Erectile Dysfunction
Conditions
Keywords
testosterone, energy, libido, erectile function, weak muscles
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.
Interventions
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population All randomized participants | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 39.6 years STANDARD_DEVIATION 13.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race, Customized Black or African American | 4 Participants |
| Race, Customized White | 20 Participants |
| Region of Enrollment United States | 24 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 24 | 7 / 24 | 5 / 24 | 3 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2452473
Time frame: Predose up to 96 hours postdose for each of the 4 treatment periods
Population: Entire study population: All randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg LY2452473 and 5 mg Tadalafil | Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2452473 | 514 nanograms*hours per milliliter (ng*h/mL) | Standard Deviation 152 |
| LY900010 (Particle Size #1) | Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2452473 | 495 nanograms*hours per milliliter (ng*h/mL) | Standard Deviation 159 |
| LY900010 (Particle Size #2) | Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2452473 | 453 nanograms*hours per milliliter (ng*h/mL) | Standard Deviation 123 |
| LY900010 (Particle Size #3) | Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2452473 | 463 nanograms*hours per milliliter (ng*h/mL) | Standard Deviation 140 |
90% CI: [0.91, 1.01]
90% CI: [0.85, 0.93]
90% CI: [0.88, 0.97]
90% CI: [0.86, 0.95]
90% CI: [0.9, 0.99]
90% CI: [0.97, 1.07]
Primary
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2452473
Time frame: Predose up to 96 hours postdose for each of the 4 treatment periods
Population: Entire study population: All randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg LY2452473 and 5 mg Tadalafil | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2452473 | 32.5 nanograms per milliliter (ng/mL) | Standard Deviation 8.16 |
| LY900010 (Particle Size #1) | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2452473 | 27.1 nanograms per milliliter (ng/mL) | Standard Deviation 6.62 |
| LY900010 (Particle Size #2) | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2452473 | 25.6 nanograms per milliliter (ng/mL) | Standard Deviation 7.41 |
| LY900010 (Particle Size #3) | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2452473 | 24.7 nanograms per milliliter (ng/mL) | Standard Deviation 5.66 |
90% CI: [0.77, 0.91]
90% CI: [0.71, 0.85]
90% CI: [0.85, 1.01]
90% CI: [0.7, 0.84]
90% CI: [0.84, 1]
90% CI: [0.91, 1.08]
Secondary
Pharmacokinetics: AUC(0-∞) of Tadalafil
Time frame: Predose up to 96 hours postdose for each of the 4 treatment periods
Population: Entire study population: All randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg LY2452473 and 5 mg Tadalafil | Pharmacokinetics: AUC(0-∞) of Tadalafil | 2410 nanograms*hours per milliliter (ng*h/mL) | Standard Deviation 893 |
| LY900010 (Particle Size #1) | Pharmacokinetics: AUC(0-∞) of Tadalafil | 2400 nanograms*hours per milliliter (ng*h/mL) | Standard Deviation 1070 |
| LY900010 (Particle Size #2) | Pharmacokinetics: AUC(0-∞) of Tadalafil | 2240 nanograms*hours per milliliter (ng*h/mL) | Standard Deviation 676 |
| LY900010 (Particle Size #3) | Pharmacokinetics: AUC(0-∞) of Tadalafil | 2290 nanograms*hours per milliliter (ng*h/mL) | Standard Deviation 825 |
90% CI: [0.93, 1.05]
90% CI: [0.89, 1]
90% CI: [0.9, 1.02]
90% CI: [0.9, 1.02]
90% CI: [0.91, 1.03]
90% CI: [0.95, 1.08]
Secondary
Pharmacokinetics: Cmax of Tadalafil
Time frame: Predose up to 96 hours postdose for each of the 4 treatment periods
Population: Entire study population: All randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg LY2452473 and 5 mg Tadalafil | Pharmacokinetics: Cmax of Tadalafil | 102 nanograms per milliliter (ng/mL) | Standard Deviation 31.2 |
| LY900010 (Particle Size #1) | Pharmacokinetics: Cmax of Tadalafil | 74.4 nanograms per milliliter (ng/mL) | Standard Deviation 28 |
| LY900010 (Particle Size #2) | Pharmacokinetics: Cmax of Tadalafil | 72.4 nanograms per milliliter (ng/mL) | Standard Deviation 19 |
| LY900010 (Particle Size #3) | Pharmacokinetics: Cmax of Tadalafil | 70.0 nanograms per milliliter (ng/mL) | Standard Deviation 17.5 |
90% CI: [0.68, 0.77]
90% CI: [0.66, 0.76]
90% CI: [0.92, 1.05]
90% CI: [0.65, 0.74]
90% CI: [0.9, 1.02]
90% CI: [0.91, 1.04]