A Safety Study of LY2811376 Single Doses in Healthy Subjects

Single-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of LY2811376 in Healthy Subjects

This is a Phase 1 study in healthy subjects to evaluate the safety and tolerability of LY2811376 single doses, how the body handles the drug, and the drug's effect on the body.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: LY2811376

Detailed Description

This is a Phase 1 study with 2 parts, both in healthy subjects. Part 1 is a subject- and investigator-blind, placebo-controlled, randomized, 3 period, crossover study. Part 1 will assess the safety and tolerability of LY2811376 single doses, how the body handles the drug, and the drug's effect on the body. Part 2 is a subject- and investigator-blind, placebo-controlled, randomized study to assess the safety and tolerability of a LY2811376 single dose, how the body handles the drug, and the drug's effect on the body including in cerebrospinal fluid.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy men and nonchild-bearing potential women
• 20 years or older
• Body mass index between 18-32kg/m2

Exclusion Criteria:

• Taking over-the-counter or prescription medication with the exception of vitamins or minerals or stable doses of thyroid or estrogen hormone replacement.
• Smoke more than 10 cigarettes per day.
• Consume more than 5 cups of coffee per day.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2811376 Part 1; LY2811376 (5 mg up to 500 mg); once a day or twice a day for 1 day in up to 3 periods.	Drug: LY2811376; Oral capsules
Placebo Comparator: Placebo Part 1; once a day or twice a day for 1 day in up to 3 periods.	Drug: Placebo; Oral capsules
Experimental: LY2811376 - Part 2 low dose; Single dose of LY2811376, dose determined by part 1	Drug: LY2811376; Oral capsules
Experimental: LY2811376 - Part 2 high dose; Single dose of LY2811376, dose determined by part 1	Drug: LY2811376; Oral capsules
Placebo Comparator: Placebo Part 2; single dose	Drug: Placebo; Oral capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical Effects	Predose and up to Day 6 of each period

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma concentration of LY2811376 (Cmax)	Predose and up to Day 6 of each period
Plasma concentration of LY2811376 (AUC)	Predose and up to Day 6 of each period
Amyloid beta 1-40 plasma concentrations	Predose and up to Day 6 of each period
Cerebrospinal fluid (CSF) concentration of LY2811376 (Cmax) (Part 2 only)	Predose and up to 36 hours
Cerebrospinal fluid (CSF) concentration of LY2811376 (AUC) (Part 2 only)	Predose and up to 36 hours
Amyloid beta 1-40 cerebrospinal fluid CSF concentrations (Part 2 only)	Predose and up to 36 hours

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Portelius E, Dean RA, Andreasson U, Mattsson N, Westerlund A, Olsson M, Demattos RB, Racke MM, Zetterberg H, May PC, Blennow K. beta-site amyloid precursor protein-cleaving enzyme 1(BACE1) inhibitor treatment induces Abeta5-X peptides through alternative amyloid precursor protein cleavage. Alzheimers Res Ther. 2014 Nov 17;6(5-8):75. doi: 10.1186/s13195-014-0075-0. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: January 23, 2009
• First Submitted That Met QC Criteria: February 5, 2009
• First Posted (Estimate): February 6, 2009

Study Record Updates

• Last Update Posted (Estimate): July 15, 2009
• Last Update Submitted That Met QC Criteria: July 14, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 12852; I3J-MC-LACE