Vardenafil demonstrates first-dose success and reliability of penetration and maintenance of erection in men with erectile dysfunction. Methods
The primary objective of this study was to assess first-dose success and reliability of vardenafil 20 mg in men with ED through 12 weeks of treatment in a placebo-controlled clinical trial. The secondary objective was to evaluate the safety and tolerability of vardenafil 20 mg compared with placebo.
RELY-II was a 12-week, multicentre, randomized, double-blind, parallel-group, placebo-controlled trial in vardenafil-naive patients. At screening, patients were entered into a 4-week, treatment-free, run-in phase and instructed to make at least 4 attempts at sexual intercourse on 4 separate days. A diary was provided for patients to record all attempts made at sexual intercourse. The patients who failed at 50% or more of their attempts at intercourse were entered into a 1-week challenge phase. Patients were then instructed to make at least 1 attempt at sexual intercourse 1 hour after administration of a single 20-mg dose of vardenafil. Medication was to be taken without regard to meals. Patients with a positive response to question 2 of the Sexual Encounter Profile (SEP2) (“Were you able to insert your penis into your partner’s vagina?”) in regard to attempts made 0.5 to 6 hours after ingestion of the study medication were randomized to receive either vardenafil 20 mg or placebo for 12 weeks. Patients were instructed to take each dose of medication without regard to meals, on an as-needed basis 1 hour before attempting sexual intercourse, with only 1 dose permitted per day. Patients recorded the date and time at which they took the study medication, the time at which they attempted sexual intercourse and their responses to questions regarding success at penetration (SEP2) and maintenance of erection sufficient enough for completion of intercourse (SEP3: “Did your erection last long enough for you to have successful intercourse?”). During the 12-week treatment period, patients were scheduled for study visits at weeks 4, 8 and 12 for assessment of efficacy, safety, tolerability and compliance.
Patient population and demographics
This study included male patients with a diagnosis of ED lasting more than 6 months, defined according to the National Institutes of Health Consensus Statement (the inability to attain or maintain penile erection sufficient for satisfactory sexual performance).2 Patients had to be aged 18 years or older and in a heterosexual relationship and to have completed written informed consent before study entry. For randomization into the treatment phase of the trial, patients had to have been unsuccessful in at least 2 of the 4 attempts at intercourse during the 4-week treatment-free period. They also had to be successful during the challenge phase assessed by the SEP2 question and to have an International Index of Erectile Function–Erectile Function (IIEF-EF) domain score of 5 or more and less than 26 at the start of the challenge phase.
During the challenge phase, SEP2 and SEP3 first-dose success rates were stratified according to comorbidities, and in the treatment phase, patients were assessed on SEP2 and SEP3 success rates. The primary efficacy end point was reliability of insertion as assessed by a positive SEP2 response after each dose of study medication. Secondary efficacy end points included reliability of maintained erection up to completion of intercourse (assessed by SEP3) and IIEF-EF domain score.
The safety population included all patients who were administered 1 or more dose(s) of vardenafil therapy or placebo and who had any treatment-period data collected. Safety and tolerability were evaluated throughout the study by assessing adverse events (AEs) from the start of the challenge phase to the end of week 12. Clinical chemistry, hematology, urinalysis, complete physical examination, 12-lead electrocardiogram and vital signs were also used as part of the safety assessments.
The primary population for the efficacy analysis was the intent-to-treat (ITT) population, which consisted of randomized patients who took at least 1 dose of either vardenafil or placebo and had postrandomization efficacy data collected. Similarly, the primary population for the safety assessment included all randomized patients who took at least 1 dose of study medication and had any safety data collected during the treatment period. The study was designed to detect a clinically meaningful treatment difference in SEP2 reliability of 15.0 (standard deviation 35.0) in the mean proportion of successes at 12 weeks, with 96% power and an α level of 0.05. We used analysis of covariance (ANCOVA) with adjusting for baseline values to compare the mean proportions of success for each treatment group. Secondary efficacy variables were analyzed with ANCOVA or logistic regression.