Healthy, Alzheimer's Disease, Mild Cognitive Impairment
Conditions
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.
Interventions
DRUGLY2599666
Administered SC
DRUGSolanezumab
Administered IV
DRUGPlacebo SC
Administered SC
DRUGPlacebo IV
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration | Baseline through 4 weeks (Part A) or 16 weeks (Part B ) | Number of participants who experienced one or more treatment-emergent serious adverse events related to study treatment. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part B | 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) | PK: Cmax of LY2599666 after multiple doses administered subcutaneously. |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-∞) of LY2599666 Part A | 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) | Area Under the Concentration versus Time Curve of zero to infinity (0 to ∞) after a single dose of LY2599666 administered subcutaneously. |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part A | 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) | PK: Cmax of LY2599666 after a single dose administered subcutaneously. |
| Plasma Amyloid Beta1-40 (Aβ1-40 ) Concentration Part A | 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) | Concentration of plasma amyloid beta 1-40 in healthy participants after single dose of LY2599666 administered subcutaneously. |
| Plasma Amyloid Beta (Aβ1-40 and Aβ1-42) Concentration Part B | 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) | Concentration of plasma amyloid beta 1-40 and 1-42, in participants with Mild Cognitive Impairment (MCI) or Alzheimer Disease, after multiple doses of LY2599666 administered subcutaneously. |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 168 Hours (AUC 0-168) of LY2599666 Part B | 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) | Area Under the Concentration time versus curve from 0-168 hours after weekly dose of LY2599666 administered subcutaneously. |
Countries
Japan, United States
Participant flow
Pre-assignment details
Following the enrollment of 7 participants into Part B Cohort 5, a decision was made to stop the development of LY2599666 based on the lack of efficacy results of another compound directed against the same target. Participants were not enrolled for Part B Cohorts 6 and 7 or Part C Cohorts 8 and 9.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Part A) Placebo matching dose given subcutaneously (SC) once. | 11 |
| 10 mg LY2599666 (Part A Cohort 1) 10 mg LY2599666 given SC once. | 8 |
| 25 mg LY2599666 (Part A Cohort 2) 25 mg LY2599666 given SC once. | 8 |
| 100 mg LY2599666 (Part A Cohort 3) 100 mg LY2599666 given SC once. | 8 |
| 200 mg LY2599666 (Part A Cohort 4) 200 mg LY2599666 given SC once. | 8 |
| Placebo (Part B) Placebo matching dose given SC. | 2 |
| 25 mg LY2599666 (Part B Cohort 5) 25 mg LY2599666 given SC once weekly for 12 weeks (13 doses). | 5 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 100 mg LY2599666 (Part A Cohort 3) | 25 mg LY2599666 (Part A Cohort 2) | 10 mg LY2599666 (Part A Cohort 1) | Placebo (Part A) | Total | 200 mg LY2599666 (Part A Cohort 4) | 25 mg LY2599666 (Part B Cohort 5) | Placebo (Part B) |
|---|---|---|---|---|---|---|---|---|
| Age, Customized Part A | 38.9 years STANDARD_DEVIATION 12.9 | 41.1 years STANDARD_DEVIATION 13.5 | 40.0 years STANDARD_DEVIATION 14.1 | 45.8 years STANDARD_DEVIATION 10.7 | 42.3 years STANDARD_DEVIATION 13 | 44.4 years STANDARD_DEVIATION 16.2 | — | — |
| Age, Customized Part B | — | — | — | — | 68.4 years STANDARD_DEVIATION 6.9 | — | 69 years STANDARD_DEVIATION 5.3 | 67 years STANDARD_DEVIATION 12.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 9 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 7 Participants | 6 Participants | 9 Participants | 41 Participants | 7 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 3 Participants | 5 Participants | 20 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 1 Participants | 4 Participants | 8 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 4 Participants | 2 Participants | 22 Participants | 4 Participants | 3 Participants | 1 Participants |
| Region of Enrollment Japan | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 8 Participants | 8 Participants | 8 Participants | 11 Participants | 47 Participants | 8 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 14 Participants | 3 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 5 Participants | 9 Participants | 36 Participants | 5 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 2 | 0 / 5 |
| other Total, other adverse events | 2 / 11 | 4 / 8 | 3 / 8 | 2 / 8 | 5 / 8 | 2 / 2 | 5 / 5 |
| serious Total, serious adverse events | 0 / 11 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 2 | 1 / 5 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration
Number of participants who experienced one or more treatment-emergent serious adverse events related to study treatment. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline through 4 weeks (Part A) or 16 weeks (Part B )
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Part A) | Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 10 mg LY2599666 (Part A Cohort 1) | Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 25 mg LY2599666 (Part A Cohort 2) | Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 100 mg LY2599666 (Part A Cohort 3) | Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 200 mg LY2599666 (Part A Cohort 4) | Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Placebo (Part B) | Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 25 mg LY2599666 (Part B Cohort 5) | Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 168 Hours (AUC 0-168) of LY2599666 Part B
Area Under the Concentration time versus curve from 0-168 hours after weekly dose of LY2599666 administered subcutaneously.
Time frame: 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)
Population: All participants who received at least one dose of drug in Part B and had evaluable AUC data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 168 Hours (AUC 0-168) of LY2599666 Part B | 76100 ng*hr/mL | Geometric Coefficient of Variation 30 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-∞) of LY2599666 Part A
Area Under the Concentration versus Time Curve of zero to infinity (0 to ∞) after a single dose of LY2599666 administered subcutaneously.
Time frame: 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)
Population: All participants who received at least one dose of drug in Part A and had evaluable AUC data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-∞) of LY2599666 Part A | NA nanograms*hour per milliliter (ng*hr/mL) | — |
| 10 mg LY2599666 (Part A Cohort 1) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-∞) of LY2599666 Part A | 96200 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 30 |
| 25 mg LY2599666 (Part A Cohort 2) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-∞) of LY2599666 Part A | 691000 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 20 |
| 100 mg LY2599666 (Part A Cohort 3) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-∞) of LY2599666 Part A | 1590000 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part A
PK: Cmax of LY2599666 after a single dose administered subcutaneously.
Time frame: 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)
Population: All participants who received at least one dose of study drug in Part A and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part A | NA nanograms per milliliter (ng/mL) | — |
| 10 mg LY2599666 (Part A Cohort 1) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part A | 780 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74 |
| 25 mg LY2599666 (Part A Cohort 2) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part A | 5310 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| 100 mg LY2599666 (Part A Cohort 3) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part A | 9810 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44 |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part B
PK: Cmax of LY2599666 after multiple doses administered subcutaneously.
Time frame: 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)
Population: All participants who received at least one dose of drug in Part B and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part B | 636 ng/mL | Geometric Coefficient of Variation 41 |
Secondary
Plasma Amyloid Beta1-40 (Aβ1-40 ) Concentration Part A
Concentration of plasma amyloid beta 1-40 in healthy participants after single dose of LY2599666 administered subcutaneously.
Time frame: 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)
Population: All participants who received at least one dose of study drug in Part A and had evaluable Aβ1-40 data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Plasma Amyloid Beta1-40 (Aβ1-40 ) Concentration Part A | 18800 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 29 |
| 10 mg LY2599666 (Part A Cohort 1) | Plasma Amyloid Beta1-40 (Aβ1-40 ) Concentration Part A | 36200 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 13 |
| 25 mg LY2599666 (Part A Cohort 2) | Plasma Amyloid Beta1-40 (Aβ1-40 ) Concentration Part A | 49500 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 10 |
| 100 mg LY2599666 (Part A Cohort 3) | Plasma Amyloid Beta1-40 (Aβ1-40 ) Concentration Part A | 67700 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 20 |
Secondary
Plasma Amyloid Beta (Aβ1-40 and Aβ1-42) Concentration Part B
Concentration of plasma amyloid beta 1-40 and 1-42, in participants with Mild Cognitive Impairment (MCI) or Alzheimer Disease, after multiple doses of LY2599666 administered subcutaneously.
Time frame: 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)
Population: All participants who received at least one dose of study drug in Part B and had evaluable Aβ1-40 or Aβ1-42 data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Plasma Amyloid Beta (Aβ1-40 and Aβ1-42) Concentration Part B | Aβ1-40 | 51400 pg/mL | Geometric Coefficient of Variation 14 |
| Placebo (Part A) | Plasma Amyloid Beta (Aβ1-40 and Aβ1-42) Concentration Part B | Aβ1-42 | 5730 pg/mL | Geometric Coefficient of Variation 10 |