A Study of LY2886721 in Healthy Participants and Participants Diagnosed With Alzheimer's Disease

NCT01807026 | Completed Phase 1 Results

• 2 other identifiers: 15107I4O-EW-BACX
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease; Healthy Volunteers

Outcome Measures

Primary Outcomes (6)

• 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.

  Predose through 96 hours after administration of study drug

• Pharmacokinetics: Maximum Concentration (Cmax) of Plasma LY2886721

  Cmax following administration of a single dose of 70 or 280 mg LY2886721.

  Predose through 96 hours after administration of study drug

• 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.

  Predose through 36 hours after administration of study drug

• Pharmacokinetics: Maximum Concentration (Cmax) of CSF LY2886721

  Cmax following administration of a single dose of 70 mg LY2886721.

  Predose through 36 hours after administration of study drug

• Pharmacodynamics (PD): Cnadir of Plasma Amyloid β (Aβ)1-40

  Plasma concentration of Aβ1-40 was summarized based on lowest observed concentration (Cnadir).

  Predose, up to 96 hours after administration of study drug

• 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.

  Predose up to 36 hours after administration of study drug

Secondary Outcomes (1)

• Cohort C: Mean QTcF Value at Cmax

  Predose up to 48 hours after administration of study drug

Study Arms (6)

Cohort A: 70 mg LY2886721

EXPERIMENTAL

Participants with Alzheimer's disease received a single, 70-milligrams (mg) (1 capsule), oral dose of LY2886721.

Drug: LY2886721

Cohort A: Placebo

PLACEBO COMPARATOR

Participants with Alzheimer's disease received a single, oral dose of LY2886721-matching placebo (1 capsule).

Drug: Placebo

Cohort B: 70 mg LY2886721

EXPERIMENTAL

Healthy participants received a single, 70-mg (1 capsule), oral dose of LY2886721.

Drug: LY2886721

Cohort B: Placebo

PLACEBO COMPARATOR

Healthy participants received a single, oral dose of LY2886721-matching placebo (1 capsule).

Drug: Placebo

Cohort C: 280 mg LY2886721

EXPERIMENTAL

Healthy participants received a single, 280-mg (4 x 70 mg capsules), oral dose of LY2886721.

Drug: LY2886721

Cohort C: Placebo

PLACEBO COMPARATOR

Healthy participants received a single, oral dose of LY2886721-matching placebo (4 capsules).

Drug: Placebo

Interventions

LY2886721 DRUG

Cohort A: 70 mg LY2886721; Cohort B: 70 mg LY2886721; Cohort C: 280 mg LY2886721

Placebo DRUG

Cohort A: Placebo; Cohort B: Placebo; Cohort C: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

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

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

N-(3-(2-amino-4a,5,7,7a-tetrahydro-4H-furo(3,4-d)(1,3)thiazin-7a-yl)-4-fluorophenyl)-5-fluoropicolinamide

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2013
• First Posted: March 8, 2013
• Study Start: March 1, 2013
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: July 19, 2019
• Results First Posted: July 19, 2019

Record last verified: 2019-05

Locations

US (1)