Alzheimer Disease, Dementia, Alzheimer Type
Conditions
Keywords
E2609, Mild Cognitive Impairment, Mild to Moderate Dementia, Alzheimer's Disease, Prodromal Alzheimer's Disease
Brief summary
This is a Phase 2 study to evaluate safety and efficacy in participants with Mild Cognitive Impairment due to Alzheimer's Disease/Prodromal Alzheimer's Disease (referred to as MCI/Prodromal) and mild to moderate dementia due to Alzheimer's Disease (referred to as mild to moderate AD). This study will have a Core Phase and an Extension Phase.
Interventions
DRUGE2609
Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.
DRUGPlacebo
Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.
Sponsors
Biogen
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Participants must meet all of the following criteria to be included in this study: 1. Meets the core clinical research criteria of the National Institute on Aging-Alzheimer's Association (NIA-AA) for MCI due to AD (which is consistent with Prodromal AD) or AD dementia and is 'staged' or classified as either MCI or mild to moderate dementia. 2. Amyloid positive Positron Emission Tomography (PET) image based on centralized PET scan reading. 3. Male or female, age 50 to 85 years, inclusive at time of consent. 4. Must have an identified caregiver or informant who is willing and able to provide follow-up information on the participant throughout the course of the study. 5. If receiving an Acetylcholinesterase Inhibitor (AChEI) or memantine, must have been on a stable dose for at least 12 weeks before the Baseline cognitive assessments, with no plans for dose adjustment in the foreseeable future. Treatment-naive participants can be entered into the study but there should be no plans to initiate treatment with AChEIs or memantine at the time of entry into the study. 6. Must have been on stable doses of all other permitted chronically used concomitant medications (that is, not related to their cognitive decline) for at least 4 weeks before randomization.
Exclusion criteria
Participants who meet any of the following criteria will be excluded from this study: 1. Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD pathology, including any co-morbidities such as cerebrovascular disease, detected by medical history, neurological examination, or magnetic resonance imaging (MRI). 2. History of transient ischemic attacks or stroke within 12 months of Screening. 3. History of epilepsy. 4. Evidence of depression on a rating scale at Screening or any psychiatric diagnosis or symptoms, (example, hallucinations, major depression, etc.) that could confound the diagnosis or could interfere with study assessments or procedures. This includes suicidal ideation or suicidal behavior within 6 months prior to Screening, or hospitalization or treatment for suicidal behavior in the past 5 years. 5. Abnormally low serum vitamin B12. 6. Thyroid stimulating hormone above the normal range. This applies to all participants regardless of whether or not they are taking thyroid supplements. 7. Participants with liver disease (hepatic impairment), at Screening or Baseline. Participant with Gilbert's syndrome need not be excluded. 8. Not able to have a MRI, PET scanning, or cerebrospinal fluid (CSF) collection by Lumbar Puncture (LP). 9. Severe visual or hearing impairment that would prevent the participant from performing psychometric tests accurately. 10. History of immunodeficiency disorders. 11. Participants with chronic viral hepatitis. 12. History of Tuberculosis (TB). Participants with no history of TB will be tested for previous TB exposure and a positive test will be exclusionary. 13. History of ophthalmic shingles or ocular Herpes Simplex Virus (HSV) infection. 14. Any live vaccine in the 3 months or any active infection within the last 4 weeks before study drug administration (that is, randomization). 15. Any chronic inflammatory disease that is not adequately controlled or requires immunosuppressive or immunomodulatory therapy. 16. T helper cell, cytotoxic T cell, or B cell absolute counts below normal. 17. Immunoglobulin (Ig) IgG, IgA, or IgM levels below normal at Screening or Baseline, unless both the Investigator and the Medical Monitor agree that the finding is not clinically significant. 18. Clinically significant deviation from normal in physical examination, vital signs, or clinical laboratory tests at Screening or Baseline. 19. Exclusionary cardiac factors include: prolonged QT interval greater than 450 millisecond from Electrocardiograms (ECGs); history of risk factors for torsade de pointes or the use of concomitant medications that prolong the QT/corrected QT interval (QTc); left bundle branch block; persistent low or high heart rate; persistent low or high blood pressure; history of cardiac arrhythmias; other clinically significant ECG abnormalities. 20. Type 1 or Type 2 diabetes mellitus that is not well controlled. 21. Malignant neoplasms within 5 years before Screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer that did not require systemic therapy; these do not exclude the participant). 22. Medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) that are not stably controlled, or which, in the opinion of the investigator(s), could affect the participant's safety or interfere with the study assessments. 23. Hypopigmentation conditions (example, albinism and vitiligo). 24. Known or suspected history of drug or alcohol dependency or abuse within 2 years, current use of recreational drugs or a positive urine drug test. 25. Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the study. 26. Participation in any other interventional clinical study related to cognitive impairment within 6 months before Screening unless it can be documented that the participant was in a placebo treatment arm. 27. Currently enrolled in another clinical study or used any investigational drug or device within 60 days or 5 half-lives of the investigational medication (whichever is longer) proceeding informed consent. 28. Hypersensitivity to the study drug or any of the excipients or to other Beta Secretase Cleaving Enzyme (BACE) inhibitors, or to the PET tracer, or components of its formulation. 29. Females who are lactating or pregnant. Females of childbearing potential who do not agree to adhere to the protocol specified methods for avoiding pregnancy. 30. Males who do not meet the protocol requirements for avoiding their partners becoming pregnant. Sperm donation is not permitted.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings | Up to 34 months | Brain MRIs are collected to assess for potential drug-related changes that might have constituted a safety concern. Safety brain MRI is assessed using a standardized procedure that included fluid-attenuated inversion recovery (FLAIR), gradient-echo, T1, and diffusion-weighted sequences to determine the presence of focal lesions including, but not limited to, evidence for ischemic and hemorrhagic stroke, subdural hematoma, neoplasm, arteriovenous malformation, micro and macrohemorrhages, superficial siderosis, lacunar infarcts, white matter abnormalities, and vasogenic edema. Participants with abnormal values related to safety brain MRI were reported. |
| Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to 21 months | A TEAE is defined as an adverse event that emerges during treatment, having been absent at pre-treatment (Baseline) or re-emerges during treatment, having been present at pre-treatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pre-treatment state, when the adverse event is continuous. |
| Core Phase: Number of Participants With Serious Adverse Events (SAEs) | Up to 21 months | A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening (that is, the participant is at immediate risk of death from the adverse event as it occurs, this does not include an event that, has it occurred in a more severe form or is allowed to continue, might have cause death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect (in the child of a participant who is exposed to the study drug). |
| Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Up to 21 months | — |
| Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Month 0(Baseline,Week 2,Week 3,Week 4);Month 1(Week 5,Week 7);Month 2(Week 9,Week 11);Month 3(Week 13);Month 4(Week 17);Month 5(Week 21);Month 6(Week 27);Month 9(Week 40);Month 12(Week 53);Month 15(Week 66);Month 18(Week 79) and Follow-up at Month 1 and 3 | Participants having no markedly abnormal vital sign values (no markedly abnormal high or no markedly abnormal low) in all core phase arms were not included in the data reported. |
| Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | Up to 21 months | QTcF interval means corrected QT interval (QTc) calculated using Fridericia's formula. |
| Extension Phase: Number of Participants With TEAEs and SAEs | Up to 34 months | TEAE: adverse event that emerges during treatment, having been absent at pre-treatment or reemerges during treatment, having been present at pre-treatment but stopped before treatment, or worsens in severity during treatment relative to pre-treatment state. Number of participants with TEAEs were reported based on safety assessments of laboratory tests, physical examination, regular measurement of vital signs, magnetic resonance imaging and electrocardiogram parameter values. SAE: any untoward medical occurrence that at any dose: results in death; is life-threatening (immediate risk of death from adverse event, this does not include event that, had it occurred in more severe form or is allowed to continue, might have caused death); requires inpatient or prolongation of existing hospitalization; results in persistent/significant disability/incapacity; is congenital anomaly/birth defect (in child of participant exposed to drug). Number of participants with TEAEs and SAEs were reported. |
| Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Up to 34 months | — |
| Extension Phase: Number of Participants With Markedly Abnormal ECG Findings | Up to 34 months | QTcF interval means QTc interval calculated using Fridericia's formula. |
| Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Up to 34 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Month 1 (Week 5) and Month 18 (Week 79) | The measurement of the amyloid proteins Abeta(1-x) and Abeta(1-42), in CSF have been shown to be important biomarkers for alzheimer's disease. |
| Core Phase: Mean Concentration of Elenbecestat in CSF | Month 1 (Week 5) and Month 18 (Week 79) | — |
| Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 0 (Week 3), Month 3 (Week 13), Month 6 (Week 27), Month 12 (Week 53): Pre-dose, 1 to 6 hours Post-dose; Month 1 (Week 5), Month 18 (Week 79): Pre-dose, 4 to 8 hours Post-dose | — |
| Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores | Baseline, at Month 3, at Month 6, at Month 9, at Month 12, at Month 15, at Month 18, at Month 21, at Month 24, at Month 28 and at Month 32 | MMSE is a 30-point scale that measures orientation to time and place, registration, immediate and delayed recall, attention, language, and drawing. Scores ranges from 0 (most impaired) to 30 (no impairment). Lower score indicates more impairment. |
| Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score | Baseline, at Month 3, at Month 6, at Month 9, at Month 12, at Month 15, at Month 18, at Month 21, at Month 24, at Month 28 and at Month 32 | The FAQ has 10 items concerned with performing daily tasks necessary for independent living. The caregiver or informant provides performance ratings on 10 complex activities of daily living performed within the preceding 4 weeks. Score ranges from 0 (independent) to 30 (dependent). Lower score indicates that participant can live independently. Higher score indicates that participant cannot live independently. |
| Extension Phase: Percent Change From Extension Phase Baseline in Plasma Amyloid (A) Beta(1-x) Measurements at Months 12 and 24 | Month 12 and Month 24 | The measurement of the amyloid protein Abeta(1-x), in plasma has been shown to be an important biomarker for alzheimer's disease. |
| Extension Phase: Percent Change From Extension Phase Baseline in Total Hippocampal Volume at Month 24 | Month 24 | Total hippocampal volume is measured by volumetric magnetic resonance imaging (vMRI). Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total hippocampal volume is calculated by summing up right and left hippocampal volumes. |
| Extension Phase: Percent Change From Extension Phase Baseline in Left and Right Hippocampal Volume at Month 24 | Month 24 | Left and right hippocampal volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Left and right hippocampal volumes represent a summary measure in the left and right hippocampal regions. |
| Extension Phase: Percent Change From Extension Phase Baseline in Whole Brain Volume at Month 24 | Month 24 | Whole brain volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Whole brain volume represents a summary measure of total brain parenchyma which includes the cerebrum, basal ganglia, diencephalon, and cerebellum. |
| Extension Phase: Percent Change From Extension Phase Baseline in Total Ventricular Volume at Month 24 | Month 24 | Total Ventricular Volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total ventricular volume represents a summary measure of total including right and left lateral ventricles, third ventricle and fourth ventricle of brain. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 30 investigative sites in the United States from 26 November 2014 to 20 December 2019.
Pre-assignment details
A total of 444 participants were screened, of which 374 participants were screen failures and 70 participants were randomized and treated, out of which 43 participants completed the core phase and 41 participants entered the extension phase. No participant completed the extension phase. This study has Core Phase and an Extension Phase.
Participants by arm
| Arm | Count |
|---|---|
| Core Phase: Placebo Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received two elenbecestat matched-placebo tablets, orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat matched-placebo in core phase. | 17 |
| Core Phase: Elenbecestat 5 mg Then 50 mg Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received one elenbecestat 5 mg tablet and one elenbecestat-matched placebo tablet (to maintain blinding), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase. | 17 |
| Core Phase: Elenbecestat 15 mg Then 50 mg Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 15 mg (one 10 mg and one 5 mg tablets), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase. | 19 |
| Core Phase: Elenbecestat 50 mg Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 50 mg (two 25 mg tablets), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase. | 17 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Core Phase | Adverse Event | 1 | 3 | 4 | 2 | 0 |
| Core Phase | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| Core Phase | Other | 0 | 0 | 1 | 0 | 0 |
| Core Phase | Participant Choice | 4 | 5 | 4 | 2 | 0 |
| Extension Phase | Adverse Event | 0 | 0 | 0 | 0 | 3 |
| Extension Phase | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| Extension Phase | Other | 0 | 0 | 0 | 0 | 3 |
| Extension Phase | Participant Choice | 0 | 0 | 0 | 0 | 6 |
| Extension Phase | Study terminated by sponsor | 0 | 0 | 0 | 0 | 28 |
Baseline characteristics
| Characteristic | Total | Core Phase: Placebo | Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Elenbecestat 50 mg |
|---|---|---|---|---|---|
| Age, Customized Greater than (>) 65 years | 58 Participants | 13 Participants | 14 Participants | 17 Participants | 14 Participants |
| Age, Customized Less than or equal to (<=) 65 years | 12 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants | 16 Participants | 17 Participants | 19 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 2 Participants | 0 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 60 Participants | 15 Participants | 17 Participants | 16 Participants | 12 Participants |
| Sex: Female, Male Female | 42 Participants | 11 Participants | 9 Participants | 12 Participants | 10 Participants |
| Sex: Female, Male Male | 28 Participants | 6 Participants | 8 Participants | 7 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 | 0 / 19 | 0 / 17 | 1 / 41 |
| other Total, other adverse events | 15 / 17 | 15 / 17 | 18 / 19 | 15 / 17 | 30 / 41 |
| serious Total, serious adverse events | 2 / 17 | 2 / 17 | 5 / 19 | 1 / 17 | 6 / 41 |
Outcome results
Primary
Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings
QTcF interval means corrected QT interval (QTc) calculated using Fridericia's formula.
Time frame: Up to 21 months
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug in the core phase and had at least 1 post-dose safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | At least one post-baseline increase of >30 millisecond (msec) in QTcF interval | 2 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | At least one post-baseline value of >480 msec in QTcF interval | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | At least one post-baseline value of >450 msec in QTcF interval | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | At least one post-baseline increase of >30 millisecond (msec) in QTcF interval | 4 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | At least one post-baseline value of >450 msec in QTcF interval | 6 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | At least one post-baseline value of >480 msec in QTcF interval | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | At least one post-baseline value of >450 msec in QTcF interval | 4 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | At least one post-baseline increase of >30 millisecond (msec) in QTcF interval | 4 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | At least one post-baseline value of >480 msec in QTcF interval | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | At least one post-baseline value of >480 msec in QTcF interval | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | At least one post-baseline value of >450 msec in QTcF interval | 3 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings | At least one post-baseline increase of >30 millisecond (msec) in QTcF interval | 2 Participants |
Primary
Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values
Participants having no markedly abnormal vital sign values (no markedly abnormal high or no markedly abnormal low) in all core phase arms were not included in the data reported.
Time frame: Month 0(Baseline,Week 2,Week 3,Week 4);Month 1(Week 5,Week 7);Month 2(Week 9,Week 11);Month 3(Week 13);Month 4(Week 17);Month 5(Week 21);Month 6(Week 27);Month 9(Week 40);Month 12(Week 53);Month 15(Week 66);Month 18(Week 79) and Follow-up at Month 1 and 3
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug in the core phase and had at least 1 post-dose safety assessment. Here number analyzed signifies participants who were evaluable for this outcome measure for specific categories at given time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Baseline) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 12: Week 53) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Follow-up: Month 3) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 1: Week 7) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Baseline) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 9: Week 40) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 2) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Follow-up: Month 3) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 3) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 6: Week 27) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 4) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 2: Week 9) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 1: Week 5) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 4: Week 17) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 1: Week 7) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Week 3) | 2 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 3: Week 13) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure (Month 9: Week 40) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 2: Week 11) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 3: Week 13) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure (Month 1: Week 5) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 4: Week 17) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 5: Week 21) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Week 4) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure (Month 0: Week 4) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 6: Week 27) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 9: Week 40) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Week 2) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Month 0: Week 3) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 12: Week 53) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Follow-up: Month 1) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 15: Week 66) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Temperature (Month 0: Week 4) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Follow-up: Month 3) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 18: Week 79) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Follow-up: Month 1) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Follow-up: Month 1) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Follow-up: Month 3) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Weight (Month 0: Baseline) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 1: Week 5) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 18: Week 79) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 0: Baseline) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 3: Week 13) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 15: Week 66) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 6: Week 27) | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Month 9: Week 40) | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 9: Week 40) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 15: Week 66) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 6: Week 27) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 6: Week 27) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Follow-up: Month 3) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Week 4) | 3 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 9: Week 40) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Month 0: Week 3) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Baseline) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 1: Week 7) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Follow-up: Month 3) | 2 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 9: Week 40) | 2 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 2) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Month 9: Week 40) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 6: Week 27) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 18: Week 79) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 3) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure (Month 9: Week 40) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 3: Week 13) | 2 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 12: Week 53) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 4) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Weight (Month 0: Baseline) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 4: Week 17) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Follow-up: Month 3) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 1: Week 5) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 2: Week 9) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Baseline) | 2 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 15: Week 66) | 3 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 1: Week 7) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 9: Week 40) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 3: Week 13) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 12: Week 53) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 0: Baseline) | 3 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 18: Week 79) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 2: Week 11) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Week 3) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure (Month 1: Week 5) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Temperature (Month 0: Week 4) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 3: Week 13) | 2 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Follow-up: Month 3) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Follow-up: Month 1) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 1: Week 5) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 4: Week 17) | 3 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Follow-up: Month 1) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure (Month 0: Week 4) | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Follow-up: Month 1) | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 5: Week 21) | 3 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Week 2) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 9: Week 40) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Baseline) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Week 2) | 2 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Week 3) | 4 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Week 4) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Temperature (Month 0: Week 4) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 1: Week 5) | 2 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 1: Week 7) | 3 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 2: Week 9) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 2: Week 11) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 3: Week 13) | 3 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 4: Week 17) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 5: Week 21) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 6: Week 27) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 9: Week 40) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 12: Week 53) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 15: Week 66) | 2 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 18: Week 79) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Follow-up: Month 1) | 2 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Follow-up: Month 3) | 4 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Weight (Month 0: Baseline) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 0: Baseline) | 2 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 3: Week 13) | 2 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 6: Week 27) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Follow-up: Month 3) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Baseline) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 2) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 3) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 4) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 1: Week 5) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 1: Week 7) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 3: Week 13) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 4: Week 17) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 6: Week 27) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 9: Week 40) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 12: Week 53) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 15: Week 66) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 18: Week 79) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Follow-up: Month 1) | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Follow-up: Month 3) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Month 0: Week 3) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure (Month 0: Week 4) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure (Month 1: Week 5) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure (Month 9: Week 40) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Month 9: Week 40) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Follow-up: Month 1) | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Follow-up: Month 3) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 6: Week 27) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 1: Week 5) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 12: Week 53) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 3: Week 13) | 2 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 0: Baseline) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Temperature (Month 0: Week 4) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 15: Week 66) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Weight (Month 0: Baseline) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Follow-up: Month 3) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Baseline) | 2 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 18: Week 79) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Follow-up: Month 1) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 18: Week 79) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Month 9: Week 40) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Follow-up: Month 1) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 15: Week 66) | 2 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 12: Week 53) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Week 4) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Follow-up: Month 3) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 9: Week 40) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 6: Week 27) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Week 3) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Month 0: Week 3) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 5: Week 21) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 4: Week 17) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Follow-up: Month 3) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure (Month 0: Week 4) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 3: Week 13) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 2: Week 11) | 2 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure (Follow-up: Month 1) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure (Month 1: Week 5) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 1: Week 7) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 2: Week 9) | 2 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 3: Week 13) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 1: Week 5) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 4) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 1: Week 7) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 4: Week 17) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 3) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 2) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature (Month 0: Week 2) | 2 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 6: Week 27) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 0: Baseline) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Follow-up: Month 3) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure (Month 9: Week 40) | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure (Month 9: Week 40) | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight (Month 9: Week 40) | 1 Participants |
Primary
Core Phase: Number of Participants With Serious Adverse Events (SAEs)
A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening (that is, the participant is at immediate risk of death from the adverse event as it occurs, this does not include an event that, has it occurred in a more severe form or is allowed to continue, might have cause death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect (in the child of a participant who is exposed to the study drug).
Time frame: Up to 21 months
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug in the core phase and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Core Phase: Placebo | Core Phase: Number of Participants With Serious Adverse Events (SAEs) | 2 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Serious Adverse Events (SAEs) | 2 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Serious Adverse Events (SAEs) | 5 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Serious Adverse Events (SAEs) | 1 Participants |
Primary
Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
A TEAE is defined as an adverse event that emerges during treatment, having been absent at pre-treatment (Baseline) or re-emerges during treatment, having been present at pre-treatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pre-treatment state, when the adverse event is continuous.
Time frame: Up to 21 months
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug in the core phase and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 15 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 15 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 18 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 15 Participants |
Primary
Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values
Time frame: Up to 21 months
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug in the core phase and had at least 1 post-dose safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Calcium | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Leukocytes | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Neutrophils | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Hemoglobin | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Lymphocytes | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Potassium | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Potassium | 2 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Alkaline Phosphatase | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Alanine Aminotransferase | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Aspartate Aminotransferase | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Gamma Glutamyl Transferase | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Glucose | 0 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Glucose | 2 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Cholesterol | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Triglycerides | 1 Participants |
| Core Phase: Placebo | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Creatinine | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Potassium | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Alanine Aminotransferase | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Creatinine | 2 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Glucose | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Triglycerides | 1 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Aspartate Aminotransferase | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Neutrophils | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Gamma Glutamyl Transferase | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Calcium | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Potassium | 4 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Hemoglobin | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Leukocytes | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Glucose | 4 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Alkaline Phosphatase | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Cholesterol | 0 Participants |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Lymphocytes | 2 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Potassium | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Calcium | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Cholesterol | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Potassium | 2 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Alkaline Phosphatase | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Creatinine | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Alanine Aminotransferase | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Aspartate Aminotransferase | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Triglycerides | 3 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Gamma Glutamyl Transferase | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Glucose | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Lymphocytes | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Leukocytes | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Glucose | 1 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Neutrophils | 0 Participants |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Hemoglobin | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Creatinine | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Alkaline Phosphatase | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Neutrophils | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Lymphocytes | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Cholesterol | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Potassium | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Glucose | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Leukocytes | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Calcium | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Aspartate Aminotransferase | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Potassium | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Gamma Glutamyl Transferase | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Triglycerides | 2 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Alanine Aminotransferase | 1 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Hemoglobin | 0 Participants |
| Core Phase: Elenbecestat 50 mg | Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Glucose | 0 Participants |
Primary
Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings
Brain MRIs are collected to assess for potential drug-related changes that might have constituted a safety concern. Safety brain MRI is assessed using a standardized procedure that included fluid-attenuated inversion recovery (FLAIR), gradient-echo, T1, and diffusion-weighted sequences to determine the presence of focal lesions including, but not limited to, evidence for ischemic and hemorrhagic stroke, subdural hematoma, neoplasm, arteriovenous malformation, micro and macrohemorrhages, superficial siderosis, lacunar infarcts, white matter abnormalities, and vasogenic edema. Participants with abnormal values related to safety brain MRI were reported.
Time frame: Up to 34 months
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug in the extension phase. Here number analyzed signifies participants who were evaluable for this outcome measure for specific categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Core Phase: Placebo | Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings | Brain Vasogenic Edema | 0 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings | Brain Microhemorrhages | 4 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings | Brain White Matter Disease: Focal Lesions | 25 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings | Brain White Matter Disease: No Lesions | 2 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings | Area of superficial siderosis | 1 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings | Space occupying lesion (extra axial): Meningioma | 1 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings | Other pituitary lesion | 1 Participants |
Primary
Extension Phase: Number of Participants With Markedly Abnormal ECG Findings
QTcF interval means QTc interval calculated using Fridericia's formula.
Time frame: Up to 34 months
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug in the extension phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Core Phase: Placebo | Extension Phase: Number of Participants With Markedly Abnormal ECG Findings | At least one post-baseline increase of >30 msec in QTcF interval | 2 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Markedly Abnormal ECG Findings | At least one post-baseline value of >450 msec in QTcF interval | 4 Participants |
Primary
Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values
Time frame: Up to 34 months
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug in the extension phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Core Phase: Placebo | Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Diastolic Blood Pressure | 1 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Diastolic Blood Pressure | 1 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Systolic Blood Pressure | 5 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Temperature | 1 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal Low: Temperature | 10 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values | Markedly Abnormal High: Weight | 1 Participants |
Primary
Extension Phase: Number of Participants With TEAEs and SAEs
TEAE: adverse event that emerges during treatment, having been absent at pre-treatment or reemerges during treatment, having been present at pre-treatment but stopped before treatment, or worsens in severity during treatment relative to pre-treatment state. Number of participants with TEAEs were reported based on safety assessments of laboratory tests, physical examination, regular measurement of vital signs, magnetic resonance imaging and electrocardiogram parameter values. SAE: any untoward medical occurrence that at any dose: results in death; is life-threatening (immediate risk of death from adverse event, this does not include event that, had it occurred in more severe form or is allowed to continue, might have caused death); requires inpatient or prolongation of existing hospitalization; results in persistent/significant disability/incapacity; is congenital anomaly/birth defect (in child of participant exposed to drug). Number of participants with TEAEs and SAEs were reported.
Time frame: Up to 34 months
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug in the extension phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Core Phase: Placebo | Extension Phase: Number of Participants With TEAEs and SAEs | TEAEs | 30 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With TEAEs and SAEs | SAEs | 6 Participants |
Primary
Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values
Time frame: Up to 34 months
Population: The safety analysis set was the group of participants who received at least 1 dose of study drug in the extension phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Core Phase: Placebo | Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Triglycerides | 2 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Lymphocytes | 4 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Neutrophils | 2 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Hemoglobin | 1 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Potassium | 4 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Alanine Aminotransferase | 1 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Gamma Glutamyl Transferase | 2 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Glucose | 3 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Creatinine | 4 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal High: Urate | 1 Participants |
| Core Phase: Placebo | Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values | Markedly Abnormal Low: Platelets | 1 Participants |
Secondary
Core Phase: Mean Concentration of Elenbecestat in CSF
Time frame: Month 1 (Week 5) and Month 18 (Week 79)
Population: The pharmacokinetic (PK) analysis set was the group of participants with at least 1 quantifiable elenbecestat plasma concentration accompanied by a documented dosing history in the core phase. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in CSF | Month 1 (Week 5) | 1.10 nanogram per milliliter (ng/mL) | Standard Deviation 0.438 |
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in CSF | Month 18 (Week 79) | 0.10 nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in CSF | Month 1 (Week 5) | 3.71 nanogram per milliliter (ng/mL) | Standard Deviation 1.36 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in CSF | Month 18 (Week 79) | 2.72 nanogram per milliliter (ng/mL) | Standard Deviation 3.197 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in CSF | Month 1 (Week 5) | 9.93 nanogram per milliliter (ng/mL) | Standard Deviation 3.568 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in CSF | Month 18 (Week 79) | 14.46 nanogram per milliliter (ng/mL) | Standard Deviation 3.411 |
Secondary
Core Phase: Mean Concentration of Elenbecestat in Plasma
Time frame: Month 0 (Week 3), Month 3 (Week 13), Month 6 (Week 27), Month 12 (Week 53): Pre-dose, 1 to 6 hours Post-dose; Month 1 (Week 5), Month 18 (Week 79): Pre-dose, 4 to 8 hours Post-dose
Population: The PK analysis set was the group of participants with at least 1 quantifiable elenbecestat plasma concentration accompanied by a documented dosing history in the core phase. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 12 (Week 53): Pre-dose | 13.84 ng/mL | Standard Deviation 18.482 |
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 3 (Week 13): Pre-dose | 1.91 ng/mL | Standard Deviation 1.703 |
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 6 (Week 27): 1 to 6 hours Post-dose | 11.11 ng/mL | Standard Deviation 15.322 |
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 3 (Week 13): 1 to 6 hours Post-dose | 6.06 ng/mL | Standard Deviation 2.456 |
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 0 (Week 3): Pre-dose | 1.43 ng/mL | Standard Deviation 1.105 |
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 6 (Week 27): Pre-dose | 2.34 ng/mL | Standard Deviation 2.196 |
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 18 (Week 79): Pre-dose | 7.88 ng/mL | Standard Deviation 5.896 |
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 1 (Week 5): Pre-dose | 1.47 ng/mL | Standard Deviation 0.87 |
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 18 (Week 79): 4 to 8 hours Post-dose | 47.16 ng/mL | Standard Deviation 28.651 |
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 12 (Week 53): 1 to 6 hours Post-dose | 49.78 ng/mL | Standard Deviation 40.656 |
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 1 (Week 5): 4 to 8 hours Post-dose | 4.80 ng/mL | Standard Deviation 2.529 |
| Core Phase: Placebo | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 0 (Week 3): 1 to 6 hours Post-dose | 4.28 ng/mL | Standard Deviation 3.185 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 3 (Week 13): Pre-dose | 6.90 ng/mL | Standard Deviation 8.126 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 0 (Week 3): Pre-dose | 5.81 ng/mL | Standard Deviation 3.785 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 0 (Week 3): 1 to 6 hours Post-dose | 18.49 ng/mL | Standard Deviation 11.272 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 1 (Week 5): Pre-dose | 6.74 ng/mL | Standard Deviation 4.246 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 1 (Week 5): 4 to 8 hours Post-dose | 19.59 ng/mL | Standard Deviation 7.94 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 3 (Week 13): 1 to 6 hours Post-dose | 20.35 ng/mL | Standard Deviation 8.893 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 6 (Week 27): Pre-dose | 9.10 ng/mL | Standard Deviation 9.018 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 6 (Week 27): 1 to 6 hours Post-dose | 25.49 ng/mL | Standard Deviation 22.247 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 12 (Week 53): Pre-dose | 21.03 ng/mL | Standard Deviation 30.897 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 12 (Week 53): 1 to 6 hours Post-dose | 58.38 ng/mL | Standard Deviation 65.148 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 18 (Week 79): Pre-dose | 7.13 ng/mL | Standard Deviation 6.99 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 18 (Week 79): 4 to 8 hours Post-dose | 51.99 ng/mL | Standard Deviation 44.656 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 1 (Week 5): 4 to 8 hours Post-dose | 66.83 ng/mL | Standard Deviation 21.37 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 18 (Week 79): Pre-dose | 19.21 ng/mL | Standard Deviation 13.602 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 12 (Week 53): Pre-dose | 16.74 ng/mL | Standard Deviation 22.804 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 1 (Week 5): Pre-dose | 15.46 ng/mL | Standard Deviation 10.463 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 0 (Week 3): Pre-dose | 15.77 ng/mL | Standard Deviation 11.281 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 12 (Week 53): 1 to 6 hours Post-dose | 82.55 ng/mL | Standard Deviation 56.084 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 3 (Week 13): 1 to 6 hours Post-dose | 75.15 ng/mL | Standard Deviation 27.852 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 0 (Week 3): 1 to 6 hours Post-dose | 70.41 ng/mL | Standard Deviation 37.681 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 6 (Week 27): Pre-dose | 12.03 ng/mL | Standard Deviation 8.962 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 3 (Week 13): Pre-dose | 12.31 ng/mL | Standard Deviation 7.007 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 18 (Week 79): 4 to 8 hours Post-dose | 70.43 ng/mL | Standard Deviation 22.5 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Mean Concentration of Elenbecestat in Plasma | Month 6 (Week 27): 1 to 6 hours Post-dose | 71.28 ng/mL | Standard Deviation 39.114 |
Secondary
Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment
The measurement of the amyloid proteins Abeta(1-x) and Abeta(1-42), in CSF have been shown to be important biomarkers for alzheimer's disease.
Time frame: Month 1 (Week 5) and Month 18 (Week 79)
Population: The pharmacodynamic (PD) analysis set was the group of participants who had a baseline PD measurement and at least 1 post-dose PD measurement in the core phase. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure for specific categories and timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core Phase: Placebo | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-x) at Month 1 (Week 5) | 6.63 percent change | Standard Deviation 12.545 |
| Core Phase: Placebo | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-x) at Month 18 (Week 79) | -1.81 percent change | — |
| Core Phase: Placebo | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-42) at Month 1 (Week 5) | -8.53 percent change | Standard Deviation 16.818 |
| Core Phase: Placebo | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-42) at Month 18 (Week 79) | -6.50 percent change | Standard Deviation 24.809 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-x) at Month 18 (Week 79) | -33.86 percent change | Standard Deviation 11.039 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-42) at Month 1 (Week 5) | -9.43 percent change | Standard Deviation 22.798 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-42) at Month 18 (Week 79) | -27.19 percent change | Standard Deviation 20.172 |
| Core Phase: Elenbecestat 5 mg Then 50 mg | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-x) at Month 1 (Week 5) | -18.16 percent change | Standard Deviation 17.873 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-42) at Month 1 (Week 5) | -20.69 percent change | Standard Deviation 15.488 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-x) at Month 18 (Week 79) | -0.71 percent change | — |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-42) at Month 18 (Week 79) | -24.02 percent change | Standard Deviation 19.949 |
| Core Phase: Elenbecestat 15 mg Then 50 mg | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-x) at Month 1 (Week 5) | -36.43 percent change | Standard Deviation 16.026 |
| Core Phase: Elenbecestat 50 mg | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-42) at Month 18 (Week 79) | -56.77 percent change | Standard Deviation 5.312 |
| Core Phase: Elenbecestat 50 mg | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-x) at Month 18 (Week 79) | 33.98 percent change | Standard Deviation 160.017 |
| Core Phase: Elenbecestat 50 mg | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-x) at Month 1 (Week 5) | -56.66 percent change | Standard Deviation 14.431 |
| Core Phase: Elenbecestat 50 mg | Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment | Percent Change from Baseline in CSF Abeta(1-42) at Month 1 (Week 5) | -38.89 percent change | Standard Deviation 16.378 |
Secondary
Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score
The FAQ has 10 items concerned with performing daily tasks necessary for independent living. The caregiver or informant provides performance ratings on 10 complex activities of daily living performed within the preceding 4 weeks. Score ranges from 0 (independent) to 30 (dependent). Lower score indicates that participant can live independently. Higher score indicates that participant cannot live independently.
Time frame: Baseline, at Month 3, at Month 6, at Month 9, at Month 12, at Month 15, at Month 18, at Month 21, at Month 24, at Month 28 and at Month 32
Population: The full analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment in the extension phase. Here number analyzed signifies participants who were evaluable for this outcome measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score | Baseline | 14.4 score on a scale | Standard Deviation 7.31 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score | Change at Month 3 | 1.3 score on a scale | Standard Deviation 5.51 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score | Change at Month 6 | 1.4 score on a scale | Standard Deviation 3.74 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score | Change at Month 9 | 2.2 score on a scale | Standard Deviation 4.33 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score | Change at Month 12 | 2.6 score on a scale | Standard Deviation 4.86 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score | Change at Month 15 | 3.0 score on a scale | Standard Deviation 5.17 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score | Change at Month 18 | 3.4 score on a scale | Standard Deviation 4.83 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score | Change at Month 21 | 3.0 score on a scale | Standard Deviation 3.88 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score | Change at Month 24 | 6.8 score on a scale | Standard Deviation 5.92 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score | Change at Month 28 | 9.2 score on a scale | Standard Deviation 4.67 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score | Change at Month 32 | 15.0 score on a scale | — |
Secondary
Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores
MMSE is a 30-point scale that measures orientation to time and place, registration, immediate and delayed recall, attention, language, and drawing. Scores ranges from 0 (most impaired) to 30 (no impairment). Lower score indicates more impairment.
Time frame: Baseline, at Month 3, at Month 6, at Month 9, at Month 12, at Month 15, at Month 18, at Month 21, at Month 24, at Month 28 and at Month 32
Population: The full analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment in the extension phase. Here number analyzed signifies participants who were evaluable for this outcome measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores | Baseline | 21.5 score on a scale | Standard Deviation 5.67 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores | Change at Month 3 | -0.6 score on a scale | Standard Deviation 2.32 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores | Change at Month 6 | -0.6 score on a scale | Standard Deviation 2.39 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores | Change at Month 9 | -0.9 score on a scale | Standard Deviation 2.89 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores | Change at Month 12 | -1.4 score on a scale | Standard Deviation 2.43 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores | Change at Month 15 | -1.8 score on a scale | Standard Deviation 2.78 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores | Change at Month 18 | -1.7 score on a scale | Standard Deviation 3.01 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores | Change at Month 21 | -2.5 score on a scale | Standard Deviation 3.27 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores | Change at Month 24 | -3.9 score on a scale | Standard Deviation 4.46 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores | Change at Month 28 | -6.4 score on a scale | Standard Deviation 4.28 |
| Core Phase: Placebo | Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores | Change at Month 32 | -2.0 score on a scale | — |
Secondary
Extension Phase: Percent Change From Extension Phase Baseline in Left and Right Hippocampal Volume at Month 24
Left and right hippocampal volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Left and right hippocampal volumes represent a summary measure in the left and right hippocampal regions.
Time frame: Month 24
Population: The full analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment in the extension phase. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core Phase: Placebo | Extension Phase: Percent Change From Extension Phase Baseline in Left and Right Hippocampal Volume at Month 24 | Percent Change at Month 24 (Left Hippocampal Volume) | -4.31 percent change | Standard Deviation 2.065 |
| Core Phase: Placebo | Extension Phase: Percent Change From Extension Phase Baseline in Left and Right Hippocampal Volume at Month 24 | Percent Change at Month 24 (Right Hippocampal Volume) | -4.37 percent change | Standard Deviation 2.667 |
Secondary
Extension Phase: Percent Change From Extension Phase Baseline in Plasma Amyloid (A) Beta(1-x) Measurements at Months 12 and 24
The measurement of the amyloid protein Abeta(1-x), in plasma has been shown to be an important biomarker for alzheimer's disease.
Time frame: Month 12 and Month 24
Population: The PD analysis set was the group of participants who had at least 1 post-treatment PD measurement in the extension phase. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. Here number analyzed signifies participants who were evaluable for this outcome measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core Phase: Placebo | Extension Phase: Percent Change From Extension Phase Baseline in Plasma Amyloid (A) Beta(1-x) Measurements at Months 12 and 24 | Percent Change from Extension Phase Baseline in plasma Abeta(1-x) at Month 12 | -71.8 percent change | Standard Deviation 23.3 |
| Core Phase: Placebo | Extension Phase: Percent Change From Extension Phase Baseline in Plasma Amyloid (A) Beta(1-x) Measurements at Months 12 and 24 | Percent Change from Extension Phase Baseline in plasma Abeta(1-x) at Month 24 | -71.1 percent change | Standard Deviation 31.2 |
Secondary
Extension Phase: Percent Change From Extension Phase Baseline in Total Hippocampal Volume at Month 24
Total hippocampal volume is measured by volumetric magnetic resonance imaging (vMRI). Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total hippocampal volume is calculated by summing up right and left hippocampal volumes.
Time frame: Month 24
Population: The full analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment in the extension phase. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Phase: Placebo | Extension Phase: Percent Change From Extension Phase Baseline in Total Hippocampal Volume at Month 24 | -4.33 percent change | Standard Deviation 2.08 |
Secondary
Extension Phase: Percent Change From Extension Phase Baseline in Total Ventricular Volume at Month 24
Total Ventricular Volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total ventricular volume represents a summary measure of total including right and left lateral ventricles, third ventricle and fourth ventricle of brain.
Time frame: Month 24
Population: The full analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment in the extension phase. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Phase: Placebo | Extension Phase: Percent Change From Extension Phase Baseline in Total Ventricular Volume at Month 24 | 15.18 percent change | Standard Deviation 8.544 |
Secondary
Extension Phase: Percent Change From Extension Phase Baseline in Whole Brain Volume at Month 24
Whole brain volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Whole brain volume represents a summary measure of total brain parenchyma which includes the cerebrum, basal ganglia, diencephalon, and cerebellum.
Time frame: Month 24
Population: The full analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment in the extension phase. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core Phase: Placebo | Extension Phase: Percent Change From Extension Phase Baseline in Whole Brain Volume at Month 24 | -3.26 percent change | Standard Deviation 1.555 |