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CompletedPhase 1Results posted

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

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

Asset

Verubecestat

Listed sites

0

Recruiting sites

-

Enrollment

16

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criterion

Age 45-85

Primary endpoints

AUC of MK-8931 From 0 to Infinity (AUC0-∞)Cmax of MK-8931(Cmax)AUC of MK-8931 From 0 to the Time of the Last Quantifiable (Above LLOQ) Sample

Identifiers

Registered as

Secondary IDCelerion Project NumberCA13011
Secondary IDMerck Protocol NumberMK-8931-016
NCT IDNCT02910739
Org study IDP08593

Timeline

Milestones

Study first posted2016-09-22estimated
Study start2016-10-11actual
Primary completion2017-04-03actual
Study completion2017-04-12actual
Last update posted2018-10-01actual
Results first posted2018-10-01actual

Assets

Drug assets

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age45 Years
Maximum age85 Years
SexAll
Healthy volunteersAccepted

Inclusion criteria

Participants with HI

1. Adult male or female participants, 45-85 years of age, inclusive, at screening.

2. Body Mass Index (BMI) ≥ 19 and ≤ 40 kg/m^2, at screening.

3. Continuous non-smokers or light smokers (< 10 cigarettes/day or the equivalent).

4. Baseline health is judged to be stable based on medical history (except for the hepatic insufficiency condition).

5. 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.

6. Part 1 only: Participant's score on the Child-Pugh scale must range from 7 to 9 (moderate HI) at screening.

7. Part 2 only: Participant's score on the Child-Pugh scale must range from 5 to 6 (mild HI) at screening.

8. 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.

9. 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.

10. 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.

11. Non-vasectomized male participants must agree to use a condom with spermicide or abstain from sexual intercourse from dosing until 90 days after dosing.

12. Male participants must agree not to donate sperm from dosing until 90 days after dosing.

13. 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.

Inclusion Criteria: Healthy Control Participants

1. Healthy adult male or female participants, 45-85 years of age, inclusive, at screening.

2. BMI ≥ 19 and ≤ 40 kg/m^2 at screening.

3. Continuous non-smokers or light smokers (< 10 cigarettes/day or the equivalent).

4. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the Investigator.

5. 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.

6. 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.

7. 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.

8. Non-vasectomized male participants must agree to use a condom with spermicide or abstain from sexual intercourse from dosing until 90 days after dosing.

9. Male participants must agree not to donate sperm from dosing until 90 days after dosing.

10. 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

Exclusion criteria

Participants with HI

1. 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.

2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator.

3. 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.

4. History or presence of alcoholism or drug abuse within the past 2 years prior to dosing.

5. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds.

6. Female participants who are pregnant or lactating.

7. 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.

8. 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.

9. Seated blood pressure is less than 90/40 mmHg or greater than 180/105 mmHg at screening.

10. Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.

11. 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.

12. Abnormal hemoglobin level deemed clinically significant by the Investigator at screening.

13. 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).

14. 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.

15. Donation of blood or had significant blood loss within 56 days prior to dosing of study drug.

16. Plasma donation within 28 days prior to dosing of study drug.

17. 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.

18. Participation in another clinical trial within 28 days prior to dosing.

19. Participant who dosed in one part (e.g., Part 1) will not be enrolled in the other part (e.g., Part 2).

Exclusion Criteria: Healthy Control Participants

1. 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.

2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator.

3. 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.

4. History or presence of alcoholism or drug abuse within the past 2 years prior to dosing.

5. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds.

6. Female participants who are pregnant or lactating.

7. Positive results for the urine drug and/or urine or breath alcohol screen at screening or check-in.

8. Positive results at screening for HIV or HBsAg or HCV with decompensated liver disease.

9. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.

10. Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.

11. QTcF is > 480 msec or has ECG findings deemed abnormal with clinical significance by the Investigator or designee at screening.

12. Abnormal hemoglobin level deemed clinically significant by the Investigator at screening.

13. 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).

14. 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.

15. Donation of blood or had significant blood loss within 56 days prior to dosing of study drug.

16. Plasma donation within 28 days prior to dosing of study drug.

17. 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.

18. Participation in another clinical trial within 28 days prior to dosing.

Endpoints (22)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK
12
Other (unclassified)
10

Safety / tolerability / PK

12 endpoints
Primary/protocol endpoint

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

concentration, descriptive

Primary/protocol endpoint

Plasma Concentration of MK-8931 at 24 Hours (C24hr)

Time frame:24 hours after MK-8931 40 mg dose

concentration, descriptive

Primary/protocol endpoint

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

time to event, event

Primary/protocol endpoint

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

concentration, descriptive

Primary/registry result

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

concentration, descriptive

Posted result

GroupValue (geometric_least_squares_mean), nanomolar (nM)Reported bounds
Part I: MK-8931 40 mg in Moderate HI Participantsn=8 Participants154-116 - 206
Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants144-108 - 192
GMR1.0790% CI0.77 - 1.50

Per study protocol, the purpose of this analysis is only to estimate the effect of moderate HI on Cmax; no hypothesis testing was planned for this outcome measure.

Primary/registry result

Plasma Concentration of MK-8931 at 24 Hours (C24hr)

Time frame:24 hours after MK-8931 40 mg dose

concentration, descriptive

Posted result

GroupValue (geometric_least_squares_mean), nMReported bounds
Part I: MK-8931 40 mg in Moderate HI Participantsn=8 Participants51.1-43.6 - 59.8
Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants47.1-40.2 - 55.2
GMR1.0890% CI0.90 - 1.30

Per study protocol, the purpose of this analysis is only to estimate the effect of moderate HI on C24hr; no hypothesis testing was planned for this outcome measure.

Primary/registry result

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

time to event, event

Posted result

GroupValue (median), hrReported bounds
Part I: MK-8931 40 mg in Moderate HI Participantsn=8 Participants1.00-0.50 - 4.00
Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants2.00-0.50 - 4.00
Primary/registry result

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

concentration, descriptive

Posted result

GroupValue (geometric_mean), hrGeometric coefficient of variation
Part I: MK-8931 40 mg in Moderate HI Participantsn=7 Participants23.015.7
Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants24.79.3
Secondary/protocol endpoint

Number of Participants Experiencing an Adverse Event

Time frame:Up to 14 days following MK-8931 40 mg administration.

event count, event

Secondary/protocol endpoint

Number of Participants Discontinuing Study Due to an Adverse Event

Time frame:Up to 14 days following MK-8931 40 mg administration.

event count, event

Secondary/registry result

Number of Participants Experiencing an Adverse Event

Time frame:Up to 14 days following MK-8931 40 mg administration.

event count, event

Posted result

GroupValue (count_of_participants), ParticipantsReported bounds
Part I: MK-8931 40 mg in Moderate HI Participantsn=8 Participants1-
Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants0-
Secondary/registry result

Number of Participants Discontinuing Study Due to an Adverse Event

Time frame:Up to 14 days following MK-8931 40 mg administration.

event count, event

Posted result

GroupValue (count_of_participants), ParticipantsReported bounds
Part I: MK-8931 40 mg in Moderate HI Participantsn=8 Participants1-
Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants0-

Other (unclassified)

10 endpoints
Primary/protocol endpoint/low confidence

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

concentration, descriptive

Primary/protocol endpoint/low confidence

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

concentration, descriptive

Primary/protocol endpoint/low confidence

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

concentration, descriptive

Primary/protocol endpoint/low confidence

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

concentration, descriptive

Primary/protocol endpoint/low confidence

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

concentration, descriptive

Primary/registry result/low confidence

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

concentration, descriptive

Posted result

GroupValue (geometric_least_squares_mean), micromolar(µM)*hour(hr)Reported bounds
Part I: MK-8931 40 mg in Moderate HI Participantsn=7 Participants3.48-2.85 - 4.25
Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants3.34-2.77 - 4.03
Geometric least-squares mean ratio (GMR)1.0490% CI0.83 - 1.30

Per study protocol, the purpose of this analysis is only to estimate the effect of moderate HI on AUC0-∞; no hypothesis testing was planned for this outcome measure.

Primary/registry result/low confidence

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

concentration, descriptive

Posted result

GroupValue (geometric_least_squares_mean), µM*hrReported bounds
Part I: MK-8931 40 mg in Moderate HI Participantsn=7 Participants3.35-2.72 - 4.11
Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants3.22-2.66 - 3.91
GMR1.0490% CI0.82 - 1.31

Per study protocol, the purpose of this analysis is only to estimate the effect of moderate HI on AUC0-last; no hypothesis testing was planned for this outcome measure.

Primary/registry result/low confidence

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

concentration, descriptive

Posted result

GroupValue (geometric_least_squares_mean), µM*hrReported bounds
Part I: MK-8931 40 mg in Moderate HI Participantsn=8 Participants1.90-1.56 - 2.32
Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants1.88-1.54 - 2.30
GMR1.0190% CI0.80 - 1.27

Per study protocol, the purpose of this analysis is only to estimate the effect of moderate HI on AUC0-24hr; no hypothesis testing was planned for this outcome measure.

Primary/registry result/low confidence

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

concentration, descriptive

Posted result

GroupValue (geometric_mean), Liters/hrGeometric coefficient of variation
Part I: MK-8931 40 mg in Moderate HI Participantsn=7 Participants28.426.3
Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants29.022.7
Primary/registry result/low confidence

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

concentration, descriptive

Posted result

GroupValue (geometric_mean), LitersGeometric coefficient of variation
Part I: MK-8931 40 mg in Moderate HI Participantsn=7 Participants94027.3
Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants103026.1

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 21, 2026
Endpoint classificationDelfa ADRD endpoint taxonomy
Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.