Alzheimer's Disease
Conditions
Brief summary
The main purpose of this study is to assess the safety and efficacy of MK-1167 administered to participants with Alzheimer's Disease (AD) receiving stable Donepezil treatment.
Interventions
DRUGMK-1167
1 mg and 5 mg oral capsules
DRUGDonepezil
10 mg oral tablets
DRUGPlacebo
MK-1167 matching placebo administered oral capsules
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Panel A participants will receive a loading dose of MK-1167 6mg or matching Placebo on Days 1 to 7 followed by once daily (QD) dosing of MK-1167 3mg or matching Placebo for 14 consecutive days (Days 8 to 21). Panel B participants will receive QD dosing of MK-1167 6mg or matching Placebo for Days 1 to 31. Panel B will be initiated following review of safety and tolerability data from Panel A.
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Reports a history of cognitive and functional decline with gradual onset and slow progression for at least 1 year before Screening, that is either corroborated by an informant who knows the subject well or is documented in medical records * Meets the criteria for a diagnosis of probable Alzheimer's disease (AD) based on the National Institute of Neurological and Communicative Disorders - Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD * Is receiving donepezil 10 mg daily for symptomatic treatment of cognitive impairment associated with AD. The dose level must be stable for at least 2 months prior to Screening. If receiving donepezil via a transdermal system (ie, patch), it should be a 10-mg/day dose and should switch prescription to a 10-mg oral daily dose, before enrollment * Has a reliable and competent trial partner/caregiver who has a close relationship with the participant, has face-to-face contact at least 3 days a week for a minimum of 6 waking hours a week, and is willing to accompany the participant, if desired, to study visits
Exclusion criteria
* History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases that are not under medical control over the past 2 months. * Has evidence of a clinically relevant or unstable psychiatric disorder, based on DSM-5 criteria, or has a history of clinically significant psychiatric disorder in the last 5 years. Generalized anxiety disorder, and/or insomnia under good control for ≥ 2 months on stable medical therapy may not be exclusionary. * History of cancer (malignancy). Participants with adequately treated disease deemed as cured, or who, in the opinion of the study investigator, are highly unlikely to sustain a recurrence for the duration of the study, may be enrolled at the discretion of the investigator and Sponsor. * History of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or nonprescription drugs or food. * Had a major surgery and/or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit. * Unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study intervention, throughout the study, until the poststudy visit. There may be certain protocol-specified medications that are permitted. * The participant is a smoker and/or has used nicotine or nicotine-containing products (eg, nicotine patch and electronic cigarette) within 3 months of screening. * Consumes greater than 3 servings of alcoholic beverages per day. Participants who consume 4 servings of alcoholic beverages per day may be enrolled at the discretion of the investigator. * The participant is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 2 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 7 weeks | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE were reported. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 4 weeks | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Panel B: AUC0-24 After Administration of 6mg of MK-1167 | Days 1, 23, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Blood samples were collected at pre-specified intervals for the determination of AUC0-24. Per protocol, AUC0-24 was based on noncompartmental analysis, and a geometric mean AUC0-24 value was presented for Panel B participants after administration of 6mg of MK-1167. |
| Panel A: Maximum Plasma Concentration (Cmax) After Administration of 6mg of MK-1167 | Day 1: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | Cmax was defined as the maximum serum concentration of MK-1167 reached. Blood samples were collected at pre-specified timepoints for the determination of Cmax. Per protocol, Cmax was based on noncompartmental analysis, and a geometric mean Cmax value was presented for Panel A participants after administration of 6mg of MK-1167. |
| Panel A: Cmax After Administration of 3mg of MK-1167 | Days 8, 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | Cmax was defined as the maximum serum concentration of MK-1167 reached. Blood samples were collected at pre-specified timepoints for the determination of Cmax. Per protocol, Cmax was based on noncompartmental analysis, and a geometric mean Cmax value was presented for Panel A participants after administration of 3mg of MK-1167. |
| Panel B: Cmax After Administration of 6mg of MK-1167 | Days 1, 23, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | Cmax was defined as the maximum serum concentration of MK-1167 reached. Blood samples were collected at pre-specified timepoints for the determination of Cmax. Per protocol, Cmax was based on noncompartmental analysis, and a geometric mean Cmax value was presented for Panel B participants after administration of 6mg of MK-1167. |
| Panel A: Plasma Concentration at 24 Hours (C24) After Administration of 6mg of MK-1167 | Day 1: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Per protocol, C24 was based on noncompartmental analysis, and a geometric mean C24 value was presented for Panel A participants after administration of 6mg of MK-1167. |
| Panel A: C24 After Administration of 3mg of MK-1167 | Days 8, 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Per protocol, C24 was based on noncompartmental analysis, and a geometric mean C24 value was presented for Panel A participants after administration of 3mg of MK-1167. |
| Panel B: C24 After Administration of 6mg of MK-1167 | Days 1, 23, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Per protocol, C24 was based on noncompartmental analysis, and a geometric mean C24 value was presented for Panel B participants after administration of 6mg of MK-1167. |
| Panel A: Time to Maximum Plasma Concentration (Tmax) After Administration of 6mg of MK-1167 | Day 1: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | Tmax was defined as time to the maximum concentration of MK-1167 reached. Blood samples were collected at pre-specified intervals for the determination of Tmax. Per protocol, Tmax was based on noncompartmental analysis, and a median Tmax value was presented for Panel A participants after administration of 6mg of MK-1167. |
| Panel A: Tmax After Administration of 3mg of MK-1167 | Days 8, 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | Tmax was defined as time to the maximum concentration of MK-1167 reached. Blood samples were collected at pre-specified intervals for the determination of Tmax. Per protocol, Tmax was based on noncompartmental analysis, and a median Tmax value was presented for Panel A participants after administration of 3mg of MK-1167. |
| Panel B: Tmax After Administration of 6mg of MK-1167 | Days 1, 23, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | Tmax was defined as time to the maximum concentration of MK-1167 reached. Blood samples were collected at pre-specified intervals for the determination of Tmax. Per protocol, Tmax was based on noncompartmental analysis, and a median Tmax value was presented for Panel B participants after administration of 6mg of MK-1167. |
| Panel A: Apparent Clearance (CL/F) After Administration of 3mg of MK-1167 | Day 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose | CL/F is the rate at which the MK-1167 is completely removed from plasma. Blood samples were collected at pre-specified intervals for the determination of CL/F. Per protocol, CL/F was based on noncompartmental analysis, and a geometric mean CL/F value was presented for Panel A participants after administration of 3mg of MK-1167. |
| Panel A: Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC0-24) After Administration of 6mg of MK-1167 | Day 1: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Blood samples were collected at pre-specified intervals for the determination of AUC0-24. Per protocol, AUC0-24 was based on noncompartmental analysis, and a geometric mean AUC0-24 value was presented for Panel A participants after administration of 6mg of MK-1167. |
| Panel A: Apparent Terminal Half-Life (t1/2) After Administration of 3mg of MK-1167 | Day 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose | t1/2 is defined as the time required to divide plasma concentration of MK-1167 by half after reaching pseudo-equilibrium. Blood samples were collected at pre-specified intervals for the determination of t1/2. Per protocol, t1/2 was based on noncompartmental analysis, and a geometric mean t1/2 value was presented for Panel A participants after administration of 3mg of MK-1167. |
| Panel B: t1/2 After Administration of 6mg of MK-1167 | Day 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose | t1/2 was defined as the time required to divide plasma concentration of MK-1167 by half after reaching pseudo-equilibrium. Blood samples were collected at pre-specified timepoints for the determination of t1/2. Per protocol, t1/2 was based on noncompartmental analysis, and a geometric mean t1/2 value was presented for Panel B participants after administration of 6mg of MK-1167. |
| Panel A: Apparent Volume of Distribution (Vz/F) After Administration of 3mg of MK-1167 | Day 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose | Vz/F was the apparent volume of distribution of MK-1167. Blood samples were collected at pre-specified intervals for the determination of Vz/F. Per protocol, Vz/F was based on noncompartmental analysis, and a geometric mean Vz/F value was presented for Panel A participants after administration of 3mg of MK-1167. |
| Panel B: Vz/F After Administration of 6mg of MK-1167 | Day 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose | Vz/F was the apparent volume of distribution of MK-1167. Blood samples were collected at pre-specified intervals for the determination of Vz/F. Per protocol, Vz/F was based on noncompartmental analysis, and a geometric mean Vz/F value was presented for Panel B participants after administration of 6mg of MK-1167. |
| Panel B: Day 23 to Day 1 Accumulation Ratio of AUC0-24 After Administration of 6mg of MK-1167 | Days 1, 23: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | Blood samples were collected at pre-specified timepoints to determine AUC0-24 on Days 1 and 23. AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Accumulation ratio of MK-1167 Day 23 to Day 1 was calculated as Day 23 AUC0-24/Day 1 AUC0-24. |
| Panel B: Day 31 to Day 1 Accumulation Ratio of AUC0-24 After Administration of 6mg of MK-1167 | Days 1, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | Blood samples were collected at pre-specified timepoints to determine AUC0-24 on Days 1 and 31. AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Accumulation ratio of MK-1167 Day 31 to Day 1 was calculated as Day 31 AUC0-24/Day 1 AUC0-24. |
| Panel B: Day 23 to Day 1 Accumulation Ratio of Cmax After Administration of 6mg of MK-1167 | Days 1, 23: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | Blood samples were collected at pre-specified timepoints to determine Cmax on Days 1 and 23. Cmax was defined as the maximum serum concentration of MK-1167 reached. Accumulation ratio of MK-1167 Day 23 to Day 1 was calculated as Day 23 Cmax/Day 1 Cmax. |
| Panel B: Day 31 to Day 1 Accumulation Ratio of Cmax After Administration of 6mg of MK-1167 | Days 1, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | Blood samples were collected at pre-specified timepoints to determine Cmax on Days 1 and 31. Cmax was defined as the maximum serum concentration of MK-1167 reached. Accumulation ratio of MK-1167 Day 31 to Day 1 was calculated as Day 31 Cmax/Day 1 Cmax. |
| Panel B: Day 23 to Day 1 Accumulation Ratio of C24 After Administration of 6mg of MK-1167 | Days 1, 23: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | Blood samples were collected at pre-specified timepoints to determine C24 on Days 1 and 23. C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Accumulation ratio of MK-1167 Day 23 to Day 1 was calculated as Day 23 C24/Day 1 C24. |
| Panel B: Day 31 to Day 1 Accumulation Ratio of C24 After Administration of 6mg of MK-1167 | Days 1, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | Blood samples were collected at pre-specified timepoints to determine C24 on Days 1 and 31. C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Accumulation ratio of MK-1167 Day 31 to Day 1 was calculated as Day 31 C24/Day 1 C24. |
| Panel B: CL/F After Administration of 6mg of MK-1167 | Day 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose | CL/F is the rate at which the MK-1167 is completely removed from plasma. Blood samples were collected at pre-specified intervals for the determination of CL/F. Per protocol, CL/F was based on noncompartmental analysis, and a geometric mean CL/F value was presented for Panel B participants after administration of 6mg of MK-1167. |
| Panel A: AUC0-24 After Administration of 3mg of MK-1167 | Days 8, 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Blood samples were collected at pre-specified intervals for the determination of AUC0-24. Per protocol, AUC0-24 was based on noncompartmental analysis, and a geometric mean AUC 0-24 value was presented for Panel A participants after administration of 3mg of MK-1167. |
Countries
United States
Participant flow
Pre-assignment details
All randomized participants
Participants by arm
| Arm | Count |
|---|---|
| Panel A: MK-1167 + Donepezil 10mg QD Participants received 6mg MK-1167 oral loading doses once daily (QD) Days 1 to 7, followed by 3mg MK-1167 oral maintenance doses QD Days 8 to 21. Participants also received 10mg oral Donepezil on Days -3 to 21. | 12 |
| Panel A: Placebo to MK-1167 + Donepezil 10mg QD Participants received dose matched placebo to MK-1167 oral QD from Days 1 to 21. Participants also received 10mg oral Donepezil QD on Days-3 to 21. | 4 |
| Panel B: MK-1167 6mg QD + Donepezil 10mg QD Participants received 6mg MK-1167 oral doses QD Days 1 to 31. Participants also received 10mg oral Donepezil on Days -3 to 31. | 9 |
| Panel B: Placebo to MK-1167 + Donepezil 10mg QD Participants received dose matched placebo to MK-1167 oral QD from Days 1 to 31. Participants also received 10mg oral Donepezil QD on Days-3 to 31. | 3 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Serious Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Panel A: Placebo to MK-1167 + Donepezil 10mg QD | Panel B: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Placebo to MK-1167 + Donepezil 10mg QD | Total | Panel A: MK-1167 + Donepezil 10mg QD |
|---|---|---|---|---|---|
| Age, Continuous | 63.5 Years STANDARD_DEVIATION 8.7 | 69.9 Years STANDARD_DEVIATION 8.6 | 75.3 Years STANDARD_DEVIATION 2.9 | 68.8 Years STANDARD_DEVIATION 8.2 | 68.2 Years STANDARD_DEVIATION 8.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants | 12 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 5 Participants | 1 Participants | 16 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 0 Participants | 11 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 6 Participants | 3 Participants | 17 Participants | 6 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 1 Participants | 13 Participants | 6 Participants |
| Sex: Female, Male Male | 1 Participants | 6 Participants | 2 Participants | 15 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 4 | 0 / 9 | 0 / 3 |
| other Total, other adverse events | 3 / 12 | 5 / 12 | 2 / 4 | 6 / 9 | 0 / 3 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 4 | 1 / 9 | 0 / 3 |
Outcome results
Primary
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE were reported.
Time frame: Up to approximately 4 weeks
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel A: MK-1167 3mg QD + Donepezil 10mg QD | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel A: Placebo to MK-1167 + Donepezil 10mg QD | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel B: MK-1167 6mg QD+ Donepezil 10mg QD | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Panel B: Placebo to MK-1167 + Donepezil 10mg QD | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE were reported.
Time frame: Up to approximately 7 weeks
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Panel A: MK-1167 3mg QD + Donepezil 10mg QD | Number of Participants Who Experienced an Adverse Event (AE) | 5 Participants |
| Panel A: Placebo to MK-1167 + Donepezil 10mg QD | Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
| Panel B: MK-1167 6mg QD+ Donepezil 10mg QD | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
| Panel B: Placebo to MK-1167 + Donepezil 10mg QD | Number of Participants Who Experienced an Adverse Event (AE) | 0 Participants |
Secondary
Panel A: Apparent Clearance (CL/F) After Administration of 3mg of MK-1167
CL/F is the rate at which the MK-1167 is completely removed from plasma. Blood samples were collected at pre-specified intervals for the determination of CL/F. Per protocol, CL/F was based on noncompartmental analysis, and a geometric mean CL/F value was presented for Panel A participants after administration of 3mg of MK-1167.
Time frame: Day 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose
Population: All Panel A randomized participants who received at least one dose of study treatment (3mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: Apparent Clearance (CL/F) After Administration of 3mg of MK-1167 | 0.879 Liter/hour | Geometric Coefficient of Variation 166.9 |
Secondary
Panel A: Apparent Terminal Half-Life (t1/2) After Administration of 3mg of MK-1167
t1/2 is defined as the time required to divide plasma concentration of MK-1167 by half after reaching pseudo-equilibrium. Blood samples were collected at pre-specified intervals for the determination of t1/2. Per protocol, t1/2 was based on noncompartmental analysis, and a geometric mean t1/2 value was presented for Panel A participants after administration of 3mg of MK-1167.
Time frame: Day 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose
Population: All Panel A randomized participants who received at least one dose of study treatment (3mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: Apparent Terminal Half-Life (t1/2) After Administration of 3mg of MK-1167 | 194 hours | Geometric Coefficient of Variation 48.2 |
Secondary
Panel A: Apparent Volume of Distribution (Vz/F) After Administration of 3mg of MK-1167
Vz/F was the apparent volume of distribution of MK-1167. Blood samples were collected at pre-specified intervals for the determination of Vz/F. Per protocol, Vz/F was based on noncompartmental analysis, and a geometric mean Vz/F value was presented for Panel A participants after administration of 3mg of MK-1167.
Time frame: Day 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose
Population: All Panel A randomized participants who received at least one dose of study treatment (3mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: Apparent Volume of Distribution (Vz/F) After Administration of 3mg of MK-1167 | 246 Liter | Geometric Coefficient of Variation 166.6 |
Secondary
Panel A: Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC0-24) After Administration of 6mg of MK-1167
AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Blood samples were collected at pre-specified intervals for the determination of AUC0-24. Per protocol, AUC0-24 was based on noncompartmental analysis, and a geometric mean AUC0-24 value was presented for Panel A participants after administration of 6mg of MK-1167.
Time frame: Day 1: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel A randomized participants who received at least one dose of study treatment (6mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC0-24) After Administration of 6mg of MK-1167 | 2.17 μM*hour |
Secondary
Panel A: AUC0-24 After Administration of 3mg of MK-1167
AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Blood samples were collected at pre-specified intervals for the determination of AUC0-24. Per protocol, AUC0-24 was based on noncompartmental analysis, and a geometric mean AUC 0-24 value was presented for Panel A participants after administration of 3mg of MK-1167.
Time frame: Days 8, 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel A randomized participants who received at least one dose of study treatment (3mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: AUC0-24 After Administration of 3mg of MK-1167 | Day 8 | 8.70 μM*hour |
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: AUC0-24 After Administration of 3mg of MK-1167 | Day 21 | 8.08 μM*hour |
Secondary
Panel A: C24 After Administration of 3mg of MK-1167
C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Per protocol, C24 was based on noncompartmental analysis, and a geometric mean C24 value was presented for Panel A participants after administration of 3mg of MK-1167.
Time frame: Days 8, 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel A randomized participants who received at least one dose of study treatment (3mg MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: C24 After Administration of 3mg of MK-1167 | Day 8 | 0.362 μmol/Liter |
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: C24 After Administration of 3mg of MK-1167 | Day 21 | 0.313 μmol/Liter |
Secondary
Panel A: Cmax After Administration of 3mg of MK-1167
Cmax was defined as the maximum serum concentration of MK-1167 reached. Blood samples were collected at pre-specified timepoints for the determination of Cmax. Per protocol, Cmax was based on noncompartmental analysis, and a geometric mean Cmax value was presented for Panel A participants after administration of 3mg of MK-1167.
Time frame: Days 8, 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel A randomized participants who received at least one dose of study treatment (3mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: Cmax After Administration of 3mg of MK-1167 | Day 8 | 0.434 μmol/Liter |
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: Cmax After Administration of 3mg of MK-1167 | Day 21 | 0.413 μmol/Liter |
Secondary
Panel A: Maximum Plasma Concentration (Cmax) After Administration of 6mg of MK-1167
Cmax was defined as the maximum serum concentration of MK-1167 reached. Blood samples were collected at pre-specified timepoints for the determination of Cmax. Per protocol, Cmax was based on noncompartmental analysis, and a geometric mean Cmax value was presented for Panel A participants after administration of 6mg of MK-1167.
Time frame: Day 1: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel A randomized participants who received at least one dose of study treatment (6mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: Maximum Plasma Concentration (Cmax) After Administration of 6mg of MK-1167 | 0.129 μmol/Liter |
Secondary
Panel A: Plasma Concentration at 24 Hours (C24) After Administration of 6mg of MK-1167
C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Per protocol, C24 was based on noncompartmental analysis, and a geometric mean C24 value was presented for Panel A participants after administration of 6mg of MK-1167.
Time frame: Day 1: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel A randomized participants who received at least one dose of study treatment (6mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: Plasma Concentration at 24 Hours (C24) After Administration of 6mg of MK-1167 | 0.0902 μmol/Liter |
Secondary
Panel A: Time to Maximum Plasma Concentration (Tmax) After Administration of 6mg of MK-1167
Tmax was defined as time to the maximum concentration of MK-1167 reached. Blood samples were collected at pre-specified intervals for the determination of Tmax. Per protocol, Tmax was based on noncompartmental analysis, and a median Tmax value was presented for Panel A participants after administration of 6mg of MK-1167.
Time frame: Day 1: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel A randomized participants who received at least one dose of study treatment (6mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: Time to Maximum Plasma Concentration (Tmax) After Administration of 6mg of MK-1167 | 1.54 hours |
Secondary
Panel A: Tmax After Administration of 3mg of MK-1167
Tmax was defined as time to the maximum concentration of MK-1167 reached. Blood samples were collected at pre-specified intervals for the determination of Tmax. Per protocol, Tmax was based on noncompartmental analysis, and a median Tmax value was presented for Panel A participants after administration of 3mg of MK-1167.
Time frame: Days 8, 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel A randomized participants who received at least one dose of study treatment (3mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: Tmax After Administration of 3mg of MK-1167 | Day 8 | 6.00 hours |
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel A: Tmax After Administration of 3mg of MK-1167 | Day 21 | 4.01 hours |
Secondary
Panel B: AUC0-24 After Administration of 6mg of MK-1167
AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Blood samples were collected at pre-specified intervals for the determination of AUC0-24. Per protocol, AUC0-24 was based on noncompartmental analysis, and a geometric mean AUC0-24 value was presented for Panel B participants after administration of 6mg of MK-1167.
Time frame: Days 1, 23, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment (6mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: AUC0-24 After Administration of 6mg of MK-1167 | Day 1 | 2.48 μM*hour |
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: AUC0-24 After Administration of 6mg of MK-1167 | Day 23 | 22.2 μM*hour |
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: AUC0-24 After Administration of 6mg of MK-1167 | Day 31 | 22.9 μM*hour |
Secondary
Panel B: C24 After Administration of 6mg of MK-1167
C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Per protocol, C24 was based on noncompartmental analysis, and a geometric mean C24 value was presented for Panel B participants after administration of 6mg of MK-1167.
Time frame: Days 1, 23, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment (6mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: C24 After Administration of 6mg of MK-1167 | Day 1 | 0.0917 μmol/Liter |
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: C24 After Administration of 6mg of MK-1167 | Day 23 | 0.729 μmol/Liter |
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: C24 After Administration of 6mg of MK-1167 | Day 31 | 0.875 μmol/Liter |
Secondary
Panel B: CL/F After Administration of 6mg of MK-1167
CL/F is the rate at which the MK-1167 is completely removed from plasma. Blood samples were collected at pre-specified intervals for the determination of CL/F. Per protocol, CL/F was based on noncompartmental analysis, and a geometric mean CL/F value was presented for Panel B participants after administration of 6mg of MK-1167.
Time frame: Day 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment (6mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: CL/F After Administration of 6mg of MK-1167 | 0.606 Liter/hour | Geometric Coefficient of Variation 32.3 |
Secondary
Panel B: Cmax After Administration of 6mg of MK-1167
Cmax was defined as the maximum serum concentration of MK-1167 reached. Blood samples were collected at pre-specified timepoints for the determination of Cmax. Per protocol, Cmax was based on noncompartmental analysis, and a geometric mean Cmax value was presented for Panel B participants after administration of 6mg of MK-1167.
Time frame: Days 1, 23, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment (6mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Cmax After Administration of 6mg of MK-1167 | Day 1 | 0.145 μmol/Liter |
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Cmax After Administration of 6mg of MK-1167 | Day 23 | 1.11 μmol/Liter |
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Cmax After Administration of 6mg of MK-1167 | Day 31 | 1.14 μmol/Liter |
Secondary
Panel B: Day 23 to Day 1 Accumulation Ratio of AUC0-24 After Administration of 6mg of MK-1167
Blood samples were collected at pre-specified timepoints to determine AUC0-24 on Days 1 and 23. AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Accumulation ratio of MK-1167 Day 23 to Day 1 was calculated as Day 23 AUC0-24/Day 1 AUC0-24.
Time frame: Days 1, 23: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment and had AUC0-24 data available for assessment on Day 1 and Day 23.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Day 23 to Day 1 Accumulation Ratio of AUC0-24 After Administration of 6mg of MK-1167 | 8.95 Ratio |
Secondary
Panel B: Day 23 to Day 1 Accumulation Ratio of C24 After Administration of 6mg of MK-1167
Blood samples were collected at pre-specified timepoints to determine C24 on Days 1 and 23. C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Accumulation ratio of MK-1167 Day 23 to Day 1 was calculated as Day 23 C24/Day 1 C24.
Time frame: Days 1, 23: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment and had C24 data available for assessment on Day 1 and Day 23.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Day 23 to Day 1 Accumulation Ratio of C24 After Administration of 6mg of MK-1167 | 7.94 Ratio |
Secondary
Panel B: Day 23 to Day 1 Accumulation Ratio of Cmax After Administration of 6mg of MK-1167
Blood samples were collected at pre-specified timepoints to determine Cmax on Days 1 and 23. Cmax was defined as the maximum serum concentration of MK-1167 reached. Accumulation ratio of MK-1167 Day 23 to Day 1 was calculated as Day 23 Cmax/Day 1 Cmax.
Time frame: Days 1, 23: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment and had at Cmax data available for assessment on Day 1 and Day 23.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Day 23 to Day 1 Accumulation Ratio of Cmax After Administration of 6mg of MK-1167 | 7.69 Ratio |
Secondary
Panel B: Day 31 to Day 1 Accumulation Ratio of AUC0-24 After Administration of 6mg of MK-1167
Blood samples were collected at pre-specified timepoints to determine AUC0-24 on Days 1 and 31. AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Accumulation ratio of MK-1167 Day 31 to Day 1 was calculated as Day 31 AUC0-24/Day 1 AUC0-24.
Time frame: Days 1, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment and had AUC0-24 data available for assessment on Day 1 and Day 31.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Day 31 to Day 1 Accumulation Ratio of AUC0-24 After Administration of 6mg of MK-1167 | 9.26 Ratio |
Secondary
Panel B: Day 31 to Day 1 Accumulation Ratio of C24 After Administration of 6mg of MK-1167
Blood samples were collected at pre-specified timepoints to determine C24 on Days 1 and 31. C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Accumulation ratio of MK-1167 Day 31 to Day 1 was calculated as Day 31 C24/Day 1 C24.
Time frame: Days 1, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment and had C24 data available for assessment on Day 1 and Day 31.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Day 31 to Day 1 Accumulation Ratio of C24 After Administration of 6mg of MK-1167 | 9.54 Ratio |
Secondary
Panel B: Day 31 to Day 1 Accumulation Ratio of Cmax After Administration of 6mg of MK-1167
Blood samples were collected at pre-specified timepoints to determine Cmax on Days 1 and 31. Cmax was defined as the maximum serum concentration of MK-1167 reached. Accumulation ratio of MK-1167 Day 31 to Day 1 was calculated as Day 31 Cmax/Day 1 Cmax.
Time frame: Days 1, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment and had at Cmax data available for assessment on Day 1 and Day 31.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Day 31 to Day 1 Accumulation Ratio of Cmax After Administration of 6mg of MK-1167 | 7.88 Ratio |
Secondary
Panel B: t1/2 After Administration of 6mg of MK-1167
t1/2 was defined as the time required to divide plasma concentration of MK-1167 by half after reaching pseudo-equilibrium. Blood samples were collected at pre-specified timepoints for the determination of t1/2. Per protocol, t1/2 was based on noncompartmental analysis, and a geometric mean t1/2 value was presented for Panel B participants after administration of 6mg of MK-1167.
Time frame: Day 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment (6mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: t1/2 After Administration of 6mg of MK-1167 | 193 hour | Geometric Coefficient of Variation 40.4 |
Secondary
Panel B: Tmax After Administration of 6mg of MK-1167
Tmax was defined as time to the maximum concentration of MK-1167 reached. Blood samples were collected at pre-specified intervals for the determination of Tmax. Per protocol, Tmax was based on noncompartmental analysis, and a median Tmax value was presented for Panel B participants after administration of 6mg of MK-1167.
Time frame: Days 1, 23, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment (6mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Tmax After Administration of 6mg of MK-1167 | Day 1 | 1.08 hours |
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Tmax After Administration of 6mg of MK-1167 | Day 23 | 4.03 hours |
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Tmax After Administration of 6mg of MK-1167 | Day 31 | 2.97 hours |
Secondary
Panel B: Vz/F After Administration of 6mg of MK-1167
Vz/F was the apparent volume of distribution of MK-1167. Blood samples were collected at pre-specified intervals for the determination of Vz/F. Per protocol, Vz/F was based on noncompartmental analysis, and a geometric mean Vz/F value was presented for Panel B participants after administration of 6mg of MK-1167.
Time frame: Day 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose
Population: All Panel B randomized participants who received at least one dose of study treatment (6mg of MK-1167) and had at least one postdose data available for assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-1167 6mg QD + Donepezil 10mg QD | Panel B: Vz/F After Administration of 6mg of MK-1167 | 169 Liter | Geometric Coefficient of Variation 19.7 |