A Study of LY2599666 in Healthy Participants and Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD)

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02614131
• Collaborator: (none)
• Enrollment: 50
• Locations: 5
• Arms: 6
• Duration (Months): 12
• Patients Per Site: 10
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy; Alzheimer's Disease; Mild Cognitive Impairment	Drug: LY2599666; Drug: Solanezumab; Drug: Placebo SC; Drug: Placebo IV	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: Dec 1, 2015
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2599666 (Part A) LY2599666 given subcutaneously (SC) once.	Drug: LY2599666; Administered SC
Placebo Comparator: Placebo (Part A) Placebo matching LY2599666 given SC once.	Drug: Placebo SC; Administered SC
Experimental: LY2599666 (Part B) LY2599666 given SC once weekly for 12 weeks (13 doses).	Drug: LY2599666; Administered SC
Placebo Comparator: Placebo (Part B) Placebo given SC once weekly for 12 weeks (13 doses).	Drug: Placebo SC; Administered SC
Experimental: Solanezumab (Part C) Solanezumab given intravenously (IV) once weekly or once every 4 weeks for 12 weeks.	Drug: Solanezumab; Administered IV; Other Names: LY2062430
Placebo Comparator: Placebo (Part C) Placebo given IV once weekly or once every 4 weeks for 12 weeks.	Drug: Placebo IV; Administered IV

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parexel Early Phase Unit at Glendale	Glendale	California	United States	91206
2	CRI Lifetree	Marlton	New Jersey	United States	08053
3	PRA Health Sciences	Salt Lake City	Utah	United States	84106
4	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.	Kobe		Japan	650-0047
5	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.	Shinjuku-Ku		Japan	169-0073

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• A Study of LY2599666 in Participants With Mild Cognitive Impairment or Alzheimer's Disease (AD)

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02614131
• Other Study ID Numbers: 15491; I2L-MC-ALCA
• First Posted: Nov 25, 2015
• Last Update Posted: Jun 17, 2020
• Last Verified: Jun 1, 2020

• Additional relevant MeSH terms: Alzheimer Disease; Cognitive Dysfunction

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Placebo (Part A - Healthy Participants)	10 mg LY2599666 (Part A Cohort 1)	25 mg LY2599666 (Part A Cohort 2)	100 mg LY2599666 (Part A Cohort 3)	200 mg LY2599666 (Part A Cohort 4)	Placebo (Part B - Cognitively Impaired)	25 mg LY2599666 (Part B Cohort 5)
Arm/Group Description	Placebo matching dose given subcutaneously (SC) once.	10 mg LY2599666 given SC once.	25 mg LY2599666 given SC once.	100 mg LY2599666 given SC once.	200 mg LY2599666 given SC once.	Placebo matching dose given SC.	25 mg LY2599666 given SC once weekly for 12 weeks (13 doses).
Period Title: Overall Study
STARTED	11	8	8	8	8	2	5
Received at Least One Dose of Drug	11	8	8	8	8	2	5
COMPLETED	10	8	8	8	8	2	4
NOT COMPLETED	1	0	0	0	0	0	1

Baseline Characteristics

Arm/Group Title	Placebo (Part A)	10 mg LY2599666 (Part A Cohort 1)	25 mg LY2599666 (Part A Cohort 2)	100 mg LY2599666 (Part A Cohort 3)	200 mg LY2599666 (Part A Cohort 4)	Placebo (Part B)	25 mg LY2599666 (Part B Cohort 5)	Total
Arm/Group Description	Placebo matching dose given subcutaneously (SC) once.	10 mg LY2599666 given SC once.	25 mg LY2599666 given SC once.	100 mg LY2599666 given SC once.	200 mg LY2599666 given SC once.	Placebo matching dose given SC.	25 mg LY2599666 given SC once weekly for 12 weeks (13 doses).	Total of all reporting groups
Overall Participants	11	8	8	8	8	2	5	50
Age, Customized (years) [Mean (Standard Deviation) ]
Part A	45.8 (10.7)	40.0 (14.1)	41.1 (13.5)	38.9 (12.9)	44.4 (16.2)	42.3 (13.0)
Part B	67 (12.7)	69 (5.3)	68.4 (6.9)
Sex: Female, Male (Count of Participants)
Female	2 18.2%	3 37.5%	1 12.5%	1 12.5%	3 37.5%	1 50%	3 60%	14 28%
Male	9 81.8%	5 62.5%	7 87.5%	7 87.5%	5 62.5%	1 50%	2 40%	36 72%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 18.2%	2 25%	1 12.5%	3 37.5%	1 12.5%	0 0%	0 0%	9 18%
Not Hispanic or Latino	9 81.8%	6 75%	7 87.5%	5 62.5%	7 87.5%	2 100%	5 100%	41 82%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	5 45.5%	3 37.5%	3 37.5%	3 37.5%	3 37.5%	1 50%	2 40%	20 40%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	4 36.4%	1 12.5%	1 12.5%	1 12.5%	1 12.5%	0 0%	0 0%	8 16%
White	2 18.2%	4 50%	4 50%	4 50%	4 50%	1 50%	3 60%	22 44%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	11 100%	8 100%	8 100%	8 100%	8 100%	1 50%	3 60%	47 94%
Japan	0 0%	0 0%	0 0%	0 0%	0 0%	1 50%	2 40%	3 6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With One or More Serious Adverse Event (SAE) Considered by the Investigator to be Related to Study Drug Administration
Description	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 )

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Placebo (Part A)	10 mg LY2599666 (Part A Cohort 1)	25 mg LY2599666 (Part A Cohort 2)	100 mg LY2599666 (Part A Cohort 3)	200 mg LY2599666 (Part A Cohort 4)	Placebo (Part B)	25 mg LY2599666 (Part B Cohort 5)
Arm/Group Description	Placebo matching dose given subcutaneously (SC) once.	10 mg LY2599666 given SC once.	25 mg LY2599666 given SC once.	100 mg LY2599666 given SC once.	200 mg LY2599666 given SC once.	Placebo matching dose given SC.	25 mg LY2599666 given SC once weekly for 12 weeks (13 doses).
Measure Participants	11	8	8	8	8	2	5
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part A
Description	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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug in Part A and had evaluable Cmax data.

Arm/Group Title	10 mg LY2599666 (Part A Cohort 1)	25 mg LY2599666 (Part A Cohort 2)	100 mg LY2599666 (Part A Cohort 3)	200 mg LY2599666 (Part A Cohort 4)
Arm/Group Description	10 mg LY2599666 given SC once.	25 mg LY2599666 given SC once.	100 mg LY2599666 given SC once.	200 mg LY2599666 given SC once.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)]	NA (NA)	780 (74)	5310 (28)	9810 (44)

3. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2599666 Part B
Description	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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of drug in Part B and had evaluable Cmax data.

Arm/Group Title	25 mg LY2599666 (Part B Cohort 5)
Arm/Group Description	25 mg LY2599666 given SC once weekly.
Measure Participants	4
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	636 (41)

4. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC 0-∞) of LY2599666 Part A
Description	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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of drug in Part A and had evaluable AUC data.

Arm/Group Title	10 mg LY2599666 (Part A Cohort 1)	25 mg LY2599666 (Part A Cohort 2)	100 mg LY2599666 (Part A Cohort 3)	200 mg LY2599666 (Part A Cohort 4)
Arm/Group Description	10 mg LY2599666 given SC once.	25 mg LY2599666 given SC once.	100 mg LY2599666 given SC once.	200 mg LY2599666 given SC once.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour per milliliter (ng*hr/mL)]	NA (NA)	96200 (30)	691000 (20)	1590000 (27)

5. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 168 Hours (AUC 0-168) of LY2599666 Part B
Description	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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of drug in Part B and had evaluable AUC data.

Arm/Group Title	25 mg LY2599666 (Part B Cohort 5) Day 85
Arm/Group Description	25 mg LY2599666 given SC once weekly.
Measure Participants	4
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	76100 (30)

6. Secondary Outcome

Title	Plasma Amyloid Beta1-40 (Aβ1-40 ) Concentration Part A
Description	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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug in Part A and had evaluable Aβ1-40 data.

Arm/Group Title	10 mg LY2599666 (Part A Cohort 1)	25 mg LY2599666 (Part A Cohort 2)	100 mg LY2599666 (Part A Cohort 3)	200 mg LY2599666 (Part A Cohort 4)
Arm/Group Description	10 mg LY2599666 given SC once.	25 mg LY2599666 given SC once.	100 mg LY2599666 given SC once.	200 mg LY2599666 given SC once.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [picograms per milliliter (pg/mL)]	18800 (29)	36200 (13)	49500 (10)	67700 (20)

7. Secondary Outcome

Title	Plasma Amyloid Beta (Aβ1-40 and Aβ1-42) Concentration Part B
Description	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)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug in Part B and had evaluable Aβ1-40 or Aβ1-42 data.

Arm/Group Title	25 mg LY2599666 (Part B Cohort 5)
Arm/Group Description	25 mg LY2599666 given SC once weekly.
Measure Participants	4
Aβ1-40	51400 (14)
Aβ1-42	5730 (10)

Adverse Events

Time Frame	Part A up to 29 days and Part B up to 113 days
Adverse Event Reporting Description	All participants who received at least one dose of study drug.
Arm/Group Title	Placebo (Part A)		10 mg LY2599666 (Part A Cohort 1)		25 mg LY2599666 (Part A Cohort 2)		100 mg LY2599666 (Part A Cohort 3)		200 mg LY2599666 (Part A Cohort 4)		Placebo (Part B)		25 mg LY2599666 (Part B Cohort 5)
Arm/Group Description	Placebo matching dose given subcutaneously (SC) once.		10 mg LY2599666 given SC once.		25 mg LY2599666 given SC once.		100 mg LY2599666 given SC once.		200 mg LY2599666 given SC once.		Placebo matching dose given SC.		25 mg LY2599666 given SC once weekly for 12 weeks (13 doses).
All Cause Mortality
	Placebo (Part A)		10 mg LY2599666 (Part A Cohort 1)		25 mg LY2599666 (Part A Cohort 2)		100 mg LY2599666 (Part A Cohort 3)		200 mg LY2599666 (Part A Cohort 4)		Placebo (Part B)		25 mg LY2599666 (Part B Cohort 5)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/2 (0%)		0/5 (0%)
Serious Adverse Events
	Placebo (Part A)		10 mg LY2599666 (Part A Cohort 1)		25 mg LY2599666 (Part A Cohort 2)		100 mg LY2599666 (Part A Cohort 3)		200 mg LY2599666 (Part A Cohort 4)		Placebo (Part B)		25 mg LY2599666 (Part B Cohort 5)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/2 (0%)		1/5 (20%)
Nervous system disorders
Syncope	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Placebo (Part A)		10 mg LY2599666 (Part A Cohort 1)		25 mg LY2599666 (Part A Cohort 2)		100 mg LY2599666 (Part A Cohort 3)		200 mg LY2599666 (Part A Cohort 4)		Placebo (Part B)		25 mg LY2599666 (Part B Cohort 5)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/11 (18.2%)		4/8 (50%)		3/8 (37.5%)		2/8 (25%)		5/8 (62.5%)		2/2 (100%)		5/5 (100%)
Blood and lymphatic system disorders
Anaemia	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Eye disorders
Ocular discomfort	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Ocular hyperaemia	0/11 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/5 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/11 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/5 (0%)	0
Faecal incontinence	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	2
Nausea	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	2
General disorders
Fatigue	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Injection site bruising	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	0/2 (0%)	0	1/5 (20%)	1
Injection site erythema	0/11 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	1/8 (12.5%)	1	3/8 (37.5%)	3	0/2 (0%)	0	1/5 (20%)	2
Injection site haemorrhage	1/11 (9.1%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/5 (0%)	0
Injection site pruritus	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Injection site rash	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	2/5 (40%)	6
Injection site reaction	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	2
Puncture site pain	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Vessel puncture site haemorrhage	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/2 (50%)	1	0/5 (0%)	0
Infections and infestations
Gastroenteritis	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/2 (50%)	1	0/5 (0%)	0
Oral herpes	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Upper respiratory tract infection	0/11 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	0/8 (0%)	0	0/2 (0%)	0	0/5 (0%)	0
Urinary tract infection	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Injury, poisoning and procedural complications
Contusion	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	0/2 (0%)	0	1/5 (20%)	3
Fall	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Thermal burn	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	2
Investigations
Blood creatinine increased	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Blood urine present	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Musculoskeletal and connective tissue disorders
Bursitis	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/2 (50%)	1	0/5 (0%)	0
Costochondritis	0/11 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	0/5 (0%)	0
Muscle spasms	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	2
Nervous system disorders
Dizziness	0/11 (0%)	0	2/8 (25%)	2	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	1/2 (50%)	1	0/5 (0%)	0
Headache	1/11 (9.1%)	1	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	2/5 (40%)	4
Hypoaesthesia	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/2 (50%)	1	0/5 (0%)	0
Migraine	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/2 (0%)	0	0/5 (0%)	0
Psychiatric disorders
Depression	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Renal and urinary disorders
Urinary incontinence	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1
Respiratory symptom	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/2 (0%)	0	0/5 (0%)	0
Skin and subcutaneous tissue disorders
Eczema	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	2
Vascular disorders
Orthostatic hypotension	0/11 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/2 (0%)	0	1/5 (20%)	1

Limitations/Caveats

Development of LY2599666 was stopped based on lack of efficacy of another compound directed against the same target. Following the enrollment of seven participants into Part B Cohort 5, enrollment was stopped.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.