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Trial record 57 of 62 for:    Baricitinib

A Relative Bioavailability and Food Effect Study of New Formulations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01398475
Recruitment Status : Completed
First Posted : July 20, 2011
Results First Posted : April 21, 2017
Last Update Posted : April 21, 2017
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Chronic Inflammatory Disorder
Arthritis, Rheumatoid
Intervention Drug: LY3009104
Enrollment 15
Recruitment Details  
Pre-assignment Details  
Arm/Group Title LY3009104 (LY) RF, LY 50-mcm Fed, LY 20-mcm, LY 50-mcm Fasted LY 20-mcm, LY RF, LY 50-mcm Fasted, LY 50-mcm Fed LY 50-mcm Fasted, LY 20-mcm, LY 50-mcm Fed, LY RF LY 50-mcm Fed, LY 50-mcm Fasted, LY RF, LY 20-mcm
Hide Arm/Group Description

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.

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.

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.

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.

Period Title: Overall Study
Started 4 3 4 4
Received First Intervention 4 3 4 4
Received Second Intervention 4 3 4 4
Received Third Intervention 4 3 4 4
Received Fourth Intervention 4 3 4 4
Completed 4 3 4 4
Not Completed 0 0 0 0
Arm/Group Title Entire Study Population
Hide Arm/Group Description

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.

Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
38.0  (9.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
1
   6.7%
Male
14
  93.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
Asian 14
White 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Singapore Number Analyzed 15 participants
15
1.Primary Outcome
Title Pharmacokinetics: Plasma Concentration-Time Curve (AUC)
Hide Description 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.
Time Frame Predose up to 48 hours postdose for each of the 4 treatment periods
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug.
Arm/Group Title LY3009104 Reference Formulation LY3009104 Test Formulation 1 (20-mcm) LY3009104 Test Formulation 2 (50-mcm, Fed) LY3009104 Test Formulation 2 (50-mcm, Fasted)
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 15 15 15 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanomoles*hours per liter (nmol*h/L)
1670
(35%)
1710
(32%)
1510
(34%)
1700
(35%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY3009104 Reference Formulation, LY3009104 Test Formulation 1 (20-mcm)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least squares (LS) mean ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 90%
0.951 to 1.10
Estimation Comments The geometric LS mean ratio (TF1 fasted divided by RF fasted) was calculated using a linear mixed-effects model adjusted for treatment, sequence, period, and participant.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY3009104 Reference Formulation, LY3009104 Test Formulation 2 (50-mcm, Fasted)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric LS mean ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 90%
0.947 to 1.09
Estimation Comments The geometric LS mean ratio (TF2 fasted divided by RF fasted) was calculated using a linear mixed-effects model adjusted for treatment, sequence, period, and participant.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LY3009104 Test Formulation 2 (50-mcm, Fed), LY3009104 Test Formulation 2 (50-mcm, Fasted)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric LS mean ratio
Estimated Value 0.888
Confidence Interval (2-Sided) 90%
0.827 to 0.953
Estimation Comments The geometric LS mean ratio (TF2 fed divided by TF2 fasted) was calculated using a linear mixed-effects model adjusted for treatment, sequence, period, and participant.
2.Secondary Outcome
Title Pharmacokinetics: Maximum Plasma Concentration (Cmax)
Hide Description [Not Specified]
Time Frame Predose up to 48 hours postdose for each of the 4 treatment periods
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug.
Arm/Group Title LY3009104 Reference Formulation LY3009104 Test Formulation 1 (20-mcm) LY3009104 Test Formulation 2 (50-mcm, Fed) LY3009104 Test Formulation 2 (50-mcm, Fasted)
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 15 15 15 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanomoles per liter (nmol/L)
259
(231% to 286%)
253
(226% to 280%)
205
(27%)
250
(222% to 275%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY3009104 Reference Formulation, LY3009104 Test Formulation 1 (20-mcm)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least squares (LS) mean ratio
Estimated Value 0.979
Confidence Interval (2-Sided) 90%
0.868 to 1.10
Estimation Comments The geometric LS mean ratio (TF1 fasted divided by RF fasted) was calculated using a linear mixed-effects model adjusted for treatment, sequence, period, and participant.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY3009104 Reference Formulation, LY3009104 Test Formulation 2 (50-mcm, Fasted)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric LS mean ratio
Estimated Value 0.962
Confidence Interval (2-Sided) 90%
0.852 to 1.08
Estimation Comments The geometric LS mean ratio (TF2 fasted divided by RF fasted) was calculated using a linear mixed-effects model adjusted for treatment, sequence, period, and participant.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LY3009104 Test Formulation 2 (50-mcm, Fed), LY3009104 Test Formulation 2 (50-mcm, Fasted)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric LS mean ratio
Estimated Value 0.820
Confidence Interval (2-Sided) 90%
0.727 to 0.925
Estimation Comments The geometric LS mean ratio (TF2 fed divided by TF2 fasted) was calculated using a linear mixed-effects model adjusted for treatment, sequence, period, and participant.
3.Secondary Outcome
Title Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax)
Hide Description [Not Specified]
Time Frame Predose up to 48 hours postdose for each of the 4 treatment periods
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug.
Arm/Group Title LY3009104 Reference Formulation LY3009104 Test Formulation 1 (20-mcm) LY3009104 Test Formulation 2 (50-mcm, Fed) LY3009104 Test Formulation 2 (50-mcm, Fasted)
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 15 15 15 15
Median (Full Range)
Unit of Measure: hours (h)
1.00
(0.50 to 3.00)
1.00
(0.50 to 3.00)
2.00
(1.00 to 4.00)
1.00
(0.50 to 2.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY3009104 Reference Formulation, LY3009104 Test Formulation 1 (20-mcm)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.719
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0
Confidence Interval (2-Sided) 90%
-0.250 to 0.500
Estimation Comments The median difference was calculated as TF1 fasted minus RF fasted.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY3009104 Reference Formulation, LY3009104 Test Formulation 2 (50-mcm, Fasted)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.960
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0
Confidence Interval (2-Sided) 90%
-0.250 to 0.750
Estimation Comments The median difference was calculated as TF2 fasted minus RF fasted.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LY3009104 Test Formulation 2 (50-mcm, Fed), LY3009104 Test Formulation 2 (50-mcm, Fasted)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.500
Confidence Interval (2-Sided) 90%
0 to 2.00
Estimation Comments The median difference was calculated as TF2 fed minus TF2 fasted.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title LY3009104 Reference Formulation LY3009104 Test Formulation 2 (50-mcm, Fed) LY3009104 Test Formulation 1 (20-mcm) LY3009104 Test Formulation 2 (50-mcm, Fasted)
Hide Arm/Group Description 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. 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. 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. 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.
All-Cause Mortality
LY3009104 Reference Formulation LY3009104 Test Formulation 2 (50-mcm, Fed) LY3009104 Test Formulation 1 (20-mcm) LY3009104 Test Formulation 2 (50-mcm, Fasted)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
LY3009104 Reference Formulation LY3009104 Test Formulation 2 (50-mcm, Fed) LY3009104 Test Formulation 1 (20-mcm) LY3009104 Test Formulation 2 (50-mcm, Fasted)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/15 (0.00%)      0/15 (0.00%)      0/15 (0.00%)      0/15 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
LY3009104 Reference Formulation LY3009104 Test Formulation 2 (50-mcm, Fed) LY3009104 Test Formulation 1 (20-mcm) LY3009104 Test Formulation 2 (50-mcm, Fasted)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/15 (6.67%)      5/15 (33.33%)      2/15 (13.33%)      2/15 (13.33%)    
Gastrointestinal disorders         
Glossodynia  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Mouth ulceration  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
General disorders         
Catheter site erythema  1  1/15 (6.67%)  1 1/15 (6.67%)  1 1/15 (6.67%)  1 0/15 (0.00%)  0
Catheter site haematoma  1  0/15 (0.00%)  0 1/15 (6.67%)  1 1/15 (6.67%)  1 0/15 (0.00%)  0
Catheter site pain  1  0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Catheter site pruritus  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Vessel puncture site haematoma  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Injury, poisoning and procedural complications         
Procedural site reaction  1  0/15 (0.00%)  0 2/15 (13.33%)  2 0/15 (0.00%)  0 1/15 (6.67%)  1
Respiratory, thoracic and mediastinal disorders         
Cough  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Nasal congestion  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01398475     History of Changes
Other Study ID Numbers: 14016
I4V-MC-JADH ( Other Identifier: Eli Lilly and Company )
First Submitted: July 19, 2011
First Posted: July 20, 2011
Results First Submitted: March 10, 2017
Results First Posted: April 21, 2017
Last Update Posted: April 21, 2017