A Bioavailability Study of LY2452473 and Tadalafil

LY2452473 Formulation Exploratory Bioavailability Study

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.

Study Overview

• Status: Completed
• Conditions: Erectile Dysfunction
• Intervention / Treatment: Drug: Tadalafil; Drug: LY2452473; Drug: LY900010

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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: Tadalafil; Administered orally; Other Names: LY450190; Cialis; Drug: LY2452473; Administered orally
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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: July 21, 2011
• First Submitted That Met QC Criteria: July 22, 2011
• First Posted (Estimate): July 25, 2011

Study Record Updates

• Last Update Posted (Actual): June 14, 2019
• Last Update Submitted That Met QC Criteria: March 11, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: testosterone; energy; libido; erectile function; weak muscles
• Additional Relevant MeSH Terms: Mental Disorders; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Erectile Dysfunction; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Tadalafil
• Other Study ID Numbers: 13326; I4K-MC-GPEA (Other Identifier: Eli Lilly and Company)