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| ID | Type | Description | Link |
|---|---|---|---|
| I4O-MC-BACA | Other Identifier | Eli Lilly and Company |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LY2886721 Part 1: Cohort A/B | Experimental | Single (7 milligram (mg), 15 mg, 25 mg, 35 mg) doses of LY2886721 administered orally in up to three of three study periods |
|
| Placebo Part 1: Cohort A/B | Placebo Comparator | Single dose in up to 1 period |
|
| LY2886721 Part 2: Cohort C | Experimental | Single 10 mg dose of LY2886721, dose determined by Part 1 |
|
| LY2886721 Part 2: Cohort D | Experimental | Single 35 mg dose of LY2886721, dose determined by Part 1 |
|
| Placebo Part 2: Cohort C/D | Placebo Comparator | Single dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY2886721 | Drug | Oral capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Clinically Significant Effects (Adverse Events) | 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. | Predose to 10-14 days after final dose of study drug (up to 42 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of LY2886721 | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 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 | 90211 |
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A (Part 1) : Sequence 1 | 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. |
| FG001 | Cohort A (Part 1): Sequence 2 | 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. |
| FG002 | Cohort A (Part 1): Sequence 3 | 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. |
| FG003 | Cohort B (Part 1): Sequence 1 | 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. |
| FG004 | Cohort B (Part 1): Sequence 2 | 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). |
| FG005 | Cohort B (Part 1): Sequence 3 | 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). |
| FG006 | Cohort C (Part 2): 10mg LY2886721 | Participants received a single 10 mg LY2886721 oral dose (low dose) in the fasted state. |
| FG007 | Cohort C (Part 2): Placebo | Participants received a single oral placebo dose in the fasted state. |
| FG008 | Cohort D (Part 2): 35 mg LY2886721 | Participants received a single 35 mg LY2886721 oral dose (high dose) in the fasted state. |
| FG009 | Cohort D (Part 2): Placebo | Participants received a single oral placebo dose in the fasted state. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Period 2 |
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| Period 3 |
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Safety analysis population
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A (Part 1): Sequence 1 | Participants received Placebo, 15 milligram (mg) LY2886721 and 35 mg LY2886721 orally as per the dosing sequence in each period. |
| BG001 | Cohort A (Part 1): Sequence 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Clinically Significant Effects (Adverse Events) | 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. | 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. | Posted | Count of Participants | Participants | No | Predose to 10-14 days after final dose of study drug (up to 42 days) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo (Part 1) | In a single 8-day period, participants received a single placebo oral dose after an overnight fast. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear discomfort | Ear and labyrinth disorders | MedDRA 13.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 | ClinicalTrials.gov@lilly.com |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000596181 | N-(3-(2-amino-4a,5,7,7a-tetrahydro-4H-furo(3,4-d)(1,3)thiazin-7a-yl)-4-fluorophenyl)-5-fluoropicolinamide |
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| Placebo | Drug | Oral capsules |
|
| 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose |
| Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) | 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. | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose |
| Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only) | 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. | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose |
| 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) | CSF Aβ 1-40 concentration was based on the lowest observed/measured concentration (Cnadir). | Predose and up to 36 hours postdose |
| Cerebrospinal Fluid (CSF) Area Under the Concentration Versus Time Curve (AUC) of LY2886721 (Part 2 Only) | Predose and up to 36 hours postdose |
| United States |
| Physician Decision |
|
| Discontinued after randomization |
|
| Received drug only in period 2 |
|
| Received drug only in period 3 |
|
| Received at Least 1 Dose of Study Drug |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Received at Least 1 Dose of Study Drug |
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| COMPLETED |
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| NOT COMPLETED |
|
Participants received 1 mg LY2886721, 15 mg LY2886721 and placebo orally as per the dosing sequence in each period.
| BG002 | Cohort A (Part 1): Sequence 3 | Participants received 1 mg LY2886721, placebo and 35 mg LY2886721 orally as per the dosing sequence in each period. |
| BG003 | Cohort B (Part 1): Sequence 1 | Participants received 7 mg LY2886721, 25 mg LY2886721 and placebo and orally as per the dosing sequence in each period. |
| BG004 | Cohort B (Part 1): Sequence 2 | Participants received 7 mg LY2886721, placebo and 7 mg LY2886721 (fed state) orally as per the dosing sequence in each period. |
| BG005 | Cohort B (Part 1): Sequence 3 | Participants received Placebo, 25 mg LY2886721 and 7 mg LY2886721 (fed state) orally as per the below dosing sequence in each period. |
| BG006 | Cohort C (Part 2): 10mg LY2886721 | Participants received a single 10 mg LY2886721 oral dose (low dose) in the fasted state. |
| BG007 | Cohort C (Part 2): Placebo | .Participants received a single oral placebo dose in the fasted state. |
| BG008 | Cohort D (Part 2): 35 mg LY2886721 | Participants received a single 35 mg LY2886721 oral dose (high dose) in the fasted state. |
| BG009 | Cohort D (Part 2): Placebo | Participants received a single oral placebo dose in the fasted state. |
| BG010 | Total | Total of all reporting groups |
| Participants |
| No |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
| OG000 |
| Placebo (Part 1) |
In a single 8-day period, participants received a single placebo oral dose after an overnight fast. |
| OG001 | 1 mg LY2886721 (Part 1) | In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast. |
| OG002 | 7 mg LY2886721 (Part 1 - Fed and Fasted) | 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). |
| OG003 | 10 mg LY2886721 (Part 2) | Participants received a single 10-mg LY2886721 oral dose after an overnight fast. |
| OG004 | 15 mg LY2886721 (Part 1) | In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast. |
| OG005 | 25 mg LY2886721 (Part 1) | In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast. |
| OG006 | 35 mg LY2886721 (Part 1) | In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast. |
| OG007 | 35 mg LY2886721 (Part 2) | Participants received a single 35-mg LY2886721 oral dose after an overnight fast. |
| OG008 | Placebo (Part 2) | Participants received a single placebo oral dose after an overnight fast. |
|
|
| Secondary | Maximum Observed Plasma Concentration (Cmax) of LY2886721 | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose |
|
|
|
| Secondary | Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*h/mL) | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose |
|
|
|
| Secondary | Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only) | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | picogram per milliliter (pg/mL) | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose |
|
|
|
| Secondary | Cerebrospinal Fluid (CSF) Maximum Observed Drug Concentration (Cmax) of LY2886721 (Part 2 Only) | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Predose and up to 36 hours postdose |
|
|
|
| Secondary | Cerebrospinal Fluid (CSF) Pharmacodynamic Biomarker Amyloid Beta (Aβ) 1-40 Concentration (Part 2 Only) | CSF Aβ 1-40 concentration was based on the lowest observed/measured concentration (Cnadir). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | picogram per milliliter (pg/mL) | Predose and up to 36 hours postdose |
|
|
|
| Secondary | Cerebrospinal Fluid (CSF) Area Under the Concentration Versus Time Curve (AUC) of LY2886721 (Part 2 Only) | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*h/mL) | Predose and up to 36 hours postdose |
|
|
|
| 0 |
| 19 |
| 4 |
| 19 |
| EG001 | 1 mg LY2886721 (Part 1) | In a single 8-day period, participants received a single 1-mg LY2886721 oral dose after an overnight fast. | 0 | 8 | 2 | 8 |
| EG002 | 7 mg LY2886721 (Part 1 - Fed and Fasted) | 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). | 0 | 8 | 1 | 8 |
| EG003 | 10 mg LY2886721 (Part 2) | Participants received a single 10-mg LY2886721 oral dose after an overnight fast. | 0 | 4 | 1 | 4 |
| EG004 | 15 mg LY2886721 (Part 1) | In a single 8-day period, participants received a single 15-mg LY2886721 oral dose after an overnight fast. | 0 | 6 | 0 | 6 |
| EG005 | 25 mg LY2886721 (Part 1) | In a single 8-day period, participants received a single 25-mg LY2886721 oral dose after an overnight fast. | 0 | 7 | 1 | 7 |
| EG006 | 35 mg LY2886721 (Part 1) | In a single 8-day period, participants received a single 35-mg LY2886721 oral dose after an overnight fast. | 0 | 6 | 3 | 6 |
| EG007 | 35 mg LY2886721 (Part 2) | Participants received a single 35-mg LY2886721 oral dose after an overnight fast. | 0 | 4 | 4 | 4 |
| EG008 | Placebo (Part 2) | Participants received a single placebo oral dose after an overnight fast. | 0 | 4 | 3 | 4 |
| Vertigo | Ear and labyrinth disorders | MedDRA 13.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Puncture site pain | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Vessel puncture site haematoma | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Procedural headache | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Procedural vomiting | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Plantar fasciitis | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
Not provided
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |