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| ID | Type | Description | Link |
|---|---|---|---|
| MK-1942-005 | Other Identifier | Merck Protocol Number |
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The study investigated the effects on safety and pharmacokinetics (PK) of MK-1942 and donepezil when co-administered to participants with Alzheimer's Disease with mild-to-moderate cognitive impairment stably treated with donepezil. The objectives of this study were to determine if the combination of MK-1942 with donepezil increases the incidence or severity of adverse events (AEs) previously reported for these agents alone, or results in unanticipated AEs in the patient population targeted for MK-1942 treatment. In addition, changes in the PK parameters of either MK-1942 or donepezil as a result of co-administration were assessed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Donepezil | Experimental | Participants receive Dose Level 1: 8-mg MK-1942 twice daily (BID) x 7 days (7D), Day 1 to Day 7; Dose Level 2: 15-mg MK-1942 BID x 7D, Day 8 to Day 14; Dose Level 3: 30-mg MK-1942 BID x 7D, Day 15 to Day 21; Dose Level 4: ≤50-mg MK-1942 BID x 7D (Provisional Dose Level), Day 22 to Day 28 All participants to receive Donepezil once daily. |
|
| Placebo | Placebo Comparator | Placebo to MK-1942 BID x 21 [28] D All participants to receive Donepezil once daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-1942 | Drug | MK-1942 1 mg, 5 mg, and/or 10 mg capsules taken twice daily (BID) by mouth. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With ≥1 Adverse Event (AE) | An AE is 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. | Up to Day 42 |
| Number of Participants Discontinuing From Study Therapy Due to an Adverse Event (AE) | An AE is 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. | Up to Day 28 |
| Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) Findings | The number of participants with clinically significant 12-lead ECGs is presented. Recordings were made throughout the study, with the participant in a semi-recumbent position having rested in this position for at least 10 minutes beforehand. | Up to Day 28 |
| Number of Participants With Abnormal (Impaired) Results on Targeted Neurological Exams | The number of participants with abnormal (impaired) results on targeted neurological exams will be presented. The targeted neurological exam contains Modules 1, 2 and 5 of the general examination, focusing on arousal, cranial nerve function, and gait and will be administered several times throughout the treatment period starting on Day 1 up until Day 29. The number of participants with abnormal (impaired) results on targeted neurological exams will be reported. Each exam will be graded as Normal or Impaired with the abnormality described. | Up to 29 days |
| Number of Participants Who Reported Suicidal Ideation and/or Behavior on Study Based on Responses to the Columbia Suicide Severity Rating Scale (C-SSRS) | The number of participants with suicidality using the C-SSRS is presented. The C-SSR will be used in this study only for the purpose of safety monitoring by measuring the incidence of different types of suicidality categories during treatment. C-SSRS assessment will be based upon a clinician's interpretation of the participant's responses to the C-SSRS questions, not by a numbered scale. Suicidal ideation and/or behaviors identified on the C-SSRS may not be considered an adverse event, based on the investigator's judgment. Participants who report at least one occurrence of suicidal behavior or suicidal ideation will be counted as having experienced suicidality. Suicidal behavior includes suicide attempt, aborted attempt, interrupted attempt, or preparatory behavior. Suicidal ideation include a wish to die or active suicidal thought with or without method, intent or plan. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to 12 Hours Postdose (AUC0-12) of MK-1942 | AUC0-12 is reported for the first day of treatment of each MK-1942 dose. | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
| AUC From Dosing to 24 Hours Postdose (AUC0-24) of MK-1942 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Woodland Research Northwest, LLC ( Site 0004) | Rogers | Arkansas | 72758-6442 | United States | ||
| Velocity Clinical Research, Hallandale Beach ( Site 0002) |
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| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
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Male and female adult (≥50 to ≤85 years of age) participants with Alzheimer's disease (AD) and mild-to-moderate cognitive impairment were enrolled at 4 study centers in the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | MK-1942 AD | Participants with AD receive donepezil 10 mg to 15 mg once daily (QD), and MK-1942 twice daily (BID), for 28 days. Doses of MK-1942 were 8 mg (Week 1), 15 mg (Week 2), 30 mg (Week 3) and 50 mg (Week 4). |
| FG001 | Placebo + Donepezil AD | Participants with AD receive donepezil 10 mg to 15 mg QD, and placebo BID, for 28 days. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | MK-1942 AD | Participants with AD receive donepezil 10 mg to 15 mg once daily (QD), and MK-1942 twice daily (BID), for 28 days. Doses of MK-1942 were 8 mg (Week 1), 15 mg (Week 2), 30 mg (Week 3) and 50 mg (Week 4). |
| BG001 | Placebo + Donepezil AD |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With ≥1 Adverse Event (AE) | An AE is 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. | All participants who received ≥1 dose of study treatment are included. | Posted | Count of Participants | Participants | Up to Day 42 |
|
Up to 42 days
All participants who received ≥1 dose of study treatment are included. Safety is reported according to MK-1942 dose or placebo treatment received.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MK-1942 8 mg BID 7 Days | Participants received MK-1942 8 mg + donepezil during Week 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Scleral hyperaemia | Eye disorders | MedDRA 25.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme LLC | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 16, 2020 | May 8, 2023 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000077265 | Donepezil |
| ID | Term |
|---|---|
| D007189 | Indans |
| D007192 | Indenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
Not provided
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| Donepezil |
| Drug |
Donepezil 5 mg and/or 10 mg tablets taken once daily (QD) by mouth. |
|
| Placebo | Drug | Placebo capsule matched to MK-1942 taken BID by mouth. |
|
| Up to 42 days |
| Change From Baseline in Heart Rate (HR) | The mean change from baseline in HR is presented. Change in HR was determined the first day of treatment with a new dose of MK-1942. A negative value indicates a decrease in HR relative to baseline, and a positive value indicates an increase. | Baseline (Day -1) and Days 1, 8, 15, and 22: 2 hours postdose |
| Change From Baseline in Systolic Blood Pressure (SBP) | The mean change from baseline in SBP is presented. Change in SBP was determined the first day of treatment with a new dose of MK-1942. Negative values represent a decrease in SBP relative to baseline, and positive values represent an increase. | Baseline (Day -1) and Days 1, 8, 15, and 22: 2 hours postdose |
| Mean Change From Baseline in Diastolic Blood Pressure (DBP) | The mean change from baseline in DBP is presented. Change in DBP was determined the first day of treatment with a new dose of MK-1942. Negative values represent a decrease in DBP relative to baseline, and positive values represent an increase. | Baseline (Day -1) and Days 1, 8, 15, and 22: 2 hours postdose |
| Number of Participants With Abnormal Clinical Chemistry Test Results Reported as Adverse Events | An AE is 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. The number of participants with abnormal chemistry-related AEs is reported. | Up to 42 days |
| Number of Participants With Abnormal Clinical Hematology Test Results Reported as Adverse Events | An AE is 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. The number of participants with abnormal hematology-related AEs is reported. | Up to 42 days |
| Number of Participants With Abnormal Urinalysis Results Reported as Adverse Events | An AE is 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. The number of participants with an abnormal urinalysis results AE is reported. | Up to 42 days |
AUC0-24 is reported for the first day of treatment of each MK-1942 dose. Due to twice daily dosing, AUC0-24 was calculated as "AUC0-24 = AUC0-12 x 2". |
| Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
| Maximum Plasma Concentration (Cmax) of MK-1942 | Cmax is reported for the first day of treatment of each MK-1942 dose. | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
| Trough Plasma Concentration (Ctrough) of MK-1942 | Ctrough is reported for the first day of treatment of each MK-1942 dose. Data from healthy elderly participants used for statistical analyses are unpublished findings from study MK-1942-004. | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
| Time to Reach Maximum Plasma Concentration (Tmax) of MK-1942 | Tmax is reported for the first day of treatment of each MK-1942 dose. | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
| Apparent Terminal Plasma Half-Life (t½) of MK-1942 | t½ is reported for MK-1942 50 mg. | Day 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
| Apparent Clearance at Steady-state (CLss/F) of MK-1942 | CLss/F is reported for MK-1942 50 mg. | Day 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
| Apparent Volume of Distribution at Steady State (Vzss/F) of MK-1942 | Vzss/F is reported for MK-1942 50 mg. | Day 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
| AUC0-24 of Donepezil | AUC0-24 is reported for donepezil 10 mg alone (Day -1) or with MK-1942 50 mg (Day 28). Due to twice daily dosing, AUC0-24 was calculated as "AUC0-12 x 2". | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
| Cmax of Donepezil | Cmax is reported for donepezil 10 mg alone (Day -1) or with MK-1942 50 mg (Day 28). | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
| Ctrough of Donepezil | Ctrough is reported for donepezil 10 mg alone (Day -1) or with MK-1942 50 mg (Day 28). | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
| Tmax of Donepezil | Tmax is reported for donepezil 10 mg alone (Day -1) or with MK-1942 50 mg (Day 28). | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
| Hallandale |
| Florida |
| 33009 |
| United States |
| iResearch Atlanta ( Site 0005) | Decatur | Georgia | 30030 | United States |
| ICON ( Site 0003) | Salt Lake City | Utah | 84124 | United States |
Participants with AD receive donepezil 10 mg to 15 mg QD, and placebo BID, for 28 days. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG002 | MK-1942 30 mg + Donepezil AD | Participants with AD received MK-1942 30 mg + donepezil during Week 3. |
| OG003 | MK-1942 50 mg + Donepezil AD | Participants with AD received MK-1942 50 mg + donepezil during Week 4. |
| OG004 | Placebo + Donepezil AD | Participants with AD receive donepezil 10 mg to 15 mg QD, and placebo BID, for 28 days. |
|
|
| Primary | Number of Participants Discontinuing From Study Therapy Due to an Adverse Event (AE) | An AE is 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. | All participants who received ≥1 dose of study treatment are included. | Posted | Count of Participants | Participants | Up to Day 28 |
|
|
|
| Primary | Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) Findings | The number of participants with clinically significant 12-lead ECGs is presented. Recordings were made throughout the study, with the participant in a semi-recumbent position having rested in this position for at least 10 minutes beforehand. | All participants who received ≥1 dose of study treatment are included. | Posted | Count of Participants | Participants | Up to Day 28 |
|
|
|
| Primary | Number of Participants With Abnormal (Impaired) Results on Targeted Neurological Exams | The number of participants with abnormal (impaired) results on targeted neurological exams will be presented. The targeted neurological exam contains Modules 1, 2 and 5 of the general examination, focusing on arousal, cranial nerve function, and gait and will be administered several times throughout the treatment period starting on Day 1 up until Day 29. The number of participants with abnormal (impaired) results on targeted neurological exams will be reported. Each exam will be graded as Normal or Impaired with the abnormality described. | All participants who received ≥1 dose of study treatment are included. | Posted | Count of Participants | Participants | Up to 29 days |
|
|
|
| Primary | Number of Participants Who Reported Suicidal Ideation and/or Behavior on Study Based on Responses to the Columbia Suicide Severity Rating Scale (C-SSRS) | The number of participants with suicidality using the C-SSRS is presented. The C-SSR will be used in this study only for the purpose of safety monitoring by measuring the incidence of different types of suicidality categories during treatment. C-SSRS assessment will be based upon a clinician's interpretation of the participant's responses to the C-SSRS questions, not by a numbered scale. Suicidal ideation and/or behaviors identified on the C-SSRS may not be considered an adverse event, based on the investigator's judgment. Participants who report at least one occurrence of suicidal behavior or suicidal ideation will be counted as having experienced suicidality. Suicidal behavior includes suicide attempt, aborted attempt, interrupted attempt, or preparatory behavior. Suicidal ideation include a wish to die or active suicidal thought with or without method, intent or plan. | All participants who received ≥1 dose of study treatment are included. | Posted | Count of Participants | Participants | Up to 42 days |
|
|
|
| Primary | Change From Baseline in Heart Rate (HR) | The mean change from baseline in HR is presented. Change in HR was determined the first day of treatment with a new dose of MK-1942. A negative value indicates a decrease in HR relative to baseline, and a positive value indicates an increase. | All participants who received ≥1 dose of study treatment are included. | Posted | Mean | Standard Error | beats/min | Baseline (Day -1) and Days 1, 8, 15, and 22: 2 hours postdose |
|
|
|
| Primary | Change From Baseline in Systolic Blood Pressure (SBP) | The mean change from baseline in SBP is presented. Change in SBP was determined the first day of treatment with a new dose of MK-1942. Negative values represent a decrease in SBP relative to baseline, and positive values represent an increase. | All participants who received ≥1 dose of study treatment are included. | Posted | Mean | Standard Error | mmHg | Baseline (Day -1) and Days 1, 8, 15, and 22: 2 hours postdose |
|
|
|
| Primary | Mean Change From Baseline in Diastolic Blood Pressure (DBP) | The mean change from baseline in DBP is presented. Change in DBP was determined the first day of treatment with a new dose of MK-1942. Negative values represent a decrease in DBP relative to baseline, and positive values represent an increase. | All participants who received ≥1 dose of study treatment are included. | Posted | Mean | Standard Error | mmHg | Baseline (Day -1) and Days 1, 8, 15, and 22: 2 hours postdose |
|
|
|
| Primary | Number of Participants With Abnormal Clinical Chemistry Test Results Reported as Adverse Events | An AE is 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. The number of participants with abnormal chemistry-related AEs is reported. | All participants who received ≥1 dose of study treatment are included. | Posted | Count of Participants | Participants | Up to 42 days |
|
|
|
| Primary | Number of Participants With Abnormal Clinical Hematology Test Results Reported as Adverse Events | An AE is 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. The number of participants with abnormal hematology-related AEs is reported. | All participants who received ≥1 dose of study treatment are included. | Posted | Count of Participants | Participants | Up to 42 days |
|
|
|
| Primary | Number of Participants With Abnormal Urinalysis Results Reported as Adverse Events | An AE is 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. The number of participants with an abnormal urinalysis results AE is reported. | All participants who received ≥1 dose of study treatment are included. | Posted | Count of Participants | Participants | Up to 42 days |
|
|
|
| Secondary | Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to 12 Hours Postdose (AUC0-12) of MK-1942 | AUC0-12 is reported for the first day of treatment of each MK-1942 dose. | A subset of treated participants who complied with the protocol sufficiently to ensure the data are likely to reflect the underlying scientific model, are included. In addition, healthy control participant data is from study MK-1942-004. | Posted | Least Squares Mean | 95% Confidence Interval | hr*nmol/L | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
|
|
|
|
| Secondary | AUC From Dosing to 24 Hours Postdose (AUC0-24) of MK-1942 | AUC0-24 is reported for the first day of treatment of each MK-1942 dose. Due to twice daily dosing, AUC0-24 was calculated as "AUC0-24 = AUC0-12 x 2". | A subset of treated participants who complied with the protocol sufficiently to ensure the data are likely to reflect the underlying scientific model, are included. In addition, healthy control participant data is from study MK-1942-004. | Posted | Least Squares Mean | 95% Confidence Interval | hr*nmol/L | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
|
|
|
|
| Secondary | Maximum Plasma Concentration (Cmax) of MK-1942 | Cmax is reported for the first day of treatment of each MK-1942 dose. | A subset of treated participants who complied with the protocol sufficiently to ensure the data are likely to reflect the underlying scientific model, are included. In addition, healthy control participant data is from study MK-1942-004. | Posted | Least Squares Mean | 95% Confidence Interval | nmol/L | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
|
|
|
|
| Secondary | Trough Plasma Concentration (Ctrough) of MK-1942 | Ctrough is reported for the first day of treatment of each MK-1942 dose. Data from healthy elderly participants used for statistical analyses are unpublished findings from study MK-1942-004. | A subset of treated participants who complied with the protocol sufficiently to ensure the data are likely to reflect the underlying scientific model, are included. In addition, healthy control participant data is from study MK-1942-004. | Posted | Least Squares Mean | 95% Confidence Interval | nmol/L | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
|
|
|
|
| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) of MK-1942 | Tmax is reported for the first day of treatment of each MK-1942 dose. | A subset of treated participants who complied with the protocol sufficiently to ensure the data are likely to reflect the underlying scientific model, are included. In addition, healthy control participant data is from study MK-1942-004. | Posted | Median | Full Range | Hours | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
|
|
|
| Secondary | Apparent Terminal Plasma Half-Life (t½) of MK-1942 | t½ is reported for MK-1942 50 mg. | A subset of treated participants who complied with the protocol sufficiently to ensure the data are likely to reflect the underlying scientific model, are included. In addition, healthy control participant data is from study MK-1942-004. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Day 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
|
|
|
| Secondary | Apparent Clearance at Steady-state (CLss/F) of MK-1942 | CLss/F is reported for MK-1942 50 mg. | A subset of treated participants who complied with the protocol sufficiently to ensure the data are likely to reflect the underlying scientific model, are included. In addition, healthy control participant data is from study MK-1942-004. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Day 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
|
|
|
| Secondary | Apparent Volume of Distribution at Steady State (Vzss/F) of MK-1942 | Vzss/F is reported for MK-1942 50 mg. | A subset of treated participants who complied with the protocol sufficiently to ensure the data are likely to reflect the underlying scientific model, are included. In addition, healthy control participant data is from study MK-1942-004. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Day 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
|
|
|
| Secondary | AUC0-24 of Donepezil | AUC0-24 is reported for donepezil 10 mg alone (Day -1) or with MK-1942 50 mg (Day 28). Due to twice daily dosing, AUC0-24 was calculated as "AUC0-12 x 2". | A subset of treated participants who complied with the protocol sufficiently to ensure the data are likely to reflect the underlying scientific model, are included. The same participant's data are used for Day -1 and Day 28 when available. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/mL | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
|
|
|
|
| Secondary | Cmax of Donepezil | Cmax is reported for donepezil 10 mg alone (Day -1) or with MK-1942 50 mg (Day 28). | A subset of treated participants who complied with the protocol sufficiently to ensure the data are likely to reflect the underlying scientific model, are included. The same participant's data are used for Day -1 and Day 28 when available. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
|
|
|
|
| Secondary | Ctrough of Donepezil | Ctrough is reported for donepezil 10 mg alone (Day -1) or with MK-1942 50 mg (Day 28). | A subset of treated participants who complied with the protocol sufficiently to ensure the data are likely to reflect the underlying scientific model, are included. The same participant's data are used for Day -1 and Day 28 when available. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
|
|
|
|
| Secondary | Tmax of Donepezil | Tmax is reported for donepezil 10 mg alone (Day -1) or with MK-1942 50 mg (Day 28). | A subset of treated participants who complied with the protocol sufficiently to ensure the data are likely to reflect the underlying scientific model, are included. The same participant's data are used for Day -1 and Day 28 when available. | Posted | Median | Full Range | Hours | Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose |
|
|
|
| 0 |
| 22 |
| 0 |
| 22 |
| 13 |
| 22 |
| EG001 | MK-1942 15 mg BID 7 Days | Participants received MK-1942 15 mg + donepezil during Week 2. | 0 | 19 | 0 | 19 | 4 | 19 |
| EG002 | MK-1942 30 mg Bid 7D | Participants received MK-1942 30 mg + donepezil during Week 3. | 0 | 15 | 0 | 15 | 4 | 15 |
| EG003 | MK-1942 50 mg BID & Days | Participants received MK-1942 50 mg + donepezil during Week 4. | 0 | 15 | 0 | 15 | 5 | 15 |
| EG004 | MK-1942 Total | Participants received MK-1924 8 mg, 15 mg, 30 mg, and 50 mg during Weeks 1, 2, 3, and 4, respectively. | 0 | 22 | 0 | 22 | 18 | 22 |
| EG005 | Placebo Bid | Participants received placebo + donepezil for 7 days. | 0 | 5 | 0 | 5 | 4 | 5 |
| Scleritis | Eye disorders | MedDRA 25.0 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 25.0 | Systematic Assessment |
|
| Anal incontinence | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Medical device site injury | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Vessel puncture site bruise | General disorders | MedDRA 25.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
|
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Blood sodium decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Electrocardiogram T wave biphasic | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Dystonia | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Nystagmus | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 25.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
|
If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
| GMR |
| 0.66 |
| 2-Sided |
| 95 |
| 0.53 |
| 0.82 |
| Other |
MK-1942 + Donepezil PK / MK-1942 Alone PK |
| 'MK-1942 Alone PK' are unpublished data from MK-1942-004 | GMR | 0.74 | 2-Sided | 95 | 0.55 | 1.00 | Other | MK-1942 + Donepezil PK / MK-1942 Alone PK |
| 'MK-1942 Alone PK' are unpublished data from MK-1942-004 | GMR | 0.77 | 2-Sided | 95 | 0.56 | 1.05 | Other | MK-1942 + Donepezil PK / MK-1942 PK Alone |
| GMR |
| 0.66 |
| 2-Sided |
| 95 |
| 0.53 |
| 0.82 |
| Other |
MK-1942 + Donepezil PK / MK-1942 Alone PK |
| 'MK-1942 Alone PK' are unpublished data from MK-1942-004 | GMR | 0.74 | 2-Sided | 95 | 0.55 | 1.00 | Other | MK-1942 + Donepezil PK / MK-1942 Alone PK |
| 'MK-1942 Alone PK' are unpublished data from MK-1942-004 | GMR | 0.77 | 2-Sided | 95 | 0.56 | 1.05 | Other | MK-1942 + Donepezil PK / MK-1942 PK Alone |
| GMR |
| 0.68 |
| 2-Sided |
| 95 |
| 0.52 |
| 0.87 |
| Other |
MK-1942 + Donepezil PK / MK-1942 Alone PK |
| 'MK-1942 Alone PK' are unpublished data from MK-1942-004 | GMR | 0.79 | 2-Sided | 95 | 0.59 | 1.06 | Other | MK-1942 + Donepezil PK / MK-1942 Alone PK |
| 'MK-1942 Alone PK' are unpublished data from MK-1942-004 | GMR | 0.74 | 2-Sided | 95 | 0.51 | 1.08 | Other | MK-1942 + Donepezil PK / MK-1942 PK Alone |
| GMR |
| 0.67 |
| 2-Sided |
| 95 |
| 0.55 |
| 0.81 |
| Other |
MK-1942 + Donepezil PK / MK-1942 Alone PK |
| 'MK-1942 Alone PK' are unpublished data from MK-1942-004 | GMR | 0.68 | 2-Sided | 95 | 0.49 | 0.93 | Other | MK-1942 + Donepezil PK / MK-1942 Alone PK |
| 'MK-1942 Alone PK' are unpublished data from MK-1942-004 | GMR | 0.72 | 2-Sided | 95 | 0.54 | 0.98 | Other | MK-1942 + Donepezil PK / MK-1942 PK Alone |