascular Administration (Vz/F)
Geometric mean apparent volume of distribution of MK-8931 during the terminal phase after extravascular administration (Vz/F) was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine Vz/F, defined as the total amount of MK-8931 administered normalized to the bioavailability of MK-8931 in the plasma during the terminal phase following oral MK-8931 administration.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose

Secondary outcomes (2)

Number of Participants Experiencing an Adverse Event
The number of participants experiencing an adverse event (AE) was assessed. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE.
Measured: Up to 14 days following MK-8931 40 mg administration.
Number of Participants Discontinuing Study Due to an Adverse Event
The number of participants discontinuing study due to an AE was assessed. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE.
Measured: Up to 14 days following MK-8931 40 mg administration.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Oct 201612 Apr 2017

First posted22 Sep 2016 (estimated)
Study start11 Oct 2016
Primary completion3 Apr 2017
Study completion12 Apr 2017

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 Amnestic Mild Cognitive ImpairmentStudies 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: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02910739
Sponsor's protocol ID: P08593
Other IDs: Celerion Project Number, Merck Protocol Number
Status last verified: Feb 2018
First submitted: 20 Sep 2016
Last updated: 1 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 1 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Two-Part, Open-Label Study to Investigate the Single-Dose Pharmacokinetics of MK-8931 When Administered to Subjects With Mild and Moderate Hepatic Insufficiency
ClinicalTrials.gov ID: NCT02910739
Acronym / sponsor ID: P08593
Conditions: Amnestic Mild Cognitive Impairment, Alzheimer's Disease, Prodromal Alzheimer's Disease
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 11 Oct 2016 (actual)
Primary completion: 3 Apr 2017 (actual)
Study completion: 12 Apr 2017 (actual)
First posted: 22 Sep 2016 (estimated)
Results: Posted 1 Oct 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Part I: MK-8931 40 mg in Moderate HI Participants	Experimental	Drug: MK-8931Single oral dose of MK-8931 40 mg tablet in participants with moderate HI in fasted state (Part I)
Part I: MK-8931 40 mg in Healthy Participants	Active comparator	Drug: MK-8931Single oral dose of MK-8931 40 mg tablet in healthy matched participants in fasted state (Part I)
Part II: MK-8931 40 mg in Mild HI Participants	Experimental	Drug: MK-8931Single oral dose of MK-8931 40 mg tablet in participants with mild HI in fasted state (Part II)
Part II: MK-8931 40 mg in Healthy Participants	Active comparator	Drug: MK-8931Single oral dose of MK-8931 40 mg tablet in healthy matched participants in fasted state (Part II)

Who may qualify

Ages: 45 to 85 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (31 listed)

Adult male or female participants, 45-85 years of age, inclusive, at screening.
Body Mass Index (BMI) ≥ 19 and ≤ 40 kg/m^2, at screening.
Continuous non-smokers or light smokers (< 10 cigarettes/day or the equivalent).
Baseline health is judged to be stable based on medical history (except for the hepatic insufficiency condition).
Participant has a 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 due to any etiology.

Key exclusion criteria (37 listed)

Participant is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator.
History of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
History or presence of alcoholism or drug abuse within the past 2 years prior to dosing.
History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds.

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-8931Also: VerubecestatMK-8931 40 mg	Drug	Part I: MK-8931 40 mg in Healthy Participants, Part I: MK-8931 40 mg in Moderate HI Participants, Part II: MK-8931 40 mg in Healthy Participants, Part II: MK-8931 40 mg in Mild HI Participants

Primary outcome

Area Under the Concentration Versus Time Curve of MK-8931 From 0 to Infinity (AUC0-∞)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose
Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine AUC0-∞, defined as the area under the MK-8931 concentration versus time curve from 0 (predose) extrapolated to infinity after a single oral dose of MK-8931 40 mg. Individual AUC0-∞ values were natural log (ln) transformed and evaluated with an analysis of covariance (ANCOVA) model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for AUC0-∞ in each arm.
Maximum Observed Plasma Concentration of MK-8931 (Cmax)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after MK-8931 40 mg dose
Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine Cmax, defined as the maximum plasma concentration of MK-8931 observed following oral dosing. Individual Cmax values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for Cmax in each arm.
Area Under the Concentration Versus Time Curve of MK-8931 From 0 to the Time of the Last Quantifiable (Above LLOQ) Sample (AUC0-last)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose
Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine AUC0-last, defined as the area under the MK-8931 concentration versus time curve from 0 (predose) to the time of the last sample with quantifiable MK-8931 (above the lower limit of quantification; LLOQ) after a single oral dose of MK-8931 40 mg. Individual AUC0-last values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for AUC0-last in each arm.
Area Under the Concentration Versus Time Curve of MK-8931 From 0 to 24 Hours (AUC0-24hr)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours after MK-8931 40 mg dose
Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine AUC0-24hr, defined as the area under the MK-8931 concentration versus time curve from 0 (predose) until 24 hours after single oral dosing of MK-8931 40 mg. Individual AUC0-24hr values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for AUC0-24hr in each arm.
Plasma Concentration of MK-8931 at 24 Hours (C24hr)
Time frame: 24 hours after MK-8931 40 mg dose
Blood samples were collected 24 hours following oral dosing of MK-8931 and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified to determine C24hr, defined as the plasma concentration of MK-8931 at 24 hours after single oral dosing of MK-8931 40 mg. Individual C24hr values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for C24hr in each arm.
Apparent Clearance of MK-8931 After Extravascular Administration (CL/F)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose
Geometric mean apparent clearance of MK-8931 after extravascular administration (CL/F) was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine CL/F, defined as the rate of MK-8931 elimination normalized to the bioavailability of MK-8931 in the plasma following oral MK-8931 administration.
Time to Maximum Observed MK-8931 Plasma Drug Concentration (Tmax)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after MK-8931 40 mg dose
Median time to maximum observed MK-8931 plasma drug concentration (Tmax) was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine Tmax, defined as the amount of time required following MK-8931 administration for the plasma concentration of MK-8931 to reach maximum observed concentration.
Apparent Terminal Half-Life of MK-8931 (t1/2)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose
Geometric mean apparent terminal half-life (t1/2) of MK-8931 was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine t1/2, defined as the time required for the plasma MK-8931 concentration to decrease to 50% of maximum.
Apparent Volume of Distribution of MK-8931 During the Terminal Phase After Extravascular Administration (Vz/F)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose
Geometric mean apparent volume of distribution of MK-8931 during the terminal phase after extravascular administration (Vz/F) was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine Vz/F, defined as the total amount of MK-8931 administered normalized to the bioavailability of MK-8931 in the plasma during the terminal phase following oral MK-8931 administration.

2 secondary outcomes

Number of Participants Experiencing an Adverse Event
Time frame: Up to 14 days following MK-8931 40 mg administration.
Number of Participants Discontinuing Study Due to an Adverse Event
Time frame: Up to 14 days following MK-8931 40 mg administration.

Results and safety

Results posted to the registry on 1 Oct 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part I: MK-8931 40 mg in Moderate HI Participants	8	7
Part I: MK-8931 40 mg in Healthy Participants	8	8
Part II: MK-8931 40 mg in Mild HI Participants	0	0
Part II: MK-8931 40 mg in Healthy Participants	0	0

Primary outcome: Area Under the Concentration Versus Time Curve of MK-8931 From 0 to Infinity (AUC0-∞)

Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose. Geometric least squares mean (95% Confidence Interval). Unit: micromolar(µM)*hour(hr)

Measure	Part I: MK-8931 40 mg in Moderate HI Participants n = 7	Part I: MK-8931 40 mg in Healthy Participants n = 8
Value	3.48 (2.85 to 4.25)	3.34 (2.77 to 4.03)

Part I: MK-8931 40 mg in Moderate HI Participants vs Part I: MK-8931 40 mg in Healthy Participants: Geometric least-squares mean ratio (GMR): 1.04 (90% CI 0.83 to 1.30)

Population analysed: All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of AUC0-∞. One participant with moderate HI discontinued study prior to collection of samples at 72, 96, and 120 hours post-dose and was excluded from analysis.

Primary outcome: Maximum Observed Plasma Concentration of MK-8931 (Cmax)

Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after MK-8931 40 mg dose. Geometric least squares mean (95% Confidence Interval). Unit: nanomolar (nM)

Measure	Part I: MK-8931 40 mg in Moderate HI Participants n = 8	Part I: MK-8931 40 mg in Healthy Participants n = 8
Value	154 (116 to 206)	144 (108 to 192)

Part I: MK-8931 40 mg in Moderate HI Participants vs Part I: MK-8931 40 mg in Healthy Participants: GMR: 1.07 (90% CI 0.77 to 1.50)

Population analysed: All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of Cmax.

Primary outcome: Area Under the Concentration Versus Time Curve of MK-8931 From 0 to the Time of the Last Quantifiable (Above LLOQ) Sample (AUC0-last)

Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose. Geometric least squares mean (95% Confidence Interval). Unit: µM*hr

Measure	Part I: MK-8931 40 mg in Moderate HI Participants n = 7	Part I: MK-8931 40 mg in Healthy Participants n = 8
Value	3.35 (2.72 to 4.11)	3.22 (2.66 to 3.91)

Part I: MK-8931 40 mg in Moderate HI Participants vs Part I: MK-8931 40 mg in Healthy Participants: GMR: 1.04 (90% CI 0.82 to 1.31)

Population analysed: All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of AUC0-last. One participant with moderate HI discontinued study prior to collection of samples at 72, 96, and 120 hours post-dose and was excluded from analysis.

Primary outcome: Area Under the Concentration Versus Time Curve of MK-8931 From 0 to 24 Hours (AUC0-24hr)

Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours after MK-8931 40 mg dose. Geometric least squares mean (95% Confidence Interval). Unit: µM*hr

Measure	Part I: MK-8931 40 mg in Moderate HI Participants n = 8	Part I: MK-8931 40 mg in Healthy Participants n = 8
Value	1.90 (1.56 to 2.32)	1.88 (1.54 to 2.30)

Part I: MK-8931 40 mg in Moderate HI Participants vs Part I: MK-8931 40 mg in Healthy Participants: GMR: 1.01 (90% CI 0.80 to 1.27)

Population analysed: All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of AUC0-24hr.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 14 days following MK-8931 40 mg administration.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part I: MK-8931 40 mg in Moderate HI Participants	1 of 8 (12.5%)	0 of 8 (0%)	0 of 8
Part I: MK-8931 40 mg in Healthy Participants	0 of 8 (0%)	0 of 8 (0%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-8931 in people with Amnestic Mild Cognitive Impairment and Alzheimer's Disease, run by Merck Sharp & Dohme LLC.

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 31 inclusion and 37 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: finished, as of the sponsor's last update on 1 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

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 1 Oct 2018). 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 Versus Time Curve of MK-8931 From 0 to Infinity (AUC0-∞) (time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02910739.

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 1 Oct 2018; AzTrials last refreshed its copy on 26 Oct 2026.