A Safety Study of LY2886721 Multiple Doses in Healthy Subjects

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01227252
• Collaborator: (none)
• Enrollment: 42
• Location: 1
• Arms: 2
• Duration (Months): 4
• Patients Per Site Per Month: 10.6

Study Details

Study Description

Brief Summary

This is a Phase 1 study in healthy subjects to evaluate the safety and tolerability of LY2886721 multiple doses, how the body handles the drug, and the drug's effect on the body.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: LY2886721; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of LY2886721 in Healthy Subjects
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2886721	Drug: LY2886721; 5 milligrams (mg) up to 35 mg, administered orally as capsules, daily for 14 days
Placebo Comparator: Placebo	Drug: Placebo; Administered orally as capsules, daily for 14 days

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinically Significant Effects [Predose up to Day 70]

   Clinically significant effects were defined as serious and nonserious adverse events. A summary of serious and all other nonserious adverse events is located in the Reported Adverse Event module. The number of participants with at least 1 adverse event in each treatment arm is reported for this outcome measure.

Secondary Outcome Measures

1. Plasma Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY2886721 [Predose (Day 14) up to Day 19]

2. Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721 [Predose (Day 14) to 24 Hours post-dose (Day 15)]

   Area under the concentration versus time curve during 1 dosing interval (1 dosing interval=24 hours) at steady state (AUCτ,ss) is being reported for this outcome measure.

3. Plasma Amyloid Beta (Aβ) 1-40 Concentration [Predose (Day 14) up to Day 19]

   The minimum concentration (Cnadir) is being reported for this outcome measure.

4. Cerebrospinal Fluid (CSF) Concentration of LY2886721 [24 Hours post-dose (Day 15)]

5. Change From Baseline to Day 15 Endpoint in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ) 1-40 Concentration [Predose (Day 14), 24 Hours post-dose (Day 15)]

   The Least Squares means were adjusted for baseline concentration.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Healthy men and non-childbearing potential women

• Body mass index between 18.0-32.0 kilograms per square meter (kg/m^2)

• Are reliable and willing to make yourself available for the duration of the study and are willing to follow study procedures and research unit policies

Exclusion Criteria:

• Taking over-the-counter or prescription medication with the exception of vitamins or minerals

• Smoke more than 10 cigarettes per day

• Drink more than 5 cups of caffeine containing beverages (for example, coffee, tea) per day

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Glendale	California	United States	91206

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

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01227252
• Other Study ID Numbers: 13734; I4O-MC-BACB
• First Posted: Oct 25, 2010
• Last Update Posted: Jul 19, 2019
• Last Verified: May 1, 2019

• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Arm/Group Title	Placebo	5 mg LY2886721	15 mg LY2886721	35 mg LY2886721
Arm/Group Description	Placebo was administered orally as capsules, once daily for 14 days.	A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.	A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.	A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
Period Title: Overall Study
STARTED	12	10	10	10
Received at Least 1 Dose of Study Drug	12	10	10	10
COMPLETED	12	7	10	10
NOT COMPLETED	0	3	0	0

Baseline Characteristics

Arm/Group Title	Placebo	5 mg LY2886721	15 mg LY2886721	35 mg LY2886721	Total
Arm/Group Description	Placebo was administered orally as capsules, once daily for 14 days.	A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.	A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.	A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.	Total of all reporting groups
Overall Participants	12	10	10	10	42
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	10 100%	10 100%	10 100%	42 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	1 10%	1 10%	1 10%	3 7.1%
Male	12 100%	9 90%	9 90%	9 90%	39 92.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	4 33.3%	5 50%	2 20%	3 30%	14 33.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 16.7%	2 20%	3 30%	1 10%	8 19%
White	6 50%	3 30%	5 50%	6 60%	20 47.6%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	12 100%	10 100%	10 100%	10 100%	42 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinically Significant Effects
Description	Clinically significant effects were defined as serious and nonserious adverse events. A summary of serious and all other nonserious adverse events is located in the Reported Adverse Event module. The number of participants with at least 1 adverse event in each treatment arm is reported for this outcome measure.
Time Frame	Predose up to Day 70

Outcome Measure Data

Analysis Population Description

All randomized participants were included in the analysis.

Arm/Group Title	Placebo	5 mg LY2886721	15 mg LY2886721	35 mg LY2886721
Arm/Group Description	Placebo was administered orally as capsules, once daily for 14 days.	A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.	A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.	A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
Measure Participants	12	10	10	10
Serious Adverse Events	0 0%	0 0%	0 0%	0 0%
Nonserious Adverse Events	2 16.7%	2 20%	3 30%	3 30%

2. Secondary Outcome

Title	Plasma Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY2886721
Time Frame	Predose (Day 14) up to Day 19

Outcome Measure Data

Analysis Population Description

All participants who received study drug on Day 14 and had evaluable pharmacokinetic data were included in the analysis.

Arm/Group Title	5 mg LY2886721	15 mg LY2886721	35 mg LY2886721
Arm/Group Description	Participants received a 5-mg oral dose of LY2886721 capsules, once daily for 14 days.	Participants received a 10-mg oral dose of LY2886721 capsules, once daily for 14 days.	Participants received a 35-mg oral dose of LY2886721 capsules, once daily for 14 days.
Measure Participants	9	10	10
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	11.6 (48)	43.0 (24)	80.0 (43)

3. Secondary Outcome

Title	Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721
Description	Area under the concentration versus time curve during 1 dosing interval (1 dosing interval=24 hours) at steady state (AUCτ,ss) is being reported for this outcome measure.
Time Frame	Predose (Day 14) to 24 Hours post-dose (Day 15)

Outcome Measure Data

Analysis Population Description

All participants who received study drug on Day 14 and had evaluable pharmacokinetic data were included in the analysis.

Arm/Group Title	5 mg LY2886721	15 mg LY2886721	35 mg LY2886721
Arm/Group Description	Participants received a 5-mg oral dose of LY2886721 capsules, once daily for 14 days.	Participants received a 10-mg oral dose of LY2886721 capsules, once daily for 14 days.	Participants received a 35-mg oral dose of LY2886721 capsules, once daily for 14 days.
Measure Participants	9	10	10
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*h/mL)]	128 (41)	447 (23)	861 (38)

4. Secondary Outcome

Title	Plasma Amyloid Beta (Aβ) 1-40 Concentration
Description	The minimum concentration (Cnadir) is being reported for this outcome measure.
Time Frame	Predose (Day 14) up to Day 19

Outcome Measure Data

Analysis Population Description

All participants who received study drug on Day 14 and had evaluable pharmacodynamic data were included in the analysis.

Arm/Group Title	Placebo	5 mg LY2886721	15 mg LY2886721	35 mg LY2886721
Arm/Group Description	Placebo was administered orally as capsules, once daily for 14 days.	A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.	A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.	A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
Measure Participants	12	9	10	10
Geometric Mean (Geometric Coefficient of Variation) [picogram per milliliter (pg/mL)]	123 (14.5)	49 (55.1)	40 (19.7)	25 (28.1)

5. Secondary Outcome

Title	Cerebrospinal Fluid (CSF) Concentration of LY2886721
Time Frame	24 Hours post-dose (Day 15)

Outcome Measure Data

Analysis Population Description

A subset of all participants who received study drug on Day 14 and had evaluable pharmacodynamic data was included in the analysis.

Arm/Group Title	5 mg LY2886721	15 mg LY2886721	35 mg LY2886721
Arm/Group Description	Participants received a 5-mg oral dose of LY2886721 capsules, once daily for 14 days.	Participants received a 10-mg oral dose of LY2886721 capsules, once daily for 14 days.	Participants received a 35-mg oral dose of LY2886721 capsules, once daily for 14 days.
Measure Participants	4	4	4
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	0.5 (64.5)	1.4 (16.6)	3.8 (22.6)

6. Secondary Outcome

Title	Change From Baseline to Day 15 Endpoint in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ) 1-40 Concentration
Description	The Least Squares means were adjusted for baseline concentration.
Time Frame	Predose (Day 14), 24 Hours post-dose (Day 15)

Outcome Measure Data

Analysis Population Description

All participants who received study drug on Day 14 and had evaluable pharmacodynamic data were included in the analysis.

Arm/Group Title	Placebo	5 mg LY2886721	15 mg LY2886721	35 mg LY2886721
Arm/Group Description	Placebo was administered orally as capsules, once daily for 14 days.	A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.	A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.	A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
Measure Participants	12	10	10	10
Least Squares Mean (95% Confidence Interval) [percent change (%)]	-3.9	-11.8	-27.5	-59.1

Adverse Events

Arm/Group Title	Placebo		5 mg LY2886721		15 mg LY2886721		35 mg LY2886721
Arm/Group Description	Placebo was administered orally as capsules, once daily for 14 days.		A 5-milligram (mg) dose of LY2886721 was administered orally as capsules, once daily for 14 days.		A 15-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.		A 35-mg dose of LY2886721 was administered orally as capsules, once daily for 14 days.
All Cause Mortality
	Placebo		5 mg LY2886721		15 mg LY2886721		35 mg LY2886721
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		5 mg LY2886721		15 mg LY2886721		35 mg LY2886721
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		5 mg LY2886721		15 mg LY2886721		35 mg LY2886721
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)		2/10 (20%)		3/10 (30%)		3/10 (30%)
Gastrointestinal disorders
Gingivitis	1/12 (8.3%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
General disorders
Chest pain	0/12 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Infections and infestations
Oral herpes	0/12 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Viral infection	0/12 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Injury, poisoning and procedural complications
Procedural headache	1/12 (8.3%)	1	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Procedural nausea	1/12 (8.3%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Investigations
Visual field tests abnormal	0/12 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms	0/12 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Nervous system disorders
Headache	0/12 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Psychiatric disorders
Libido decreased	0/12 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Sinus congestion	0/12 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Vascular disorders
Orthostatic hypotension	0/12 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

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.