Alzheimer Disease
Conditions
Keywords
Alzheimer's Disease, JNJ-54861911, Placebo
Brief summary
The purpose of this study is to evaluate the long-term safety and tolerability of JNJ-54861911 in participants in the early Alzheimer's disease (AD \[progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks\]) spectrum that have completed a Phase 1b or Phase 2 clinical trial with JNJ-54861911, who are willing to continue their assigned treatment.
Detailed description
Participants in the early Alzheimer's Disease (AD) spectrum, enrolled in ongoing or future clinical trials with JNJ-54861911 (Phase 1b or Phase 2 studies) will be provided the opportunity to participate in this study upon completion of their treatment period under the parent protocol. The study will consist of a Screening phase and 2 sequential treatment phases (a 12-month double-blind \[DB\] treatment phase \[placebo controlled\] and an open-label \[OL\] phase \[active\]) followed by an End-of-Treatment visit. Treatment in OL phase will continue until registration of JNJ-54861911; unless safety issues emerge as determined by the Data Review Committee (DRC) that would warrant termination of the study. Blood and cerebrospinal fluid (CSF) samples will be collected to evaluate the plasma and CSF pharmacokinetics of JNJ-54861911, as well as amyloid beta fragments. Participants' safety will be monitored throughout the study.
Interventions
Participants will self-administer JNJ-54861911 tablet, 10 mg (2\*5 mg), orally, once daily.
Participants will self-administer 1 tablet of JNJ-54861911, containing 25 mg orally, once daily.
DRUGPlacebo
Participants will self administer placebo matching to JNJ-54861911 orally once daily.
DRUGJNJ-54861911, 5 mg
Participants will self-administer JNJ-54861911 tablet, 5 mg, orally, once daily.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Participants in the early Alzheimer's disease (AD) spectrum at time of enrollment under the parent protocol and according to its inclusion and
Exclusion criteria
, must have very recently completed their treatment in a Phase 1b or Phase 2 JNJ-54861911 clinical study (example \[e.g.\], 54861911ALZ2002) under the parent protocol. Enrollment in this study should be completed (Day 1 of double-blind \[DB\] treatment phase) as soon as possible, but within 6 weeks, following completion of their treatment period under the parent protocol. If not defined under the parent protocol, completion of the treatment period is defined as having completed all study related procedures of the last visit of the treatment period under the parent protocol. A screening phase of up to 12 weeks may be allowed following written approval of the Sponsor * Participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol * Each Participants (or their legally acceptable representative and caregiver depending on disease state and local requirements) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study * Participants must have a reliable informant (relative, partner, or friend). The informant must be willing to participate as a source of information and has at least weekly contact with the participant (contact can be in-person, via telephone or other audio/visual communication). The informant must have sufficient contact such that the Investigator feels he/she can provide meaningful information about the participant's daily function. If possible, an alternate informant meeting these criteria who can replace the primary informant should be identified prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Up to 3 years | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between administration of study drug and up to 3 years that were absent before treatment or that worsened relative to pre-treatment state. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | Baseline, Double-blind (DB) Day 1 and DB Week 52 | CSF samples were obtained for measuring levels of different ABeta fragments such as ABeta 1-37, ABeta 1-38, ABeta 1-40, and ABeta 1-42. ABeta fragments of different length produced by cleavage of amyloid precursor protein (APP) by beta-secretase (BACE) and gamma-secretase complex in brain and excreted into CSF. Participants were classified as asymptomatic at risk: cognitively and functionally normal (Clinical Dementia Rating Scale score \[CDR\] =0), but with biomarker pattern consistent with early stage AD (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674). |
| Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | Baseline, DB Day 1 and DB Week 52 | The CSF samples were obtained for measuring levels of different soluble amyloid precursor protein (sAPP) fragments (sAPP-alpha, sAPP-beta). Participants were classified as asymptomatic at risk: cognitively and functionally normal (CDR score =0), but with biomarker pattern consistent with early stage alzheimer's disease (AD) (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674). |
| Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Baseline, DB Day 1, DB Week 24, and DB Week 52 | Plasma samples were obtained for measuring levels of different ABeta fragments such as ABeta 1-38, ABeta 1-40, ABeta 1-42. ABeta fragments of different length were produced by cleavage of APP by beta-secretase (BACE) and gamma-secretase complex in different peripheral tissues, including white blood cells and were measured in plasma. Participants classified as asymptomatic at risk: cognitively and functionally normal (CDR score =0), but with biomarker pattern consistent with early stage AD (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674). |
| Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | Baseline, DB Day 1 and DB Week 52 | The CSF samples were obtained for measuring levels of Tau protein and phosphorylated (p)-tau protein. Participants were classified as asymptomatic at risk: cognitively and functionally normal (CDR score =0), but with biomarker pattern consistent with early stage AD (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674). |
Countries
Belgium, France, Germany, Netherlands, Spain, Sweden
Participant flow
Pre-assignment details
Participants who completed their treatment period as described under the parent protocol in study 54861911ALZ2002 (NCT02260674) or any ongoing/future Phase 1b or Phase 2 atabecestat clinical study were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Double-blind Treatment Phase (Period 1): Placebo Participants received placebo matched to atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase. | 35 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg Participants received 10 milligram (mg) of atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase. | 29 |
| Double-blind Treatment Phase (Period 1): Atabecestat 25 mg Participants received 25 mg of atabecestat orally, once daily from Day 1 up to Week 52 in the Double-blind treatment phase. | 26 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Double-blind Treatment Phase (Period 1) | Adverse Event | 0 | 2 | 1 | 0 | 0 | 0 | 0 |
| Double-blind Treatment Phase (Period 1) | Physician Decision | 3 | 0 | 1 | 0 | 0 | 0 | 0 |
| Double-blind Treatment Phase (Period 1) | Subject Refused Further Study Treatment | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Double-blind Treatment Phase (Period 1) | Withdrawal by Subject | 2 | 1 | 1 | 0 | 0 | 0 | 0 |
| Open-label Phase (Period 2) | Adverse Event | 0 | 0 | 0 | 2 | 2 | 0 | 0 |
| Open-label Phase (Period 2) | At Spouse Request With PI Agreement | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Open-label Phase (Period 2) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Open-label Phase (Period 2) | Study Terminated by Sponsor | 0 | 0 | 0 | 11 | 7 | 24 | 19 |
| Open-label Phase (Period 2) | Subject not Compliant to Study Procedure | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Open-label Phase (Period 2) | Withdrawal by Subject | 0 | 0 | 0 | 2 | 4 | 0 | 2 |
Baseline characteristics
| Characteristic | Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Atabecestat 25 mg | Total | Double-blind Treatment Phase (Period 1): Placebo |
|---|---|---|---|---|
| Age, Continuous | 71.4 years STANDARD_DEVIATION 7.04 | 67.9 years STANDARD_DEVIATION 8.87 | 70 years STANDARD_DEVIATION 7.06 | 70.4 years STANDARD_DEVIATION 5.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 25 Participants | 83 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 1 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized White Non-Hispanic | 25 Participants | 25 Participants | 83 Participants | 33 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 26 Participants | 89 Participants | 35 Participants |
| Region of Enrollment BELGIUM | 4 Participants | 3 Participants | 13 Participants | 6 Participants |
| Region of Enrollment FRANCE | 2 Participants | 1 Participants | 7 Participants | 4 Participants |
| Region of Enrollment GERMANY | 3 Participants | 6 Participants | 13 Participants | 4 Participants |
| Region of Enrollment NETHERLANDS | 1 Participants | 3 Participants | 8 Participants | 4 Participants |
| Region of Enrollment SPAIN | 17 Participants | 10 Participants | 37 Participants | 10 Participants |
| Region of Enrollment SWEDEN | 2 Participants | 3 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male Female | 16 Participants | 12 Participants | 47 Participants | 19 Participants |
| Sex: Female, Male Male | 13 Participants | 14 Participants | 43 Participants | 16 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 | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 29 | 0 / 26 | 0 / 15 | 0 / 14 | 0 / 26 | 0 / 22 |
| other Total, other adverse events | 17 / 35 | 11 / 29 | 14 / 26 | 10 / 15 | 11 / 14 | 12 / 26 | 11 / 22 |
| serious Total, serious adverse events | 3 / 35 | 4 / 29 | 4 / 26 | 2 / 15 | 4 / 14 | 0 / 26 | 1 / 22 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between administration of study drug and up to 3 years that were absent before treatment or that worsened relative to pre-treatment state. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Up to 3 years
Population: Safety analysis set included all participants who received at least 1 dose of study drug in the study (during Period 1 and 2).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-blind Treatment Phase (Period 1): Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with Serious TEAEs | 3 Participants |
| Double-blind Treatment Phase (Period 1): Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with TEAEs | 22 Participants |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with TEAEs | 15 Participants |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with Serious TEAEs | 4 Participants |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with TEAEs | 21 Participants |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with Serious TEAEs | 4 Participants |
| Open-label (OL) Phase (Period 2): Placebo to Atabecestat 5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with TEAEs | 10 Participants |
| Open-label (OL) Phase (Period 2): Placebo to Atabecestat 5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with Serious TEAEs | 2 Participants |
| OL Phase (Period 2): Placebo to Atabecestat 25 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with Serious TEAEs | 4 Participants |
| OL Phase (Period 2): Placebo to Atabecestat 25 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with TEAEs | 11 Participants |
| OL Phase (Period 2): Atabecestat 10 mg to Atabecestat 5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with TEAEs | 19 Participants |
| OL Phase (Period 2): Atabecestat 10 mg to Atabecestat 5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with Serious TEAEs | 0 Participants |
| OL Phase (Period 2): Atabecestat 25 mg to Atabecestat 25 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with TEAEs | 16 Participants |
| OL Phase (Period 2): Atabecestat 25 mg to Atabecestat 25 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Number of Participants with Serious TEAEs | 1 Participants |
Secondary
Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels
CSF samples were obtained for measuring levels of different ABeta fragments such as ABeta 1-37, ABeta 1-38, ABeta 1-40, and ABeta 1-42. ABeta fragments of different length produced by cleavage of amyloid precursor protein (APP) by beta-secretase (BACE) and gamma-secretase complex in brain and excreted into CSF. Participants were classified as asymptomatic at risk: cognitively and functionally normal (Clinical Dementia Rating Scale score \[CDR\] =0), but with biomarker pattern consistent with early stage AD (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674).
Time frame: Baseline, Double-blind (DB) Day 1 and DB Week 52
Population: The Double-blind (DB) Safety Analysis Set included all participants (asymptomatic at risk and prodromal at baseline) who received study treatment during Period 1. Here 'n' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-42: Asymptomatic at Risk: DB Week 52 | -10.1 Percent change | Standard Deviation 7.81 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-42: Prodromal: DB Day 1 | 8.0 Percent change | Standard Deviation 7.44 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-38: Prodromal: DB Day 1 | 10.2 Percent change | Standard Deviation 15.41 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-38: Prodromal: DB Week 52 | -9.7 Percent change | Standard Deviation 16.52 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-40: Prodromal: DB Day 1 | 8.6 Percent change | Standard Deviation 17.19 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-37: Asymptomatic at Risk: DB Week 52 | -9.9 Percent change | Standard Deviation 7.32 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-40: Asymptomatic at Risk: DB Week 52 | -9.7 Percent change | Standard Deviation 6.12 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-37: Prodromal: DB Day 1 | 6.1 Percent change | Standard Deviation 10.09 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-37: Prodromal: DB Week 52 | -8.8 Percent change | Standard Deviation 17.75 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-40: Prodromal: DB Week 52 | -14.5 Percent change | Standard Deviation 20.48 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-42: Prodromal: DB Week 52 | -15.0 Percent change | Standard Deviation 20.51 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-38: Asymptomatic at Risk: DB Week 52 | -9.3 Percent change | Standard Deviation 7.02 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-40: Asymptomatic at Risk: DB Week 52 | -46.2 Percent change | Standard Deviation 18.22 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-40: Prodromal: DB Week 52 | -60.7 Percent change | Standard Deviation 13.52 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-42: Prodromal: DB Week 52 | -52.5 Percent change | Standard Deviation 11.6 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-42: Asymptomatic at Risk: DB Week 52 | -39.6 Percent change | Standard Deviation 24.28 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-37: Prodromal: DB Week 52 | -62.0 Percent change | Standard Deviation 11.02 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-38: Asymptomatic at Risk: DB Week 52 | -42.9 Percent change | Standard Deviation 17.49 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-38: Prodromal: DB Week 52 | -58.6 Percent change | Standard Deviation 10.21 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-37: Asymptomatic at Risk: DB Week 52 | -65.4 Percent change | — |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-42: Prodromal: DB Week 52 | -57.6 Percent change | Standard Deviation 31.42 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-37: Asymptomatic at Risk: DB Week 52 | -90.0 Percent change | — |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-37: Prodromal: DB Week 52 | -65.9 Percent change | Standard Deviation 23.16 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-38: Asymptomatic at Risk: DB Week 52 | -83.5 Percent change | Standard Deviation 4.84 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-38: Prodromal: DB Week 52 | -70.4 Percent change | Standard Deviation 23.53 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-40: Asymptomatic at Risk: DB Week 52 | -84.6 Percent change | Standard Deviation 5.43 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-40: Prodromal: DB Week 52 | -72.8 Percent change | Standard Deviation 22.3 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-42: Asymptomatic at Risk: DB Week 52 | -76.7 Percent change | Standard Deviation 11.01 |
| Unknown | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-42: Asymptomatic at Risk: DB Day 1 | — Percent change | — |
| Unknown | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-40: Asymptomatic at Risk: DB Day 1 | — Percent change | — |
| Unknown | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-38: Asymptomatic at Risk: DB Day 1 | — Percent change | — |
| Unknown | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) (1-37, 1-38, 1-40, 1-42) Levels | CSF ABeta 1-37: Asymptomatic at Risk: DB Day 1 | — Percent change | — |
Secondary
Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels
The CSF samples were obtained for measuring levels of different soluble amyloid precursor protein (sAPP) fragments (sAPP-alpha, sAPP-beta). Participants were classified as asymptomatic at risk: cognitively and functionally normal (CDR score =0), but with biomarker pattern consistent with early stage alzheimer's disease (AD) (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674).
Time frame: Baseline, DB Day 1 and DB Week 52
Population: The Double-blind (DB) Safety Analysis Set included all participants (asymptomatic at risk and prodromal at baseline) who received study treatment during Period 1. Here 'n' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-Beta: Asymptomatic at Risk: DB Week 52 | -10.8 Percent change | Standard Deviation 8.44 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-Beta: Prodromal: DB Week 52 | -11.7 Percent change | Standard Deviation 14.47 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-alpha: Prodromal: DB Day 1 | 0.9 Percent change | Standard Deviation 24.97 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-alpha: Prodromal: DB Week 52 | -11.2 Percent change | Standard Deviation 14.01 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-alpha: Asymptomatic at Risk: DB Week 52 | -4.7 Percent change | Standard Deviation 12.78 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-Beta: Prodromal: DB Day 1 | 0.4 Percent change | Standard Deviation 18.93 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-alpha: Asymptomatic at Risk: DB Week 52 | 50.1 Percent change | Standard Deviation 13.67 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-alpha: Prodromal: DB Week 52 | 60.2 Percent change | Standard Deviation 24.03 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-Beta: Asymptomatic at Risk: DB Week 52 | -57.5 Percent change | Standard Deviation 8.06 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-Beta: Prodromal: DB Week 52 | -63.5 Percent change | Standard Deviation 5.19 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-Beta: Prodromal: DB Week 52 | -73.0 Percent change | Standard Deviation 21.79 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-alpha: Asymptomatic at Risk: DB Week 52 | 77.8 Percent change | — |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-alpha: Prodromal: DB Week 52 | 85.1 Percent change | Standard Deviation 39.35 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-Beta: Asymptomatic at Risk: DB Week 52 | -90.8 Percent change | — |
| Unknown | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-Beta: Asymptomatic at Risk: DB Day 1 | — Percent change | — |
| Unknown | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein (sAPP) Fragments (sAPP-alpha and sAPP-beta) Levels | CSF sAPP-alpha: Asymptomatic at Risk: DB Day 1 | — Percent change | — |
Secondary
Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level
The CSF samples were obtained for measuring levels of Tau protein and phosphorylated (p)-tau protein. Participants were classified as asymptomatic at risk: cognitively and functionally normal (CDR score =0), but with biomarker pattern consistent with early stage AD (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674).
Time frame: Baseline, DB Day 1 and DB Week 52
Population: The Double-blind (DB) Safety Analysis Set included all participants (asymptomatic at risk and prodromal at baseline) who received study treatment during Period 1. Here 'n' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF p-Tau Protein: Asymptomatic at Risk:DB Week 52 | -4.6 Percent change | Standard Deviation 6.47 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF p-Tau Protein: Prodromal: Week 52 | 2.2 Percent change | Standard Deviation 12.93 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF Tau Protein: Prodromal: DB Day 1 | 6.1 Percent change | Standard Deviation 6.82 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF Tau Protein: Prodromal: DB Week 52 | 13.6 Percent change | Standard Deviation 45.55 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF Tau Protein: Asymptomatic at Risk: DB Week 52 | -1.4 Percent change | Standard Deviation 14.1 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF p-Tau Protein: Prodromal: DB Day 1 | -0.6 Percent change | Standard Deviation 7.81 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF Tau Protein: Asymptomatic at Risk: DB Week 52 | 3.2 Percent change | Standard Deviation 15.04 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF Tau Protein: Prodromal: DB Week 52 | 2.1 Percent change | Standard Deviation 13.82 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF p-Tau Protein: Asymptomatic at Risk:DB Week 52 | -4.9 Percent change | Standard Deviation 1.4 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF p-Tau Protein: Prodromal: Week 52 | -2.7 Percent change | Standard Deviation 10.52 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF p-Tau Protein: Prodromal: Week 52 | -2.6 Percent change | Standard Deviation 8.52 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF Tau Protein: Asymptomatic at Risk: DB Week 52 | 22.4 Percent change | — |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF Tau Protein: Prodromal: DB Week 52 | 1.4 Percent change | Standard Deviation 8.2 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF p-Tau Protein: Asymptomatic at Risk:DB Week 52 | 8.3 Percent change | — |
| Unknown | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF p-Tau Protein: Asymptomatic at Risk: DB Day 1 | — Percent change | — |
| Unknown | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Cerebrospinal Fluid (CSF) Tau Protein and Phosphorylated Tau (p-Tau) Protein Level | CSF Tau Protein: Asymptomatic at Risk: DB Day 1 | — Percent change | — |
Secondary
Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels
Plasma samples were obtained for measuring levels of different ABeta fragments such as ABeta 1-38, ABeta 1-40, ABeta 1-42. ABeta fragments of different length were produced by cleavage of APP by beta-secretase (BACE) and gamma-secretase complex in different peripheral tissues, including white blood cells and were measured in plasma. Participants classified as asymptomatic at risk: cognitively and functionally normal (CDR score =0), but with biomarker pattern consistent with early stage AD (preclinical stage); and prodromal: had some limited cognitive impairment (CDR =0.5), and still functionally normal, with biomarker pattern consistent with early stage (predementia) AD, but had as of yet no dementia (predementia stage). Here, 'Number analyzed=0' signifies that either CSF concentration was below lower limit of quantification for assay or sample was collected under parent study 54861911ALZ2002 (NCT02260674).
Time frame: Baseline, DB Day 1, DB Week 24, and DB Week 52
Population: The Double-blind (DB) Safety Analysis Set included all participants (asymptomatic at risk and prodromal at baseline) who received study treatment during Period 1. Here 'n' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-42:Asymptomatic at Risk: DB Week 52 | -6.0 Percent change | Standard Deviation 2.69 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-38:Asymptomatic at Risk: DB Week 24 | -9.9 Percent change | Standard Deviation 0.83 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40: Prodromal: DB Week 24 | 8.6 Percent change | Standard Deviation 18.57 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-42: Prodromal: DB Day 1 | -1.9 Percent change | Standard Deviation 5.54 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-38: Prodromal: DB Week 24 | 3.0 Percent change | Standard Deviation 24.32 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40: Prodromal: DB Week 52 | 10.5 Percent change | Standard Deviation 17.09 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-42: Prodromal: DB Week 24 | 15.9 Percent change | Standard Deviation 17.15 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40: Asymptomatic at Risk: DB Day 1 | 19.2 Percent change | — |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-38: Prodromal: DB Week 52 | 20.3 Percent change | Standard Deviation 35.48 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-38: Asymptomatic at Risk:DB Week 52 | -5.3 Percent change | — |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40:Asymptomatic at Risk: DB Week 24 | -2.3 Percent change | Standard Deviation 12.38 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-42: Asymptomatic at Risk: DB Day 1 | -5.9 Percent change | — |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-38: Prodromal: DB Day 1 | -5.0 Percent change | Standard Deviation 10.07 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40:Asymptomatic at Risk: DB Week 52 | 0.0 Percent change | Standard Deviation 10.85 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-42:Asymptomatic at Risk:DB Week 24 | -7.3 Percent change | Standard Deviation 9.33 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-42: Prodromal: DB Week 52 | 5.1 Percent change | Standard Deviation 17.68 |
| Double-blind Treatment Phase (Period 1): Placebo | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40: Prodromal: DB Day 1 | 2.9 Percent change | Standard Deviation 15.48 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40:Asymptomatic at Risk: DB Week 24 | -75.2 Percent change | Standard Deviation 10.16 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40: Asymptomatic at Risk: DB Day 1 | -4.9 Percent change | — |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40: Prodromal: DB Week 52 | -70.9 Percent change | Standard Deviation 9.24 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40:Asymptomatic at Risk: DB Week 52 | -74.9 Percent change | Standard Deviation 6.76 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40: Prodromal: DB Day 1 | 25.8 Percent change | Standard Deviation 66.03 |
| Double-blind Treatment Phase (Period 1): Atabecestat 10 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40: Prodromal: DB Week 24 | -68.6 Percent change | Standard Deviation 8.2 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40:Asymptomatic at Risk: DB Week 52 | -80.8 Percent change | Standard Deviation 7.6 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-38: Prodromal: DB Day 1 | -6.6 Percent change | Standard Deviation 13.56 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40: Asymptomatic at Risk: DB Day 1 | 4.7 Percent change | Standard Deviation 40.27 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40:Asymptomatic at Risk: DB Week 24 | -82.6 Percent change | Standard Deviation 5.59 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40: Prodromal: DB Day 1 | -24.2 Percent change | Standard Deviation 41.31 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40: Prodromal: DB Week 24 | -82.5 Percent change | Standard Deviation 7.38 |
| Double-blind Treatment Phase(Period 1): Atabecestat, 25 mg | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-40: Prodromal: DB Week 52 | -75.3 Percent change | Standard Deviation 22.15 |
| Unknown | Double-blind Treatment Phase (Period 1): Percent Change From Baseline in Plasma Amyloid Beta (ABeta) (1-38, 1-40, 1-42) Levels | Plasma ABeta 1-38: Asymptomatic at Risk: DB Day 1 | — Percent change | — |