Study of LY2886721 in Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease

Alzheimer's Disease Clinical Trial

Official title:

Assessment of Safety, Tolerability, and Pharmacodynamic Effects of LY2886721 in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01561430
• Other study ID #: 13735
• Secondary ID: I4O-MC-BACC2011-
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: March 2012
• Est. completion date: August 2013

Study information

• Verified date: May 2018
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this Phase 1/Phase 2 study is to evaluate how the body handles the drug and the drug's effect on the body of participants with mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or mild AD and who test positive for amyloid plaque.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 70
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

Meets criteria for MCI due to AD or Mild AD

All participants will be required to undergo assessment via the Mini Mental State Examination (MMSE) scale at screening

• Participants with MMSE scores of 20 to 26, inclusive, may be enrolled provided they meet the criteria for mild AD, as follows:

• Participant meets the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD

• Clinical Dementia Rating Scale (CDR) score of 0.5 or 1

• Positive scan for the presence of amyloid beta

• Participants with MMSE of 27 to 30, inclusive, may be enrolled as participants with MCI due to AD provided they meet the following criteria:

• Gradual and progressive change in memory function as reported by the participant or a caregiver during a period of more than 6 months

• Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR): free recall =22 and total recall =46

• Absence of dementia

• Preservation of functional independence

• Exclusion of other potential (vascular, traumatic, or medical) causes of cognitive decline, where possible

• Positive scan for the presence of amyloid beta

• Women must be postmenopausal

• Men are required to use an approved barrier method of contraception if their partners are pregnant, or of childbearing potential and not using approved contraceptive methods

Exclusion Criteria:

• Participant in another drug or device study

• Have a history of frontotemporal dementia, Lewy body disease, vascular dementia, Huntington's disease, Parkinson's disease, progressive supranuclear palsy (PSNP), or other movement disorder

• Participants are not on a stable standard of care (acetylcholinesterase inhibitors, memantine) initiated less than 2 months prior to entry or have less than 4 weeks of stable therapy. Note: Stable standard of care is allowed.

• Have had a serious infectious disease affecting the brain in the past 5 years

• Have had a serious or repeat head injury

• Have significant retinal impairment or disease

• Have had a stroke or other circulation problems that are affecting current health

• Have had a seizure

• Have major depressive disorder and are not on a stable dose of medication. Participants who no longer meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV) criteria for major depression may be included

• History of schizophrenia, bipolar disorder, or severe mental illness

• History of alcohol or drug abuse

• Have asthma, chronic obstructive pulmonary disease (COPD), or other breathing disease that is not controlled with medicine

• Have human immunodeficiency virus (HIV) or syphilis

• Are taking blood thinners

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Cognitive Dysfunction

Intervention

Drug:
• LY2886721

• Placebo

Locations

Country	Name	City	State
Italy	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Biella
Italy	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pisa
Italy	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rome
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tokyo
Netherlands	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Amsterdam
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Barcelona
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Getafe
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madrid
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sant Cugal Del Valles
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Albany	New York
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Boca Raton	Florida
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chicago	Illinois
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Dayton	Ohio
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Decatur	Georgia
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Delray Beach	Florida
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Denver	Colorado
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Durham	North Carolina
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fort Myers	Florida
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lexington	Kentucky
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Long Beach	California
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Monroe	New Jersey
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	New Haven	Connecticut
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ocala	Florida
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Orlando	Florida
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Phoenix	Arizona
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Plymouth	Massachusetts
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Portland	Oregon
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Quincy	Massachusetts
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Salt Lake City	Utah
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	San Francisco	California
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sun City	Arizona
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tucson	Arizona
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Italy,  Japan,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aß)1-40 and Aß1-42 Concentrations	Percent change in lumbar CSF concentrations of Aß1-40 and Aß1-42 from baseline at 12 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect.	Baseline, 12 weeks
Primary	Change From Baseline to 26 Weeks in CSF Aß1-40 and Aß1-42 Concentrations	Percent change in lumbar CSF concentrations of Aß1-40 and Aß1-42 from baseline at 26 weeks post-dose was to be calculated. The units for CSF were picograms per milliliter (pg/mL). LS means of percent change in concentration from baseline was calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect.	Baseline, 26 weeks
Secondary	Change From Baseline in Plasma Amyloid Beta (Aß)1-40 and Aß1-42 Concentrations	Percent change in plasma concentrations of Aß1-40 and Aß1-42 from baseline at 12 weeks and 26 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL).	Baseline, 12 weeks, 26 weeks
Secondary	Change From Baseline to 26 Weeks in Neuropsychological Test Battery (NTB)	The NTB is a composite cognitive measure in clinical Alzheimer's disease studies and is a collection of several written and oral tests that examines verbal and nonverbal brain functions. NTB Z-score typically ranges from -3 to 3, with lower scores suggesting greater cognitive impairment. LS means were calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect.	Baseline, 26 weeks
Secondary	Change From Baseline to 26 Weeks in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)	ADAS-Cog11 is an 11-item instrument measuring impairment in memory (Items 1-4, 7, 11), praxis (Items 4 and 5), orientation (Item 6), and language (Items 8-10). Item 1 ranged 0 (all items recalled correctly)-10 (none recalled correctly); Items 2-5 and 8-11 ranged 0 (all items named, performed, drawn, spoken, remember correctly/clearly)-5 (none correct/not clearly spoken); Item 6 ranged 0 (no incorrect responses)-8 (all incorrect); and Item 7 ranged 0 (all words remembered correctly)-12 (no words remembered correctly) for a total ADAS-Cog11 score of 0-70 with higher scores indicating greater disease severity. A score of 0-10 for delayed free recall and a conversion code of 0-5 for digit cancellation and maze completion was added to the total ADAS-Cog11 score for a total ADAS-Cog14 score ranging 0-90 with higher scores indicating greater impairment. LS means were calculated using Mixed Model Repeated Measures (MMRM) with Treatment + Visit + Treatment*Visit + Baseline + Baseline*Visit.	Baseline, 26 weeks
Secondary	Change From Baseline to 26 Weeks in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)	The CDR-SB is a composite measure of 6 domains of cognitive and functional performance: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Scores ranged from 0 to 18, with higher scores indicating greater impairment. LS means were calculated using MMRM with Treatment + Visit + Treatment*Visit + Baseline + Baseline*Visit.	Baseline, 26 weeks
Secondary	Change From Baseline to 26 Weeks in Mini Mental State Examination (MMSE)	The MMSE (Folstein et al. 1975) is one of the most widely used screening instruments for cognitive impairment. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and provides a total score ranging from 0 to 30, with lower scores indicative of greater cognitive impairment. LS means were calculated using MMRM with Treatment + Visit + Treatment*Visit + Baseline + Baseline*Visit.	Baseline, 26 weeks
Secondary	Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations	Percent change in lumbar CSF tau and ptau-181 concentrations from baseline at 12 weeks post-dose and 26 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect.	Baseline, 12 weeks, 26 weeks