E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061461 |
E.1.2 | Term | Erectile dysfunction |
|
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 evaluate the efficacy of tadalafil 5 mg compared with placebo, when taken orally once a day over 12 weeks, in improving erectile function in men with ED as measured by the Erectile Function Domain (Sum of Questions 1 through 5 and Question 15) of the International Index of Erectile Function (IIEF) and Sexual Encounter Profile (SEP) diary questions 2 and 3. • To evaluate the effect of tadalafil 5 mg compared with placebo, when taken once a day over 12 weeks in improving the sexual quality of life of the subject and partner as measured by the Sexual Quality of Life (QOL) domain of the Sexual Life Quality Questionnaire (SLQQ).
|
|
E.2.2 | Secondary objectives of the trial |
Subject related objectives: •To evaluate the efficacy of tadalafil 5 mg once a day compared to placebo as measured by the Global Assessment Questionnaire. •To evaluate sexual satisfaction in men treated with tadalafil 5 mg once a day compared to placebo as measured IIEF Intercourse Satisfaction (IS) and Overall Satisfaction (OS) domains and SEP diary question 4 and 5 . •To evaluate treatment satisfaction of tadalafil 5 mg once a day compared to placebo as measured by the SLQQ treatment satisfaction domain. •To evaluate psychosocial outcomes of tadalafil 5 mg once a day compared to placebo. •To assess the safety of tadalafil 5 mg administered once a day compared to placebo in men with ED.
Partner related objectives: •To evaluate the efficacy of tadalafil 5 mg once a day compared to placebo. •To evaluate sexual satisfaction in partners of men with ED treated with tadalafil 5 mg once a day compared to placebo. •To evaluate partner treatment satisfaction with tadalafil 5 mg.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject Inclusion Criteria: [1] Are male and at least 18 years of age at Visit 1. [2] Are able to read, understand and provide signed informed consent. [3] Have a history of erectile dysfunction (ED: defined as the consistent inability to achieve and/or maintain an erection sufficient to permit satisfactory sexual intercourse) of at least 3 months duration. [4] Anticipate having the same adult female sexual partner during the study who is willing to participate in recording responses to efficacy questionnaires, sexual quality of life questionnaires, and other instruments used in this study. [5] Agree to make at least four sexual intercourse attempts with the female sexual study partner during the 4-week run-in phase without medication. [6] Agree not to use any other ED treatment, including herbal therapy, during the 4-week run-in phase before being randomized to therapy for the double-blind treatment phase of the study, and for 96 hours after the final study visit.
Partner Inclusion Criteria: [8] Are female and at least 18 years of age at Visit 1 and who will have the same male study subject as her sexual partner during the study. [9] Able to read, understand and provide signed informed consent. [10] Agree to make at least four sexual intercourse attempts with the male sexual study partner during the 4-week run-in phase without medication. [11] Adequate sexual function not consistent with sexual dysfunction as determined by a FSFI total score > 26.55 [12] Motivated to support the male partner’s treatment for ED as demonstrated by a score of at least 2 on the following commitment items: •Item A; How important is sexual activity to you? •Item B; Overall, how important is it for you to maintain or improve sexual activity with your partner? [13] Willing to participate in recording responses to efficacy questionnaires, sexual quality of life questionnaires, and other instruments used in this study
|
|
E.4 | Principal exclusion criteria |
Subjects will be excluded from the study if they meet any of the following criteria: [14] Previous or current treatment with tadalafil. [15] Present with ED caused by other primary sexual disorders including premature ejaculation or ED caused by untreated or inadequately treated endocrine disease (for example, hypopituitarism, hypogonadism, or uncorrected hypothyroidism,). The subject may be included if, in the opinion of the investigator, the ED persists after adequate treatment of the underlying endocrine disease. [16] Have a sexual partner that is not willing to complete the scales. [17] Have a history of radical prostatectomy, or other pelvic surgery with subsequent failure to achieve any erection. [18] Have a history of penile implant. [19] Have a clinically significant penile deformity in the opinion of the investigator. [20] Exhibit evidence of clinically significant renal insufficiency as determined by the investigator. [21] Exhibit evidence of clinically significant hepatobiliary disease as determined by the investigator. [22] Exhibit Hemoglobin A1c >13% at Visit 1. [23] 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. [24] Have met the criteria for unstable angina (Attachment LVGH.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. [25] 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), or use an automatic internal cardioverter-defibrillator. [26] Have a history of sudden cardiac arrest. [27] Exhibit any evidence of congestive heart failure (NYHA Class 2 or above, Attachment LVGH.4) within 6 months before Visit 1. [28] Have had a new, significant cardiac conduction defect within 90 days before Visit 1. [29] Exhibit systolic blood pressure >170 or <90 mm Hg or diastolic blood pressure >100 or <50 mm Hg at screening (if stress is suspected, retest under basal conditions), or have history of malignant hypertension. [30] Have a history of significant central nervous system injuries (including stroke or spinal cord injury) within the last 6 months. [31] Have a history of Human Immunodeficiency Virus (HIV) infection. [32] Have any 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 subject at increased risk, or might confound the interpretation of the study results. [33] Currently receive treatment with nitrates, cancer chemotherapy, or antiandrogens [except finasteride taken as Propecia or Proscar, or Avodart (dutasteride)]. [34] Have a history of drug, alcohol, or substance abuse within the past 6 months, as assessed by the investigator. [35] Are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [36] Are employed by Lilly or ICOS (that is, employees, temporary contract workers, or designees responsible for the conduct of the study). Immediate family of Lilly employees may participate in Lilly-sponsored clinical trials, but are not permitted to participate at a Lilly facility. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [37] Have previously completed or withdrawn from this study or any other study investigating tadalafil. [38] Have received treatment within the last 30 days with a drug (not including study drug) that has not received regulatory approval for any indication at the time of study entry. [39] Prior treatment with PDE5 inhibitors judged by the investigator to be ineffective. [40] 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy measures are: •The IIEF Erectile Function Domain defined as the sum of Questions 1, 2, 3, 4, 5 and Question 15 of the IIEF. The IIEF is a validated, multidimensional, self-administered questionnaire commonly employed to assess therapeutic efficacy of ED therapy. •The percentage of “yes” responses to Question 2 and 3 of the subject SEP diary. Question 2 asks if the subject was able to insert his penis into his partner’s vagina. Question 3 asks if the subject’s erection lasted long enough to have successful intercourse. The baseline and endpoint score for each SEP question 2 and 3 are the subject’s percentage of “yes” responses to those questions during the run-in period and postbaseline period, respectively.
Sexual Quality of Life Measure: The SLQQ questionnaire is a validated, multidimensional instrument that consists of two domains; Sexual Quality of Life (QOL) [10 questions] and Treatment Satisfaction [6 questions]. The SLQQ-QOL domain compares the subject’s and his partner’s current sexual experience with their experience prior to the onset of the subject’s ED. (Woodward et al. 2002). The SLQQ-QOL domain will be the primary outcome measuring the change from baseline in improvement of the subjects’ and partners’ sexual quality of life. The SLQQ-QOL questions will be answered by the subject and partner at Visit 1, the end of the treatment free run-in phase (Visit 2), and Visit 4 or the final visit.
|
|
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 | No |
E.6.4 | Safety | No |
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 |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
|
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 | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |