Trial Outcomes & Findings for A Relative Bioavailability and Food Effect Study of New Formulations (NCT NCT01398475)
NCT ID: NCT01398475
Last Updated: 2017-04-21
Results Overview
The area under the concentration-time curve from time 0 to infinity \[AUC(0-inf)\] is reported for participants who received either LY3009104 tablets or capsules in a fasted or fed state.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
15 participants
Primary outcome timeframe
Predose up to 48 hours postdose for each of the 4 treatment periods
Results posted on
2017-04-21
Participant Flow
Participant milestones
| Measure |
LY3009104 (LY) RF, LY 50-mcm Fed, LY 20-mcm, LY 50-mcm Fasted
First intervention: 8-milligram (mg) dose of LY3009104 reference formulation (RF, two 4-mg phosphate salt capsules) administered once in a fasted state.
Second intervention: 8-mg dose of LY3009104 test formulation 2 \[TF2, one 8-mg tablet, free base formulation, target active pharmaceutical ingredient (API) particle size of 50 micrometers (mcm)\] administered once with a high-fat, high calorie meal.
Third intervention: 8-mg dose of LY3009104 test formulation 1 (TF1, one 8-mg tablet, free base formulation, target API particle size of 20 mcm) administered once in a fasted state.
Fourth intervention: 8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once in a fasted state.
There was a washout period of 5 to 7 days between doses of study drug.
|
LY 20-mcm, LY RF, LY 50-mcm Fasted, LY 50-mcm Fed
First intervention: 8-mg dose of LY3009104 TF1 (one 8-mg tablet, free base formulation, target API particle size of 20 mcm) administered once in a fasted state.
Second intervention: 8-mg dose of LY3009104 RF (two 4-mg phosphate salt capsules) administered once in a fasted state.
Third intervention: 8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once in a fasted state.
Fourth intervention: 8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once with a high-fat, high calorie meal.
There was a washout period of 5 to 7 days between doses of study drug.
|
LY 50-mcm Fasted, LY 20-mcm, LY 50-mcm Fed, LY RF
First intervention: 8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once in a fasted state.
Second intervention: 8-mg dose of LY3009104 TF1 (one 8-mg tablet, free base formulation, target API particle size of 20 mcm) administered once in a fasted state.
Third intervention: 8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once with a high-fat, high calorie meal.
Fourth intervention: 8-mg dose of LY3009104 RF (two 4-mg phosphate salt capsules) administered once in a fasted state.
There was a washout period of 5 to 7 days between doses of study drug.
|
LY 50-mcm Fed, LY 50-mcm Fasted, LY RF, LY 20-mcm
First intervention: 8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once with a high-fat, high calorie meal.
Second intervention: 8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once in a fasted state.
Third intervention: 8-mg dose of LY3009104 RF (two 4-mg phosphate salt capsules) administered once in a fasted state.
Fourth Intervention: 8-mg dose of LY3009104 TF1 (one 8-mg tablet, free base formulation, target API particle size of 20 mcm) administered once in a fasted state.
There was a washout period of 5 to 7 days between doses of study drug.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
3
|
4
|
4
|
|
Overall Study
Received First Intervention
|
4
|
3
|
4
|
4
|
|
Overall Study
Received Second Intervention
|
4
|
3
|
4
|
4
|
|
Overall Study
Received Third Intervention
|
4
|
3
|
4
|
4
|
|
Overall Study
Received Fourth Intervention
|
4
|
3
|
4
|
4
|
|
Overall Study
COMPLETED
|
4
|
3
|
4
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Relative Bioavailability and Food Effect Study of New Formulations
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=15 Participants
Includes groups randomized to receive any of the following study drugs as the first intervention.
LY3009104 Reference Formulation (RF): 8-milligram (mg) dose of LY3009104 RF (two 4-mg phosphate salt capsules) administered once in a fasted state.
LY3009104 Test Formulation 1 (TF1), 20 micrometers (mcm): 8-mg dose of LY3009104 TF1 \[one 8-mg tablet, free base formulation, target active pharmaceutical ingredient (API) particle size of 20 mcm\] administered once in a fasted state.
LY3009104 Test Formulation 2 (TF2), 50 mcm, fasted: 8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once in a fasted state.
LY3009104 TF2, 50 mcm, fed: 8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once with a high-fat, high calorie meal.
|
|---|---|
|
Age, Continuous
|
38.0 years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
14 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Singapore
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose up to 48 hours postdose for each of the 4 treatment periodsPopulation: Randomized participants who received at least 1 dose of study drug.
The area under the concentration-time curve from time 0 to infinity \[AUC(0-inf)\] is reported for participants who received either LY3009104 tablets or capsules in a fasted or fed state.
Outcome measures
| Measure |
LY3009104 Reference Formulation
n=15 Participants
8-milligram (mg) dose of LY3009104 reference formulation (RF, two 4-mg phosphate salt capsules) administered once in a fasted state in Period 1, 2, 3, or 4.
|
LY3009104 Test Formulation 1 (20-mcm)
n=15 Participants
8-mg dose of LY3009104 test formulation 1 \[TF1, one 8-mg tablet, free base formulation, target active pharmaceutical ingredient (API) particle size of 20 micrometers (mcm)\] administered once in a fasted state in Period 1, 2, 3, or 4.
|
LY3009104 Test Formulation 2 (50-mcm, Fed)
n=15 Participants
8-mg dose of LY3009104 test formulation 2 (TF2, one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once with a high-fat, high calorie meal in Period 1, 2, 3, or 4.
|
LY3009104 Test Formulation 2 (50-mcm, Fasted)
n=15 Participants
8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once in a fasted state in Period 1, 2, 3, or 4.
|
|---|---|---|---|---|
|
Pharmacokinetics: Plasma Concentration-Time Curve (AUC)
|
1670 nanomoles*hours per liter (nmol*h/L)
Geometric Coefficient of Variation 35
|
1710 nanomoles*hours per liter (nmol*h/L)
Geometric Coefficient of Variation 32
|
1510 nanomoles*hours per liter (nmol*h/L)
Geometric Coefficient of Variation 34
|
1700 nanomoles*hours per liter (nmol*h/L)
Geometric Coefficient of Variation 35
|
SECONDARY outcome
Timeframe: Predose up to 48 hours postdose for each of the 4 treatment periodsPopulation: Randomized participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
LY3009104 Reference Formulation
n=15 Participants
8-milligram (mg) dose of LY3009104 reference formulation (RF, two 4-mg phosphate salt capsules) administered once in a fasted state in Period 1, 2, 3, or 4.
|
LY3009104 Test Formulation 1 (20-mcm)
n=15 Participants
8-mg dose of LY3009104 test formulation 1 \[TF1, one 8-mg tablet, free base formulation, target active pharmaceutical ingredient (API) particle size of 20 micrometers (mcm)\] administered once in a fasted state in Period 1, 2, 3, or 4.
|
LY3009104 Test Formulation 2 (50-mcm, Fed)
n=15 Participants
8-mg dose of LY3009104 test formulation 2 (TF2, one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once with a high-fat, high calorie meal in Period 1, 2, 3, or 4.
|
LY3009104 Test Formulation 2 (50-mcm, Fasted)
n=15 Participants
8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once in a fasted state in Period 1, 2, 3, or 4.
|
|---|---|---|---|---|
|
Pharmacokinetics: Maximum Plasma Concentration (Cmax)
|
259 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 26 • Interval 231.0 to 286.0
|
253 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 19 • Interval 226.0 to 280.0
|
205 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 27
|
250 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 30 • Interval 222.0 to 275.0
|
SECONDARY outcome
Timeframe: Predose up to 48 hours postdose for each of the 4 treatment periodsPopulation: Randomized participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
LY3009104 Reference Formulation
n=15 Participants
8-milligram (mg) dose of LY3009104 reference formulation (RF, two 4-mg phosphate salt capsules) administered once in a fasted state in Period 1, 2, 3, or 4.
|
LY3009104 Test Formulation 1 (20-mcm)
n=15 Participants
8-mg dose of LY3009104 test formulation 1 \[TF1, one 8-mg tablet, free base formulation, target active pharmaceutical ingredient (API) particle size of 20 micrometers (mcm)\] administered once in a fasted state in Period 1, 2, 3, or 4.
|
LY3009104 Test Formulation 2 (50-mcm, Fed)
n=15 Participants
8-mg dose of LY3009104 test formulation 2 (TF2, one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once with a high-fat, high calorie meal in Period 1, 2, 3, or 4.
|
LY3009104 Test Formulation 2 (50-mcm, Fasted)
n=15 Participants
8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once in a fasted state in Period 1, 2, 3, or 4.
|
|---|---|---|---|---|
|
Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax)
|
1.00 hours (h)
Interval 0.5 to 3.0
|
1.00 hours (h)
Interval 0.5 to 3.0
|
2.00 hours (h)
Interval 1.0 to 4.0
|
1.00 hours (h)
Interval 0.5 to 2.0
|
Adverse Events
LY3009104 Reference Formulation
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
LY3009104 Test Formulation 2 (50-mcm, Fed)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
LY3009104 Test Formulation 1 (20-mcm)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
LY3009104 Test Formulation 2 (50-mcm, Fasted)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LY3009104 Reference Formulation
n=15 participants at risk
8-milligram (mg) dose of LY3009104 reference formulation (RF, two 4-mg phosphate salt capsules) administered once in a fasted state in Period 1, 2, 3, or 4.
|
LY3009104 Test Formulation 2 (50-mcm, Fed)
n=15 participants at risk
8-mg dose of LY3009104 test formulation 2 \[TF2, one 8-mg tablet, free base formulation, target active pharmaceutical ingredient (API) particle size of 50 micrometer (mcm)\] administered once with a high-fat, high calorie meal in Period 1, 2, 3, or 4.
|
LY3009104 Test Formulation 1 (20-mcm)
n=15 participants at risk
8-mg dose of LY3009104 test formulation 1 (TF1, one 8-mg tablet, free base formulation, target API particle size of 20 mcm) administered once in a fasted state in Period 1, 2, 3, or 4.
|
LY3009104 Test Formulation 2 (50-mcm, Fasted)
n=15 participants at risk
8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once in a fasted state in Period 1, 2, 3, or 4.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Glossodynia
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Catheter site erythema
|
6.7%
1/15 • Number of events 1
|
6.7%
1/15 • Number of events 1
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
|
General disorders
Catheter site haematoma
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
|
General disorders
Catheter site pain
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
|
General disorders
Catheter site pruritus
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
|
General disorders
Vessel puncture site haematoma
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Procedural site reaction
|
0.00%
0/15
|
13.3%
2/15 • Number of events 2
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place