Erectile Function, Erection Hardness and Tolerability in Men Treated With Sildenafil 100 mg vs. 50 mg for Erectile Dysfunction

M. Kirby; D. L. Creanga; V. J. Stecher

Disclosures

Int J Clin Pract. 2013;67(10):1034-1039. 

In This Article

Patients and Methods

Study Design

The five fixed-dose studies were parallel design with a DBPC period of at least 8 weeks and enrolled a general population of men with ED who were phosphodiesterase type 5 (PDE5) inhibitor naïve (studies 148–102, −106, −361 and −364) or had received ≤ 6 total doses of a PDE5 inhibitor and none within 4 weeks of randomisation (A1481239). In these five studies, patients were randomly assigned to sildenafil 25 mg, 50 mg, 100 mg or placebo for 24 weeks (study 148–102; efficacy data at weeks 2, 8 and 12 included in these analyses); sildenafil 50 mg, 100 mg, 200 mg and placebo for 12 weeks (studies 148–106 and 148–361); sildenafil 25 mg, 50 mg, 100 mg or placebo for 12 weeks after a 4-week run-in period (study 148–364); and sildenafil 50 mg, 100 mg and placebo for 8 weeks (study A1481239). Because most of these trials predated establishment of ClinicalTrials.gov, identifiers exist for only the latter study (NCT00245258). Patients were instructed to take sildenafil approximately 1 h before sexual activity, but not more than once daily. Only results for sildenafil 50 mg, 100 mg and placebo were included in the current report. Appropriate Institutional Review Board approval and patient informed consent were obtained for all studies.

Participants were generally required to have a documented history of ED for at least 6 months and to be in a stable sexual relationship. The inclusion and exclusion criteria of the studies were broadly in line with the prescribing information for sildenafil used for the treatment of ED.[4] In most of the studies, men receiving nitrate therapy and nitric oxide donors were excluded. In the most recent study (A1481239), to avoid potential hypotension, any patient who was currently prescribed, taking and/or likely to be treated with an α-blocker was excluded from entering the trial. There were no restrictions on other vasoactive and antihypertensive medications.

Men with severe cardiac failure, unstable angina or a recent history (i.e. within 3–6 months) of stroke or myocardial infarction were excluded. Otherwise, efficacy and safety were assessed in men with a variety of comorbid conditions that share risk factors with ED, including diabetes mellitus, hypertension, cardiovascular disease (coronary artery disease, angina, myocardial infarction and stroke), radical prostatectomy, spinal cord injury and depression.

Comparative Efficacy of Sildenafil 100 mg and 50 mg

Erectile function was assessed using the Erectile Function (EF) domain of the International Index of Erectile Function (IIEF) in these five fixed-dose studies. According to the IIEF-EF, ED is characterised as mild (score, 22–25 of 30), mild-to-moderate (17–21), moderate (11–16) and severe (6–10).[5]

Erection hardness was assessed by use of the Erection Hardness Score (EHS) in four of the five fixed-dose studies (148–102, 148–106, 148–361 and A1481239), and EHS data were available from two of these studies (148–102 and A1481239) at 2 and 8 weeks. The EHS is an ED-specific, psychometrically validated, single-item, patient-reported outcome that enables men to score their erection hardness as follows: EHS0 (no erection), EHS1 (penis is larger, but not hard), EHS2 (penis is hard, but not hard enough for penetration), EHS3 (penis is hard enough for penetration, but not completely hard) and EHS4 (penis is completely hard and fully rigid).[6]

Assessment of Tolerability

Data from the five DBPC fixed-dose studies were presented by dose. Each event was presented using Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (version 10.0) and with causality and severity assessed by the trial investigator. Severity was classified as mild (usually transient, required no special treatment and did not interfere with daily activities), moderate (low level of inconvenience and may have interfered with daily activities; usually ameliorated by simple therapeutic measures) or severe (interrupted daily activity and required systemic drug therapy or other medical treatment). A serious adverse event was defined as any untoward medical occurrence that resulted in death, was life threatening, required inpatient hospitalisation or prolongation of existing hospitalisation, or resulted in a persistent or significant disability/incapacity or a congenital anomaly/birth defect. Common adverse events were defined as those occurring in ≥ 2% of men in at least one treatment group. Also listed were vision events presumed to be associated with the inhibition of PDE6, an enzyme located in retinal rods and cones and related to PDE5, the main target of sildenafil inhibition.

Main Outcome Measures

The change from baseline to the end of the DBPC treatment phase (week 12 for study 148–102) in the IIEF-EF score was compared between the 100-mg and 50-mg groups, and between each of these active treatment groups and the placebo group, using analysis of covariance (ANCOVA) models with terms for baseline, centre and treatment group. The ANCOVA model for one of the studies (A1481239) also included terms for age, ED aetiology and ED duration.

The per-patient estimated percentage of occasions that a specified EHS was achieved was computed from logistic regression, adjusting for model covariates: treatment group, baseline percentage, duration of ED, aetiology of ED and patient age. The odds of achieving EHS3 and EHS4 erections were compared between the 100-mg and 50-mg groups.

The incidence of adverse events overall (including severe and serious events), the incidence of common treatment-related adverse events (those occurring in ≥ 2% of men in at least one treatment group) and the incidence of treatment-related vision events presumed to be associated with the inhibition of PDE6 were summarised by treatment.

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