Alzheimer's DiseasePhase 2/3EPOCHNCT01739348

An Efficacy and Safety Trial of Verubecestat (MK-8931) in Mild to Moderate Alzheimer's Disease (P07738)

A Phase 2/3 study testing Verubecestat (Part I and Part II) and Verubecestat (Part II) in people with Alzheimer's Disease, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 55 to 85 years
Conditions the study is for: Alzheimer's Disease
What is being tested?: Verubecestat (Part I and Part II) and Verubecestat (Part II)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 2,211 participants
Where: No sites listed yet
Study dates: 30 Nov 2012to 14 Apr 2017
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 55 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Diagnosis of probable AD based on both a) the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and b) the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for AD
AD is of mild to moderate severity
Clear history of cognitive and functional decline over at least one year that is either a) documented in medical records or b) documented by history from an informant who knows the subject well
Able to read at a 6th grade level or equivalent, and must have a history of academic achievement and/or employment sufficient to exclude mental retardation
If a participant is receiving an acetylcholinesterase inhibitor, memantine, medical food/supplement (e.g., vitamin E) and/or herbal medications for AD, the dose must have been stable for at least three months before Screening, and the participant must be willing to remain on the same dose for the duration of the trial. Participants may need to be on AD treatments in accordance with local requirements
Participant must have a reliable and competent trial partner/caregiver who must have a close relationship with the subject
Tolerated study drug and completed the initial 78-week period of the trial (Part I)
Participant must have a reliable and competent trial partner who must have a close relationship with the subject

Who cannot join

History of stroke
Evidence of a neurological disorder other than the disease being studied (i.e., probable AD)
History of seizures or epilepsy within the last 5 years before Screening
Evidence of a clinically relevant or unstable psychiatric disorder, excluding major depression in remission
Participant is at imminent risk of self-harm or of harm to others
History of alcoholism or drug dependency/abuse within the last 5 years before Screening

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Participant does not have a magnetic resonance imaging (MRI) scan obtained within 12 months of Screening and is unwilling or not eligible to undergo an MRI scan at the Screening Visit. With Sponsor approval, a head computed tomography (CT) scan may be substituted for MRI scan to evaluate eligibility
History of hepatitis or liver disease that has been active within the six months prior to Screening Visit
Recent or ongoing, uncontrolled, clinically significant medical condition within 3 months of the Screening Visit (e.g., diabetes, hypertension, thyroid or endocrine disease, congestive heart failure, angina, cardiac or gastrointestinal disease, dialysis, or abnormal renal function) other than the condition being studied such that participation in the trial would pose a significant medical risk to the subject. Controlled co-morbid conditions are not exclusionary if stable within three months of the Screening Visit
History or current evidence of long QT syndrome, corrected QT (QTc) interval ≥470 milliseconds (for male subjects) or ≥480 milliseconds (for female subjects), or torsades de pointes
History of malignancy occurring within the five years before Screening, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or localized prostate carcinoma; or malignancy which has been treated with potentially curative therapy with no evidence of recurrence for ≥3 year post-therapy
Clinically significant vitamin B12 or folate deficiency in the six months before Screening Visit
Use of any investigational drugs within 30 days (or longer depending on drug) before Screening or participation in studies involving repeated cognitive testing within 30 days before Screening. Participation in an observational study, such as those involving annual cognitive assessments and/or neuroimaging, may be allowed if approved by Sponsor
History of a hypersensitivity reaction to more than three drugs
Has tested positive for human immunodeficiency virus (HIV)
Close family member (including the caregiver, the spouse or any children) who is among the personnel of the investigational or sponsor staff directly involved with this trial
Additional Exclusion Criteria for Safety Cohort:
History of an ongoing medical condition that has been poorly controlled within 6 months of the Screening Visit (e.g., hypotension, diabetes, hypertension, cerebrovascular disease, thyroid disease, endocrine disturbance, congestive heart failure, cardiac or gastrointestinal disease, dialysis, or abnormal renal function) other than the condition being studied such that a subject's participation in the trial would pose a significant medical risk
History of congestive heart failure (moderate or greater severity), myocardial infarction, heart surgery, syncope, bradycardia, or clinically significant hypotension within one year before Screening
Participant is at imminent risk of self-harm or of harm to others
Has developed a recent or ongoing, uncontrolled, clinically significant medical condition other than AD
Has history of or has developed during Part I evidence of long QT syndrome, QTc interval ≥470 milliseconds (for male subjects) or ≥480 milliseconds (for female subjects), or torsades de pointes
Has developed a form of dementia that is not AD

About this study

Official title: A Randomized, Placebo Controlled, Parallel-Group, Double Blind Efficacy and Safety Trial of MK-8931 With a Long Term Double-Blind Extension in Subjects With Mild to Moderate Alzheimer's Disease (Protocol No. MK-8931-017-10)(Also Known as SCH 900931, P07738)

This study consists of two parts, Part I and Part II. The purpose of Part I of the study is to assess the efficacy and safety of verubecestat (MK-8931) compared with placebo administered for 78 weeks in the treatment of Alzheimer's Disease (AD). The primary study hypotheses for Part I are that at least one verubecestat dose is superior to placebo at 78 weeks of treatment with respect to change from baseline in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) score and that at least one verubecestat dose is superior to placebo at 78 weeks of treatment with respect to change from baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) score. The first approximately 400 participants entering Part I of the study are identified as the Safety Cohort. Participants who complete Part I of the study may choose to participate in Part II, which is a long term double-blind extension to assess efficacy and safety of verubecestat administered for up to an additional 260 weeks.

Read the detailed description

Two substudies are included in Part I of the study: 1) a medical imaging substudy to evaluate changes in brain amyloid protein load using positron emission tomography (PET) and an amyloid tracer ([18F]flutemetamol); and 2) a cerebrospinal fluid (CSF) biomarker substudy to evaluate changes in CSF concentrations of amyloid-β related peptides, total tau, and phosphorylated tau (p-tau). The substudies will be conducted only at designated investigational sites. Participants are not required to take part in a substudy in order to take part in the larger trial.

Conditions: Alzheimer's Disease
Being tested: Verubecestat (Part I and Part II), Placebo (Part I), Verubecestat (Part II)
Medical subject headings: Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Verubecestat (Part I and Part II)Drug
Also called SCH 900931
Single 12 mg verubecestat tablet once daily, taken orally
Verubecestat (Part I and Part II)Drug
Also called SCH 900931
Single 40 mg verubecestat tablet once daily, taken orally
Verubecestat (Part I and Part II)Drug
Also called SCH 900931
Single 60 or 40 mg verubecestat tablet once daily, taken orally
Placebo (Part I)Drug
Single placebo tablet matching verubecestat treatment once daily, taken orally
Verubecestat (Part II)Drug
Also called SCH 900931
Single 40 mg verubecestat tablet once daily, taken orally

Study groups in NCT01739348
Study group	Role	What they receive
Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II]	Experimental	[Part I] Verubecestat 12 mg once daily for 78 weeks in Study Part I (Base Study). [Part II] Participants completing Study Part I and continuing to Study Part II (Extension Study) receive Verubecestat 12 mg once daily for an additional 260 weeks. Receives: Drug: Verubecestat (Part I and Part II)
Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II]	Experimental	[Part I] Verubecestat 40 mg once daily for 78 weeks in Study Part I (Base Study). [Part II] Participants completing Study Part I and continuing to Study Part II (Extension Study) receive Verubecestat 40 mg once daily for an additional 260 weeks. Receives: Drug: Verubecestat (Part I and Part II)
Arm C. Verubecestat 60mg/40mg [Part I]; 40 mg [Part II]	Experimental	[Part I] Verubecestat 60 mg once daily until the first IA in Study Part I (Base Study). Following IA, participants in this group were switched to Verubecestat 40 mg once daily, for the remainder of Study Part I (total dosing period: 78 weeks). [Part II] Participants completing Study Part I and continuing to Study Part II (Extension Study) receive Verubecestat 40 mg once daily for an additional 260 weeks. Receives: Drug: Verubecestat (Part I and Part II)
Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II]	Placebo comparator	[Part I] Placebo once daily for 78 weeks in Study Part I (Base Study). [Part II] Participants completing Study Part I and continuing to Study Part II (Extension Study) receive Verubecestat 40 mg once daily for an additional 260 weeks. Receives: Drug: Placebo (Part I); Drug: Verubecestat (Part II)

What is being measured

The primary outcome is the main question the study is designed to answer.

[Part I (Base Study)] Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score
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.
Measured: Baseline and week 78
[Part I (Base Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score
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.
Measured: Baseline and week 78
[Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score
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.
Measured: Baseline and week 104
[Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score
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.
Measured: Baseline and week 104
[Part I (Base Study)] Number of Participants Who Experienced an Adverse Event
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.
Measured: Up to week 80 (up to 2 weeks following cessation of study treatment in Part I)
[Part II (Extension Study)] Number of Participants Who Experienced an Adverse Event
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.
Measured: From week 78 (end of treatment in Part I) up to week 262 of Part II
[Part I (Base Study)] Number of Participants Who Discontinued From Study Drug Due to an Adverse Event
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.
Measured: Up to week 78
[Part II (Extension Study)] Number of Participants Who Discontinued From Study Drug Due to an Adverse Event
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.
Measured: From week 78 (end of treatment in Part I) up to week 260 of Part II

Secondary outcomes (7)

[Part I (Base Study)] Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score
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.
Measured: Baseline and week 78
[Part I (Base Study)] Percent Change From Baseline in Total Hippocampal Volume (THV)
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).
Measured: Baseline and week 78
[Part I (Base Study)] Fold Change From Baseline in Cerebrospinal Fluid (CSF) Total Tau
Least squares mean fold change from baseline at week 78 was calculated for Total Tau concentration in CSF, a measure of brain tau pathology. Per protocol, CSF Total Tau concentration was analyzed as part of a substudy in Part I, with testing occurring only at select trial sites. Least squares mean fold change from baseline >1 indicates increased Total Tau concentration in the CSF.
Measured: Baseline and week 78
[Part I (Base Study)] Change From Baseline in Cortical Amyloid Load Assessed by [18F]Flutemetamol PET Standard Uptake Value Ratio (SUVR)
Least squares mean change from baseline at week 78 was calculated for SUVR, a measure of brain cortical amyloid load. Per protocol, SUVR was analyzed as part of a substudy in Part I, with testing occurring only at select trial sites. Participants receive the PET tracer [18F]Flutemetamol (IV). After 90 minutes, participants receive 4 PET scans (5 minutes each in duration). Using these PET scan images, specific brain ROIs (frontal, temporal, and parietal lobes; anterior and posterior cingulate and precuneus) are used to calculate regional SUVRs, defined as the relative ratio of pixel intensities at a specific ROI compared to a reference region (RR; subcortical white matter). These regional SUVRs are then averaged to compute a composite cortical SUVR for each participant. Higher composite cortical SUVR values indicate increased amyloid load, with negative changes in composite cortical SUVR over time indicating decreases in brain amyloid load.
Measured: Baseline and week 78
[Part I (Base Study)] Percentage of Participants Achieving Responder Status
The percentage of participants achieving responder status at week 78 was assessed. To determine which participants were considered responders, a linear regression was conducted at the participant level, yielding an estimated 78-week rate of change (i.e., a slope) for each participant with respect to ADAS-Cog and ADCS-ADL. To be declared a responder, a participant must have: 1) ADAS-Cog and ADCS-ADL observations at baseline and 78 weeks of treatment; 2) an ADAS-Cog slope > 4.0 over 78 weeks, and 3) an ADCS-ADL slope > -6.3 over 78 weeks. A participant failing to meet any of these criteria was designated as a non-responder at Week 78.
Measured: Week 78
[Part I (Base Study)] Change From Baseline in Neuropsychiatric Inventory (NPI) Score
Least squares mean change from baseline at week 78 was assessed for NPI score. NPI is a clinical assessment of psychiatric status, covering 12 domains: delusion; hallucination; agitation/aggression; depression/dysphoria; anxiety; elation/euphoria; apathy/indifference; disinhibition; irritability/lability; aberrant motor behavior; sleep/nighttime behaviors; and appetite/eating disorders. Based on an interview of the participant's caregiver, each domain is assessed for symptom frequency [range: 1 (occasional) to 4 (very frequent)] and severity [range: 1 (mild) to 3 (severe)]. Domain scores [range: 0 to 12] are calculated as the product of the frequency and severity scores (i.e. frequency x severity); if no symptoms are present, domain score is 0. The 12 domain scores sum to a total NPI score [range: 0 (no symptoms in any domain) to 144]. Higher scores reflect more severe psychiatric impairment, with increases in impairment reflected by increases in NPI score.
Measured: Baseline and week 78
[Part I (Base Study)] Change From Baseline in Mini-Mental State Examination (MMSE) Score
Least squares mean change from baseline at week 78 was assessed for MMSE score. The MMSE is a cognitive assessment of 5 domains including: orientation; attention; memory; language; and constructional praxis. These domains are assessed over the course of 11 total questions related to the participant. Participants are scored based on the number of correct responses; depending on the question, potential scores range from 0 (no correct response) to either 1 (4 questions), 2 (1 question), 3 (3 questions), or 5 (3 questions). Scores from each question are summed to the total MMSE score, with total scores ranging from 0-30. Higher scores indicate better cognitive performance. Further, deterioration in cognitive performance would be reflected by decreases in MMSE score.
Measured: Baseline and week 78

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Nov 201214 Apr 2017

First posted3 Dec 2012 (estimated)
Study start30 Nov 2012
Primary completion14 Apr 2017
Study completion14 Apr 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (7)Papers the sponsor has linked to this study.
Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 2,211 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01739348
Sponsor's protocol ID: P07738
Other IDs: MK-8931-017, 2011-003151-20, 132229
Acronym: EPOCH
Status last verified: Sep 2018
First submitted: 29 Nov 2012
Last updated: 24 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Sur C, Adamczuk K, Scott D, Kost J, Sampat M, Buckley C, Farrar G, Newton B, Suhy J, Bennacef I, Egan MF. Evaluation of 18F-flutemetamol amyloid PET image analysis parameters on the effect of verubecestat on brain amlyoid load in Alzheimer's disease. Mol Imaging Biol. 2022 Dec;24(6):862-873. doi: 10.1007/s11307-022-01735-z. Epub 2022 Jul 7.
PubMed 35794343
Dockendorf MF, Jaworowicz D, Humphrey R, Anderson M, Breidinger S, Ma L, Taylor T, Dupre N, Jones C, Furtek C, Kantesaria B, Bateman KP, Woolf E, Egan MF, Stone JA. A Model-Based Approach to Bridging Plasma and Dried Blood Spot Concentration Data for Phase 3 Verubecestat Trials. AAPS J. 2022 Apr 6;24(3):53. doi: 10.1208/s12248-022-00682-5.
PubMed 35384522
Sur C, Kost J, Scott D, Adamczuk K, Fox NC, Cummings JL, Tariot PN, Aisen PS, Vellas B, Voss T, Mahoney E, Mukai Y, Kennedy ME, Lines C, Michelson D, Egan MF. BACE inhibition causes rapid, regional, and non-progressive volume reduction in Alzheimer's disease brain. Brain. 2020 Dec 1;143(12):3816-3826. doi: 10.1093/brain/awaa332.
PubMed 33253354
Sergott RC, Raji A, Kost J, Sur C, Jackson S, Locco A, Patel A, Furtek C, Mattson B, Egan MF. Retinal Optical Coherence Tomography Metrics Are Unchanged in Verubecestat Alzheimer's Disease Clinical Trial but Correlate with Baseline Regional Brain Atrophy. J Alzheimers Dis. 2021;79(1):275-287. doi: 10.3233/JAD-200735.
PubMed 33252075
Egan MF, Mukai Y, Voss T, Kost J, Stone J, Furtek C, Mahoney E, Cummings JL, Tariot PN, Aisen PS, Vellas B, Lines C, Michelson D. Further analyses of the safety of verubecestat in the phase 3 EPOCH trial of mild-to-moderate Alzheimer's disease. Alzheimers Res Ther. 2019 Aug 7;11(1):68. doi: 10.1186/s13195-019-0520-1.
PubMed 31387606
Egan MF, Kost J, Tariot PN, Aisen PS, Cummings JL, Vellas B, Sur C, Mukai Y, Voss T, Furtek C, Mahoney E, Harper Mozley L, Vandenberghe R, Mo Y, Michelson D. Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease. N Engl J Med. 2018 May 3;378(18):1691-1703. doi: 10.1056/NEJMoa1706441.
PubMed 29719179
Kennedy ME, Stamford AW, Chen X, Cox K, Cumming JN, Dockendorf MF, Egan M, Ereshefsky L, Hodgson RA, Hyde LA, Jhee S, Kleijn HJ, Kuvelkar R, Li W, Mattson BA, Mei H, Palcza J, Scott JD, Tanen M, Troyer MD, Tseng JL, Stone JA, Parker EM, Forman MS. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS beta-amyloid in animal models and in Alzheimer's disease patients. Sci Transl Med. 2016 Nov 2;8(363):363ra150. doi: 10.1126/scitranslmed.aad9704.
PubMed 27807285

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 24 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Placebo Controlled, Parallel-Group, Double Blind Efficacy and Safety Trial of MK-8931 With a Long Term Double-Blind Extension in Subjects With Mild to Moderate Alzheimer's Disease (Protocol No. MK-8931-017-10)(Also Known as SCH 900931, P07738)
ClinicalTrials.gov ID: NCT01739348
Acronym / sponsor ID: EPOCH / P07738
Conditions: Alzheimer's Disease
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Terminated
Enrolment: 2,211 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 30 Nov 2012 (actual)
Primary completion: 14 Apr 2017 (actual)
Study completion: 14 Apr 2017 (actual)
First posted: 3 Dec 2012 (estimated)
Results: Posted 16 May 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II]	Experimental	Drug: Verubecestat (Part I and Part II)[Part I] Verubecestat 12 mg once daily for 78 weeks in Study Part I (Base Study). [Part II] Participants completing Study Part I and continuing to Study Part II (Extension Study) receive Verubecestat 12 mg once daily for an additional 260 weeks.
Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II]	Experimental	Drug: Verubecestat (Part I and Part II)[Part I] Verubecestat 40 mg once daily for 78 weeks in Study Part I (Base Study). [Part II] Participants completing Study Part I and continuing to Study Part II (Extension Study) receive Verubecestat 40 mg once daily for an additional 260 weeks.
Arm C. Verubecestat 60mg/40mg [Part I]; 40 mg [Part II]	Experimental	Drug: Verubecestat (Part I and Part II)[Part I] Verubecestat 60 mg once daily until the first IA in Study Part I (Base Study). Following IA, participants in this group were switched to Verubecestat 40 mg once daily, for the remainder of Study Part I (total dosing period: 78 weeks). [Part II] Participants completing Study Part I and continuing to Study Part II (Extension Study) receive Verubecestat 40 mg once daily for an additional 260 weeks.
Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II]	Placebo comparator	Drug: Placebo (Part I), Drug: Verubecestat (Part II)[Part I] Placebo once daily for 78 weeks in Study Part I (Base Study). [Part II] Participants completing Study Part I and continuing to Study Part II (Extension Study) receive Verubecestat 40 mg once daily for an additional 260 weeks.

Who may qualify

Ages: 55 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Diagnosis of probable AD based on both a) the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and b) the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for AD
AD is of mild to moderate severity
Clear history of cognitive and functional decline over at least one year that is either a) documented in medical records or b) documented by history from an informant who knows the subject well
Able to read at a 6th grade level or equivalent, and must have a history of academic achievement and/or employment sufficient to exclude mental retardation
If a participant is receiving an acetylcholinesterase inhibitor, memantine, medical food/supplement (e.g., vitamin E) and/or herbal medications for AD, the dose must have been stable for at least three months before Screening, and the participant must be willing to remain on the same dose for the duration of the trial. Participants may need to be on AD treatments in accordance with local requirements

Key exclusion criteria (23 listed)

History of stroke
Evidence of a neurological disorder other than the disease being studied (i.e., probable AD)
History of seizures or epilepsy within the last 5 years before Screening
Evidence of a clinically relevant or unstable psychiatric disorder, excluding major depression in remission
Participant is at imminent risk of self-harm or of harm to others

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Verubecestat (Part I and Part II)Also: SCH 900931Single 12 mg verubecestat tablet once daily, taken orally	Drug	Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II]
Verubecestat (Part I and Part II)Also: SCH 900931Single 40 mg verubecestat tablet once daily, taken orally	Drug	Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II]
Verubecestat (Part I and Part II)Also: SCH 900931Single 60 or 40 mg verubecestat tablet once daily, taken orally	Drug	Arm C. Verubecestat 60mg/40mg [Part I]; 40 mg [Part II]
Placebo (Part I)Single placebo tablet matching verubecestat treatment once daily, taken orally	Drug	Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II]
Verubecestat (Part II)Also: SCH 900931Single 40 mg verubecestat tablet once daily, taken orally	Drug	Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II]

Primary outcome

[Part I (Base Study)] Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score
Time frame: 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.
[Part I (Base Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score
Time frame: 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.
[Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score
Time frame: 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.
[Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score
Time frame: 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.
[Part I (Base Study)] Number of Participants Who Experienced an Adverse Event
Time frame: 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.
[Part II (Extension Study)] Number of Participants Who Experienced an Adverse Event
Time frame: 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.
[Part I (Base Study)] Number of Participants Who Discontinued From Study Drug Due to an Adverse Event
Time frame: 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.
[Part II (Extension Study)] Number of Participants Who Discontinued From Study Drug Due to an Adverse Event
Time frame: 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.

7 secondary outcomes

[Part I (Base Study)] Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score
Time frame: Baseline and week 78
[Part I (Base Study)] Percent Change From Baseline in Total Hippocampal Volume (THV)
Time frame: Baseline and week 78
[Part I (Base Study)] Fold Change From Baseline in Cerebrospinal Fluid (CSF) Total Tau
Time frame: Baseline and week 78
[Part I (Base Study)] Change From Baseline in Cortical Amyloid Load Assessed by [18F]Flutemetamol PET Standard Uptake Value Ratio (SUVR)
Time frame: Baseline and week 78
[Part I (Base Study)] Percentage of Participants Achieving Responder Status
Time frame: Week 78
[Part I (Base Study)] Change From Baseline in Neuropsychiatric Inventory (NPI) Score
Time frame: Baseline and week 78
[Part I (Base Study)] Change From Baseline in Mini-Mental State Examination (MMSE) Score
Time frame: Baseline and week 78

Results and safety

Results posted to the registry on 16 May 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II]	703	501
Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II]	700	497
Arm C. Verubecestat 60mg/40mg [Part I]; 40 mg [Part II]	103	77
Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II]	705	516

Primary outcome: [Part I (Base Study)] Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score

Time frame: Baseline and week 78. Least squares mean (95% Confidence Interval). Unit: Score on a Scale

Measure	Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] n = 631	Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II] n = 626	Arm C. Verubecestat 60mg/40mg [Part I]; 40 mg [Part II] n = 0	Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II] n = 644
Value	7.9 (7.2 to 8.6)	8.0 (7.3 to 8.7)	–	7.7 (7.0 to 8.4)

Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] vs Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II]: Difference in Least Squares Mean: 0.2 (97.51% CI -0.9 to 1.3), p = 0.6287, Longitudinal ANCOVA
Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II] vs Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II]: Difference in Least Squares Mean: 0.4 (97.51% CI -0.8 to 1.5), p = 0.4625, Longitudinal ANCOVA

Population analysed: 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.

Primary outcome: [Part I (Base Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score

Time frame: Baseline and week 78. Least squares mean (95% Confidence Interval). Unit: Score on a Scale

Measure	Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] n = 627	Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II] n = 622	Arm C. Verubecestat 60mg/40mg [Part I]; 40 mg [Part II] n = 0	Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II] n = 636
Value	-8.4 (-9.5 to -7.4)	-8.2 (-9.2 to -7.1)	–	-8.9 (-9.9 to -8.0)

Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] vs Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II]: Difference in Least Squares Means: 0.5 (97.51% CI -1.1 to 2.1), p = 0.4925, Longitudinal ANCOVA
Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II] vs Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II]: Difference in Least Squares Means: 0.7 (97.51% CI -0.9 to 2.3), p = 0.3221, Longitudinal ANCOVA

Population analysed: 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.

Primary outcome: [Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score

Time frame: Baseline and week 104. Mean (Standard Deviation). Unit: Score on a Scale

Measure	Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] n = 207	Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II] n = 208	Arm C. Verubecestat 60mg/40mg [Part I]; 40 mg [Part II] n = 0	Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II] n = 216
Value	10.1 (9.9)	8.5 (9.5)	–	9.6 (9.5)

Population analysed: 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.

Primary outcome: [Part II (Extension Study)] Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score

Time frame: Baseline and week 104. Mean (Standard Deviation). Unit: Score on a Scale

Measure	Arm A. Verubecestat 12 mg [Part I]; 12 mg [Part II] n = 207	Arm B. Verubecestat 40 mg [Part I]; 40 mg [Part II] n = 209	Arm C. Verubecestat 60mg/40mg [Part I]; 40 mg [Part II] n = 0	Arm D. Placebo [Part I]; Verubecestat 40 mg [Part II] n = 216
Value	-10.7 (13.7)	-9.2 (12.7)	–	-9.3 (12.0)

Population analysed: 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.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: [Part I]: Up to week 80 of Part I (up to 2 weeks following cessation of study treatment in Part I); [Part II]: From week 78 (end of treatment in Part I) up to week 262 of Study Part II. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm A. Verubecestat 12 mg [Part I]	134 of 702 (19.1%)	408 of 702 (58.1%)	9 of 702
Arm B. Verubecestat 40 mg [Part I]	162 of 700 (23.1%)	440 of 700 (62.9%)	13 of 700
Arm C. Verubecestat 60mg/40mg [Part I]	24 of 103 (23.3%)	66 of 103 (64.1%)	3 of 103
Arm D. Placebo [Part I]	121 of 705 (17.2%)	337 of 705 (47.8%)	6 of 705
Arm A. Verubecestat 12 mg [Part II]	57 of 379 (15%)	135 of 379 (35.6%)	6 of 379
Arm B. Verubecestat 40 mg [Part II]	56 of 365 (15.3%)	102 of 365 (27.9%)	4 of 365
Arm C. Verubecestat 40 mg [Part II]	22 of 61 (36.1%)	37 of 61 (60.7%)	4 of 61
Arm D. Verubecestat 40 mg [Part II]	69 of 394 (17.5%)	144 of 394 (36.5%)	8 of 394

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35794343Sur C, Adamczuk K, Scott D, Kost J, Sampat M, Buckley C, Farrar G, Newton B, Suhy J, Bennacef I, Egan MF. Evaluation of 18F-flutemetamol amyloid PET image analysis parameters on the effect of verubecestat on brain amlyoid load in Alzheimer's disease. Mol Imaging Biol. 2022 Dec;24(6):862-873. doi: 10.1007/s11307-022-01735-z. Epub 2022 Jul 7.
Derived from this study: PubMed 35384522Dockendorf MF, Jaworowicz D, Humphrey R, Anderson M, Breidinger S, Ma L, Taylor T, Dupre N, Jones C, Furtek C, Kantesaria B, Bateman KP, Woolf E, Egan MF, Stone JA. A Model-Based Approach to Bridging Plasma and Dried Blood Spot Concentration Data for Phase 3 Verubecestat Trials. AAPS J. 2022 Apr 6;24(3):53. doi: 10.1208/s12248-022-00682-5.
Derived from this study: PubMed 33253354Sur C, Kost J, Scott D, Adamczuk K, Fox NC, Cummings JL, Tariot PN, Aisen PS, Vellas B, Voss T, Mahoney E, Mukai Y, Kennedy ME, Lines C, Michelson D, Egan MF. BACE inhibition causes rapid, regional, and non-progressive volume reduction in Alzheimer's disease brain. Brain. 2020 Dec 1;143(12):3816-3826. doi: 10.1093/brain/awaa332.
Derived from this study: PubMed 33252075Sergott RC, Raji A, Kost J, Sur C, Jackson S, Locco A, Patel A, Furtek C, Mattson B, Egan MF. Retinal Optical Coherence Tomography Metrics Are Unchanged in Verubecestat Alzheimer's Disease Clinical Trial but Correlate with Baseline Regional Brain Atrophy. J Alzheimers Dis. 2021;79(1):275-287. doi: 10.3233/JAD-200735.
Derived from this study: PubMed 31387606Egan MF, Mukai Y, Voss T, Kost J, Stone J, Furtek C, Mahoney E, Cummings JL, Tariot PN, Aisen PS, Vellas B, Lines C, Michelson D. Further analyses of the safety of verubecestat in the phase 3 EPOCH trial of mild-to-moderate Alzheimer's disease. Alzheimers Res Ther. 2019 Aug 7;11(1):68. doi: 10.1186/s13195-019-0520-1.
Derived from this study: PubMed 29719179Egan MF, Kost J, Tariot PN, Aisen PS, Cummings JL, Vellas B, Sur C, Mukai Y, Voss T, Furtek C, Mahoney E, Harper Mozley L, Vandenberghe R, Mo Y, Michelson D. Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease. N Engl J Med. 2018 May 3;378(18):1691-1703. doi: 10.1056/NEJMoa1706441.
Derived from this study: PubMed 27807285Kennedy ME, Stamford AW, Chen X, Cox K, Cumming JN, Dockendorf MF, Egan M, Ereshefsky L, Hodgson RA, Hyde LA, Jhee S, Kleijn HJ, Kuvelkar R, Li W, Mattson BA, Mei H, Palcza J, Scott JD, Tanen M, Troyer MD, Tseng JL, Stone JA, Parker EM, Forman MS. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS beta-amyloid in animal models and in Alzheimer's disease patients. Sci Transl Med. 2016 Nov 2;8(363):363ra150. doi: 10.1126/scitranslmed.aad9704.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Verubecestat (Part I and Part II) and Verubecestat (Part II) in people with Alzheimer's Disease, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

[Part I (Base Study)] Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score (time frame: Baseline and week 78). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01739348, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2018.