Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With Placebo (IDENTITY-2)

Lilly

Status and phase: Completed; Phase 3

Conditions: Alzheimer's Disease

Treatments: Drug: LY450139; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00762411

H6L-MC-LFBC (Other Identifier)

11271 (Registry Identifier)

Details and patient eligibility

About

Alzheimer's disease (AD) is a fatal degenerative disease of the brain for which there is no cure. AD causes brain cells to die. AD is thought to be caused by an excess of beta amyloid (β-amyloid), a sticky protein in the brain that forms amyloid plaques. At autopsy, AD patients are required to have these amyloid plaques in the brain in order to have a definitive diagnosis of AD. Inhibiting the enzyme gamma-secretase (γ-secretase) lowers the production of β-amyloid. Semagacestat (LY450139) is a functional γ-secretase inhibitor and was shown to lower β-amyloid in blood and spinal fluid in humans tested thus far and in blood, spinal fluid and brain in animals tested thus far. This study used several different tests to measure the effect of semagacestat on both β-amyloid and amyloid plaques for some patients. The buildup of amyloid plaques was measured by a brain scan that takes a picture of amyloid plaques in the brain. Other tests measured the overall function of the brain and brain size in some patients. In this trial, patients who initially received placebo (inactive sugar pill) were, at a certain point in the study, switched over to active drug, semagacestat. In other words, all patients could eventually receive active drug. Each patient's participation could last approximately 2 years. Patients taking approved AD medications were permitted to participate in this study and continue taking these medications during the study. All patients who completed this study had the option to continue receiving semagacestat by participating in an open label study.

Preliminary results from this study (LFBC) (and another similar study LFAN [NCT00594568]) showed semagacestat did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. Study drug was stopped in all studies. LFBC, LFAN and open label LFBF (NCT01035138) have been amended to continue collecting safety data, including cognitive scores, for at least seven months. The CT-Registry will reflect results of analyses from the original protocol in addition to those from the amended protocol.

Enrollment: 1,111 patients

Sex: All

Ages: 55+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Meets criteria for mild to moderate Alzheimer's disease (AD) with Mini-Mental State Examination score of 16 through 26 at visit 1
• Modified Hachinski Ischemia Scale score of less than or equal to 4
• Geriatric Depression Scale score of less than or equal to 6
• A magnetic resonance imaging (MRI) or computerized tomography (CT) scan in the last 2 years with no findings inconsistent with a diagnosis of AD
• If female, must be without menstruation for a least 12 consecutive months or have had both ovaries removed.

Exclusion criteria

• Is not capable of swallowing whole oral medication
• Has serious or unstable illnesses
• Does not have a reliable caregiver
• Chronic alcohol and/or drug abuse within the past 5 years
• Has ever had a active vaccination for AD

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,111 participants in 2 patient groups, including a placebo group

LY450139

Experimental group

Description:

Participants received 60 milligrams (mg) LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.

Treatment:

Drug: LY450139

Placebo

Placebo Comparator group

Description:

Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.

Treatment:

Drug: Placebo