Treatment of hypoactive sexual desire disorder in premenopausal women: efficacy of flibanserin in the DAISY study.

INTRODUCTION: Hypoactive Sexual Desire Disorder (HSDD) is characterized by low sexual desire that causes marked distress or interpersonal difficulty. AIM: To assess the efficacy and tolerability of flibanserin, a postsynaptic 5-HT1A agonist/5-HT2A antagonist, in the treatment of premenopausal women with HSDD. METHODS: North American premenopausal women with HSDD (mean age 35 years) were randomized to 24 weeks' treatment with flibanserin 25 mg twice daily (N=396), 50 mg twice daily (N=392), 100 mg once daily at bedtime (N=395), or placebo (N=398). MAIN OUTCOME MEASURES: Co-primary endpoints were changed from baseline to study end in number of satisfying sexual events (SSE) and sexual desire score, measured daily using an eDiary. Secondary endpoints included change in Female Sexual Distress Scale-Revised (FSDS-R) total score and Item 13 score (distress due to low sexual desire), Female Sexual Function Index (FSFI) total and desire domain scores, and Patient's Global Impression of Improvement. RESULTS: Flibanserin 100 mg once daily was associated with an increase in SSE (P<0.01 vs. placebo) but the 25 mg and 50 mg twice daily doses were not. No group showed a significant increase in eDiary desire score vs. placebo. All flibanserin regimens improved FSDS-R total, FSDS-R Item 13, FSFI total, and FSFI desire domain scores vs. placebo (P<0.05, for all). More women receiving flibanserin 50 mg twice daily and 100 mg once daily considered their HSDD to have improved than women receiving placebo (44.1% and 47.0% vs. 30.3%, respectively) (P<0.000, 1 vs. placebo). The most frequently reported adverse events in women receiving flibanserin were somnolence (11.8%), dizziness (10.5%), and fatigue (10.3%). CONCLUSION: In premenopausal women with HSDD, flibanserin 100 mg once daily was well tolerated and associated with statistically significant improvements in SSE, sexual desire (FSFI desire domain score but not eDiary desire score), sexual function, and decrease in sexual distress vs. placebo.

Long-term safety and efficacy of aliskiren and valsartan combination with or without the addition of HCT in patients with hypertension.

OBJECTIVE: To assess the long-term safety and antihypertensive efficacy of aliskiren/valsartan 300/320 mg combination. METHODS: This was a 54-week, multicenter, open-label study (core phase), followed by a 26-week extension phase. Efficacy variables were change in msDBP and msSBP from baseline to endpoint (54-week and 80-week). Safety was assessed by monitoring and recording adverse events (AEs). ClinicalTrials.gov Identifier: NCT00386607 RESULTS: A total of 601 patients (msDBP ≥ 90 and <110 mmHg) entered the 54-week core study. Optional add-on HCT was allowed at week 10 onwards if BP was ≥ 140/90 mmHg at two consecutive visits. Of the 486 patients completed the core study, 180 patients entered the extension phase and received aliskiren/valsartan and add-on HCT (12.5 or 25 mg). Overall the combination of aliskiren/valsartan was well-tolerated and the majority of AEs were mild-to-moderate in severity. The incidence of SAEs was low (core phase: n = 22 [3.7%]; extension phase: n = 4 [2.2%]). Elevated serum potassium (>5.5 mmol/L at any time during the study) was observed in 21 (3.6%) patients. The majority of these elevations were transient and returned to normal in subsequent visits, and the discontinuation rate due to elevated serum potassium was low (0.3% [n = 2]). Decreased serum potassium levels (<3.5 mmol/L at any time during the study) was observed in 26 (4.4%) patients, mainly in patients receiving aliskiren/valsartan/HCT (n = 22; 7.1%). At the 54-week endpoint, a mean BP reduction of 20.5/13.4 mmHg from baseline (baseline BP: 152.9/97.0 mmHg) was observed and 66.9% (n = 398/595) of patients achieved BP control with aliskiren/valsartan with or without HCT. At the end of the extension phase (80-week endpoint), additional reduction in BP was obtained (overall, 28.8/18.3 mmHg) and 86.6% (n = 155/179) of patients achieved BP control with aliskiren/valsartan/HCT. A limitation is the absence of an active comparator group. CONCLUSION: Long-term treatment with the combination of aliskiren/valsartan with or without HCT provided clinically meaningful BP reductions and high rates of BP control and was well-tolerated.

Long-term safety, tolerability and efficacy of aliskiren in combination with valsartan in patients with hypertension: a 6-month interim analysis.

BACKGROUND: Renin-angiotensin system (RAS) blockade with ACE inhibitor and/or angiotensin receptor blocker therapy can lead to increased potassium levels, hence the need to assess dual blockade involving a direct renin inhibitor. Here we report the results of a pre-planned 6-month interim analysis of a long-term, open-label study examining the safety, tolerability and efficacy of the aliskiren/valsartan 300/320-mg combination in patients with hypertension. METHODS: A total of 601 patients with hypertension (msDBP > or = 90 and < 110 mmHg) received a combination of aliskiren/valsartan 150/160 mg for 2 weeks followed by forced titration to aliskiren/valsartan 300/320 mg once daily for a targeted duration of 52 weeks. Optional hydrochlorothiazide (HCTZ) addition was allowed from week 8 for inadequate BP control (> or = 140/90 mmHg). The primary objective was to assess the safety of combination therapy; potassium elevations were a predefined safety outcome. BP was measured at regular intervals during the study. RESULTS: At the 6-month cut-off date, 512 patients (85.2%) were still ongoing with study treatment, and 192 patients had received at least one dose of HCTZ add-on during this period. Combination therapy was generally well-tolerated; the most commonly reported adverse events were headache (7.5%), dizziness (7.3%) and nasopharyngitis (7.2%). Ten patients (2.5%) receiving aliskiren/valsartan and two patients (1.0%) receiving aliskiren/valsartan/HCTZ had serum potassium elevations > 5.5 mmol/L. Only one patient (0.2%) exhibited potassium levels > or = 6.0 mmol/L during this period and the patient was treated with aliskiren/valsartan. Mean msSBP/DBP reductions of 22.3/14.4 mmHg were observed at 6-month endpoint (LOCF analysis) and 73.4% of patients achieved BP control (< 140/90 mmHg; LOCF). CONCLUSIONS: Although lack of an active comparator group is a limitation of the study, our findings show that long-term treatment with the aliskiren/valsartan 300/320-mg combination provided clinically significant BP lowering, was well-tolerated and was associated with a very low rate of potassium elevations in patients with hypertension.

Preference for and satisfaction of Canadian women with the transdermal contraceptive patch versus previous contraceptive method: an open-label, multicentre study.

OBJECTIVE: To document Canadian women's experience with the transdermal contraceptive patch, a method delivering 150 microg norelgestromin and 20 microg ethinyl estradiol daily. METHODS: We conducted an open-label, multicentre, descriptive cohort study of the contraceptive patch over 9 cycles in 392 women requiring contraception. A single treatment cycle consisted of 3 consecutive 7-day patch applications followed by 1 patch-free week. At the final visit, overall satisfaction and preference for the patch was rated and compared with the previously used contraceptive method. RESULTS: At baseline, 80.9% of participants were either very satisfied or somewhat satisfied with their previous contraceptive method, 89% having used oral contraceptives. At final observation, 60.6% of participants preferred the patch, 9.3% had no preference; and 30% preferred their previous method (n = 376). A total of 279 participants (71.2%) completed 9 cycles of patch use. Of these, 91% were satisfied with the patch and 74.9% preferred the patch to their previous contraceptive (43% strongly preferred and 31.9% preferred); 9% had no preference; and 16.1% preferred their previous method. Of those who preferred the patch, 82.7% preferred it because of its convenience or simplicity. Across all cycles, 88% of participants recorded perfect compliance. The most common adverse event was application site reactions (most of which were mild), experienced by 49% of participants: 33.7%, 16.5%, and 14.7% at cycles 1, 4, and 9, respectively. CONCLUSION: Both preference for and satisfaction with the transdermal contraceptive patch were high. Most participants.

Treatment of acute bacterial conjunctivitis: 1% fusidic acid viscous drops vs. 0.3% tobramycin drops.

BACKGROUND: A frequent cause of conjunctivitis is an acute bacterial infection, presenting with mucopurulent discharge and conjunctival hyperemia. The authors compared the clinical and microbiologic efficacy, safety and acceptability of 1% fusidic acid viscous drops (Fucithalmic) with 0.3% tobramycin ophthalmic solution (Tobrex) in the treatment of suspected bacterial conjunctivitis. METHODS: Patients were recruited at 20 sites in Ontario, Saskatchewan and Alberta from October 1995 to December 1998. Patients who presented to their primary care physician with suspected bacterial conjunctivitis, as identified by conjunctival hyperemia and purulent or mucopurulent discharge, were eligible for the study. Patients were randomly assigned to receive 7 days of treatment with either 1% fusidic acid (one drop applied twice daily) or 0.3% tobramycin (one to two drops applied four to six times daily). The investigators were blinded as to treatment status. Bacteriologic samples were taken from the inferior conjunctival cul-de-sac on day 0 and at the end of treatment. Signs and symptoms of conjunctivitis were assessed at baseline and after 3 and 7 days of treatment. The acceptability of treatment was assessed by having the patient or the parent or guardian complete a questionnaire on degree of compliance and ease of use after 3 and 7 days of treatment. RESULTS: Conjunctival swabs were obtained from 484 patients (410 over 9 years of age and 74 aged 2 to 9 years) to determine baseline bacteriology. Of the 484, 319 (65.9%) (63% of the older patients and 80% of those aged 2 to 9 years) had positive results of culture for bacteria. Ninety-four patients (19%) (63 [15%] of the older patients and 31 [42%] of those aged 2 to 9 years) had per-protocol pathogens as defined by quantitative bacteriology criteria. There was a direct correlation between the presence of mucopurulent discharge and the presence of per-protocol pathogens. There were no significant differences in clinical or bacteriologic efficacy between the treatment groups. Treatment compliance was similar between the treatment groups for the older patients; however, for those aged 2 to 9 years, compliance was significantly better in the fusidic acid group than in the tobramycin group (85% vs. 47%) (p < 0.001). Significantly more patients in the fusidic acid group than in the tobramycin group rated treatment as convenient or very convenient, particularly among younger patients (97% vs. 54%) (p < 0.001). INTERPRETATION: The clinical and bacteriologic efficacy of fusidic acid viscous drops combined with the convenience of a twice-daily dosage regimen establishes this antibiotic as first-line treatment for suspected acute bacterial conjunctivitis and a favourable alternative to other broad-spectrum antibiotics.

A controlled, double-blind, multicenter study comparing clarithromycin extended-release tablets and levofloxacin tablets in the treatment of community-acquired pneumonia.

BACKGROUND: Macrolides and fluoroquinolones are frequently used for the empiric treatment of community-acquired pneumonia (CAP). OBJECTIVE: The aim of the study was to compare the safety profile and efficacy of clarithromycin extended-release (ER) tablets with those of levofloxacin tablets for the treatment of CAP in ambulatory adult patients. METHODS: In a Phase III, double-blind, randomized, parallel-group, multicenter study, ambulatory adult patients (> or = 18 years) with signs and symptoms of CAP received a 7-day course of treatment with either clarithromycin ER (two 500-mg tablets once daily) or levofloxacin (two 250-mg tablets once daily). A diagnosis of CAP was confirmed by radiography of the chest and physical examination, and sputum samples were analyzed to identify etiologic pathogen(s). Tolerability was assessed through subjective reports of adverse events and through changes in physical findings, concomitant medications, and laboratory values. RESULTS: There were no statistically significant differences between treatment groups in terms of sex, age, race, or body weight. The mean age was 50 years (range, 18-91 years). Of 299 patients randomized and treated, 252 were clinically evaluable (128 clarithromycin ER, 124 levofloxacin). The 95% CI for the difference between cure rates demonstrated equivalence of the 2 treatments. Among clinically evaluable patients at the test-of-cure visit, clinical cure rates were 88% (113/128) and 86% (107/124), and radiographic success rates were 95% (117/123) and 88% (104/118) for clarithromycin ER and levofloxacin, respectively. Both treatment regimens were effective in resolving and improving clinical signs and symptoms of CAP. Among clinically and bacteriologically evaluable pa- tients, bacteriologic cure rates were 86% (80/93) and 88% (85/97) for clarithromycin ER and levofloxacin, respectively. No statistically significant differences were observed between the 2 treatment groups in the overall incidence of adverse events. CONCLUSIONS: Clarithromycin ER demonstrated equivalent efficacy and tolerability to the fluoroquinolone levofloxacin in a group of ambulatory adult patients with CAP. Clarithromycin ER also appeared to be safe in the population studied.