A Study of LY2886721 in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01534273
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 4
• Duration (Months): 5
• Patients Per Site Per Month: 6

Study Details

Study Description

Brief Summary

The purpose of this phase I study in healthy participants will be to evaluate the safety and tolerability of LY2886721 single and multiple doses, to evaluate how the body handles the drug, and to evaluate the drug's effect on the body.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: LY2886721; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Single- and Multiple-Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of LY2886721 in Healthy Subjects
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Single oral dose and/or once daily (QD) oral dosing for 14 consecutive days	Drug: Placebo; Administered orally.
Experimental: 35 mg LY2886721 QD oral dosing for 14 consecutive days	Drug: LY2886721; Administered orally.
Experimental: 70 mg LY2886721 Single oral dose or single oral dose followed by QD oral dosing for 14 consecutive days	Drug: LY2886721; Administered orally.
Experimental: 140 mg LY2886721 Single oral dose	Drug: LY2886721; Administered orally.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinically Significant Effects [Predose up to Day 23]

   Data presented are the number of participants who experienced treatment-emergent adverse events. A summary of serious adverse events and other non-serious adverse events, regardless of causality is reported in the Adverse Events module.

Secondary Outcome Measures

1. Pharmacokinetics: Plasma Maximum Observed Concentration (Cmax) of LY2886721 [Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose]

2. Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of LY2886721 [Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose]

3. Pharmacokinetics: Plasma Maximum Observed Concentration at Steady State (Cmax,ss) of LY2886721 [Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose]

4. Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721 [Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose]

   AUC over the dosing interval at steady state (AUCtau,ss) is reported for participants who received multiple doses of LY2886721.

5. Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at Day 15 [Baseline, Day 15]

   Least squares (LS) mean percent changes from baseline to Day 15 in CSF amyloid 1-40 concentrations for participants in Cohort B are reported. LS means were calculated from an analysis of covariance (ANCOVA) with treatment group and predose CSF amyloid 1-40 concentration as fixed effects. The 95% confidence interval (CI) of the percent change from baseline was computed by back-transforming the mean difference between endpoint and baseline.

6. Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at 24 Hours Post-dose [Baseline, 24 hours post-dose]

   LS mean percent changes from baseline to 24 hours post-dose in CSF amyloid 1-40 concentrations for participants in Cohort C are reported. LS means were calculated from an ANCOVA with treatment group and predose CSF amyloid 1-40 concentration as fixed effects. The 95% CI of the percent change from baseline was computed by back-transforming the mean difference between endpoint and baseline.

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 (BMI) between 18.0 and 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: NCT01534273
• Other Study ID Numbers: 14464; I4O-MC-BACJ
• First Posted: Feb 16, 2012
• Last Update Posted: Aug 28, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Eli Lilly and Company: Mild Cognitive Impairment

Study Results

Participant Flow

Arm/Group Title	Placebo (Cohort A)	35 mg LY2886721 (Cohort A)	Placebo (Cohort B)	70 mg LY2886721 (Cohort B)	Placebo (Cohort C)	70 mg LY2886721 (Cohort C)	140 mg LY2886721 (Cohort C)
Arm/Group Description	Placebo: once daily (QD) oral dosing for 14 consecutive days	35 milligrams (mg) LY2886721: QD oral dosing for 14 consecutive days	Placebo: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2)	70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2)	Placebo: single oral dose	70 mg LY2886721: single oral dose	140 mg LY2886721: single oral dose
Period Title: Period 1
STARTED	3	6	2	7	3	3	6
Received at Least 1 Dose of Study Drug	3	6	2	7	3	3	6
COMPLETED	3	6	2	6	3	3	6
NOT COMPLETED	0	0	0	1	0	0	0
Period Title: Period 1
STARTED	0	0	2	6	0	0	0
COMPLETED	0	0	2	6	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Placebo	35 mg LY2886721	70 mg LY2886721	140 mg LY2886721	Total
Arm/Group Description	Placebo: once daily (QD) oral dosing for 14 consecutive days	Participants received 35 mg LY2886721: oral dosing for 14 consecutive days	Participants received 70 mg LY2886721: single oral dose followed by QD oral dosing for 14 consecutive days or single oral dose.	Participants received 140 mg LY2886721: single oral dose	Total of all reporting groups
Overall Participants	8	6	10	6	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	6 100%	10 100%	6 100%	30 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	8 100%	6 100%	10 100%	6 100%	30 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 25%	1 16.7%	3 30%	2 33.3%	8 26.7%
Not Hispanic or Latino	6 75%	5 83.3%	7 70%	4 66.7%	22 73.3%
Unknown or Not Reported	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%
Asian	1 12.5%	0 0%	3 30%	0 0%	4 13.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 12.5%	2 33.3%	1 10%	2 33.3%	6 20%
White	6 75%	4 66.7%	5 50%	4 66.7%	19 63.3%
More than one race	0 0%	0 0%	1 10%	0 0%	1 3.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	8 100%	6 100%	10 100%	6 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinically Significant Effects
Description	Data presented are the number of participants who experienced treatment-emergent adverse events. A summary of serious adverse events and other non-serious adverse events, regardless of causality is reported in the Adverse Events module.
Time Frame	Predose up to Day 23

Outcome Measure Data

Analysis Population Description

All enrolled participants. Ten participants, 7 in Cohort B and 3 in Cohort C, received 70 mg LY2886721 as a single dose. Six of the participants in Cohort B went on to receive QD dosing for 14 consecutive days. These 6 participants are included in the 70 mg LY2886721 Single Dose arm and the 70 mg LY2886721 Multiple Dose arm.

Arm/Group Title	Placebo	35 mg LY2886721	70 mg LY2886721 Multiple Dose	70 mg LY2886721 Single Dose	140 mg LY2886721
Arm/Group Description	Placebo: QD oral dosing for 14 consecutive days (Cohort A), single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B), or single oral dose (Cohort C)	35 mg LY2886721: QD oral dosing for 14 consecutive days (Cohort A)	70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B)	70 mg LY2886721: single oral dose (Cohort B [Period 1] and Cohort C)	140 mg LY2886721: single oral dose (Cohort C)
Measure Participants	8	6	6	10	6
Count of Participants [Participants]	3 37.5%	1 16.7%	3 30%	2 33.3%	1 3.3%

2. Secondary Outcome

Title	Pharmacokinetics: Plasma Maximum Observed Concentration (Cmax) of LY2886721
Time Frame	Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

Outcome Measure Data

Analysis Population Description

All randomized participants who received a single 70- or 140-mg dose of LY2886721 and had evaluable single-dose LY2886721 concentration data.

Arm/Group Title	70 mg LY2886721 Single Dose	140 mg LY2886721
Arm/Group Description	70 mg LY2886721: single oral dose (Cohort B [Period 1] and Cohort C)	140 mg LY2886721: single oral dose (Cohort C)
Measure Participants	10	6
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter (ng/mL)]	182 (26)	419 (16)

3. Secondary Outcome

Title	Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of LY2886721
Time Frame	Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose

Outcome Measure Data

Analysis Population Description

All randomized participants who received a single 70- or 140-mg dose of LY2886721 and had evaluable single-dose LY2886721 concentration data.

Arm/Group Title	70 mg LY2886721 Single Dose	140 mg LY2886721
Arm/Group Description	70 mg LY2886721: single oral dose (Cohort B [Period 1] and Cohort C)	140 mg LY2886721: single oral dose (Cohort C)
Measure Participants	10	6
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hours/milliliter (ng*hr/mL)]	2110 (23)	4660 (10)

4. Secondary Outcome

Title	Pharmacokinetics: Plasma Maximum Observed Concentration at Steady State (Cmax,ss) of LY2886721
Time Frame	Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

All randomized participants who received LY2886721 and had evaluable steady-state plasma LY2886721 concentration data.

Arm/Group Title	35 mg LY2886721	70 mg LY2886721 Multiple Dose
Arm/Group Description	35 mg LY2886721: QD oral dosing for 14 consecutive days (Cohort A)	70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B)
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	112 (35)	230 (26)

5. Secondary Outcome

Title	Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721
Description	AUC over the dosing interval at steady state (AUCtau,ss) is reported for participants who received multiple doses of LY2886721.
Time Frame	Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

All randomized participants who received LY2886721 and had evaluable steady-state plasma LY2886721 concentration data.

Arm/Group Title	35 mg LY2886721	70 mg LY2886721 Multiple Dose
Arm/Group Description	35 mg LY2886721: QD oral dosing for 14 consecutive days (Cohort A)	70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B)
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1100 (26)	2400 (24)

6. Secondary Outcome

Title	Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at Day 15
Description	Least squares (LS) mean percent changes from baseline to Day 15 in CSF amyloid 1-40 concentrations for participants in Cohort B are reported. LS means were calculated from an analysis of covariance (ANCOVA) with treatment group and predose CSF amyloid 1-40 concentration as fixed effects. The 95% confidence interval (CI) of the percent change from baseline was computed by back-transforming the mean difference between endpoint and baseline.
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

All randomized participants in Cohort B who received multiple doses of placebo or 70 mg LY2886721 and had evaluable CSF amyloid 1-40 concentrations.

Arm/Group Title	Placebo (Cohort B)	70 mg LY2886721 Multiple Dose (Cohort B)
Arm/Group Description	Placebo: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2)	70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2)
Measure Participants	2	6
Least Squares Mean (95% Confidence Interval) [Percent change]	-0.97	-74.46

7. Secondary Outcome

Title	Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at 24 Hours Post-dose
Description	LS mean percent changes from baseline to 24 hours post-dose in CSF amyloid 1-40 concentrations for participants in Cohort C are reported. LS means were calculated from an ANCOVA with treatment group and predose CSF amyloid 1-40 concentration as fixed effects. The 95% CI of the percent change from baseline was computed by back-transforming the mean difference between endpoint and baseline.
Time Frame	Baseline, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All randomized participants in Cohort C who received placebo or LY2886721 and had measurable CSF amyloid 1-40 concentration data.

Arm/Group Title	Placebo (Cohort C)	70 mg LY2886721 (Cohort C)	140 mg LY2886721 (Cohort C)
Arm/Group Description	Placebo: single oral dose	70 mg LY2886721: single oral dose	140 mg LY2886721: single oral dose
Measure Participants	3	3	6
Least Squares Mean (95% Confidence Interval) [Percent change]	-11.59	-64.75	-72.05

Adverse Events

Arm/Group Title	Placebo		35 mg LY2886721		70 mg LY2886721 Multiple Dose		70 mg LY2886721 Single Dose		140 mg LY2886721
Arm/Group Description	Placebo: QD oral dosing for 14 consecutive days (Cohort A), single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B), or single oral dose (Cohort C)		35 mg LY2886721: QD oral dosing for 14 consecutive days (Cohort A)		70 mg LY2886721: single oral dose (Period 1) followed by QD oral dosing for 14 consecutive days (Period 2) (Cohort B)		70 mg LY2886721: single oral dose(Cohort B [Period 1] and Cohort C)		140 mg LY2886721: single oral dose (Cohort C)
All Cause Mortality
	Placebo		35 mg LY2886721		70 mg LY2886721 Multiple Dose		70 mg LY2886721 Single Dose		140 mg LY2886721
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		35 mg LY2886721		70 mg LY2886721 Multiple Dose		70 mg LY2886721 Single Dose		140 mg LY2886721
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/10 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		35 mg LY2886721		70 mg LY2886721 Multiple Dose		70 mg LY2886721 Single Dose		140 mg LY2886721
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/8 (37.5%)		1/6 (16.7%)		3/6 (50%)		2/10 (20%)		1/6 (16.7%)
Eye disorders
Scotoma	1/8 (12.5%)	1	0/6 (0%)	0	0/6 (0%)	0	0/10 (0%)	0	0/6 (0%)	0
Gastrointestinal disorders
Dry mouth	1/8 (12.5%)	1	0/6 (0%)	0	0/6 (0%)	0	0/10 (0%)	0	0/6 (0%)	0
General disorders
Fatigue	0/8 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/10 (0%)	0	0/6 (0%)	0
Infections and infestations
Upper respiratory tract infection	1/8 (12.5%)	1	0/6 (0%)	0	0/6 (0%)	0	0/10 (0%)	0	0/6 (0%)	0
Injury, poisoning and procedural complications
Procedural dizziness	0/8 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/10 (10%)	1	1/6 (16.7%)	1
Procedural headache	1/8 (12.5%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/10 (0%)	0	0/6 (0%)	0
Procedural pain	0/8 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1
Investigations
Liver function test abnormal	0/8 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/10 (10%)	1	0/6 (0%)	0
Psychiatric disorders
Insomnia	0/8 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/10 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/8 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/10 (0%)	0	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/8 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/10 (0%)	0	0/6 (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.