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| ID | Type | Description | Link |
|---|---|---|---|
| I6F-MC-JJCE | Other Identifier | Eli Lilly and Company |
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The main purpose of this study is to investigate the safety of the study drug known as LY3039478 and evaluate two different formulations of LY3039478 in healthy participants. Part A has three periods. Either LY3039478 or placebo will be given once by mouth in each period. Part B has two periods. Participants will receive both formulations of LY3039478, by mouth, over the course of the study. Both parts of the study will also explore how much LY3039478 gets into the bloodstream and how long it takes the body to get rid of it. Information about any side effects will also be collected. Participants may only enroll in one part. The study will last at least 33 days, not including screening. Screening must be performed up to 30 days before enrollment.
Part B was added by protocol amendment approved in April, 2016.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: Placebo | Placebo Comparator | Single oral dose of placebo administered in one of three study periods |
|
| Part A: LY3039478 Capsule Formulation (Formulation 3) | Experimental | Escalating single oral dose of 25 milligram (mg), 50 mg, and 75 mg capsule formulation (formulation 3) LY3039478 administered in two of three study periods |
|
| Part B: LY3039478 Drug-In Capsule (Reference, Formulation 1) | Experimental | Single oral 50 mg dose of drug-in capsule (reference, formulation 1) LY3039478 administered in one of two study periods |
|
| Part B: LY3039478 Formulated Capsule (Test, Formulation 3) | Experimental | Single oral 50 mg dose of formulated capsule (test, formulation 3) LY3039478 administered in one of two study periods |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Administered orally |
| |
| LY3039478 Capsule Formulation (Formulation 3) |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK): Mean Time-Matched Difference in Placebo-Adjusted QTcF Interval With Time Matched Concentrations Between LY3039478 Capsule Formulation (Formulation 3) Part A | PK: mean time-matched difference in QTcF interval with time-matched concentrations between LY3039478 capsule formulation (formulation 3) compared to placebo. Analyses of QTcF was assessed by the mean change in QTcF as a function of plasma drug concentration. Triplicate measures at each time point was averaged prior to analysis. The primary analysis was based on the time-matched placebo-adjusted QTcF (ΔQTcF) for each time point, which was calculated by subtracting each participant's time-matched placebo QTcF from their QTcF results after receiving LY3039478. The relationship between plasma concentrations of LY3039478 and ΔQTcF was evaluated using a linear mixed-effects modeling approach. The response variable was ΔQTcF, and concentrations was fitted as a fixed effect with participants as a random effect. The regression slope was presented with the unit in "milliseconds per nanogram per milliliter" abbreviated as "ms/ng/mL". | Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose |
| Measure | Description | Time Frame |
|---|---|---|
| PK: Cmax of LY3039478 Capsule Formulation (Formulation 3) Part A | PK is Cmax of LY3039478 capsule formulation (formulation 3) in part A. | Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose |
| PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3039478 Capsule Formulation (Formulation 3) Part A |
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Inclusion Criteria:
- Body mass index (BMI) of 18 to 32 kilogram per meter square (kg/m²)
Exclusion Criteria:
- Known allergies to LY3039478, related compounds or any components of the formulation
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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 |
|---|---|---|---|---|---|---|
| Covance | Daytona Beach | Florida | 32117 | United States |
Participants were randomized to 1 of 3 treatment sequences with a placebo-control in at least 1 of the 3 study periods in Part A. Each period was separated by a washout period of ≥14 days. Participants were randomized to 1 of 2 treatment sequences in Part B. Each period was separated by a washout of ≥14 days.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: Group 1 (25 mg LY3039478 First, Then 50 mg LY3039478, Followed by Placebo) | Single oral dose of LY3039478 capsule formulation (formulation 3) administered in one of three periods. |
| FG001 | Part A: Group 2 (25 mg LY3039478 First, Then Placebo, Followed by 75 mg LY3039478) | Single oral dose of LY3039478 capsule formulation (formulation 3) administered in one of three periods. |
| FG002 | Part A: Group 3 (Placebo First, Then 50 mg LY3039478, Followed by 75 mg LY3039478) | Single oral dose of LY3039478 capsule formulation (formulation 3) administered in one of three periods. |
| FG003 | Part B: 50 mg LY3039478 (Reference Formulation 1 First, Then Test Formulation 3) | Single oral dose of 50 mg drug-in capsule LY3039478 (reference, formulation 1) was administered in period 1, then 50 mg LY3039478 (test, formulation 3) was administered in period 2. |
| FG004 | Part B: 50 mg LY3039478 (Test Formulation 3 First, Then Reference Formulation 1) | Single oral dose of 50 mg formulated capsule LY3039478 (test, formulation 3) administered in period 1, then 50 mg LY3039478 (reference, formulation 1) was administered in period 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Period 2 |
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| Period 3 |
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All participants in Part A and Part B.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A | Single oral dose of LY3039478 capsule formulation (formulation 3) administered in one of three periods. A washout period occurred after each period. |
| BG001 | Part B | Single oral dose of 50 mg drug-in capsule LY3039478 (reference, formulation 1) administered in one of two study periods. Single oral dose of 50 mg formulated capsule LY3039478 (test, formulation 3) administered in one of two study periods |
| 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 | Pharmacokinetics (PK): Mean Time-Matched Difference in Placebo-Adjusted QTcF Interval With Time Matched Concentrations Between LY3039478 Capsule Formulation (Formulation 3) Part A | PK: mean time-matched difference in QTcF interval with time-matched concentrations between LY3039478 capsule formulation (formulation 3) compared to placebo. Analyses of QTcF was assessed by the mean change in QTcF as a function of plasma drug concentration. Triplicate measures at each time point was averaged prior to analysis. The primary analysis was based on the time-matched placebo-adjusted QTcF (ΔQTcF) for each time point, which was calculated by subtracting each participant's time-matched placebo QTcF from their QTcF results after receiving LY3039478. The relationship between plasma concentrations of LY3039478 and ΔQTcF was evaluated using a linear mixed-effects modeling approach. The response variable was ΔQTcF, and concentrations was fitted as a fixed effect with participants as a random effect. The regression slope was presented with the unit in "milliseconds per nanogram per milliliter" abbreviated as "ms/ng/mL". | All randomized participants who received at least one dose of study drug and had evaluable mean time-matched difference in QTcF interval data in part A. Data from all dose levels were combined due to analysis is looking at QTcF as a function of concentration of LY in the blood, not as a function of dose per protocol and statistical analysis plan. | Posted | Mean | 90% Confidence Interval | ms/ng/mL | Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose |
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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 | Part A: Placebo | Single oral dose placebo administered in one of three study periods. A washout period occurred after each period. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1 | 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 |
|---|---|
| C000654634 | crenigacestat |
| D004304 | Dosage Forms |
| ID | Term |
|---|---|
| D004364 | Pharmaceutical Preparations |
| D013678 | Technology, Pharmaceutical |
| D008919 | Investigative Techniques |
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| Drug |
Administered orally |
|
|
| LY3039478 Drug-in Capsule (Reference, Formulation 1) | Drug | Administered orally |
|
|
| LY3039478 Formulated Capsule (Test, Formulation 3) | Drug | Administered orally |
|
|
PK is the area under the concentration versus time curve from zero to infinity (AUC[0-∞]) of LY3039478 capsule formulation (formulation 3) in part A. |
| Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose |
| PK: Cmax of the 2 Formulations of LY3039478 Part B | PK is the Cmax of the 2 formulations of LY3039478 in part B | Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose |
| PK: AUC(0-∞) of the 2 Formulations of LY3039478 Part B | PK is the AUC(0-∞) of the 2 formulations of LY3039478 in part B. | Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose |
| Adverse Event |
|
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| BG002 | Total | Total of all reporting groups |
| Participants |
| No |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
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| Region of Enrollment | Count of Participants | Participants | No |
|
|
|
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| Secondary | PK: Cmax of LY3039478 Capsule Formulation (Formulation 3) Part A | PK is Cmax of LY3039478 capsule formulation (formulation 3) in part A. | All randomized participants who received at least one dose of study drug and had evaluable PK data in part A. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/milliliter (ng/mL) | Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose |
|
|
|
| Secondary | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3039478 Capsule Formulation (Formulation 3) Part A | PK is the area under the concentration versus time curve from zero to infinity (AUC[0-∞]) of LY3039478 capsule formulation (formulation 3) in part A. | All randomized participants who received at least one dose of study drug and had evaluable PK data in Part A | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour/milliliter (ng*h/mL) | Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose |
|
|
|
| Secondary | PK: Cmax of the 2 Formulations of LY3039478 Part B | PK is the Cmax of the 2 formulations of LY3039478 in part B | All randomized participants who received at least one dose of study drug and had evaluable PK data in part B. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose |
|
|
|
| Secondary | PK: AUC(0-∞) of the 2 Formulations of LY3039478 Part B | PK is the AUC(0-∞) of the 2 formulations of LY3039478 in part B. | All randomized participants who received at least one dose of study drug and had evaluable PK data in part B. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose |
|
|
|
| 0 |
| 14 |
| 1 |
| 14 |
| EG001 | Part A: 25 mg of LY3039478 Capsule Formulation (Formulation 3) | Single oral dose of 25 mg of LY3039478 capsule formulation (formulation 3) administered in one of three periods. | 0 | 10 | 1 | 10 |
| EG002 | Part A: 50 mg of LY3039478 Capsule Formulation (Formulation 3) | Single oral dose of 50 mg of LY3039478 capsule formulation (formulation 3) administered in one of three periods. | 0 | 9 | 1 | 9 |
| EG003 | Part A: 75 mg of LY3039478 Capsule Formulation (Formulation 3) | Single oral dose of 75 mg of LY3039478 (formulation 3) or placebo administered one of three study periods. | 0 | 10 | 0 | 10 |
| EG004 | Part B: LY3039478 Reference, Formulation 1 | Single oral dose of LY3039478 reference, formulation 1 administered in one of two study periods. | 0 | 13 | 1 | 13 |
| EG005 | Part B: LY3039478 Test, Formulation 3 | Single oral dose of LY3039478 test, formulation 3 administered in one of two study periods | 0 | 14 | 1 | 14 |
| Chills | General disorders | MedDRA 18.1 | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 18.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Scab | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
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