Clinical trial NCT00765115: A Study of Healthy Subjects to Assess the Effect of LY450139 on Amyloid Beta Peptide Production Rate and or Dose Response.
Official title: Assessment of LY450139-Mediated Inhibition of Amyloid Beta Formation Determined by 13C6-Leucine In Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer Disease
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-10-02
Enrollment: 27
Sex: MALE
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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).
timeFrame: 0-36 hours post dose
Secondary outcomes:
measure: 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.
timeFrame: 0-36 hours post dose
measure: To study and evaluate other biomarkers, such as sAPPB and sAPPA that may enable drug effectiveness to be predicted.
timeFrame: 0-36 hours post dose
measure: To measure concentrations of Amyloid Beta(1-40), Amyloid Beta(1-42), and leucine in CSF by mass spectrometry.
timeFrame: 0-36 hours post dose
measure: To explore the relationship between Amyloid Beta plasma decrease and Amyloid Beta synthesis rate as determined by CSF measurements.
timeFrame: 0-36 hours post dose
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: 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
state: Missouri
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM-5PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: 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.