A Study of Healthy Subjects to Assess the Effect of LY450139 on Amyloid Beta Peptide Production Rate and or Dose Response.

Assessment of LY450139-Mediated Inhibition of Amyloid Beta Formation Determined by 13C6-Leucine In Healthy Subjects

To test that LY450139, a gamma-secretase inhibitor, will reduce the rate of newly synthesize Amyloid Beta by determining the amount of newly synthesized 13C6 leucine-labeled Amyloid Beta in lumbar cerebrospinal fluid from LY450139 treated subjects compared with placebo treated subjects.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: placebo; Drug: LY450139

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63130
      • For additional information regarding investigtive sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy volunteers: Men within the ages of 21 and 50

Exclusion Criteria:

• Have serious or unstable medical conditions
• Have a history of serious infections affecting the brain or head trauma resulting in protracted loss of consciousness within the last 5 years or multiple episodes of head trauma
• Have a history of primary or recurrent malignant disease
• Have a recent laboratory result indicating a clinically significant laboratory abnormality as determined by the investigator
• Have a history of chronic alcohol or drug abuse within the past 5 years
• Have a known history of Human immunodeficiency virus (HIV), afebrile seizures, or clinically significant multiple drug allergies
• Are judged clinically by the investigator to be at serious risk for suicide
• Have electrocardiogram abnormalities obtained at visit 1 that in the opinion of the investigator are clinically significant
• Use of prescription or over the counter medications that cannot safely be discontinued within 14 days prior to visit 2
• Have criteria that would preclude a LP such as allergy to all local anesthetics; have a local infection at the site of the LP or have any medical condition requiring treatment with warfarin or heparin.
• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Are investigator site personnel directly affiliated with this study and or immediate families.
• Are Lilly employees

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4; Placebo	Drug: placebo
Experimental: 1; 100 mg LY 450139 oral	Drug: LY450139
Experimental: 2; 140 mg LY450139 oral	Drug: LY450139
Experimental: 3; 280 mg LY450139 oral	Drug: LY450139

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To test hypothesis that LY450139, a gamma-secretase inhibitor, will reduce the rate of synthesis of 13C6-leucine-labeled Aβ (newly synthesized) in lumbar cerebrospinal fluid (CSF).	0-36 hours post dose

Secondary Outcome Measures

Outcome Measure	Time Frame
To test the hypothesis that LY450139 has an effect on fractional clearance rate of Amyloid Beta assayed from CSF samples in LY450139-treated subjects compared to placebo-treated subjects.	0-36 hours post dose
To study and evaluate other biomarkers, such as sAPPB and sAPPA that may enable drug effectiveness to be predicted.	0-36 hours post dose
To measure concentrations of Amyloid Beta(1-40), Amyloid Beta(1-42), and leucine in CSF by mass spectrometry.	0-36 hours post dose
To explore the relationship between Amyloid Beta plasma decrease and Amyloid Beta synthesis rate as determined by CSF measurements.	0-36 hours post dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Holtta M, Dean RA, Siemers E, Mawuenyega KG, Sigurdson W, May PC, Holtzman DM, Portelius E, Zetterberg H, Bateman RJ, Blennow K, Gobom J. A single dose of the gamma-secretase inhibitor semagacestat alters the cerebrospinal fluid peptidome in humans. Alzheimers Res Ther. 2016 Mar 7;8(1):11. doi: 10.1186/s13195-016-0178-x.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: September 30, 2008
• First Submitted That Met QC Criteria: September 30, 2008
• First Posted (Estimate): October 2, 2008

Study Record Updates

• Last Update Posted (Estimate): October 2, 2008
• Last Update Submitted That Met QC Criteria: September 30, 2008
• Last Verified: September 1, 2008

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: 9384; H6L-MC-LFAM