A Bioavailability Study of LY2452473 and Tadalafil
Study Details
Study Description
Brief Summary
This study compares LY2452473 taken orally as a 5 milligram (mg) capsule at the same time as a 5 mg tadalafil tablet with three different combination tablets (LY900010) of 5 mg LY2452473 and 5 mg tadalafil taken orally. The study will evaluate the amount of LY2452473 and tadalafil circulating in the blood for each treatment. Side effects will be documented. This study is approximately 34 days not including screening.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: 5 mg LY2452473 + 5 mg Tadalafil 5-mg LY2452473 oral capsule and 5-mg tadalafil oral tablet, administered orally, once only. There will be a washout period of at least 7 days between doses of study drug. |
Drug: LY2452473
Administered orally
Drug: Tadalafil
Administered orally
Other Names:
|
Experimental: LY900010 (particle size #1) Single combination tablet containing 5 mg tadalafil and 5 mg LY2452473 with a smaller particle size (d90 = 10 microns), administered orally, once only. There will be a washout period of at least 7 days between doses of study drug. d90 is a measurement of the distribution of particle widths such that 90% of the particles have a diameter less than the specified value. |
Drug: LY900010
Administered orally
|
Experimental: LY900010 (particle size #2) Single combination tablet containing 5 mg tadalafil and 5 mg LY2452473 with an intermediate particle size (d90 = 25 microns), administered orally, once only. There will be a washout period of at least 7 days between doses of study drug. d90 is a measurement of the distribution of particle widths such that 90% of the particles have a diameter less than the specified value. |
Drug: LY900010
Administered orally
|
Experimental: LY900010 (particle size #3) Single combination tablet containing 5 mg tadalafil and 5 mg LY2452473 with a larger particle size (d90 = 40 microns), administered orally, once only. There will be a washout period of at least 7 days between doses of study drug. d90 is a measurement of the distribution of particle widths such that 90% of the particles have a diameter less than the specified value. |
Drug: LY900010
Administered orally
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2452473 [Predose up to 96 hours postdose for each of the 4 treatment periods]
- Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2452473 [Predose up to 96 hours postdose for each of the 4 treatment periods]
Secondary Outcome Measures
- Pharmacokinetics: AUC(0-∞) of Tadalafil [Predose up to 96 hours postdose for each of the 4 treatment periods]
- Pharmacokinetics: Cmax of Tadalafil [Predose up to 96 hours postdose for each of the 4 treatment periods]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Overtly healthy male, as determined by medical history and physical examination
-
Are between a body mass index of 18.5 and 30 kilograms per meter squared (kg/m²), inclusive at screening
-
Have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator
-
Normal blood pressure and heart rate (HR; sitting) as determined by the investigator
-
Have venous access sufficient to allow blood sampling
-
Are reliable and willing to make themselves available for the duration of the study, and will abide by the research unit policies and procedures and study restrictions
-
Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site
-
Men must agree to use a reliable method of birth control (for example, vasectomy, condom with contraceptive foam, abstinence, or female partner's use of oral contraceptives or Norplant®; a reliable barrier method of birth control [diaphragm with contraceptive jelly]; or intrauterine device), during the study and for 1 month following the last dose of study drug
Exclusion Criteria:
-
Have known allergies to LY2452473, tadalafil, or related compounds
-
History of severe allergies or multiple adverse drug reactions
-
Have a history or presence of cardiovascular, respiratory, hepatic (including history of cholecystectomy), renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
-
Any abnormality in the 12-lead electrocardiogram (ECG) that in the opinion of the investigator places the subject at an unacceptable risk for study participation
-
Show evidence of significant active neuropsychiatric disease
-
History of significant retinal pathology
-
Have a history of glaucoma
-
Have a history of unexplained syncope episodes
-
Show evidence of hepatitis C and/or positive hepatitis C antibody
-
Show evidence of hepatitis B and/or positive hepatitis B surface antigen
-
Show evidence of human immunodeficiency virus (HIV) and/or positive HIV antibodies
-
Intended use of over-the-counter or herbal remedies within 7 days prior to dosing or during the study
-
Intended use of prescription medication within 14 days prior to dosing or during the study
-
Are not willing to refrain from consumption of any food, or drink any beverage containing grapefruit, pomelo, or starfruit for at least 2 weeks prior to the start of the study until its conclusion
-
Heavy caffeine drinkers defined by a regular intake of more than 5 cups of coffee (or equivalent in xanthine-containing beverages) per day or subjects who have not had consistent daily caffeine consumption for 1 month prior to study entry or subjects not willing to maintain consistent caffeine consumption during the study
-
Use of drugs of abuse, as evidenced by history, and/or positive findings on urinary drug screening
-
Have an average weekly alcohol intake that exceeds 14 units per week or are unwilling to stop alcohol consumption for the duration of the study (1 unit = 12 ounces [oz] or 360 milliliters (mL) of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
-
Is currently a smoker or uses tobacco products on a regular basis and has not had consistent daily tobacco use for 1 month prior to study entry or subjects not willing to maintain consistent tobacco use during the study
-
Have a history of blood donation of 1 unit (approximately 450 mL) or more in the last 3 months prior to study entry
-
Have previously completed or withdrawn from this study or any other study investigating LY2452473
-
Within 30 days of the initial dose of study drug, have received treatment with a drug that has not received regulatory approval for any indication
-
Deemed unsuitable by the investigator for any other reason
-
Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device (other than the study drug/device used in this study), or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
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. | Madison | Wisconsin | United States | 53704 |
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.- 13326
- I4K-MC-GPEA
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Sequence 1 | Sequence 2 | Sequence 3 | Sequence 4 |
---|---|---|---|---|
Arm/Group Description | First intervention: A 5-milligram (mg) LY2452473 capsule and 5-mg tadalafil tablet administered orally, once. Second intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) administered orally, once. Third intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) administered orally, once. Fourth intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) administered orally, once. There was a washout period of at least 7 days between each intervention. d90 is a measurement of the distribution of particle widths such that 90% of the particles have a diameter less than the specified value. | First intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) administered orally, once. Second intervention: A 5-mg LY2452473 capsule and 5-mg tadalafil tablet administered orally, once. Third intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) administered orally, once. Fourth intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) administered orally, once. There was a washout period of at least 7 days between each intervention. d90 is a measurement of the distribution of particle widths such that 90% of the particles have a diameter less than the specified value. | First intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) administered orally, once. Second intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) administered orally, once. Third intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 =40 microns, and 5 mg tadalafil) administered orally, once. Fourth intervention: A 5-mg LY2452473 capsule and 5-mg tadalafil tablet administered orally, once. There was a washout period of at least 7 days between each intervention. d90 is a measurement of the distribution of particle widths such that 90% of the particles have a diameter less than the specified value. | First intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) administered orally, once. Second intervention: A single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) administered orally, once. Third intervention: A 5-mg LY2452473 capsule and 5-mg tadalafil tablet administered orally, once. Fourth intervention: A single combination tablet LY900010 (5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) administered orally, once. There was a washout period of at least 7 days between each intervention. d90 is a measurement of the distribution of particle widths such that 90% of the particles have a diameter less than the specified value. |
Period Title: First Intervention | ||||
STARTED | 6 | 6 | 6 | 6 |
COMPLETED | 6 | 6 | 6 | 6 |
NOT COMPLETED | 0 | 0 | 0 | 0 |
Period Title: First Intervention | ||||
STARTED | 6 | 6 | 6 | 6 |
COMPLETED | 6 | 6 | 6 | 6 |
NOT COMPLETED | 0 | 0 | 0 | 0 |
Period Title: First Intervention | ||||
STARTED | 6 | 6 | 6 | 6 |
COMPLETED | 6 | 6 | 6 | 6 |
NOT COMPLETED | 0 | 0 | 0 | 0 |
Period Title: First Intervention | ||||
STARTED | 6 | 6 | 6 | 6 |
COMPLETED | 6 | 6 | 6 | 6 |
NOT COMPLETED | 0 | 0 | 0 | 0 |
Period Title: First Intervention | ||||
STARTED | 6 | 6 | 6 | 6 |
COMPLETED | 6 | 6 | 6 | 6 |
NOT COMPLETED | 0 | 0 | 0 | 0 |
Period Title: First Intervention | ||||
STARTED | 6 | 6 | 6 | 6 |
COMPLETED | 6 | 6 | 6 | 6 |
NOT COMPLETED | 0 | 0 | 0 | 0 |
Period Title: First Intervention | ||||
STARTED | 6 | 6 | 6 | 6 |
COMPLETED | 6 | 6 | 6 | 6 |
NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Entire Study Population |
---|---|
Arm/Group Description | All randomized participants |
Overall Participants | 24 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
39.6
(13.8)
|
Sex: Female, Male (Count of Participants) | |
Female |
0
0%
|
Male |
24
100%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
1
4.2%
|
Not Hispanic or Latino |
23
95.8%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (Count of Participants) | |
United States |
24
100%
|
Race, Customized (Count of Participants) | |
Black or African American |
4
16.7%
|
White |
20
83.3%
|
Outcome Measures
Title | Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2452473 |
---|---|
Description | |
Time Frame | Predose up to 96 hours postdose for each of the 4 treatment periods |
Outcome Measure Data
Analysis Population Description |
---|
Entire study population: All randomized participants. |
Arm/Group Title | 5 mg LY2452473 and 5 mg Tadalafil | LY900010 (Particle Size #1) | LY900010 (Particle Size #2) | LY900010 (Particle Size #3) |
---|---|---|---|---|
Arm/Group Description | Participants who were administered a 5-milligram (mg) LY2452473 capsule and 5-mg tadalafil tablet during any study period. | Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) during any study period. | Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) during any study period. | Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) during any study period. |
Measure Participants | 24 | 24 | 24 | 24 |
Mean (Standard Deviation) [nanograms*hours per milliliter (ng*h/mL)] |
514
(152)
|
495
(159)
|
453
(123)
|
463
(140)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | 5 mg LY2452473 and 5 mg Tadalafil, LY900010 (Particle Size #1) |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | AUC(0-∞) was log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence, and period, and random factor for participant. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric Least Squares (LS) Mean Ratio |
Estimated Value | 0.96 | |
Confidence Interval |
(2-Sided) 90% 0.91 to 1.01 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | 5 mg LY2452473 and 5 mg Tadalafil, LY900010 (Particle Size #2) |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | AUC(0-∞) was log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence, and period, and random factor for participant. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.89 | |
Confidence Interval |
(2-Sided) 90% 0.85 to 0.93 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | LY900010 (Particle Size #1), LY900010 (Particle Size #2) |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | AUC(0-∞) was log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence, and period, and random factor for participant. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.93 | |
Confidence Interval |
(2-Sided) 90% 0.88 to 0.97 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | 5 mg LY2452473 and 5 mg Tadalafil, LY900010 (Particle Size #3) |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | AUC(0-∞) was log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence, and period, and random factor for participant. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.90 | |
Confidence Interval |
(2-Sided) 90% 0.86 to 0.95 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | LY900010 (Particle Size #1), LY900010 (Particle Size #3) |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | AUC(0-∞) was log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence, and period, and random factor for participant. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.94 | |
Confidence Interval |
(2-Sided) 90% 0.90 to 0.99 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | LY900010 (Particle Size #2), LY900010 (Particle Size #3) |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | AUC(0-∞) was log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence, and period, and random factor for participant. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 1.02 | |
Confidence Interval |
(2-Sided) 90% 0.97 to 1.07 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Title | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2452473 |
---|---|
Description | |
Time Frame | Predose up to 96 hours postdose for each of the 4 treatment periods |
Outcome Measure Data
Analysis Population Description |
---|
Entire study population: All randomized participants. |
Arm/Group Title | 5 mg LY2452473 and 5 mg Tadalafil | LY900010 (Particle Size #1) | LY900010 (Particle Size #2) | LY900010 (Particle Size #3) |
---|---|---|---|---|
Arm/Group Description | Participants who were administered a 5-milligram (mg) LY2452473 capsule and 5-mg tadalafil tablet during any study period. | Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) during any study period. | Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size# 2, d90 = 25 microns, and 5 mg tadalafil) during any study period. | Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) during any study period. |
Measure Participants | 24 | 24 | 24 | 24 |
Mean (Standard Deviation) [nanograms per milliliter (ng/mL)] |
32.5
(8.16)
|
27.1
(6.62)
|
25.6
(7.41)
|
24.7
(5.66)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | 5 mg LY2452473 and 5 mg Tadalafil, LY900010 (Particle Size #1) |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | Cmax was log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence, and period, and random factor for participant. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.84 | |
Confidence Interval |
(2-Sided) 90% 0.77 to 0.91 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | 5 mg LY2452473 and 5 mg Tadalafil, LY900010 (Particle Size #2) |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | Cmax was log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence, and period, and random factor for participant. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.78 | |
Confidence Interval |
(2-Sided) 90% 0.71 to 0.85 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | LY900010 (Particle Size #1), LY900010 (Particle Size #2) |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | Cmax was log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence, and period, and random factor for participant. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.93 | |
Confidence Interval |
(2-Sided) 90% 0.85 to 1.01 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | 5 mg LY2452473 and 5 mg Tadalafil, LY900010 (Particle Size #3) |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | Cmax was log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence, and period, and random factor for participant. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.77 | |
Confidence Interval |
(2-Sided) 90% 0.70 to 0.84 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | LY900010 (Particle Size #1), LY900010 (Particle Size #3) |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | Cmax was log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence, and period, and random factor for participant. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.91 | |
Confidence Interval |
(2-Sided) 90% 0.84 to 1.00 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | LY900010 (Particle Size #2), LY900010 (Particle Size #3) |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | Cmax was log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence, and period, and random factor for participant. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.99 | |
Confidence Interval |
(2-Sided) 90% 0.91 to 1.08 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Title | Pharmacokinetics: AUC(0-∞) of Tadalafil |
---|---|
Description | |
Time Frame | Predose up to 96 hours postdose for each of the 4 treatment periods |
Outcome Measure Data
Analysis Population Description |
---|
Entire study population: All randomized participants. |
Arm/Group Title | 5 mg LY2452473 and 5 mg Tadalafil | LY900010 (Particle Size #1) | LY900010 (Particle Size #2) | LY900010 (Particle Size #3) |
---|---|---|---|---|
Arm/Group Description | Participants who were administered a 5-milligram (mg) LY2452473 capsule and 5-mg tadalafil tablet during any study period. | Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) during any study period. | Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) during any study period. | Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) during any study period. |
Measure Participants | 24 | 24 | 24 | 24 |
Mean (Standard Deviation) [nanograms*hours per milliliter (ng*h/mL)] |
2410
(893)
|
2400
(1070)
|
2240
(676)
|
2290
(825)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | 5 mg LY2452473 and 5 mg Tadalafil, LY900010 (Particle Size #1) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.99 | |
Confidence Interval |
(2-Sided) 90% 0.93 to 1.05 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | 5 mg LY2452473 and 5 mg Tadalafil, LY900010 (Particle Size #2) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.94 | |
Confidence Interval |
(2-Sided) 90% 0.89 to 1.00 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | LY900010 (Particle Size #1), LY900010 (Particle Size #2) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.96 | |
Confidence Interval |
(2-Sided) 90% 0.90 to 1.02 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | 5 mg LY2452473 and 5 mg Tadalafil, LY900010 (Particle Size #3) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.96 | |
Confidence Interval |
(2-Sided) 90% 0.90 to 1.02 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | LY900010 (Particle Size #1), LY900010 (Particle Size #3) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.97 | |
Confidence Interval |
(2-Sided) 90% 0.91 to 1.03 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | LY900010 (Particle Size #2), LY900010 (Particle Size #3) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 1.01 | |
Confidence Interval |
(2-Sided) 90% 0.95 to 1.08 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Pharmacokinetics: Cmax of Tadalafil |
---|---|
Description | |
Time Frame | Predose up to 96 hours postdose for each of the 4 treatment periods |
Outcome Measure Data
Analysis Population Description |
---|
Entire study population: All randomized participants. |
Arm/Group Title | 5 mg LY2452473 and 5 mg Tadalafil | LY900010 (Particle Size #1) | LY900010 (Particle Size #2) | LY900010 (Particle Size #3) |
---|---|---|---|---|
Arm/Group Description | Participants who were administered a 5-milligram (mg) LY2452473 capsule and 5-mg tadalafil tablet during any study period. | Participants who were administered a single combination tablet LY900010 (5 mg LY2452473 with a smaller particle size #1, d90 = 10 micron, and 5 mg tadalafil) during any study period. | Participants who were administered a single combination tablet LY900010 (5 mg LY2452473 with an intermediate particle size #2, d90 = 25 micron, and 5 mg tadalafil) during any study period. | Participants who were administered a single combination tablet LY900010 (5 mg LY2452473 with a larger particle size #3, d90 = 40 micron, and 5 mg tadalafil) during any study period. |
Measure Participants | 24 | 24 | 24 | 24 |
Mean (Standard Deviation) [nanograms per milliliter (ng/mL)] |
102
(31.2)
|
74.4
(28.0)
|
72.4
(19.0)
|
70.0
(17.5)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | 5 mg LY2452473 and 5 mg Tadalafil, LY900010 (Particle Size #1) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.72 | |
Confidence Interval |
(2-Sided) 90% 0.68 to 0.77 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | 5 mg LY2452473 and 5 mg Tadalafil, LY900010 (Particle Size #2) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.71 | |
Confidence Interval |
(2-Sided) 90% 0.66 to 0.76 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | LY900010 (Particle Size #1), LY900010 (Particle Size #2) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.98 | |
Confidence Interval |
(2-Sided) 90% 0.92 to 1.05 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | 5 mg LY2452473 and 5 mg Tadalafil, LY900010 (Particle Size #3) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.69 | |
Confidence Interval |
(2-Sided) 90% 0.65 to 0.74 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | LY900010 (Particle Size #1), LY900010 (Particle Size #3) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.96 | |
Confidence Interval |
(2-Sided) 90% 0.90 to 1.02 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | LY900010 (Particle Size #2), LY900010 (Particle Size #3) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 0.98 | |
Confidence Interval |
(2-Sided) 90% 0.91 to 1.04 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Formulation, sequence, and period were included in the model as fixed effects, and participant as a random factor. |
Adverse Events
Time Frame | ||||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||||
Arm/Group Title | 5 mg LY2452473 and 5 mg Tadalafil | LY900010 (Particle Size #1) | LY900010 (Particle Size #2) | LY900010 (Particle Size #3) | ||||
Arm/Group Description | Participants who were administered a 5-mg LY2452473 capsule and 5-mg tadalafil tablet during any study period. | Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a smaller particle size #1, d90 = 10 microns, and 5 mg tadalafil) during any study period. | Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with an intermediate particle size #2, d90 = 25 microns, and 5 mg tadalafil) during any study period. | Participants who were administered a single combination tablet LY900010 (containing 5 mg LY2452473 with a larger particle size #3, d90 = 40 microns, and 5 mg tadalafil) during any study period. | ||||
All Cause Mortality |
||||||||
5 mg LY2452473 and 5 mg Tadalafil | LY900010 (Particle Size #1) | LY900010 (Particle Size #2) | LY900010 (Particle Size #3) | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
5 mg LY2452473 and 5 mg Tadalafil | LY900010 (Particle Size #1) | LY900010 (Particle Size #2) | LY900010 (Particle Size #3) | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
5 mg LY2452473 and 5 mg Tadalafil | LY900010 (Particle Size #1) | LY900010 (Particle Size #2) | LY900010 (Particle Size #3) | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/24 (12.5%) | 7/24 (29.2%) | 5/24 (20.8%) | 3/24 (12.5%) | ||||
Eye disorders | ||||||||
Scleral hyperaemia | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 | 0/24 (0%) | 0 |
Gastrointestinal disorders | ||||||||
Abdominal discomfort | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 |
Abdominal pain | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 0/24 (0%) | 0 |
Diarrhoea | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 |
Nausea | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 |
Vomiting | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 |
General disorders | ||||||||
Fatigue | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 | 0/24 (0%) | 0 |
Feeling hot | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 | 0/24 (0%) | 0 |
Sensation of pressure | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 1/24 (4.2%) | 2 | 0/24 (0%) | 0 |
Vessel puncture site haematoma | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 | 0/24 (0%) | 0 |
Vessel puncture site pain | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 0/24 (0%) | 0 |
Vessel puncture site swelling | 0/24 (0%) | 0 | 1/24 (4.2%) | 2 | 0/24 (0%) | 0 | 0/24 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||
Decreased appetite | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 0/24 (0%) | 0 |
Nervous system disorders | ||||||||
Dizziness | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 |
Dysgeusia | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 |
Headache | 1/24 (4.2%) | 1 | 5/24 (20.8%) | 5 | 2/24 (8.3%) | 2 | 1/24 (4.2%) | 1 |
Somnolence | 1/24 (4.2%) | 1 | 1/24 (4.2%) | 1 | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 |
Reproductive system and breast disorders | ||||||||
Penis disorder | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 | 0/24 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||
Hyperhidrosis | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 | 0/24 (0%) | 0 |
Rash | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 |
Seborrhoeic dermatitis | 0/24 (0%) | 0 | 0/24 (0%) | 0 | 1/24 (4.2%) | 1 | 0/24 (0%) | 0 |
Limitations/Caveats
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 |
- 13326
- I4K-MC-GPEA