Benign Prostatic Hyperplasia
Conditions
Brief summary
The purpose of this study is to investigate the pharmacokinetics of tadalafil in Japanese and non-Japanese men with Benign Prostatic Hyperplasia (BPH). The safety of tadalafil will also be studied.
Interventions
DRUGTadalafil
5 mg, administered orally, daily for 10 days
Sponsors
Eli Lilly and Company
Study design
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have had lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS) (as diagnosed by a qualified physician) \>6 months at screening visit. Lower urinary tract symptoms (LUTS) include those associated with voiding (obstructive symptoms, such as incomplete emptying, intermittency, weak stream, straining) and/or storage (irritative symptoms, such as frequency, urgency, nocturia). * Have BPH-LUTS with moderate-to-severe symptoms confirmed by an International Prostate Symptom Score (IPSS) \>12. (The IPSS total score is defined as the sum of Questions 1 through 7 and does not include the IPSS Quality of Life.) * Taking into account the age and disease status, subjects determined to be in good health according to medical history, physical examination, electrocardiogram (ECG), and laboratory safety assessments. * Body mass index between 18 and 30 kg/m\^2 inclusive. * Agree not to use any other approved or experimental pharmacologic BPH, erectile dysfunction (ED), and/or overactive bladder (OAB) treatments, including alpha blockers, phosphodiesterase type 5 (PDE5) inhibitors, or herbal preparations at least 1 week prior to dosing and through to follow-up. * Subjects with a serum prostate-specific antigen (PSA) \<10.0 ng/mL. Subjects with a serum PSA greater than or equal to 4.0 and \<10.0 ng/mL must have documentation of a negative histologic biopsy of carcinoma of the prostate within 12 months prior to screening.
Exclusion criteria
* History of radical prostatectomy, or other pelvic surgery or procedure, including any pelvic surgical procedure on the urinary tract apart from transurethral resection, pelvic surgery for malignancy or bowel resection, or a history of lower urinary tract malignancy or trauma. History of urinary retention or lower urinary tract (bladder) stones within 6 months of screening. * Current or previous history of malignant disease of the prostate. * Concomitant treatment with or ingestion of cytochrome P 450 3A4 (CYP3A4)-inducing or -inhibiting agents from 2 weeks prior to dosing and through the end of the study. Including herbal/food and other supplements, fruit, or fruit juices containing grapefruit or pomegranate components. * History of loss of vision in one eye because of nonarteritic anterior ischemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure. * Subjects with chronic stable angina treated with long-acting nitrates, subjects with chronic stable angina who required short-acting nitrates in the 90 days prior to screening visit, or subjects with angina occurring during sexual intercourse in the 6 months prior to screening. * Subjects having met the criteria for unstable angina within 6 months prior to screening, history of myocardial infarction or coronary artery bypass graft surgery within 90 days prior to screening, or percutaneous coronary intervention (for example, angioplasty or stent placement) within 90 days prior to screening. * Any evidence of heart disease (New York Heart Association \[NYHA\] greater than or equal to Class III) within 6 months of screening. * A history of cardiac arrest.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710 | 1 day and 10 days | AUC for Day 1 is reported as AUC(tau \[t\], day 1), which is AUC from time zero to 24 hours (t) postdose on Day 1. AUC for Day 10 is reported as AUC(t,steady state \[ss\]), which is AUC during one 24-hour dosing interval at steady-state. |
| Pharmacokinetics: Concentration Maximum (Cmax) of Tadalafil and Metabolite IC710 | 1 day and 10 days | — |
| Pharmacokinetics: Time to Concentration Maximum (Tmax) of Tadalafil and Metabolite IC710 | 1 day and 10 days | — |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Japanese Participants Japanese participants who received 5 mg of tadalafil once daily for 10 days | 12 |
| Caucasian Participants Caucasian participants who received 5 mg of tadalafil once daily for 10 days | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Japanese Participants | Total | Caucasian Participants |
|---|---|---|---|
| Age Continuous | 57.0 years STANDARD_DEVIATION 9.9 | 58.8 years STANDARD_DEVIATION 8.7 | 60.6 years STANDARD_DEVIATION 7.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 24 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 12 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 12 Participants | 12 Participants |
| Region of Enrollment Germany | 0 participants | 12 participants | 12 participants |
| Region of Enrollment Japan | 12 participants | 12 participants | 0 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 24 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 12 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710
AUC for Day 1 is reported as AUC(tau \[t\], day 1), which is AUC from time zero to 24 hours (t) postdose on Day 1. AUC for Day 10 is reported as AUC(t,steady state \[ss\]), which is AUC during one 24-hour dosing interval at steady-state.
Time frame: 1 day and 10 days
Population: All enrolled participants
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Japanese Participants | Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710 | Day 1 Tadalafil | 1410 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
| Japanese Participants | Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710 | Day 10 Tadalafil | 2710 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
| Japanese Participants | Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710 | Day 1 Metabolite IC710 | 525 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
| Japanese Participants | Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710 | Day 10 Metabolite IC710 | 2270 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 30 |
| Caucasian Participants | Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710 | Day 10 Metabolite IC710 | 2290 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 48 |
| Caucasian Participants | Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710 | Day 1 Tadalafil | 1340 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 17 |
| Caucasian Participants | Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710 | Day 1 Metabolite IC710 | 399 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 23 |
| Caucasian Participants | Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710 | Day 10 Tadalafil | 3410 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 51 |
90% CI: [0.84, 1.32]
90% CI: [0.64, 1]
90% CI: [1.05, 1.64]
90% CI: [0.79, 1.24]
Primary
Pharmacokinetics: Concentration Maximum (Cmax) of Tadalafil and Metabolite IC710
Time frame: 1 day and 10 days
Population: All enrolled participants
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Japanese Participants | Pharmacokinetics: Concentration Maximum (Cmax) of Tadalafil and Metabolite IC710 | Day 1 Tadalafil | 102 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
| Japanese Participants | Pharmacokinetics: Concentration Maximum (Cmax) of Tadalafil and Metabolite IC710 | Day 10 Tadalafil | 173 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| Japanese Participants | Pharmacokinetics: Concentration Maximum (Cmax) of Tadalafil and Metabolite IC710 | Day 1 Metabolite IC710 | 32.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| Japanese Participants | Pharmacokinetics: Concentration Maximum (Cmax) of Tadalafil and Metabolite IC710 | Day 10 Metabolite IC710 | 105 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31 |
| Caucasian Participants | Pharmacokinetics: Concentration Maximum (Cmax) of Tadalafil and Metabolite IC710 | Day 10 Metabolite IC710 | 102 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| Caucasian Participants | Pharmacokinetics: Concentration Maximum (Cmax) of Tadalafil and Metabolite IC710 | Day 1 Tadalafil | 104 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19 |
| Caucasian Participants | Pharmacokinetics: Concentration Maximum (Cmax) of Tadalafil and Metabolite IC710 | Day 1 Metabolite IC710 | 24.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| Caucasian Participants | Pharmacokinetics: Concentration Maximum (Cmax) of Tadalafil and Metabolite IC710 | Day 10 Tadalafil | 215 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 36 |
90% CI: [0.81, 1.18]
90% CI: [0.67, 0.97]
90% CI: [1.07, 1.67]
90% CI: [0.83, 1.29]
Primary
Pharmacokinetics: Time to Concentration Maximum (Tmax) of Tadalafil and Metabolite IC710
Time frame: 1 day and 10 days
Population: All enrolled participants
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Japanese Participants | Pharmacokinetics: Time to Concentration Maximum (Tmax) of Tadalafil and Metabolite IC710 | Day 1 Tadalafil | 4.00 hours |
| Japanese Participants | Pharmacokinetics: Time to Concentration Maximum (Tmax) of Tadalafil and Metabolite IC710 | Day 10 Tadalafil | 3.00 hours |
| Japanese Participants | Pharmacokinetics: Time to Concentration Maximum (Tmax) of Tadalafil and Metabolite IC710 | Day 1 Metabolite IC710 | 23.83 hours |
| Japanese Participants | Pharmacokinetics: Time to Concentration Maximum (Tmax) of Tadalafil and Metabolite IC710 | Day 10 Metabolite IC710 | 4.00 hours |
| Caucasian Participants | Pharmacokinetics: Time to Concentration Maximum (Tmax) of Tadalafil and Metabolite IC710 | Day 10 Metabolite IC710 | 8.00 hours |
| Caucasian Participants | Pharmacokinetics: Time to Concentration Maximum (Tmax) of Tadalafil and Metabolite IC710 | Day 1 Tadalafil | 2.00 hours |
| Caucasian Participants | Pharmacokinetics: Time to Concentration Maximum (Tmax) of Tadalafil and Metabolite IC710 | Day 1 Metabolite IC710 | 24.00 hours |
| Caucasian Participants | Pharmacokinetics: Time to Concentration Maximum (Tmax) of Tadalafil and Metabolite IC710 | Day 10 Tadalafil | 2.53 hours |
Wilcoxon (Mann-Whitney)
Wilcoxon (Mann-Whitney)
Wilcoxon (Mann-Whitney)
Wilcoxon (Mann-Whitney)