Back to resultsA Study of LY2886721 in Healthy Participants and Participants Diagnosed With Alzheimer's Disease
Primary Purpose
Alzheimer Disease, Healthy Volunteers
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
LY2886721
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Alzheimer Disease
Eligibility Criteria
Inclusion Criteria:
- Healthy participants have a body mass index (BMI) of 19 to 32 kilograms per square meter (kg/m^2), inclusive, at screening. There are no restrictions on BMI in participants diagnosed with Alzheimer's disease.
- Healthy participants should not be taking any concomitant medications. For participants with Alzheimer's disease, concomitant medications will be determined by the investigator in consultation with the Lilly clinical pharmacologist on an individual basis.
Cohort A:
- Participants are defined as otherwise healthy males or females as determined by medical history and physical examination, and a diagnosis of Alzheimer's disease and must be at least 45 years of age.
- Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable Alzheimer's disease, as determined by a clinician approved by the sponsor or designee.
- Mini Mental State Examination (MMSE) score of 16 through 28 at screening.
- Modified Hachinski Ischemia Scale (MHIS) score of <4.
- Capable of understanding and signing their own informed consent, in the opinion of the investigator, or if the participant has a Legally Authorized Representative (LAR), then the LAR must be capable of understanding and signing the assent form, and the participant may or may not sign the informed consent, as to be determined by the investigator.
- If receiving concurrent treatment with an acetylcholinesterase inhibitor (AChEI) and/or memantine, the participant has been on a stable dose for at least 4 weeks before Day 1. Dosing must remain stable throughout the study. Note: If a participant has recently stopped ACHEIs and/or memantine, he or she must have discontinued treatment for at least 4 weeks before Day 1.
Exclusion Criteria:
- Have an abnormality in the 12-lead electrocardiogram (ECG).
- Have abnormal blood pressure.
- Have abnormal thyroid function as reflected by thyroid stimulating hormone (TSH) values outside of the normal range.
- Show evidence of human immunodeficiency virus (HIV) infection and/or positive HIV antibodies.
- Show evidence of hepatitis C and/or positive hepatitis C antibody.
- Have had multiple episodes of head trauma, or have a history within the last 5 years of a serious infectious disease affecting the brain.
- Have chronic hepatic disease.
- Have evidence or history of significant active bleeding or a coagulation disorder.
- Cohort A: have any neurological disorders other than Alzheimer's disease.
- For healthy participants (Cohorts B and C) only: Use or intend to use over the- counter or prescription medication, including herbal medications within 14 days prior to dosing or during the study.
Sites / Locations
- 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.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Cohort A: 70 mg LY2886721
Cohort A: Placebo
Cohort B: 70 mg LY2886721
Cohort B: Placebo
Cohort C: 280 mg LY2886721
Cohort C: Placebo
Arm Description
Participants with Alzheimer's disease received a single, 70-milligrams (mg) (1 capsule), oral dose of LY2886721.
Participants with Alzheimer's disease received a single, oral dose of LY2886721-matching placebo (1 capsule).
Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.
Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
Healthy participants received a single, oral dose of LY2886721-matching placebo (4 capsules).
Outcomes
Primary Outcome Measures
Pharmacokinetics: Area Under the Curve Extrapolated to Infinity (AUC0-∞) of Plasma LY2886721
AUC0-∞ following administration of a single dose of 70 or 280 mg LY2886721.
Pharmacokinetics: Maximum Concentration (Cmax) of Plasma LY2886721
Cmax following administration of a single dose of 70 or 280 mg LY2886721.
Pharmacokinetics: Area Under the Curve Extrapolated to Infinity (AUC0-∞) of Cerebrospinal Fluid (CSF) LY2886721
AUC0-∞ following administration of a single dose of 70 mg LY2886721.
Pharmacokinetics: Maximum Concentration (Cmax) of CSF LY2886721
Cmax following administration of a single dose of 70 mg LY2886721.
Pharmacodynamics (PD): Cnadir of Plasma Amyloid β (Aβ)1-40
Plasma concentration of Aβ1-40 was summarized based on lowest observed concentration (Cnadir).
PD: Cnadir of CSF Aβ 1-40
Plasma concentration of Aβ1-40 was summarized based on Cnadir following administration of a single dose of 70 mg LY2886721 or a single dose of LY2886721-matching placebo.
Secondary Outcome Measures
Cohort C: Mean QTcF Value at Cmax
The mean QTcF value at Cmax for participants administered a single dose of 280 mg LY2886721 was reported. The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Time matched mean change from baseline in QTcF = time matched plasma concentration + participant + random error.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01807026
Brief Title
A Study of LY2886721 in Healthy Participants and Participants Diagnosed With Alzheimer's Disease
Official Title
A Safety, Pharmacokinetic, and Pharmacodynamic Study of LY2886721 in Healthy Subjects and Patients Diagnosed With Alzheimer's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is being done for the following reasons:
To determine the safety of LY2886721 and any side effects that may be associated with it and to see how much of the study drug is in the blood and the cerebrospinal fluid (CSF) when one dose is given to healthy participants and participants diagnosed with Alzheimer's disease. It will also look at how safe and tolerable the study drug is when given to healthy participants in higher doses.
This research study is being conducted in three groups, referred to as Groups (Cohorts) A, B, or C.
Group A will enroll participants with Alzheimer's disease while Groups B and C will enroll healthy participants.
For Group A or B, participation in this research study could last up to 34 days. For Group C, participation could last up to 60 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease, Healthy Volunteers
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A: 70 mg LY2886721
Arm Type
Experimental
Arm Description
Participants with Alzheimer's disease received a single, 70-milligrams (mg) (1 capsule), oral dose of LY2886721.
Arm Title
Cohort A: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants with Alzheimer's disease received a single, oral dose of LY2886721-matching placebo (1 capsule).
Arm Title
Cohort B: 70 mg LY2886721
Arm Type
Experimental
Arm Description
Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.
Arm Title
Cohort B: Placebo
Arm Type
Placebo Comparator
Arm Description
Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).
Arm Title
Cohort C: 280 mg LY2886721
Arm Type
Experimental
Arm Description
Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.
Arm Title
Cohort C: Placebo
Arm Type
Placebo Comparator
Arm Description
Healthy participants received a single, oral dose of LY2886721-matching placebo (4 capsules).
Intervention Type
Drug
Intervention Name(s)
LY2886721
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Pharmacokinetics: Area Under the Curve Extrapolated to Infinity (AUC0-∞) of Plasma LY2886721
Description
AUC0-∞ following administration of a single dose of 70 or 280 mg LY2886721.
Time Frame
Predose through 96 hours after administration of study drug
Title
Pharmacokinetics: Maximum Concentration (Cmax) of Plasma LY2886721
Description
Cmax following administration of a single dose of 70 or 280 mg LY2886721.
Time Frame
Predose through 96 hours after administration of study drug
Title
Pharmacokinetics: Area Under the Curve Extrapolated to Infinity (AUC0-∞) of Cerebrospinal Fluid (CSF) LY2886721
Description
AUC0-∞ following administration of a single dose of 70 mg LY2886721.
Time Frame
Predose through 36 hours after administration of study drug
Title
Pharmacokinetics: Maximum Concentration (Cmax) of CSF LY2886721
Description
Cmax following administration of a single dose of 70 mg LY2886721.
Time Frame
Predose through 36 hours after administration of study drug
Title
Pharmacodynamics (PD): Cnadir of Plasma Amyloid β (Aβ)1-40
Description
Plasma concentration of Aβ1-40 was summarized based on lowest observed concentration (Cnadir).
Time Frame
Predose, up to 96 hours after administration of study drug
Title
PD: Cnadir of CSF Aβ 1-40
Description
Plasma concentration of Aβ1-40 was summarized based on Cnadir following administration of a single dose of 70 mg LY2886721 or a single dose of LY2886721-matching placebo.
Time Frame
Predose up to 36 hours after administration of study drug
Secondary Outcome Measure Information:
Title
Cohort C: Mean QTcF Value at Cmax
Description
The mean QTcF value at Cmax for participants administered a single dose of 280 mg LY2886721 was reported. The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Time matched mean change from baseline in QTcF = time matched plasma concentration + participant + random error.
Time Frame
Predose up to 48 hours after administration of study drug
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy participants have a body mass index (BMI) of 19 to 32 kilograms per square meter (kg/m^2), inclusive, at screening. There are no restrictions on BMI in participants diagnosed with Alzheimer's disease.
Healthy participants should not be taking any concomitant medications. For participants with Alzheimer's disease, concomitant medications will be determined by the investigator in consultation with the Lilly clinical pharmacologist on an individual basis.
Cohort A:
Participants are defined as otherwise healthy males or females as determined by medical history and physical examination, and a diagnosis of Alzheimer's disease and must be at least 45 years of age.
Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable Alzheimer's disease, as determined by a clinician approved by the sponsor or designee.
Mini Mental State Examination (MMSE) score of 16 through 28 at screening.
Modified Hachinski Ischemia Scale (MHIS) score of <4.
Capable of understanding and signing their own informed consent, in the opinion of the investigator, or if the participant has a Legally Authorized Representative (LAR), then the LAR must be capable of understanding and signing the assent form, and the participant may or may not sign the informed consent, as to be determined by the investigator.
If receiving concurrent treatment with an acetylcholinesterase inhibitor (AChEI) and/or memantine, the participant has been on a stable dose for at least 4 weeks before Day 1. Dosing must remain stable throughout the study. Note: If a participant has recently stopped ACHEIs and/or memantine, he or she must have discontinued treatment for at least 4 weeks before Day 1.
Exclusion Criteria:
Have an abnormality in the 12-lead electrocardiogram (ECG).
Have abnormal blood pressure.
Have abnormal thyroid function as reflected by thyroid stimulating hormone (TSH) values outside of the normal range.
Show evidence of human immunodeficiency virus (HIV) infection and/or positive HIV antibodies.
Show evidence of hepatitis C and/or positive hepatitis C antibody.
Have had multiple episodes of head trauma, or have a history within the last 5 years of a serious infectious disease affecting the brain.
Have chronic hepatic disease.
Have evidence or history of significant active bleeding or a coagulation disorder.
Cohort A: have any neurological disorders other than Alzheimer's disease.
For healthy participants (Cohorts B and C) only: Use or intend to use over the- counter or prescription medication, including herbal medications within 14 days prior to dosing or during the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
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.
City
Salt Lake City
State/Province
Utah
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of LY2886721 in Healthy Participants and Participants Diagnosed With Alzheimer's Disease
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