Trial · NCT01739348
An Efficacy and Safety Trial of Verubecestat (MK-8931) in Mild to Moderate Alzheimer's Disease (P07738)
NCT01739348, Phase 2, Phase 3, Terminated, Merck Sharp & Dohme LLC; results first posted 2018-05-16
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. An Efficacy and Safety Trial of Verubecestat (MK-8931) in Mild to Moderate Alzheimer's Disease (P07738). Trials, record NCT01739348. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01739348
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- An Efficacy and Safety Trial of Verubecestat (MK-8931) in Mild to Moderate Alzheimer's Disease (P07738)
- NCT number
- NCT01739348
- Status
- Terminated
- Phases
- Phase 2, Phase 3
- Enrollment
- 2,211 participants, actual
- Lead sponsor
- Merck Sharp & Dohme LLC
- Conditions
- Alzheimer's Disease
- Interventions
- Verubecestat (Part I and Part II), Verubecestat (Part I and Part II), Verubecestat (Part I and Part II), Placebo (Part I), Verubecestat (Part II)
- First posted
- 2012-12-03
- Last updated
- 2018-10-24
- Other registries' IDs
- eudract:2011-003151-20
- Results first posted
- 2018-05-16
Source ClinicalTrials.gov
Registered outcomes15
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | [Part I (Base Study)] Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score | Baseline and week 78 | Least squares mean change from baseline at week 78 was assessed for the ADAS-Cog score. ADAS-Cog measures cognition by assessing 11 metrics impaired in Alzheimer's Disease (AD): speech; speech comprehension; word finding; word recall; object/finger naming; orientation; obeying commands; ideational praxis; constructional praxis; word recognition; and remembering instruction. For each metric, scores range from 0 (no impairment) to (depending on the metric) either 5 (8 metrics), 8, 10, or 12 (1 metric each); higher scores indicate more severe impairment. Individual scores sum to a total ADAS-Cog score, ranging from 0-70. Higher total scores indicate greater cognitive impairment and AD severity. Further, increases in AD severity over time would be reflected by increases in ADAS-Cog score. |
| Primary | [Part I (Base Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score | Baseline and week 78 | Least squares mean change from baseline at week 78 was assessed for the ADCS-ADL score. The ADCS-ADL score measures the performance of activities of daily living, calculated from a 24-question survey. For each of the 24 questions, scores range from 0 (no independence) to (depending on the question) either 2 (1 question), 3 (17 questions), 4 (5 questions), or 5 (1 question), with higher scores indicating greater independence in activity performance. Scores from individual questions are summed into a total ADCS-ADL score, with total scores ranging from 0 to 78. Lower scores indicate less independence in activity performance and, as a result, greater AD severity. Further, increases in AD severity over time would be reflected by decreases in ADCS-ADL score. |
| Primary | [Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score | Baseline and week 104 | Mean change from baseline at week 104 was assessed for the ADAS-Cog score. ADAS-Cog measures cognition by assessing 11 metrics impaired in Alzheimer's Disease (AD): speech; speech comprehension; word finding; word recall; object/finger naming; orientation; obeying commands; ideational praxis; constructional praxis; word recognition; and remembering instruction. For each metric, scores range from 0 (no impairment) to (depending on the metric) either 5 (8 metrics), 8, 10, or 12 (1 metric each); higher scores indicate more severe impairment. Individual scores sum to a total ADAS-Cog score, ranging from 0-70. Higher total scores indicate greater cognitive impairment and AD severity. Further, increases in AD severity over time would be reflected by increases in ADAS-Cog score. Per study protocol, the baseline measurement to be used was the baseline measurement obtained in Part I. |
| Primary | [Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score | Baseline and week 104 | Mean change from baseline at week 104 was assessed for the ADCS-ADL score. The ADCS-ADL score measures the performance of activities of daily living, calculated from a 24-question survey. For each of the 24 questions, scores range from 0 (no independence) to (depending on the question) either 2 (1 question), 3 (17 questions), 4 (5 questions), or 5 (1 question), with higher scores indicating greater independence in activity performance. Scores from individual questions are summed into a total ADCS-ADL score, with total scores ranging from 0 to 78. Lower scores indicate less independence in activity performance and, as a result, greater AD severity. Further, increases in AD severity over time would be reflected by decreases in ADCS-ADL score. Per study protocol, the baseline measurement to be used was the baseline measurement obtained in Part I. |
| Primary | [Part I (Base Study)] Number of Participants Who Experienced an Adverse Event | Up to week 80 (up to 2 weeks following cessation of study treatment in Part I) | The number of participants experiencing an adverse event (AE) in Part I was assessed. An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product is also an AE. |
| Primary | [Part II (Extension Study)] Number of Participants Who Experienced an Adverse Event | From week 78 (end of treatment in Part I) up to week 262 of Part II | The number of participants experiencing an adverse event (AE) in Part II was assessed. An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product is also an AE. |
| Primary | [Part I (Base Study)] Number of Participants Who Discontinued From Study Drug Due to an Adverse Event | Up to week 78 | The number of participants discontinuing from study drug due to an AE in Part I was assessed. An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product is also an AE. |
| Primary | [Part II (Extension Study)] Number of Participants Who Discontinued From Study Drug Due to an Adverse Event | From week 78 (end of treatment in Part I) up to week 260 of Part II | The number of participants discontinuing from study drug due to an AE in Part II was assessed. An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product is also an AE. |
| Secondary | [Part I (Base Study)] Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score | Baseline and week 78 | Least squares mean change from baseline at week 78 was assessed for CDR-SB score. The CDR-SB score is a clinical rating of global cognitive function, comprised of 6 domains including: memory; orientation; judgment and problem solving; community affairs; home and hobbies; and personal care. For each domain, the degree of impairment is assessed by a semi-structured interview of the participant as well as the participant's caregiver. For each domain, potential scores range from 0 (no impairment) to 3 (severe impairment). Scores from each individual domain are summed to the total CDR-SB score, with total scores ranging from 0-18. Higher scores indicate more severe cognitive impairment. Further, increases in cognitive impairment would be reflected by increases in CDR-SB score. |
| Secondary | [Part I (Base Study)] Percent Change From Baseline in Total Hippocampal Volume (THV) | Baseline and week 78 | Least squares mean percent change from baseline at week 78 was calculated for Total Hippocampal Volume (THV) as measured by volumetric magnetic resonance imaging (vMRI). Longitudinal analysis of within-participant THV is computed using a change analysis algorithm using tensor-based morphometry. This technique produces one measure of volume change calculated from the registration of serial vMRI scans at the follow-up time point relative to baseline. Negative percent changes from baseline indicate decreases in THV (i.e. increased hippocampal atrophy). |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 registered outcomesOutcomes15
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | [Part I (Base Study)] Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score | Baseline and week 78 | All randomized participants with a baseline and ≥1 within-analysis-window ADAS-Cog observation subsequent to ≥1 dose of study drug (FAS population). Per protocol, the 200 participants enrolled before IA (all arms) and all participants receiving 60mg Verubecestat (Arm C) were excluded. | Score on a Scale | LEAST_SQUARES_MEAN |
| PRIMARY | [Part I (Base Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score | Baseline and week 78 | All randomized participants with a baseline and ≥1 within-analysis-window ADCS-ADL observation subsequent to ≥1 dose of study drug (FAS population). Per protocol, the 200 participants enrolled before IA (all arms) and all participants receiving 60mg Verubecestat (Arm C) were excluded. | Score on a Scale | LEAST_SQUARES_MEAN |
| PRIMARY | [Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score | Baseline and week 104 | All randomized participants continuing to Part II, with a baseline and ≥1 within-analysis-window ADAS-Cog observation subsequent to ≥1 dose of study drug (FAS population), having an ADAS-Cog observation at week 104. Per protocol, the 200 participants enrolled before IA (all arms) and all participants receiving 60mg Verubecestat were excluded. | Score on a Scale | MEAN |
| PRIMARY | [Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score | Baseline and week 104 | All randomized participants continuing to Part II, with a baseline and ≥1 within-analysis-window ADCS-ADL observation subsequent to ≥1 dose of study drug (FAS population), having an ADCS-ADL observation at week 104. Per protocol, the 200 participants enrolled before IA (all arms) and all participants receiving 60mg Verubecestat were excluded. | Score on a Scale | MEAN |
| PRIMARY | [Part I (Base Study)] Number of Participants Who Experienced an Adverse Event | Up to week 80 (up to 2 weeks following cessation of study treatment in Part I) | Includes all randomized participants in Part I receiving ≥1 dose of trial treatment. | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | [Part II (Extension Study)] Number of Participants Who Experienced an Adverse Event | From week 78 (end of treatment in Part I) up to week 262 of Part II | Includes all randomized participants continuing to Part II, receiving ≥1 dose of trial treatment in Part II. For included participants, the data reflect AEs occurring in Part II only. | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | [Part I (Base Study)] Number of Participants Who Discontinued From Study Drug Due to an Adverse Event | Up to week 78 | Includes all randomized participants in Part I receiving ≥1 dose of trial treatment. | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | [Part II (Extension Study)] Number of Participants Who Discontinued From Study Drug Due to an Adverse Event | From week 78 (end of treatment in Part I) up to week 260 of Part II | Includes all randomized participants continuing to Part II, receiving ≥1 dose of trial treatment in Part II. For included participants, the data reflect treatment discontinuations occurring in Part II only. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | [Part I (Base Study)] Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score | Baseline and week 78 | All randomized participants with a baseline and ≥1 within-analysis-window CDR-SB observation subsequent to ≥1 dose of study drug (FAS population). Per protocol, the 200 participants enrolled before IA (all arms) and all participants receiving 60mg Verubecestat (Arm C) were excluded. | Score on a Scale | LEAST_SQUARES_MEAN |
| SECONDARY | [Part I (Base Study)] Percent Change From Baseline in Total Hippocampal Volume (THV) | Baseline and week 78 | All randomized participants with a baseline and ≥1 within-analysis-window THV observation subsequent to ≥1 dose of study drug (FAS population). Per protocol, the 200 participants enrolled prior to IA (all arms) and all participants receiving 60mg Verubecestat (Arm C) were excluded. | Percent Change | LEAST_SQUARES_MEAN |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 outcomesResults by group49
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| [Part I (Base Study)] Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score | Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] | 7.9 | 95% Confidence Interval 7.2 to 8.6 | Score on a Scale | |
| [Part I (Base Study)] Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score | Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II] | 8.0 | 95% Confidence Interval 7.3 to 8.7 | Score on a Scale | |
| [Part I (Base Study)] Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score | Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II] | 7.7 | 95% Confidence Interval 7.0 to 8.4 | Score on a Scale | |
| [Part I (Base Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score | Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] | -8.4 | 95% Confidence Interval -9.5 to -7.4 | Score on a Scale | |
| [Part I (Base Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score | Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II] | -8.2 | 95% Confidence Interval -9.2 to -7.1 | Score on a Scale | |
| [Part I (Base Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score | Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II] | -8.9 | 95% Confidence Interval -9.9 to -8.0 | Score on a Scale | |
| [Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score | Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] | 10.1 | Standard Deviation 9.9 | Score on a Scale | |
| [Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score | Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II] | 8.5 | Standard Deviation 9.5 | Score on a Scale | |
| [Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score | Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II] | 9.6 | Standard Deviation 9.5 | Score on a Scale | |
| [Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score | Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] | -10.7 | Standard Deviation 13.7 | Score on a Scale |
1 to 10 of 49Source ClinicalTrials.gov
See all 49 results by groupParticipant flow32
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Part I (Base Study) | STARTED | Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] | 703 | |
| Part I (Base Study) | STARTED | Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II] | 700 | |
| Part I (Base Study) | STARTED | Arm C. Verubecestat 60mg/40mg [Part I]; 40 mg [Part II] | 103 | |
| Part I (Base Study) | STARTED | Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II] | 705 | |
| Part I (Base Study) | Treated | Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] | 702 | |
| Part I (Base Study) | Treated | Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II] | 700 | |
| Part I (Base Study) | Treated | Arm C. Verubecestat 60mg/40mg [Part I]; 40 mg [Part II] | 103 | |
| Part I (Base Study) | Treated | Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II] | 705 | |
| Part I (Base Study) | COMPLETED | Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] | 501 | |
| Part I (Base Study) | COMPLETED | Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II] | 497 |
1 to 10 of 32Source ClinicalTrials.gov
See all 32 participant flowAdverse events3,160
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Arm A. Verubecestat 12 mg [Part I] | 8 | 702 | 8 |
| other | Anaemia | Blood and lymphatic system disorders | Arm B. Verubecestat 40 mg [Part I] | 11 | 700 | 11 |
| other | Anaemia | Blood and lymphatic system disorders | Arm C. Verubecestat 60mg/40mg [Part I] | 1 | 103 | 1 |
| other | Anaemia | Blood and lymphatic system disorders | Arm D. Placebo [Part I] | 6 | 705 | 6 |
| other | Anaemia | Blood and lymphatic system disorders | Arm A. Verubecestat 12 mg [Part II] | 5 | 379 | 5 |
| other | Anaemia | Blood and lymphatic system disorders | Arm B. Verubecestat 40 mg [Part II] | 1 | 365 | 1 |
| other | Anaemia | Blood and lymphatic system disorders | Arm C. Verubecestat 40 mg [Part II] | 4 | 61 | 5 |
| other | Anaemia | Blood and lymphatic system disorders | Arm D. Verubecestat 40 mg [Part II] | 5 | 394 | 5 |
| other | Constipation | Gastrointestinal disorders | Arm A. Verubecestat 12 mg [Part I] | 30 | 702 | 32 |
| other | Constipation | Gastrointestinal disorders | Arm B. Verubecestat 40 mg [Part I] | 27 | 700 | 29 |
1 to 10 of 3,160Source ClinicalTrials.gov
See all 3,160 adverse eventsAdverse event totals24
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Arm A. Verubecestat 12 mg [Part I] | 9 | 702 |
| Total, all-cause mortality | Arm B. Verubecestat 40 mg [Part I] | 13 | 700 |
| Total, all-cause mortality | Arm C. Verubecestat 60mg/40mg [Part I] | 3 | 103 |
| Total, all-cause mortality | Arm D. Placebo [Part I] | 6 | 705 |
| Total, all-cause mortality | Arm A. Verubecestat 12 mg [Part II] | 6 | 379 |
| Total, all-cause mortality | Arm B. Verubecestat 40 mg [Part II] | 4 | 365 |
| Total, all-cause mortality | Arm C. Verubecestat 40 mg [Part II] | 4 | 61 |
| Total, all-cause mortality | Arm D. Verubecestat 40 mg [Part II] | 8 | 394 |
| Total, other adverse events | Arm A. Verubecestat 12 mg [Part I] | 408 | 702 |
| Total, other adverse events | Arm B. Verubecestat 40 mg [Part I] | 440 | 700 |
1 to 10 of 24Source ClinicalTrials.gov
See all 24 adverse event totalsPapers7
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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