Low price sildenafil

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A randomisation list was generated using random permuted blocks through a computer algorithm and a pseudorandom number generator.

The list indicated, for each bottle number, the drug assigned to the corresponding study medication bottle. The patient was assigned a screening number at visit one (screening) and, if eligible for participation, was then assigned a randomisation number at visit two (baseline). The investigator was provided a sealed copy of the randomisation codes and was instructed to break the treatment code only in the event of an emergency. Active treatment and corresponding placebo tablets were identical in packaging and appearance. During the DB phase, the primary efficacy variables were responses to questions “When you attempted sexual intercourse, how often were you able to penetrate your partner?” (Q3) and “When you attempted sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner?” (Q4) of the 15 item International Index of Erectile Function (IIEF).

The IIEF is a validated questionnaire that has been used for the clinical assessment of ED.

18 Each question of the IIEF is scored on a categorical scale of 1 (“almost never/never”) to 5 (“almost always/always”), with a score of 0 indicating “did not attempt sexual intercourse”. Secondary efficacy variables were responses to three global efficacy questions (GEQs):

GEQ1

sexual

final

19 The Erection Distress Scale is a disease specific instrument with five questions on the patient’s concerns with his erection problems. These were: “Were you frustrated about your erection problems?”, “Did you feel weighed down by your erection problems?”, “Were you discouraged by your erection problems?”, “Did you feel despair over your erection problems?”, and “Were your erection problems a worry in your life?”.

Responses to each question of the Life Satisfaction Checklist and the Erection

Distress

Based upon a difference of 1.33 in mean scores and assuming a common standard deviation for sildenafil and placebo of 2.0, a sample size of 50 patients per treatment arm was sufficient to achieve a power of 90% to detect the specified difference between the two treatment groups using an approximation (two sided, ? = 0.05) to the test comparing two means for normally distributed responses. Assuming an overall drop out rate of 25%, a 1:1 randomisation ratio of sildenafil to placebo, sufficient power to be able to conduct the primary analysis of efficacy, analysis of covariance, including terms for treatment group, centre, baseline value for efficacy variables, and other covariates as required, 250 patients, 125 in each arm, were to be randomised to study drug; in total, 218 patients were randomised.

Intent-to-treat analyses were performed on all efficacy and QoL variables, and included all patients with at least one assessment after randomisation who had taken at least one dose of study drug. To be eligible for inclusion in safety analyses, patients must have taken at least one dose of study drug. Statistical analysis of responses to IIEF Q3 and Q4 and GEQ3 was performed for each question using analysis of covariance. Statistical analysis of responses to GEQ1 and GEQ2 (yes/no) was performed for each question using a logistic regression model.

The mean frequency of responses to each question of the Life Satisfaction Checklist and to the five questions of the Erection Distress Scale for each treatment was calculated and expressed as the least squares mean±standard error (SE).

Each question was fitted with an analysis of covariance model, which included terms for treatment group, centre, patient age, baseline score, ED duration, baseline ED severity, and smoking status. All statistical tests were two sided and performed at the 5% significance level. A total of 217 men (mean age: 46 years; mean duration of ED: 5.7 years; mean duration of MS: 10.4 years) from 20 sites in the United States and Europe received treatment with sildenafil (n = 104) or placebo (n = 113) for 12 weeks. The patients in the two treatment groups had similar demographic characteristics with respect to age, duration of ED, duration of MS, and EDSS score (table 1), but men in the placebo group reported more frequent use of antihypertensive agents and less use of corticosteroids compared with the treatment group.

At the end of the 12 week period, almost two thirds of men (64%) receiving sildenafil were taking the 100 mg dose, compared with 32% on the 50 mg dose, and 4% on the 25 mg dose. In the placebo group, 96% of men were taking the 100 mg dose, and 4% were taking the 50 mg dose. Download figure Open in new tab Download powerpoint. Download figure Open in new tab Download powerpoint.

Download figure Open in new tab Download powerpoint. Download figure Open in new tab Download powerpoint. Quality of life variables that improved with sildenafil treatment (black bars)

compared

Of the 26 subjects who discontinued, 17 (8%) did so for reasons not related to treatment (AEs, n = 3; laboratory abnormalities, n = 1; lost to follow up, withdrawal of consent, other, n = 14). The most common AEs are shown in table 2, and were comparable in nature and rate of occurrence to AEs reported in the DB phase of the study.

Overall, 12 patients (6%) reported treatment emergent serious AEs during the OLE phase, most of which (n = 9) were relapses of MS or aggravation of MS symptoms, requiring hospitalisation.

Seven subjects experiencing these relapses had received sildenafil during the DB phase of the study and two patients had received placebo. In all cases, the subject returned to the study and completed the OLE phase without further worsening of the MS symptoms.

None of the serious AEs were attributed to the study medication. Sildenafil significantly improved erectile function and the ability to engage in satisfactory sexual activity in men with ED due to MS. Treatment with sildenafil was well tolerated, with 98% of the patients completing the study.

Furthermore, oral sildenafil treatment resulted in significant improvements in both general and disease specific QoL variables, and the treatment therefore represents an important advance in the management of ED in this group of patients. Although men participating in this study were ambulatory, indicative of their relatively mild spinal cord involvement (Kurtzke EDSS 13, 14 Although the pharmacological mechanism of sildenafil is not expected to affect desire and orgasmic function, both domains showed improvement in this current study. These improvements are thought to happen secondary to improvements in erectile function, with men feeling good about their ability to resume sexual activity and sildenafil enabling them to sustain an erection until orgasm is achieved.

During the DB phase, AEs associated with sildenafil use occurred more frequently than in the placebo group, raising an issue about patients being unblinded and introducing bias when answering subjective questionnaires. However, this is a potential issue in many clinical trials and the incidence of AEs related to sildenafil treatment in this study was comparable to that in other trials, for example, in patients with diabetes, 20 depression, 21 or SCI 22 (range, 31–40%). Efficacy of sildenafil is comparable in men with ED and concomitant MS (current study) or SCI.

13, 14 The ability to achieve an erection (IIEF Q3) was improved 1.6-fold in MS patients and 1.8-fold in SCI patients, whereas the ability to maintain an erection (IIEF Q4) improved 1.9-fold in MS patients and 2.1-fold in SCI patients.