Efficacy and tolerability of oral zolmitriptan in menstrually associated migraine: a randomized, prospective, parallel-group, double-blind, placebo-controlled study

BACKGROUND: Approximately 60% of female migraineurs report experiencing migraine in association with menstruation, while 7% to 25% experience attacks almost exclusively with menstruation. OBJECTIVE: To examine the efficacy and tolerability of oral zolmitriptan in the acute treatment of menstrually associated migraine. In this study, menstrually associated migraine was defined as migraine that consistently occurred from 72 hours before to 5 days after onset of menses. Methods.-Participants were women with regular menstrual cycles, aged 18 to 55 years, who had experienced migraine with at least two thirds of prior menstrual cycles. Subjects were randomized to treat one attack per menstrual cycle for 3 months with either zolmitriptan or placebo. Treatment was intensity based: mild migraines were treated with half of a 2.5-mg zolmitriptan tablet, moderate migraines were treated with zolmitriptan 2.5 mg, and severe migraines were treated with 5 mg (two 2.5-mg tablets) of zolmitriptan, or placebo. RESULTS: Of the 579 women enrolled in the study, 260 were treated with zolmitriptan and 251 were assigned placebo. Twelve hundred thirty-two attacks were treated, and a 2-hour headache response was achieved in 48% of zolmitriptan-treated attacks as compared with 27% of placebo-assigned attacks (P <.0001). Zolmitriptan was superior to placebo in achieving a headache response as early as 30 minutes (18% versus 14%, P=.03) and at 1 hour (33% versus 23%, P <.001). Drug-related adverse events were reported in 16% of subjects receiving zolmitriptan and 9% of subjects receiving placebo. CONCLUSION: Oral zolmitriptan exhibits efficacy and good tolerability in the treatment of menstrually associated migraine. Improvement over placebo was observed as early as 30 minutes following treatment.     

Efficacy and tolerability of enalapril and sustained-release verapamil in older patients with mild to moderate essential hypertension

The study involved 113 patients over age 50 years with mild to moderate essential hypertension, randomly assigned to treatment with enalapril (n = 54) or sustained-release verapamil (n = 59). During an eight-week titration period, doses were adjusted to achieve supine diastolic blood pressures (DBP) below 90 mmHg; patients were then given maintenance doses for eight weeks. Mean blood pressures were reduced significantly from 147.7/93.9 mmHg at baseline to 137.7/84.5 mmHg at the end of the maintenance period in the enalapril group and from 155.1/95.1 to 142.4/86.2 mmHg in the verapamil group. In the patients who completed treatment, the mean daily doses required to maintain DBP below 90 mmHg were 9.6 mg of enalapril and 244.9 mg of verapamil. There were 11 treatment failures in the enalapril group and 22 in the verapamil group: eight of the enalapril and 17 of the verapamil patients did not attain goal blood pressures and three and five were withdrawn because of side effects. It is concluded that both enalapril and sustained-release verapamil were generally effective and well tolerated in the treatment of mild to moderate hypertension in the middle-aged and older patients.     

Efficacy and tolerability of almotriptan in adolescents: a randomized, double-blind, placebo-controlled trial

Objectives.— To assess the efficacy and safety of almotriptan 6.25 mg, 12.5 mg, and 25 mg vs placebo for acute migraine treatment in adolescents. Patients and Methods.— In this double‐blind, placebo‐controlled, parallel‐group, multicenter trial, 866 patients aged 12 to 17 years with a >1 year history of migraine (per International Headache Society criteria) were randomized to treat one migraine headache with almotriptan 6.25 mg, 12.5 mg, 25 mg, or placebo. The primary efficacy endpoint was headache pain relief 2 hours after dosing, adjusted for baseline severity, with absence of nausea, photophobia, and phonophobia 2 hours after dosing as coprimary endpoints. Results.— The 2‐hour pain‐relief rate was significantly higher with almotriptan 25 mg compared with placebo (66.7% vs 55.3%; P = .022). The incidence of nausea, photophobia, and phonophobia at 2 hours (adjusted for baseline pain intensity) for the almotriptan 25 mg and placebo groups was not significantly different. The 2‐hour pain‐relief rates (unadjusted) were significantly higher with almotriptan 6.25 mg (71.8%), 12.5 mg (72.9%), and 25 mg (66.7%) than with placebo (55.3%; P = .001, P < .001, and P = .028, respectively). Rates for sustained pain relief also were significantly greater with almotriptan 6.25 mg (67.2%), 12.5 mg (66.9%), and 25 mg (64.5%) than with placebo group (52.4%), P < .01 for the 6.25‐ and 12.5‐mg doses and P < .05 for the 25‐mg dose. Age group subanalysis demonstrated significantly greater 2‐hour pain‐relief rates with all 3 doses of almotriptan compared with placebo for patients aged 15 to 17 years, a significantly lower incidence of photophobia and phonophobia at 2 hours with almotriptan 12.5 mg compared with placebo for patients aged 15 to 17 years, and a significantly lower incidence of photophobia with almotriptan 12.5 mg compared with placebo for those aged 12 to 14 years. Almotriptan treatment was well tolerated, with the most common adverse events (>2%) of nausea, dizziness, and somnolence. Conclusions.— Oral almotriptan was efficacious for relieving migraine headache pain in adolescents, with the 12.5‐mg dose associated with the most favorable efficacy profile with respect to relieving headache pain and associated symptoms of migraine (photophobia and phonophobia). Almotriptan treatment was well tolerated in this adolescent population.     

Efficacy,safety, and tolerability of valsartan/hydrochlorothiazide in Asian patients with essential hypertension

Introduction  

Previous studies have demonstrated that hypertensive patients need concomitant therapy with one or more drugs from different classes of antihypertensive agents to achieve their blood pressure control targets. We performed the first multinational observational study of valsartan/hydrochlorothiazide (HCTZ) single pill combination in Asia to determine the efficacy, safety, and tolerability in hypertensive patients. The objective of this multinational, multicenter, 24-week follow-up observational study is to evaluate the efficacy, safety, and tolerability of valsartan/hydrochlorothiazide single pill combination in the treatment of essential hypertension in the Asia-Pacific region.     

Efficacy and tolerability of Hairgain in individuals with hair loss: a placebo-controlled, double-blind study

This randomized, placebo-controlled, double-blind study was designed to investigate the efficacy and tolerability of a new agent for the treatment of hair loss, based on a marine protein, minerals and vitamins. Sixty subjects with hair loss of different aetiologies participated in the 6-month blinded phase of the study. Objective assessments indicated that the treatment was effective and subjective assessments showed a statistically significant positive effect of treatment. Exposure to the active preparation for a further 6 months in an open phase indicated a further improvement in hair growth. Exposure of the patients previously treated with placebo to the active preparation for 12 months gave similar results. Tolerability was good and no side-effects were reported. The product investigated may provide an alternative to pharmacotherapy for the treatment of hair-loss problems in individuals with androgenic alopecia.     

Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study

BACKGROUND: Evaluation of exenatide monotherapy in patients with type 2 diabetes may be of clinical interest based on improvements in glycemic control and weight that have been reported with the use of exenatide in combination with oral antidiabetic agents. OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of exenatide monotherapy in patients with type 2 diabetes naive to antidiabetic agents and whose disease was inadequately controlled with diet and exercise alone. METHODS: This 24-week, double-blind, placebo-controlled, parallel-group study was conducted at 23 centers across the United States, Puerto Rico, Romania, Russia, and India. Patients aged >or=18 years with type 2 diabetes were randomly assigned to receive exenatide 5 microg, exenatide 10 microg, or placebo administered SC BID. Patients were instructed by investigators to maintain their individualized prestudy diet and exercise regimens throughout the study. Efficacy measures included: glycosylated hemoglobin (HbA(1c)); fasting serum glucose (FSG); 6-point self-monitored blood glucose; percentages of patients achieving HbA(1c) values or=1 treatment-emergent adverse event. Nausea was reported with the greatest incidence (5 microg, 3%; 10 microg, 13%; placebo, 0%; P = 0.010 for the combined exenatide group vs placebo). Most (88%) treatment-emergent adverse events were mild or moderate in intensity. Hypoglycemia was reported in 5%, 4%, and 1% of patients in the exenatide 5- and 10-microg and placebo groups, respectively (P = NS), with no incidents of severe hypoglycemia reported. CONCLUSIONS: In these patients with type 2 diabetes naive to treatment with antidiabetic agents, exenatide monotherapy was associated with improved HbA(1c), improved fasting and postprandial glucose control, reduced weight, improved beta-cell function (HOMA-B), and improved blood pressure, and was well tolerated. These results suggest that exenatide monotherapy may provide a viable treatment option beyond diet and exercise and support further study of exenatide monotherapy in antidiabetic drug-naive patients with type 2 diabetes.     

Efficacy and tolerability of nebivolol monotherapy by baseline systolic blood pressure: A retrospective analysis of pooled data from two multicenter, 12-week,randomized, double-blind,placebo-controlled,parallel-group,dose-ranging studies in patients with mild to moderate essential hypertension

Background: In clinical studies, nebivolol at doses of 2.5 to 40 mg once daily was associated with significant decreases in systolic blood pressure (SBP) and diastolic BP (DBP) in patients with hypertension and was well tolerated.Objectives: This post hoc analysis of pooled data from 2 previously published registration studies was conducted to further evaluate the antihypertensive efficacy and tolerability of nebivolol in patients with mild to moderate (stage 1–2) hypertension.Methods: The 2 trials were similarly designed multicenter, 12-week, randomized, double-blind, placebocontrolled, parallel-group, dose-ranging studies in patients 18 years of age and older with stage 1 or 2 hypertension (SBP 140–159 mm Hg and/or DBP 90–99 mm Hg [stage 1] or SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg [stage 2]). The primary efficacy end point of the 2 studies was the change from baseline in mean trough SiDBP at week 12. A secondary end point was the change from baseline to week 12 in mean trough sitting SBP (SiSBP). The present analysis included only patients who received nebivolol 5, 10, or 20 mg (the doses were common to both studies) or placebo, including analyses stratified by baseline SBP, although DBP represented a criterion for entry into the studies. Baseline SBP stratification levels were 140 to 149 mm Hg, 150 to 159 mm Hg, 160 to 169 mm Hg, and 170 to 179 mm Hg. For the tolerability analysis, the prevalences of treatment-emergent adverse events (AEs) were compared between the 3 nebivolol dose groups and the placebo group.Results: Of the 1716 randomized patients who received study medication in the 2 trials, data from 1385 patients were included in this pooled analysis (759 men, 626 women; median age, ~54 years; 13.6% black). Mean (SD) baseline SiSBP and SiDBP values were 151.9 to 152.7 and 99.2 to 99.5 mm Hg, respectively. Reductions from baseline in trough SiSBP were ?10.8 (13.5), ?10.7 (14.7), and ?12.4 (15.5) mm Hg with nebivolol 5, 10, and 20 mg, respectively, compared with ?4.5 (13.4) mm Hg with placebo (all, P < 0.001). Reductions from baseline in trough SiDBP (the primary end point) were ?9.8 (7.9), ?10.5 (8.2), and ?11.1 (8.6) mm Hg with nebivolol 5, 10, and 20 mg, respectively, compared with ?5.1 (8.1) mm Hg with placebo (all, P < 0.001). In a subgroup of 1227 patients stratified by baseline SBP, the reductions in SBP and DBP were significantly greater (P < 0.03 and P < 0.001, respectively) with nebivolol at each dose compared with placebo in those with baseline SBP of 140 to 149 mm Hg and 150 to 159 mm Hg (the lowest 2 baseline strata); in the highest 2 baseline strata (SBP 160–169 and 170–179 mm Hg), the reductions in SBP with nebivolol 5 mg and nebivolol 20 mg in the 160 to 169-mm Hg baseline SBP stratum and in DBP with nebivolol 20 mg in the 170 to 179-mm Hg baseline stratum were significantly greater (P < 0.03) compared with placebo. The most common AE in the nebivolol 5?, 10?, and 20-mg groups and the placebo group was headache (36/409 [8.8%], 25/410 [6.1%], 27/410 [6.6%], and 10/156 [6.4], respectively), fol-lowed by fatigue (9/409 [2.2%], 10/410 [2.4%], 25/410 [6.1%], and 3/156 [1.9%]) and dizziness (6/409 [1.5%], 9/410 [2.2%], 15/410 [3.7%], and 4/156 [2.6%]).Conclusion: The present analysis of pooled data from 2 previously published registration studies found that nebivolol was associated with significant reductions in BP compared with placebo in these patients with stage 1 or 2 hypertension, with a tolerability similar to that of placebo.     

Efficacy of carvedilol in mild to moderate essential hypertension and effects on microalbuminuria: a multicenter, randomized, open-label, controlled study versus atenolol

In this randomized, open-label, multicenter comparison, 140 adults with mild to moderate essential hypertension were treated with the nonselective beta blocker carvedilol (25 mg once daily) or the selective beta 1 blocker atenolol (100 mg once daily) orally for 2 months. Systolic and diastolic blood pressure and heart rate were measured monthly in the supine and standing positions. Urinary albumin levels and blood lipid profile were determined at baseline and at study end. The occurrence of cold extremities was monitored throughout the study. Both treatments significantly decreased systolic and diastolic blood pressure at a comparable level. At the final assessment, 88% of the carvedilol group achieved a supine diastolic blood pressure of 90 mm Hg or lower, compared with 82% of the atenolol group. Atenolol produced the greater decrease in heart rate, but between-group differences were significant only for standing measurements. With carvedilol, urinary albumin decreased in 25% of patients and increased in 2%; corresponding figures with atenolol were 13% and 12%. At study end, 10% of the carvedilol group and 37% of the atenolol group complained of cold extremities. No major between-group differences were observed in the percentage of patients with an increase in high-density lipoprotein or a decrease in low-density lipoprotein cholesterol. Triglycerides and total cholesterol tended to decrease in a greater percentage of patients taking carvedilol than atenolol.     

Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension

BACKGROUND: Patients with hypertension may require combination therapy to attain the blood pressure targets recommended by US and European treatment guidelines. Combination therapy with a calcium channel blocker and an angiotensin II-receptor blocker would be expected to provide enhanced efficacy. OBJECTIVES: Two studies were conducted to compare the efficacy of various combinations of amlodipine and valsartan administered once daily with their individual components and placebo in patients with mild to moderate essential hypertension (mean sitting diastolic blood pressure [MSDBP] >/=95 and < 110 mm Hg). A secondary objective was to evaluate safety and tolerability. METHODS: The 2 studies were multinational, multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group trials. In study 1, patients were randomized to receive amlodipine 2.5 or 5 mg once daily, valsartan 40 to 320 mg once daily, the combination of amlodipine 2.5 or 5 mg with valsartan 40 to 320 mg once daily, or placebo. In study 2, patients were randomized to receive amlodipine 10 mg once daily, valsartan 160 or 320 mg once daily, the combination of amlodipine 10 mg with valsartan 160 or 320 mg once daily, or placebo. The primary efficacy variable in both studies was change from baseline in MSDBP at the end of the study. Secondary variables included the change in mean sitting systolic blood pressure (MSSBP), response rate (the proportion of patients achieving an MSDBP <90 mm Hg or a >/= 10-mm Hg decrease from baseline), and control rate (the proportion of patients achieving an MSDBP <90 mm Hg). Safety was assessed in terms of adverse events (spontaneously reported or elicited by questioning), vital signs, and laboratory values. RESULTS: A total of 1911 patients were randomized to treatment in study 1 (1022 amlodipine + valsartan; 507 valsartan; 254 amlodipine; 128 placebo); 1250 were randomized to treatment in study 2 (419, 415, 207, and 209, respectively). In all treatment groups in both studies, the majority of patients were white (79.5% study 1, 79.4% study 2) and male (53.5% and 50.3%, respectively). The overall mean age was 54.4 years in study 1 and 56.9 years in study 2. The mean weight of patients in study 1 was higher than that in study 2 (88.8 vs 79.7 kg). The overall baseline mean sitting BP was 152.8/99.3 mm Hg in study 1 and 156.7/99.1 mm Hg in study 2. With the exception of a few combinations that included amlodipine 2.5 mg, the combination regimens in both studies were associated with significantly greater reductions in MSDBP and MSSBP compared with their individual components and placebo (P < 0.05). A positive dose response was observed for all combinations. The highest response rate in study 1 was associated with the highest dose of combination therapy (amlodipine 5 mg + valsartan 320 mg: 91.3%). Amlodipine 5 mg, valsartan 320 mg, and placebo were associated with response rates of 71.9%, 73.4%, and 40.9%, respectively. In study 2, the 2 doses of combination therapy were associated with similar response rates (amlodipine 10 mg + valsartan 160 mg: 88.5%; amlodipine 10 mg + valsartan 320 mg: 87.5%). Amlodipine 10 mg was associated with a response rate of 86.9%; valsartan 160 and 20 mg were associated with response rates of 74.9% and 72.0%, respectively; and placebo was associated with a response rate of 49.3%. Control rates followed a similar pattern. The incidence of peripheral edema with combination therapy was significantly lower compared with amlodipine monotherapy (5.4% vs 8.7%, respectively; P = 0.014), was significantly higher compared with valsartan monotherapy (2.1%; P < 0.001), and did not differ significantly from placebo (3.0%). CONCLUSIONS: In these adult patients with mild to moderate hypertension, the combination of amlodipine + valsartan was associated with significantly greater blood pressure reductions from baseline compared with amlodipine or valsartan monotherapy or placebo. The incidence of peripheral edema was significantly lower with combination therapy than with amlodipine monotherapy.     

Efficacy and tolerability of two formulations of ramipril in Korean adults with mild to moderate essential hypertension: An 8-week,multicenter, prospective,randomized, open-label,parallel-group noninferiority trial

Objective: This study was designed to compare the efficacy and tolerability of a new generic formulation of ramipril (test) and the branded formulation of ramipril (reference) to satisfy regulatory requirements for marketing of the generic product for use in Korean patients with mild to moderate hypertension.Methods: This was an 8-week, multicenter, prospective, randomized, open-label, parallel-group non-inferiority trial in adult patients (age > 18 years) with mild to moderate essential hypertension (sitting dia-stolic blood pressure [SiDBP] 90–109 mm Hg). After a 2-week washout of previous antihypertensive medications, eligible patients were randomized to receive either ramipril 5 mg/d in the morning (low-dose group: baseline SiDBP 90–99 mm Hg) or ramipril 10 mg/d (high-dose group: baseline SiDBP 100–109 mm Hg) for the first 4 weeks. If SiDBP was ≥ 90 mm Hg after 4 weeks of treatment, the dose was increased to 10 mg/d for the remaining 4 weeks in the low-dose group, and hydrochlorothiazide 12.5 mg was added to the regimen for the remaining 4 weeks in the high-dose group. The primary end point was the change in SiDBP from baseline to week 8. Secondary end points included a noninferiority analysis of the test and reference formulations with respect to the change in mean sitting systolic blood pressure (SiSBP) from baseline to week 8; SiDBP and SiSBP response rates (proportion of patients achieving an SiDBP < 90 mm Hg and SiSBP < 140 mm Hg, respectively) at 8 weeks; and changes from baseline in SiSBP, pulse wave velocity (PWV), exercise capacity, left-ventricular diastolic function (LVDF), and levels of brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP). Laboratory and clinical adverse events (AEs) were monitored at each study visit (4 and 8 weeks).Results: The modified intent-to-treat population consisted of 89 patients (45 test, 44 reference; 60 men, 29 women; mean age, 49.7 years; mean weight, 69.9 kg). At week 8, mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (test: from 145.0 [9.7]/98.1 [5.3] mm Hg to 132.2 [11.1]/ 91.8 [7.1] mm Hg [P < 0.001]; reference: from 145.1 [11.4]/98.0 [5.7] mm Hg to 134.0 [14.6]/92.5 [7.9] mm Hg [P < 0.001]). The changes in blood pressure at week 8 did not differ significantly between the test and reference groups or between the low- and highdose groups in a subgroup analysis. Blood pressure response rates at 8 weeks did not differ significantly between the groups receiving the test and reference formulations (SiDBP: 26.7% and 31.8%, respectively; SiSBP: 37.8% and 40.9%). In addition, there were no significant between-group differences in the change in PWV (?63.8 and ?38.7 cm/sec), LVDF at rest or after exercise, or levels of BNP or hs-CRP. The incidence of AEs was 64.4% in the test formulation group and 68.2% in the reference group formulation (P = NS). The most common AE in both groups was cough (10/45 [22.2%] and 10/44 [22.7%]).Conclusions: There were no significant differences in the efficacy and tolerability of the test and reference formulations of ramipril in these Korean adults with mild to moderate hypertension. The new generic formulation was noninferior to the reference formulation in terms of the change in SiDBP at week 8.     

Efficacy and tolerability of Hypericum extract STW 3-VI in patients with moderate depression: A double-blind,randomized, placebo-controlled clinical trial

In this double-blind, randomized, placebo-controlled, prospective study, the clinical efficacy and tolerability of oral Hypericum extract STW 3-VI (Laif) 900 mg once daily was compared with that of placebo. A total of 140 outpatients (94 women; 46 men) with moderate depressive disorders and a 17-item Hamilton Depression Scale (HAMD-17) score of 20 to 24 were enrolled in this study. Following a single-blind placebo run-in period of 7 days, the patients were randomized to Hypericum extract 900 mg or placebo for the 6-week treatment period. Nineteen patients have been excluded from the per protocol collective because of violations of protocol regarding the scheduling of study visits and intake of study medication. The primary endpoint for treatment efficacy was the change in total HAMD-17 score at the end of the 6-week treatment period. The HAMD-17 total score decreased significantly from baseline by approximately 11.1 +/- 4.5 points (from 22.8 +/- 1.1 to 11.8 +/- 4.4) in the Hypericum group and by approximately 3.4 +/- 3.9 points (from 22.6 +/- 1.2 to 19.2 +/- 3.8) in the placebo group (P < .001). Comparable group differences in favor of Hypericum were revealed by an additional responder analysis, the von Zerssen's Adjective Mood Scale, the Clinical Global Impressions scale, and a global efficacy assessment. Tolerability was very good in both groups; neither serious adverse events nor clinically relevant changes in safety parameters were observed, and only 2 cases demonstrated a possible connection between an adverse event and the study medication. The final safety assessment showed no differences between the Hypericum extract and placebo groups. The study provided evidence that Hypericum extract STW 3-VI in a once-daily dosing regimen may be an effective and well-tolerated option for patients with moderate depressive disorders.     

Efficacy and tolerability of cycletanine in aged patients with hypertension

Moderate arterial hypertension of the elderly has to be treated but the efficacy has to be progressive. Cicletanine has a pharmacokinetic profile well fitted to the therapy of this age group. The mechanism of action is characterized by synthesis of prostacyclin. A double blind prospective randomized study was conducted at two institutions on 132 patients aged more than 60, with diastolic arterial pressure over 95 mmHg and systolic over 160 mmHg. 62.9% of them were aged more than 75. The analysis of those two studies shows that the three groups with cicletanine (respectively 50, 100 and 150 mg per day) had a significant decrease of both pressures versus placebo. In the 50 mg group, 40% of arterial pressures were normalized after 3 months of treatment. There were no difference between 50 and 100 mg. There were no adverse drug reaction like falling down, day or night, or orthostatic hypotension. The biological tolerance, more particularly renal, was excellent with this dose of 50 mg a day. Cicletanine at the dose of 50 mg/day is a recommended treatment in arterial hypertension of the elderly.     

Efficacy,tolerability and development of resistance in HIV-positive patients treated with fluconazole for secondary prevention of oropharyngeal candidiasis: a randomized,double-blind,placebo-controlled trial

Over 37 months, we conducted a prospective double-blind, randomized study in a cohort of 138 HIV-infected patients to compare the effect of two different strategies on the prevention and treatment of oropharyngeal candidiasis relapses and on the development of clinical and microbiological resistance to fluconazole. Each episode was treated with a 7 day course of fluconazole 200 mg/day, followed by secondary prophylaxis with fluconazole 150 mg once weekly matched to placebo. The duration of the double-blind phase of the study, from the day of randomization to the first primary end-point, was 347 +/- 186 days for the fluconazole group and 196 +/- 128 days for the placebo group (P < 0.001). A total of 33 patients remained relapse-free during the course of the study. Clinical failure was observed in a total of five patients (four in the fluconazole group, one in the placebo group; P = 0.15). Microbiological resistance was recorded in 12 patients (eight in the fluconazole group, four in the placebo group; P = 0.20). There were no significant treatment group differences in microbiological resistance whether comparisons were made for all cases or for cases up to 1 month post-study. In the few patients who developed clinical and/or microbiological resistance, the cumulative dose of fluconazole before entry into the study was a mean value of 8.6 g (compared with 2.9 g in patients without clinical and/or microbiological resistance). In summary, patients treated with secondary prophylaxis suffered fewer relapses of oropharyngeal candidiasis. Development of resistant candidiasis (clinical and/or microbiological) was rarely seen in either group and its incidence was not significantly different.     

Comparison of efficacy and tolerability of amlodipine orotate versus amlodipine besylate in adult patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group, 8-week follow-up, noninferiority trial

OBJECTIVE: The purpose of this study was to compare the efficacy and tolerability of amlodipine orotate with those of amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study was designed as a noninferiority study. To be included in the study, previously untreated patients had to have a sitting diastolic blood pressure (SiDBP) of 90 to 109 mm Hg. Previously treated patients had to discontinue their current annhypertensive medications and have a baseline SiDBP between 90 and 109 mm Hg after a 2-week washout period. Patients who met the inclusion criteria were randomly assigned to receive 5 mg amlodipine orotate or 5 mg amlodipine besylate for 8 weeks. The medication dose was doubled (10 mg QD for either amlodipine orotate or amlodipine besylate) 4 weeks after enrollment if SiDBP was >or=90 mm Hg. The primary efficacy analysis was noninferiority of the difference in mean trough SiDBP changes from baseline for amlodipin eorotate as compared with amlodipine besylate after 8 weeks of treatment. For the secondary efficacy analysis, 2 other measures were analyzed after 8 weeks of treatment. The SiDBP response rate was defined as an SiDBP measurement<90 mm Hg at the last clinical follow-up visit or an absolute reduction of >or=10 mm Hg in SiDBP from baseline until the last clinical follow-up visit. In addition, noninferiority of the difference in mean trough sitting systolic blood pressure (SiSBP) changes from baseline was analyzed for amlodipine orotate as compared with amlodipine besylate. The drug compliance rate was estimated by pillcount. RESULTS: Eligible patients (n=109; 43 women and 66 men) were randomly assigned to receive amlodipine orotate (n=53) or amlodipine besylate (n=56). No significant differences were found in sex, age, weight, or current smoking between the groups (all, P=NS). The proportion of patients with previous antihypertensive medications was not different between the groups (47.2% [25/53] in the amlodipine orotate group and 50.0% [28/56] in the amlodipine besylate group; P=NS). No significant differences were found in baseline SiDBP (mean [SD], 100 [6] mm Hg [range, 90-109 mm Hg] in the amlodipine orotate group and 100 [6] mm Hg [range, 90-108 mm Hg] in the amlodipine besylate group; P=NS) or in baseline SiSBP (mean [SD], 149 [14] mm Hg [range, 125-179 mm Hg] in the amlodipine orotate group and 146 [10] mm Hg [range, 123-167 mm Hg] in the amlodipine besylate group; p=NS). The mean (SD) changes in SiDBP were -15.6 (6.3) mm Hg for the amlodipine orotate group and -14.5 (5.5) mm Hg for the amlodipine besylate groups was 1.1 (5.9) mm Hg (95% CI, -0.87 to infinity), and because the lower boundary of the 95% CI was greater than -5 mm Hg, amlodipine orotate was considered noninferior to amlodipine besylate. The response rate was 48 of 51 (94.1%) in the amlodipine orotate group compared with 50 (92.6%) of 54 in the amlodipine besylate group after 8 weeks of treatment (P=NS). The mean (SD) compliance rates were 97.6% (3.6%) in the amlodipine orotate group and 96.5% (4.3%) in the amlodipine besylate group (P=NS). The incidence of drug-related adverse events (AEs) was similar between the groups (1/53 [1.9%]) in the amlodipine orotate group vs 4/55 [7.3%] in the amlodipine besylate group; P=NS). The most common drug-related AE overall was peripheral edema (2/55 [3.6%]), and the most common of all the AEs was upper respiratory tract infection (4/55 [7.3%]) in the amlodipine besylate group. The most common drug-related AE was headache (1/53 [1.9%]) in the amlodipine orotate group and peripheral edema (2/55 [3.6%]) in the amlodipine besylate group. No severe AEs were found in either group. CONCLUSION: The reduction in SiDBP after 8 weeks of amlodipine orotate treatment was noninferior to that of amlodipine besylate in these Korean patients with mild to moderate hypertension. The SiDBP response rate and the reduction in SISBP after 8 weeks of amlodipine orotate treatment were not significantly different from those of amlodipine besylate treatment. Both agents were wel tolerated.     

卡维地洛治疗轻、中度原发性高血压的临床疗效

目的 :观察卡维地洛治疗轻、中度原发性高血压的降压疗效。方法 :60例原发性高血压患者被随机分为卡维地洛组 (卡组 )和阿替洛尔组 (对照组 ) ,各 3 0例 ,分别给予卡维地洛 10～ 40mg/d和阿替洛尔 2 5～ 10 0mg/d ,疗程 8周。治疗前及治疗后 2、4、6、8周末测量坐位血压及心率 ,记录不良反应。结果 :( 1)治疗后两组病人的血压均有明显下降。卡组SBP/DBP降低 2 8.3 / 2 0 .1mmHg( 16.9%/ 19.5 %) ,对照组SBP/DBP降低 2 3 .5 / 16.9mmHg( 14 .3 %/ 16.5 %) ,分别与治疗前比较有显著性差异 (P <0 .0 1) ;两组间差异不显著 (P >0 .0 5 )。 ( 2 )卡组与对照组总有效率分别为 86.7%和 76.7%,总显效率分别为 66.7%和 60 .0 %,两组间差异不显著 (P >0 .0 5 )。 ( 3 ) 8周末 ,两组心率均降低 ,分别与治疗前比较有显著性差异 (P <0 .0 1) ,两组间差异不显著 (P >0 .0 5 )。结论 :卡维地洛治疗轻、中度高血压疗效确切、安全     

Efficacy and tolerability of a nutraceutical combination of red yeast rice,guggulipid, and chromium picolinate evaluated in a randomized,placebo-controlled,double-blind study

Hypercholesterolemia is the major risk factor in the development of coronary heart disease. Coronary heart disease is a leading cause of morbidity and mortality in many countries worldwide. An increasing attention is now paid to nutraceuticals development for prevention and cure of dyslipidemia, especially for patients who do not wish to use chemical statins. The cholesterol lowering effect and the tolerability of NutraforChol®, a nutraceutical product containing red yeast rice extract, guggulipid extract and chromium picolinate, was evaluated on subjects who had total cholesterol level 200−239 mg/dL and LDL cholesterol level 100-159 mg/dL. In this study, a randomized, placebo-controlled, double-blind study which consisted of 4 weeks run-in period and 8 weeks treatment period was performed. Based on the study results, NutraforChol® effectively decreased total cholesterol (−15.9 %) and LDL level (-19.9 %) after two weeks consumption. The total cholesterol and LDL reduction were maintained during 8 weeks study period. At study termination (week 8), there was a significant difference between total cholesterol level of NutraforChol® treated group (173.5 ± 21.7 mg/dL) and placebo-treated group (204.5 ± 22.8 mg/dL) (p < 0.05). In addition, there was a significant difference between LDL level at week 8 in NutraforChol® group (115.5 ± 22.2 mg/dL) and placebo-treated group (145.1 ± 23.7 mg/dL) (p < 0.05). The tolerability of NutraforChol® was also evaluated. There were no significant changes (p > 0.05) on renal and liver function parameters between baseline and study termination. Thus, NutraforChol® may be considered as a complementary or alternative safe nutraceuticals for the treatment of mild dyslipidemic subjects.