A Safety Study of LY2886721 Single Doses in Healthy Subjects
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01133405
Collaborator
(none)
40
1
5
4
10
Study Details
Study Description
Brief Summary
This is a Phase 1 study in healthy subjects to evaluate the safety and tolerability of LY2886721 single doses, how the body handles the drug, and the drug's effect on the body.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is a Phase 1 study with 2 parts, both in healthy subjects. Part 1 is a subject- and investigator-blind, placebo-controlled, randomized, 3-period, crossover study. Part 1 will assess the safety and tolerability of LY2886721 single doses, how the body handles the drug, and the drug's effect on the body. Part 2 is a subject- and investigator-blind, placebo-controlled, randomized study to assess the safety and tolerability of an LY2886721 single dose, how the body handles the drug, and the drug's effect on the body including in cerebrospinal fluid.
Study Design
Study Type:
Interventional
Actual Enrollment
:
40 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Basic Science
Official Title:
Single-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of LY2886721 in Healthy Subjects
Study Start Date
:
Jun 1, 2010
Actual Primary Completion Date
:
Oct 1, 2010
Actual Study Completion Date
:
Oct 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LY2886721 Part 1: Cohort A/B Single (7 milligram (mg), 15 mg, 25 mg, 35 mg) doses of LY2886721 administered orally in up to three of three study periods |
Drug: LY2886721
Oral capsules
|
| Placebo Comparator: Placebo Part 1: Cohort A/B Single dose in up to 1 period |
Drug: Placebo
Oral capsules
|
| Experimental: LY2886721 Part 2: Cohort C Single 10 mg dose of LY2886721, dose determined by Part 1 |
Drug: LY2886721
Oral capsules
|
| Experimental: LY2886721 Part 2: Cohort D Single 35 mg dose of LY2886721, dose determined by Part 1 |
Drug: LY2886721
Oral capsules
|
| Placebo Comparator: Placebo Part 2: Cohort C/D Single dose |
Drug: Placebo
Oral capsules
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Clinically Significant Effects (Adverse Events) [Predose to 10-14 days after final dose of study drug (up to 42 days)]
A summary of serious adverse events and other nonserious adverse events located in Reported Adverse Event section. To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in other LY2886721 groups received LY2886721 in fasted state. Due to crossover design in Part 1, results reported by treatment; thus, participants are included in multiple arms.
Secondary Outcome Measures
- Maximum Observed Plasma Concentration (Cmax) of LY2886721 [0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose]
To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in the other LY2886721 groups received LY2886721 in the fasted state. Due to the crossover design in Part 1, results are reported by treatment; therefore, participants are included in multiple arms.
- Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) [0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose]
Pharmacokinetic AUC for LY2886721 from time 0 to infinity. To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in the other LY2886721 groups received LY2886721 in the fasted state. Due to the crossover design in Part 1, results are reported by treatment; therefore, participants are included in multiple arms.
- Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only) [0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose]
Plasma concentrations of Aβ1-40 were based on the lowest observed/measured concentration (Cnadir). To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in the other LY2886721 groups received LY2886721 in the fasted state. Due to the crossover design in Part 1, results are reported by treatment; therefore, participants are included in multiple arms.
- Cerebrospinal Fluid (CSF) Maximum Observed Drug Concentration (Cmax) of LY2886721 (Part 2 Only) [Predose and up to 36 hours postdose]
- Cerebrospinal Fluid (CSF) Pharmacodynamic Biomarker Amyloid Beta (Aβ) 1-40 Concentration (Part 2 Only) [Predose and up to 36 hours postdose]
CSF Aβ 1-40 concentration was based on the lowest observed/measured concentration (Cnadir).
- Cerebrospinal Fluid (CSF) Area Under the Concentration Versus Time Curve (AUC) of LY2886721 (Part 2 Only) [Predose and up to 36 hours postdose]
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 nonchild-bearing potential women
-
20 years or older
-
Body mass index between 18-32 kilograms per square meter (kg/m^2)
Exclusion Criteria:
-
Taking over-the-counter or prescription medication with the exception of vitamins or minerals or stable doses of thyroid or estrogen hormone replacement
-
Smoke more than 10 cigarettes 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. | Beverly Hills | California | United States | 90211 |
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:
NCT01133405
Other Study ID Numbers:
- 13733
- I4O-MC-BACA
First Posted:
May 28, 2010
Last Update Posted:
Sep 16, 2019
Last Verified:
May 1, 2019
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | The study consists of 2-parts. Part A was a cross-over study and was conducted in 2 alternating cohorts (Cohorts A and B). Part B was a single-dose, single period study in 2 cohorts (Cohorts C and D). All doses were administered in the fasted state, unless otherwise indicated. Each oral dose was followed by a washout period of at least 14 days. |
| Arm/Group Title | Cohort A (Part 1) : Sequence 1 | Cohort A (Part 1): Sequence 2 | Cohort A (Part 1): Sequence 3 | Cohort B (Part 1): Sequence 1 | Cohort B (Part 1): Sequence 2 | Cohort B (Part 1): Sequence 3 | Cohort C (Part 2): 10mg LY2886721 | Cohort C (Part 2): Placebo | Cohort D (Part 2): 35 mg LY2886721 | Cohort D (Part 2): Placebo |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received Placebo, 15 milligram (mg) LY2886721 and 35 mg LY2886721 orally as per the below dosing sequence in each period. Period 1: Placebo, Period 2: 15 mg LY2886721 and Period 3: 35 mg LY2886721. | Participants received 1 mg LY2886721, 15 mg LY2886721 and placebo orally as per the below dosing sequence in each period. Period 1: 1 mg LY2886721, Period 2: 15 mg LY2886721 and Period 3: Placebo. | Participants received 1 mg LY2886721, placebo and 35 mg LY2886721 orally as per the below dosing sequence in each period. Period 1: 1 mg LY2886721, Period 2: Placebo and Period 3: 35 mg LY2886721. | Participants received 7 mg LY2886721, 25 mg LY2886721 and placebo and orally as per the below dosing sequence in each period. Period 1: 7 mg LY2886721, Period 2: 25 mg LY2886721 and Period 3: Placebo. | Participants received 7 mg LY2886721, placebo and 7 mg LY2886721 (fed state) orally as per the below dosing sequence in each period. Period 1: 7 mg LY2886721 Period 2: Placebo and Period 3: 7 mg LY2886721 (fed state). | Participants received Placebo, 25 mg LY2886721 and 7 mg LY2886721 (fed state) orally as per the below dosing sequence in each period. Period 1: Placebo, Period 2: 25 mg LY2886721 and Period 3: 7 mg LY2886721 (fed state). | Participants received a single 10 mg LY2886721 oral dose (low dose) in the fasted state. | Participants received a single oral placebo dose in the fasted state. | Participants received a single 35 mg LY2886721 oral dose (high dose) in the fasted state. | Participants received a single oral placebo dose in the fasted state. |
| Period Title: Period 1 | ||||||||||
| STARTED | 3 | 6 | 5 | 5 | 3 | 5 | 5 | 2 | 4 | 2 |
| Safety Analysis Population | 2 | 6 | 5 | 5 | 3 | 5 | 5 | 2 | 4 | 2 |
| Received at Least 1 Dose of Drug | 2 | 4 | 4 | 3 | 3 | 4 | 4 | 2 | 4 | 2 |
| COMPLETED | 2 | 3 | 4 | 1 | 3 | 3 | 4 | 2 | 4 | 2 |
| NOT COMPLETED | 1 | 3 | 1 | 4 | 0 | 2 | 1 | 0 | 0 | 0 |
| Period Title: Period 1 | ||||||||||
| STARTED | 2 | 4 | 4 | 3 | 3 | 4 | 0 | 0 | 0 | 0 |
| Received at Least 1 Dose of Study Drug | 2 | 4 | 4 | 3 | 3 | 4 | 0 | 0 | 0 | 0 |
| COMPLETED | 2 | 3 | 3 | 2 | 3 | 2 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 1 | 1 | 1 | 0 | 2 | 0 | 0 | 0 | 0 |
| Period Title: Period 1 | ||||||||||
| STARTED | 2 | 4 | 4 | 2 | 3 | 2 | 0 | 0 | 0 | 0 |
| Received at Least 1 Dose of Study Drug | 2 | 4 | 4 | 2 | 3 | 2 | 0 | 0 | 0 | 0 |
| COMPLETED | 2 | 4 | 4 | 2 | 3 | 2 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Cohort A (Part 1): Sequence 1 | Cohort A (Part 1): Sequence 2 | Cohort A (Part 1): Sequence 3 | Cohort B (Part 1): Sequence 1 | Cohort B (Part 1): Sequence 2 | Cohort B (Part 1): Sequence 3 | Cohort C (Part 2): 10mg LY2886721 | Cohort C (Part 2): Placebo | Cohort D (Part 2): 35 mg LY2886721 | Cohort D (Part 2): Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received Placebo, 15 milligram (mg) LY2886721 and 35 mg LY2886721 orally as per the dosing sequence in each period. | Participants received 1 mg LY2886721, 15 mg LY2886721 and placebo orally as per the dosing sequence in each period. | Participants received 1 mg LY2886721, placebo and 35 mg LY2886721 orally as per the dosing sequence in each period. | Participants received 7 mg LY2886721, 25 mg LY2886721 and placebo and orally as per the dosing sequence in each period. | Participants received 7 mg LY2886721, placebo and 7 mg LY2886721 (fed state) orally as per the dosing sequence in each period. | Participants received Placebo, 25 mg LY2886721 and 7 mg LY2886721 (fed state) orally as per the below dosing sequence in each period. | Participants received a single 10 mg LY2886721 oral dose (low dose) in the fasted state. | .Participants received a single oral placebo dose in the fasted state. | Participants received a single 35 mg LY2886721 oral dose (high dose) in the fasted state. | Participants received a single oral placebo dose in the fasted state. | Total of all reporting groups |
| Overall Participants | 2 | 6 | 5 | 5 | 3 | 5 | 5 | 2 | 4 | 2 | 39 |
| Age (Count of Participants) | |||||||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
100%
|
6
100%
|
5
100%
|
5
100%
|
3
100%
|
5
100%
|
5
100%
|
2
100%
|
4
100%
|
2
100%
|
39
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||||||||||
| Female |
0
0%
|
0
0%
|
3
60%
|
0
0%
|
2
66.7%
|
0
0%
|
1
20%
|
1
50%
|
0
0%
|
0
0%
|
7
17.9%
|
| Male |
2
100%
|
6
100%
|
2
40%
|
5
100%
|
1
33.3%
|
5
100%
|
4
80%
|
1
50%
|
4
100%
|
2
100%
|
32
82.1%
|
| Race (NIH/OMB) (Count of Participants) | |||||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
2
5.1%
|
| Asian |
1
50%
|
3
50%
|
1
20%
|
3
60%
|
0
0%
|
3
60%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
11
28.2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
2
33.3%
|
0
0%
|
1
20%
|
0
0%
|
2
40%
|
4
80%
|
2
100%
|
1
25%
|
1
50%
|
13
33.3%
|
| White |
1
50%
|
1
16.7%
|
3
60%
|
0
0%
|
2
66.7%
|
0
0%
|
1
20%
|
0
0%
|
2
50%
|
1
50%
|
11
28.2%
|
| More than one race |
0
0%
|
0
0%
|
1
20%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
5.1%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||||||||||
| United States |
2
100%
|
6
100%
|
5
100%
|
5
100%
|
3
100%
|
5
100%
|
5
100%
|
2
100%
|
4
100%
|
2
100%
|
39
100%
|
Outcome Measures
| Title | Number of Participants With Clinically Significant Effects (Adverse Events) |
|---|---|
| Description | A summary of serious adverse events and other nonserious adverse events located in Reported Adverse Event section. To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in other LY2886721 groups received LY2886721 in fasted state. Due to crossover design in Part 1, results reported by treatment; thus, participants are included in multiple arms. |
| Time Frame | Predose to 10-14 days after final dose of study drug (up to 42 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 39 of the 40 participants who were entered and randomized into the study and who had undergone study procedures were included in the safety analyses. One participant, who was entered and randomized into the study but did not undergo study procedures, was excluded from the analysis. |
| Arm/Group Title | Placebo (Part 1) | 1 mg LY2886721 (Part 1) | 7 mg LY2886721 (Part 1 - Fed and Fasted) | 10 mg LY2886721 (Part 2) | 15 mg LY2886721 (Part 1) | 25 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 2) | Placebo (Part 2) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | In a single 8-day period, participants received a single placebo oral dose after an overnight fast. | In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after completing breakfast (Fed). In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast (Fasted). | Participants received a single 10-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast. | Participants received a single 35-mg LY2886721 oral dose after an overnight fast. | Participants received a single placebo oral dose after an overnight fast. |
| Measure Participants | 19 | 8 | 8 | 4 | 6 | 7 | 6 | 4 | 4 |
| Serious Adverse Events |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Other Nonserious Adverse Events |
4
200%
|
2
33.3%
|
1
20%
|
1
20%
|
0
0%
|
1
20%
|
3
60%
|
4
200%
|
3
75%
|
| Title | Maximum Observed Plasma Concentration (Cmax) of LY2886721 |
|---|---|
| Description | To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in the other LY2886721 groups received LY2886721 in the fasted state. Due to the crossover design in Part 1, results are reported by treatment; therefore, participants are included in multiple arms. |
| Time Frame | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of LY2886721 and have evaluable pharmacokinetic data were included in the analysis. One participant from Part 2, who experienced an adverse event before receiving study medication, was not included in the analysis. |
| Arm/Group Title | 1 mg LY2886721 (Part 1) | 7 mg LY2886721 Fed (Part 1) | 7 mg LY2886721 Fasted (Part 1) | 10 mg LY2886721 (Part 2) | 15 mg LY2886721 (Part 1) | 25 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 2) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after completing breakfast. | In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast. | Participants received a single 10-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast. | Participants received a single 35-mg LY2886721 oral dose after an overnight fast. |
| Measure Participants | 8 | 5 | 6 | 4 | 6 | 7 | 6 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)] |
1.9
(65)
|
22.5
(23)
|
18.2
(64)
|
6.6
(60)
|
41.6
(24)
|
79.1
(25)
|
78.2
(45)
|
53.3
(44)
|
| Title | Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) |
|---|---|
| Description | Pharmacokinetic AUC for LY2886721 from time 0 to infinity. To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in the other LY2886721 groups received LY2886721 in the fasted state. Due to the crossover design in Part 1, results are reported by treatment; therefore, participants are included in multiple arms. |
| Time Frame | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of LY2886721 and have evaluable pharmacokinetic data were included in the analysis. One participant in Part 2, who experienced an adverse event before receiving study medication, was not included in the analysis. |
| Arm/Group Title | 1 mg LY2886721 (Part 1) | 7 mg LY2886721 Fed (Part 1) | 7 mg LY2886721 Fasted (Part 1) | 10 mg LY2886721 (Part 2) | 15 mg LY2886721 (Part 1) | 25 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 2) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after completing breakfast. | In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast. | Participants received a single 10-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast. | Participants received a single 35-mg LY2886721 oral dose after an overnight fast. |
| Measure Participants | 8 | 5 | 6 | 4 | 6 | 7 | 6 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*h/mL)] |
NA
(NA)
|
311
(14)
|
212
(41)
|
144
(580)
|
468
(20)
|
926
(16)
|
954
(37)
|
800
(38)
|
| Title | Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only) |
|---|---|
| Description | Plasma concentrations of Aβ1-40 were based on the lowest observed/measured concentration (Cnadir). To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in the other LY2886721 groups received LY2886721 in the fasted state. Due to the crossover design in Part 1, results are reported by treatment; therefore, participants are included in multiple arms. |
| Time Frame | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of LY2886721 in Part 1 and have evaluable pharmacodynamic data were included in the analysis. One participant who was entered and randomized into the study but did not undergo study procedures, was excluded from the analysis. |
| Arm/Group Title | Placebo (Part 1) | 1 mg LY2886721 (Part 1) | 7 mg LY2886721 (Part 1 - Fed and Fasted) | 15 mg LY2886721 (Part 1) | 25 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 1) |
|---|---|---|---|---|---|---|
| Arm/Group Description | In a single 8-day period, participants received a single placebo oral dose after an overnight fast. | In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after completing breakfast (Fed). In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast (Fasted). | In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast. |
| Measure Participants | 19 | 8 | 6 | 6 | 7 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [picogram per milliliter (pg/mL)] |
121
(23.6)
|
80
(19.5)
|
56
(41.3)
|
35
(37.7)
|
34
(28.4)
|
36
(11.7)
|
| Title | Cerebrospinal Fluid (CSF) Maximum Observed Drug Concentration (Cmax) of LY2886721 (Part 2 Only) |
|---|---|
| Description | |
| Time Frame | Predose and up to 36 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of LY2886721 in Part 2 and have evaluable pharmacokinetic data were included in the analysis. One participant, who experienced an adverse event before receiving study medication, was not included in the analysis. |
| Arm/Group Title | 10 mg LY2886721 (Part 2) | 35 mg LY2886721 (Part 2) |
|---|---|---|
| Arm/Group Description | Participants received a single 10-mg LY2886721 oral dose after an overnight fast. | Participants received a single 35-mg LY2886721 oral dose by mouth after an overnight fast. |
| Measure Participants | 4 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)] |
0.93
(60)
|
5.99
(39)
|
| Title | Cerebrospinal Fluid (CSF) Pharmacodynamic Biomarker Amyloid Beta (Aβ) 1-40 Concentration (Part 2 Only) |
|---|---|
| Description | CSF Aβ 1-40 concentration was based on the lowest observed/measured concentration (Cnadir). |
| Time Frame | Predose and up to 36 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of LY2886721 in Part 2 and have evaluable pharmacodynamic data were included in the analysis. One participant, who experienced an adverse event before receiving study medication, was not included in the analysis. |
| Arm/Group Title | 10 mg LY2886721 (Part 2) | 35 mg LY2886721 (Part 2) | Placebo (Part 2) |
|---|---|---|---|
| Arm/Group Description | Participants received a single 10-mg LY2886721 oral dose after an overnight fast. | Participants received a single 35-mg LY2886721 oral dose after an overnight fast. | Participants received a single placebo oral dose after an overnight fast. |
| Measure Participants | 4 | 4 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [picogram per milliliter (pg/mL)] |
8080
(48.8)
|
5650
(51.1)
|
7150
(62.4)
|
| Title | Cerebrospinal Fluid (CSF) Area Under the Concentration Versus Time Curve (AUC) of LY2886721 (Part 2 Only) |
|---|---|
| Description | |
| Time Frame | Predose and up to 36 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of LY2886721 in Part 2 and have evaluable pharmacokinetic data were included in the analysis. One participant, who experienced an adverse event before receiving study medication, was not included in the analysis. |
| Arm/Group Title | 10 mg LY2886721 (Part 2) | 35 mg LY2886721 (Part 2) |
|---|---|---|
| Arm/Group Description | Participants received a single 10-mg LY2886721 oral dose after an overnight fast. | Participants received a single 35-mg LY2886721 oral dose after an overnight fast. |
| Measure Participants | 4 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*h/mL)] |
27
(89)
|
121
(30)
|
Adverse Events
| Time Frame | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||
| Arm/Group Title | Placebo (Part 1) | 1 mg LY2886721 (Part 1) | 7 mg LY2886721 (Part 1 - Fed and Fasted) | 10 mg LY2886721 (Part 2) | 15 mg LY2886721 (Part 1) | 25 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 2) | Placebo (Part 2) | |||||||||
| Arm/Group Description | In a single 8-day period, participants received a single placebo oral dose after an overnight fast. | In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast, but 15 minutes after breakfast (Fed). In a single 8-day period, participants received a single 7-mg LY2886721 oral dose after an overnight fast (Fasted). | Participants received a single 10-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast. | In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast. | Participants received a single 35-mg LY2886721 oral dose after an overnight fast. | Participants received a single placebo oral dose after an overnight fast. | |||||||||
All Cause Mortality |
||||||||||||||||||
| Placebo (Part 1) | 1 mg LY2886721 (Part 1) | 7 mg LY2886721 (Part 1 - Fed and Fasted) | 10 mg LY2886721 (Part 2) | 15 mg LY2886721 (Part 1) | 25 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 2) | Placebo (Part 2) | ||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||||||
Serious Adverse Events |
||||||||||||||||||
| Placebo (Part 1) | 1 mg LY2886721 (Part 1) | 7 mg LY2886721 (Part 1 - Fed and Fasted) | 10 mg LY2886721 (Part 2) | 15 mg LY2886721 (Part 1) | 25 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 2) | Placebo (Part 2) | ||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/19 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/6 (0%) | 0/7 (0%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | |||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||
| Placebo (Part 1) | 1 mg LY2886721 (Part 1) | 7 mg LY2886721 (Part 1 - Fed and Fasted) | 10 mg LY2886721 (Part 2) | 15 mg LY2886721 (Part 1) | 25 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 1) | 35 mg LY2886721 (Part 2) | Placebo (Part 2) | ||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/19 (21.1%) | 2/8 (25%) | 1/8 (12.5%) | 1/4 (25%) | 0/6 (0%) | 1/7 (14.3%) | 3/6 (50%) | 4/4 (100%) | 3/4 (75%) | |||||||||
| Ear and labyrinth disorders | ||||||||||||||||||
| Ear discomfort | 1/19 (5.3%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 |
| Vertigo | 0/19 (0%) | 0 | 0/8 (0%) | 0 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||
| Nausea | 1/19 (5.3%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 |
| General disorders | ||||||||||||||||||
| Chest pain | 0/19 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 |
| Puncture site pain | 0/19 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 2 | 0/4 (0%) | 0 |
| Vessel puncture site haematoma | 1/19 (5.3%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||
| Procedural headache | 0/19 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 4/4 (100%) | 5 | 1/4 (25%) | 1 |
| Procedural vomiting | 0/19 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||
| Arthralgia | 0/19 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 |
| Muscle spasms | 0/19 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 |
| Pain in extremity | 0/19 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 |
| Plantar fasciitis | 1/19 (5.3%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||
| Dizziness | 1/19 (5.3%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 |
| Dysgeusia | 0/19 (0%) | 0 | 1/8 (12.5%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 |
| Headache | 1/19 (5.3%) | 1 | 1/8 (12.5%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 |
| Syncope | 0/19 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 |
| Psychiatric disorders | ||||||||||||||||||
| Anxiety | 0/19 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||
| Rhinitis allergic | 0/19 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||
| Dermatitis contact | 1/19 (5.3%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (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.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
| ClinicalTrials.gov@lilly.com |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01133405
Other Study ID Numbers:
- 13733
- I4O-MC-BACA
First Posted:
May 28, 2010
Last Update Posted:
Sep 16, 2019
Last Verified:
May 1, 2019