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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
Lead sponsor
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
Timeline
Milestones
Assets
Drug assets
Study populations
Who this study enrolls
Eligibility
Who can enroll
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:
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:
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 endpointsMaximum 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
Plasma Concentration of MK-8931 at 24 Hours (C24hr)
Time frame:24 hours after MK-8931 40 mg dose
concentration, descriptive
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
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
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
| Group | Value (geometric_least_squares_mean), nanomolar (nM) | Reported bounds |
|---|---|---|
| Part I: MK-8931 40 mg in Moderate HI Participantsn=8 Participants | 154 | -116 - 206 |
| Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants | 144 | -108 - 192 |
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.
Plasma Concentration of MK-8931 at 24 Hours (C24hr)
Time frame:24 hours after MK-8931 40 mg dose
concentration, descriptive
Posted result
| Group | Value (geometric_least_squares_mean), nM | Reported bounds |
|---|---|---|
| Part I: MK-8931 40 mg in Moderate HI Participantsn=8 Participants | 51.1 | -43.6 - 59.8 |
| Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants | 47.1 | -40.2 - 55.2 |
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.
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
| Group | Value (median), hr | Reported bounds |
|---|---|---|
| Part I: MK-8931 40 mg in Moderate HI Participantsn=8 Participants | 1.00 | -0.50 - 4.00 |
| Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants | 2.00 | -0.50 - 4.00 |
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
| Group | Value (geometric_mean), hr | Geometric coefficient of variation |
|---|---|---|
| Part I: MK-8931 40 mg in Moderate HI Participantsn=7 Participants | 23.0 | 15.7 |
| Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants | 24.7 | 9.3 |
Number of Participants Experiencing an Adverse Event
Time frame:Up to 14 days following MK-8931 40 mg administration.
event count, event
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
Number of Participants Experiencing an Adverse Event
Time frame:Up to 14 days following MK-8931 40 mg administration.
event count, event
Posted result
| Group | Value (count_of_participants), Participants | Reported bounds |
|---|---|---|
| Part I: MK-8931 40 mg in Moderate HI Participantsn=8 Participants | 1 | - |
| Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants | 0 | - |
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
| Group | Value (count_of_participants), Participants | Reported bounds |
|---|---|---|
| Part I: MK-8931 40 mg in Moderate HI Participantsn=8 Participants | 1 | - |
| Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants | 0 | - |
Other (unclassified)
10 endpointsArea 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
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
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
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
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
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
| Group | Value (geometric_least_squares_mean), micromolar(µM)*hour(hr) | Reported bounds |
|---|---|---|
| Part I: MK-8931 40 mg in Moderate HI Participantsn=7 Participants | 3.48 | -2.85 - 4.25 |
| Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants | 3.34 | -2.77 - 4.03 |
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.
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
| Group | Value (geometric_least_squares_mean), µM*hr | Reported bounds |
|---|---|---|
| Part I: MK-8931 40 mg in Moderate HI Participantsn=7 Participants | 3.35 | -2.72 - 4.11 |
| Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants | 3.22 | -2.66 - 3.91 |
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.
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
| Group | Value (geometric_least_squares_mean), µM*hr | Reported bounds |
|---|---|---|
| Part I: MK-8931 40 mg in Moderate HI Participantsn=8 Participants | 1.90 | -1.56 - 2.32 |
| Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants | 1.88 | -1.54 - 2.30 |
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.
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
| Group | Value (geometric_mean), Liters/hr | Geometric coefficient of variation |
|---|---|---|
| Part I: MK-8931 40 mg in Moderate HI Participantsn=7 Participants | 28.4 | 26.3 |
| Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants | 29.0 | 22.7 |
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
| Group | Value (geometric_mean), Liters | Geometric coefficient of variation |
|---|---|---|
| Part I: MK-8931 40 mg in Moderate HI Participantsn=7 Participants | 940 | 27.3 |
| Part I: MK-8931 40 mg in Healthy Participantsn=8 Participants | 1030 | 26.1 |
Provenance
Sources
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.