Clinical trial NCT02614131: A Study of LY2599666 in Healthy Participants and Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD)
Official title: Single-Dose and Multiple-Dose, Dose-Escalation Study With LY2599666 to Evaluate the Safety, Pharmacokinetics, and Tolerability in Healthy Subjects and Patients With Mild Cognitive Impairment Due to Alzheimer's Disease and Mild-to-Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Alzheimer's Disease
Mild Cognitive Impairment
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2015-11-25
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the safety and tolerability of the study drug known as LY2599666 in different groups of people - those who are healthy, those who have mild cognitive impairment due to Alzheimer's Disease (AD), and those with mild-to-moderate AD. The study will measure how much LY2599666 gets into the bloodstream and how long it takes the body to get rid of it. It will also evaluate how LY2599666 affects the body. The study has three parts. Part A will last about 2 months. Parts B and C will each last about 23 weeks. Participants may only enroll in one part.


Eligibility criteria: Inclusion Criteria:

Healthy Participants Part A:

* Overtly healthy males or females as determined by medical history and physical examination
* Have a body mass index (BMI) between 18.0 and 32.0 kilograms per meter squared (kg/m²), inclusive

Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD) \[Part B and C\]:

* Participants are at least 50 years old at screening
* Present with Mild Cognitive Impairment (MCI) due to Alzheimer's Disease (AD) or mild-to-moderate AD
* Have a caregiver/study informant who provides a separate written informed consent to participate
* Have adequate vision and hearing for neuropsychological testing in the opinion of the investigator
* Positive florbetapir scan

Exclusion Criteria:

All Participants

* Are currently enrolled in a clinical trial involving an investigational product or off-label use of a drug or device or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
* Have known allergies to LY2599666, solanezumab, or any related compounds or components of the formulations, or have a history of significant atopy
* Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study
* Have an abnormal blood pressure as determined by the investigator
* Have significant allergies to humanized monoclonal antibodies, diphenhydramine, epinephrine, or methylprednisone
* Require treatment with other monoclonal antibodies

Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD) \[Part B and C\]

* Have medical or surgical conditions in which lumbar puncture and or/catheter insertion is contraindicated
* Have any contraindication for magnetic resonance imaging (MRI) studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI

Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD) \[Part C\]

* Have had lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen post treatment

Primary outcomes:
measure: Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline through 4 weeks (Part A) or 16 weeks (Part B )
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part A
timeFrame: Day 1: Pre-dose and 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part A)
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part B
timeFrame: Day 85: Pre-dose, 2, 4, 8, 12, 24, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part B)
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-∞) of LY2599666 Part A
timeFrame: Day 1: Pre-dose and 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part A)
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 168 Hours (AUC 0-168) of LY2599666 Part B
timeFrame: Day 85: Pre-dose, 2, 4, 8, 12, 24, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 96, 120, 168 hours post-dose (Part B)
measure: Plasma Amyloid Beta1-40 (Aβ1-40 ) Concentration Part A
timeFrame: Day 1: Pre-dose and 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part A)
measure: Plasma Amyloid Beta (Aβ1-40 and Aβ1-42) Concentration Part B
timeFrame: Day 85: Pre-dose, 2, 4, 8, 12, 24, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 96, 120, 168, 216, 264, 336, 504, 672 hours post-dose (Part B)
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Parexel Early Phase Unit at Glendale
state: California
city: Marlton
country: United States
facility: CRI Lifetree
state: New Jersey
city: Salt Lake City
country: United States
facility: PRA Health Sciences
state: Utah
city: Kobe
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
city: Shinjuku-Ku
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: