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

NCT00765115 | Completed Phase 1

• 2 other identifiers: 9384H6L-MC-LFAM
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (4)

1

EXPERIMENTAL

100 mg LY 450139 oral

Drug: LY450139

2

EXPERIMENTAL

140 mg LY450139 oral

Drug: LY450139

3

EXPERIMENTAL

280 mg LY450139 oral

Drug: LY450139

4

EXPERIMENTAL

Placebo

Drug: placebo

Interventions

LY450139 DRUG

1; 2; 3

placebo DRUG

4

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

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

St Louis, Missouri, 63130, United States

Location

Related Publications (1)

• 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.

  PMID: 26948580 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide

Condition Hierarchy (Ancestors)

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

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM-5PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 30, 2008
• First Posted: October 2, 2008
• Study Start: July 1, 2006
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: October 2, 2008

Record last verified: 2008-09

Locations

US (1)