A Bioavailability Study of LY2452473 and Tadalafil

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01401543
Collaborator
(none)
24
Enrollment
1
Location
4
Arms
2
Duration (Months)
11.8
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
LY2452473 Formulation Exploratory Bioavailability Study
Study Start Date :
Jul 1, 2011
Actual Primary Completion Date :
Sep 1, 2011
Actual Study Completion Date :
Sep 1, 2011

Arms and Interventions

ArmIntervention/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:
  • LY450190
  • Cialis
  • 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

    1. 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]

    2. Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2452473 [Predose up to 96 hours postdose for each of the 4 treatment periods]

    Secondary Outcome Measures

    1. Pharmacokinetics: AUC(0-∞) of Tadalafil [Predose up to 96 hours postdose for each of the 4 treatment periods]

    2. Pharmacokinetics: Cmax of Tadalafil [Predose up to 96 hours postdose for each of the 4 treatment periods]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    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

    SiteCityStateCountryPostal Code
    1For 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.MadisonWisconsinUnited States53704

    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.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01401543
    Other Study ID Numbers:
    • 13326
    • I4K-MC-GPEA
    First Posted:
    Jul 25, 2011
    Last Update Posted:
    Jun 14, 2019
    Last Verified:
    Mar 1, 2019
    Keywords provided by Eli Lilly and Company
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleSequence 1Sequence 2Sequence 3Sequence 4
    Arm/Group DescriptionFirst 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
    STARTED6666
    COMPLETED6666
    NOT COMPLETED0000
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    NOT COMPLETED0000
    Period Title: First Intervention
    STARTED6666
    COMPLETED6666
    NOT COMPLETED0000
    Period Title: First Intervention
    STARTED6666
    COMPLETED6666
    NOT COMPLETED0000
    Period Title: First Intervention
    STARTED6666
    COMPLETED6666
    NOT COMPLETED0000
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    STARTED6666
    COMPLETED6666
    NOT COMPLETED0000
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    STARTED6666
    COMPLETED6666
    NOT COMPLETED0000

    Baseline Characteristics

    Arm/Group TitleEntire Study Population
    Arm/Group DescriptionAll randomized participants
    Overall Participants24
    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

    1. Primary Outcome
    TitlePharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2452473
    Description
    Time FramePredose 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 Title5 mg LY2452473 and 5 mg TadalafilLY900010 (Particle Size #1)LY900010 (Particle Size #2)LY900010 (Particle Size #3)
    Arm/Group DescriptionParticipants 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 Participants24242424
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric Least Squares (LS) Mean Ratio
    Estimated Value0.96
    Confidence Interval (2-Sided) 90%
    0.91 to 1.01
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.89
    Confidence Interval (2-Sided) 90%
    0.85 to 0.93
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.93
    Confidence Interval (2-Sided) 90%
    0.88 to 0.97
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.90
    Confidence Interval (2-Sided) 90%
    0.86 to 0.95
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.94
    Confidence Interval (2-Sided) 90%
    0.90 to 0.99
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value1.02
    Confidence Interval (2-Sided) 90%
    0.97 to 1.07
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, sequence, and period were included in the model as fixed effects, and participant as a random factor.
    2. Primary Outcome
    TitlePharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2452473
    Description
    Time FramePredose 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 Title5 mg LY2452473 and 5 mg TadalafilLY900010 (Particle Size #1)LY900010 (Particle Size #2)LY900010 (Particle Size #3)
    Arm/Group DescriptionParticipants 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 Participants24242424
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.84
    Confidence Interval (2-Sided) 90%
    0.77 to 0.91
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.78
    Confidence Interval (2-Sided) 90%
    0.71 to 0.85
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.93
    Confidence Interval (2-Sided) 90%
    0.85 to 1.01
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.77
    Confidence Interval (2-Sided) 90%
    0.70 to 0.84
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.91
    Confidence Interval (2-Sided) 90%
    0.84 to 1.00
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.99
    Confidence Interval (2-Sided) 90%
    0.91 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, sequence, and period were included in the model as fixed effects, and participant as a random factor.
    3. Secondary Outcome
    TitlePharmacokinetics: AUC(0-∞) of Tadalafil
    Description
    Time FramePredose 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 Title5 mg LY2452473 and 5 mg TadalafilLY900010 (Particle Size #1)LY900010 (Particle Size #2)LY900010 (Particle Size #3)
    Arm/Group DescriptionParticipants 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 Participants24242424
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.99
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.94
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.96
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.96
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.97
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value1.01
    Confidence Interval (2-Sided) 90%
    0.95 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    TitlePharmacokinetics: Cmax of Tadalafil
    Description
    Time FramePredose 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 Title5 mg LY2452473 and 5 mg TadalafilLY900010 (Particle Size #1)LY900010 (Particle Size #2)LY900010 (Particle Size #3)
    Arm/Group DescriptionParticipants 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 Participants24242424
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.72
    Confidence Interval (2-Sided) 90%
    0.68 to 0.77
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.71
    Confidence Interval (2-Sided) 90%
    0.66 to 0.76
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.98
    Confidence Interval (2-Sided) 90%
    0.92 to 1.05
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.69
    Confidence Interval (2-Sided) 90%
    0.65 to 0.74
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.96
    Confidence Interval (2-Sided) 90%
    0.90 to 1.02
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterGeometric LS Mean Ratio
    Estimated Value0.98
    Confidence Interval (2-Sided) 90%
    0.91 to 1.04
    Parameter Dispersion Type:
    Value:
    Estimation CommentsFormulation, 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 Title5 mg LY2452473 and 5 mg TadalafilLY900010 (Particle Size #1)LY900010 (Particle Size #2)LY900010 (Particle Size #3)
    Arm/Group DescriptionParticipants 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 TadalafilLY900010 (Particle Size #1)LY900010 (Particle Size #2)LY900010 (Particle Size #3)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    5 mg LY2452473 and 5 mg TadalafilLY900010 (Particle Size #1)LY900010 (Particle Size #2)LY900010 (Particle Size #3)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/24 (0%) 0/24 (0%) 0/24 (0%) 0/24 (0%)
    Other (Not Including Serious) Adverse Events
    5 mg LY2452473 and 5 mg TadalafilLY900010 (Particle Size #1)LY900010 (Particle Size #2)LY900010 (Particle Size #3)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/24 (12.5%) 7/24 (29.2%) 5/24 (20.8%) 3/24 (12.5%)
    Eye disorders
    Scleral hyperaemia0/24 (0%) 01/24 (4.2%) 10/24 (0%) 00/24 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort0/24 (0%) 00/24 (0%) 00/24 (0%) 01/24 (4.2%) 1
    Abdominal pain1/24 (4.2%) 10/24 (0%) 00/24 (0%) 00/24 (0%) 0
    Diarrhoea0/24 (0%) 00/24 (0%) 00/24 (0%) 01/24 (4.2%) 1
    Nausea0/24 (0%) 01/24 (4.2%) 11/24 (4.2%) 10/24 (0%) 0
    Vomiting0/24 (0%) 00/24 (0%) 01/24 (4.2%) 10/24 (0%) 0
    General disorders
    Fatigue0/24 (0%) 01/24 (4.2%) 10/24 (0%) 00/24 (0%) 0
    Feeling hot0/24 (0%) 01/24 (4.2%) 10/24 (0%) 00/24 (0%) 0
    Sensation of pressure0/24 (0%) 00/24 (0%) 01/24 (4.2%) 20/24 (0%) 0
    Vessel puncture site haematoma0/24 (0%) 01/24 (4.2%) 10/24 (0%) 00/24 (0%) 0
    Vessel puncture site pain1/24 (4.2%) 10/24 (0%) 00/24 (0%) 00/24 (0%) 0
    Vessel puncture site swelling0/24 (0%) 01/24 (4.2%) 20/24 (0%) 00/24 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite1/24 (4.2%) 10/24 (0%) 00/24 (0%) 00/24 (0%) 0
    Nervous system disorders
    Dizziness0/24 (0%) 01/24 (4.2%) 11/24 (4.2%) 10/24 (0%) 0
    Dysgeusia0/24 (0%) 00/24 (0%) 00/24 (0%) 01/24 (4.2%) 1
    Headache1/24 (4.2%) 15/24 (20.8%) 52/24 (8.3%) 21/24 (4.2%) 1
    Somnolence1/24 (4.2%) 11/24 (4.2%) 11/24 (4.2%) 10/24 (0%) 0
    Reproductive system and breast disorders
    Penis disorder0/24 (0%) 01/24 (4.2%) 10/24 (0%) 00/24 (0%) 0
    Skin and subcutaneous tissue disorders
    Hyperhidrosis0/24 (0%) 01/24 (4.2%) 10/24 (0%) 00/24 (0%) 0
    Rash0/24 (0%) 00/24 (0%) 01/24 (4.2%) 10/24 (0%) 0
    Seborrhoeic dermatitis0/24 (0%) 00/24 (0%) 01/24 (4.2%) 10/24 (0%) 0

    Limitations/Caveats

    [Not Specified]

    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/TitleChief Medical Officer
    OrganizationEli Lilly and Company
    Phone800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01401543
    Other Study ID Numbers:
    • 13326
    • I4K-MC-GPEA
    First Posted:
    Jul 25, 2011
    Last Update Posted:
    Jun 14, 2019
    Last Verified:
    Mar 1, 2019