Sub-setting systemic lupus erythematosus by combined molecular phenotypes defines divergent populations in two phase III randomized trials.

Objectives: Heterogeneity of SLE patients in clinical trials remains a challenge for developing new therapies. This study used a combinatorial analysis of four molecular biomarkers to define key sources of heterogeneity.

Methods: Combinations of IFN (high/low), anti-dsDNA (+/-) and C3 and C4 (low/normal) were used to subset n = 1747 patients from two randomized phase III trials.

IUPACpal: efficient identification of inverted repeats in IUPAC-encoded DNA sequences.

Background: An inverted repeat is a DNA sequence followed downstream by its reverse complement, potentially with a gap in the centre. Inverted repeats are found in both prokaryotic and eukaryotic genomes and they have been linked with countless possible functions. Many international consortia provide a comprehensive description of common genetic variation making alternative sequence representations, such as IUPAC encoding, necessary for leveraging the full potential of such broad variation datasets.

Clinical trial parameters that influence outcomes in lupus trials that use the systemic lupus erythematosus responder index.

Objective: The SLE Responder Index (SRI) is a composite endpoint used in SLE trials. This investigation examined the clinical trial elements that drive response measured by the SRI.

Methods: Analyses are based on data from two phase 3 trials (n = 2262) that evaluated the impact of an anti-B-cell activating factor antibody on disease activity using SRI-5 as the primary endpoint (ClinicalTrials.

Direct effects of tadalafil on lower urinary tract symptoms versus indirect effects mediated through erectile dysfunction symptom improvement: integrated data analyses from 4 placebo controlled clinical studies.

Purpose: Tadalafil has regulatory approval for the treatment of men with signs/symptoms of benign prostatic hyperplasia with and without erectile dysfunction. We assessed whether the effects of treatment with tadalafil for lower urinary tract symptoms/benign prostatic hyperplasia are independent of improvements in erectile dysfunction.

Materials And Methods: Four separate analyses used integrated data from 4 randomized, double-blind, placebo controlled studies in men with lower urinary tract symptoms/benign prostatic hyperplasia with and without erectile dysfunction to test whether total I-PSS (International Prostate Symptom Score) improvement was due to improvement in IIEF-EF (International Index of Erectile Function-Erectile Function domain score).

Efficacy and safety of tadalafil 5 mg once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: subgroup analyses of pooled data from 4 multinational, randomized, placebo-controlled clinical studies.

Objective: To assess the efficacy and safety of tadalafil, a phosphodiesterase 5 (PDE5) inhibitor efficacious for erectile dysfunction and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), in population subgroups, using pooled data from 4 international, randomized, placebo-controlled studies in men with LUTS/BPH.

Methods: The safety database included 1500 men randomized to tadalafil 5 mg once daily or placebo for 12 weeks. Changes in total International Prostate Symptom Score (IPSS), IPSS-quality of life index, and BPH impact index were examined overall, and changes in IPSS or adverse events (AEs) were examined across subgroups of interest.

Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia in men with or without erectile dysfunction.

Objectives: To compare the safety and efficacy of the daily erectogenic therapy, tadalafil, on lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS) in men with or without comorbid erectile dysfunction (ED).

Methods: Following a 4-week placebo run-in period, men with moderate-to-severe BPH-LUTS were randomized to placebo or tadalafil 2.5, 5, 10, or 20 mg once daily for 12 weeks.

Likelihood of tadalafil-associated adverse events in integrated multiclinical trial database: classification tree analysis in men with erectile dysfunction.

Objectives: To identify the patient demographic factors, comorbidities, and concomitant medications associated with a change in the likelihood of tadalafil-associated adverse events (AEs) in men with erectile dysfunction.

Methods: Pooled safety data were analyzed from 3488 tadalafil-treated men who participated in 21 placebo-controlled clinical trials of tadalafil taken as needed or once daily. Three categories of tadalafil-associated AEs were defined: vasodilatory (headache, flushing, nasal congestion, nasopharyngitis, and dizziness); musculoskeletal (back pain and myalgia); and gastrointestinal (dyspepsia).

Efficacy and safety of tadalafil once daily: considerations for the practical application of a daily dosing option.

Objective: To provide clinically relevant information on tadalafil 2.5 or 5 mg once daily for the treatment of erectile dysfunction (ED), by reviewing safety and efficacy study findings. Findings from an integrated analysis of trials of tadalafil 10 and 20 mg as needed are presented to provide context for the daily dosing regime.

An evaluation of semen characteristics in men 45 years of age or older after daily dosing with tadalafil 20mg: results of a multicenter, randomized, double-blind, placebo-controlled, 9-month study.

Objectives: Assess the effects on spermatogenesis of daily tadalafil 20mg over three spermatogenesis cycles in men >or= 45 yr.

Methods: In this double-blind, placebo-controlled, noninferiority study, healthy men (or with mild erectile dysfunction) were randomized to receive tadalafil 20mg (n=125) or placebo (n=128) for 9 mo followed by a 6-mo, treatment-free period. Semen and serum samples were provided at baseline and every 10-12 wk.

A comparison of the efficacy and tolerability of tadalafil 10 mg and 20 mg in Japanese patients with severe erectile dysfunction.

Introduction: Tadalafil is a phosphodiesterase type 5 inhibitor with documented efficacy in the treatment of erectile dysfunction (ED).

Aim: To compare the efficacy and tolerability of tadalafil 10 mg and 20 mg in men with severe ED.

Methods: A prespecified subgroup analysis was conducted to compare the efficacy of tadalafil 10 and 20 mg measured by the International Index of Erectile Function (IIEF) erectile function (EF) domain and Sexual Encounter Profile (SEP) among patients with severe ED (EF domain score = 1-10) in a Japanese placebo-controlled study (PCT).

Efficacy and safety of tadalafil 5, 10, and 20 mg in Japanese men with erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled study.

Objectives: To investigate the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in Japanese men with erectile dysfunction (ED).

Methods: This multicenter, randomized, double-blind, placebo-controlled, 12-week study enrolled 343 Japanese men with ED. The men were stratified into those with mild, moderate, or severe ED and then randomly assigned 1:1:1:1 to placebo and 5 mg, 10 mg, and 20 mg tadalafil.

Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years.

Objective: Raloxifene hydrochloride (60 mg/day) is a selective estrogen receptor modulator indicated for the prevention and treatment of postmenopausal osteoporosis. Raloxifene treatment for 3 years increases bone mineral density (BMD) and, unlike tamoxifen (a triphenylethylene selective estrogen receptor modulator), does not stimulate the endometrium in healthy postmenopausal women. The effect of longer duration of treatment with raloxifene is not known.