| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10052003 |
| E.1.2 | Term | Erectile dysfunction NOS |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To test the hypothesis that tadalafil given orally at 5 mg or 2.5 mg once a day for 8 weeks achieves superior psychosocial outcomes to sildenafil citrate given orally at 100 mg or 50 mg as needed (PRN) for 8 weeks in the treatment of men with erectile dysfunction, as measured by the change from baseline in the Sexual Self-Confidence domain of Psychological and Interpersonal Relationship Scales (PAIRS). |
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| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to compare tadalafil 5 mg or 2.5 mg once a day with sildenafil citrate 100 mg or 50 mg PRN, and tadalafil 5 mg or 2.5 mg once a day with tadalafil 20 mg or 10 mg PRN, at 8 weeks with respect to:
- Psychosocial outcomes, as measured by Sexual Self-Confidence, Spontaneity, and Time Concerns domains of PAIRS; the Self-Esteem And Relationship (SEAR) questionnaire; and Questions 1 to 4 of the Patient Perception and Feelings Questions (PPF-Q).
- Efficacy, as measured by the Erectile Function domain (sum of Items 1 through 5 and Item 15) of the International Index of Erectile Function (IIEF) and the frequency of morning erection.
- Sexual satisfaction, as measured by the Intercourse Satisfaction and Overall Satisfaction domains of the IIEF.
- Treatment satisfaction, as measured by the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS).
- Safety and tolerability. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] Are male and at least 18 years of age at Visit 1.
[2] Are able to read, understand and provide informed consent.
[3] Have history of erectile dysfunction (ED) based on the disease diagnostic criteria (Protocol Section 4.1.1).
[4] Have had satisfactory response (in the opinion of the investigator) to an oral PDE5 inhibitor PRN (tadalafil, sildenafil citrate, or vardenafil HCl) for treatment of ED, for a period of at least 6 months, at an average minimum frequency of 1 dose per week.
[5] Anticipate frequent use (at least one dose per week, on average) of PDE5 inhibitors when administered PRN during the study.
[6] Have never used tadalafil 5 mg or 2.5 mg once a day therapy.
[7] Anticipate having the same adult female sexual partner during the study. (If a qualifying participant has more than one female partner during the study the participant will not be excluded from the trial, however the participant will be required to respond to questionnaires based on his sexual interactions with only one of these partners.)
[8] Agree to make at least four sexual intercourse attempts with the female sexual study partner during the 4-week run-in period without medication. (Subjects who do not make at least four sexual attempts during the run-in period will not be enrolled in the study; these subjects will be considered screen failures.)
[9] Agree not to use any other ED treatment, including herbal therapy, during the run-in period, the open-label treatment phase of the study, and for 96 hours after the final study visit is completed.
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| E.4 | Principal exclusion criteria |
[10] Present with impotence caused by other primary sexual disorders including premature ejaculation or impotence caused by untreated endocrine disease (for example, hypopituitarism, hypothyroidism, or hypogonadism).
[11] Have a history of radical prostatectomy, or other pelvic surgery with subsequent failure to achieve erection.
[12] Have a history of penile implant.
[13] Have a clinically significant penile deformity (such as Peyronie’s disease) in the opinion of the investigator.
[14] Exhibit evidence of clinically significant renal insufficiency as determined by the investigator.
[15] Exhibit evidence of active symptomatic hepatobiliary disease, as determined by the investigator.
[16] Exhibit Hemoglobin A1c >11% at Visit 1, in subjects with a history of diabetes mellitus of any type.
[17] Present with chronic stable angina treated with long-acting nitrates, or with chronic stable angina requiring short-acting nitrates in the last 90 days, or with angina occurring during sexual intercourse in the last 6 months.
[18] Have met the criteria for unstable angina (Protocol Attachment S024.3) within 6 months before Visit 1, or have a history of myocardial infarction or coronary artery bypass graft surgery within 90 days before Visit 1, or percutaneous coronary intervention (for example, angioplasty or stent placement) within 90 days before Visit 1.
[19] Have any supraventricular arrhythmia with an uncontrolled ventricular response (mean heart rate >100 bpm) at rest, or have any history of spontaneous or induced sustained ventricular tachycardia (heart rate >100 bpm for ≥30 sec) despite medical or device therapy, or use an internal cardioverter-defibrillator.
[20] Have a history of sudden cardiac arrest despite medical or device therapy.
[21] Exhibit any evidence of congestive heart failure (NYHA Class 2 or above, Protocol Attachment S024.4) within 6 months before Visit 1.
[22] Have had a new or significant conduction defect within 90 days before Visit 1.
[23] Exhibit systolic blood pressure >170 or <90 mmHg or diastolic blood pressure >100 or <50 mmHg at screening (if stress is suspected, retest under basal conditions), or have a history of malignant hypertension.
[24] Have a history of significant central nervous system injuries (including stroke and spinal cord injury) within the last 6 months.
[25] Have a 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.
[26] Have retinitis pigmentosa.
[27] Have a history of human immunodeficiency virus (HIV) infection.
[28] Have a condition that in the opinion of the investigator would interfere with the subject’s ability to provide informed consent or comply with study instructions, would place the subject at increased risk, or might confound the interpretation of study results.
[29] Currently receive treatment with nitrates, nonselective alpha [1]-adrenergic blockers (such as doxazosin), cancer chemotherapy, or antiandrogens (except finasteride taken as Propecia™ or Proscar® or Avodart® [dutasteride]).
[30] Have a history of drug, alcohol, or substance abuse within the past 6 months, as assessed by the investigator.
[31] Have rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption Lactose intolerance.
[32] Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
[33] Are Lilly employees.
[34] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
[35] Have previously completed or withdrawn from this study or any other study investigating tadalafil once a day therapy.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Improvement in psychosocial outcomes, assessed by the change from baseline to endpoint in the Psychological and Interpersonal Relationship Scales (PAIRS) Sexual Self-Confidence domain.
PAIRS is a self-administered 29-item scale containing four domains (Sexual Self-Confidence, Spontaneity, Time Concerns, and Sexual Miscommunication) related to the broader psychological and interpersonal outcomes associated with erectile dysfunction and its treatment. The Sexual Self-Confidence domain of PAIRS was selected as the primary measure in this study because it best represents the overall psychosocial impact of a different dosing approach. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 22 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 15 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 15 |
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