Placebo Run-in Period (placebo + run-in_period)

Distribution by Scientific Domains

Selected Abstracts

Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes

T. Vilsbøll
Objective: To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes. Methods: After a 2 week placebo run-in period, eligible patients inadequately controlled on long-acting, intermediate-acting or premixed insulin (HbA1c , 7.5% and , 11%), were randomised 1:1 to the addition of once-daily sitagliptin 100 mg or matching placebo over a 24-week study period. The study capped the proportion of randomised patients on insulin plus metformin at 75%. Further, the study capped the proportion of randomised patients on premixed insulin at 25%. The metformin dose and the insulin dose were to remain stable throughout the study. The primary endpoint was HbA1c change from baseline at week 24. Results: Mean baseline characteristics were similar between the sitagliptin (n = 322) and placebo (n = 319) groups, including HbA1c (8.7 vs. 8.6%), diabetes duration (13 vs. 12 years), body mass index (31.4 vs. 31.4 kg/m2), and total daily insulin dose (51 vs. 52 IU), respectively. At 24 weeks, the addition of sitagliptin significantly (p < 0.001) reduced HbA1c by 0.6% compared with placebo (0.0%). A greater proportion of patients achieved an HbA1c level < 7% while randomised to sitagliptin as compared with placebo (13 vs. 5% respectively; p < 0.001). Similar HbA1c reductions were observed in the patient strata defined by insulin type (long-acting and intermediate-acting insulins or premixed insulins) and by baseline metformin treatment. The addition of sitagliptin significantly (p < 0.001) reduced fasting plasma glucose by 15.0 mg/dl (0.8 mmol/l) and 2-h postmeal glucose by 36.1 mg/dl (2.0 mmol/l) relative to placebo. A higher incidence of adverse experiences was reported with sitagliptin (52%) compared with placebo (43%), due mainly to the increased incidence of hypoglycaemia (sitagliptin, 16% vs. placebo, 8%). The number of hypoglycaemic events meeting the protocol-specified criteria for severity was low with sitagliptin (n = 2) and placebo (n = 1). No significant change from baseline in body weight was observed in either group. Conclusion: In this 24-week study, the addition of sitagliptin to ongoing, stable-dose insulin therapy with or without concomitant metformin improved glycaemic control and was generally well tolerated in patients with type 2 diabetes. [source]

The efficacy of telmisartan compared with perindopril in patients with mild-to-moderate hypertension

I. Nalbantgi
Summary In this study, efficacy of the angiotensin II type 1 receptor blocker telmisartan given as monotherapy was compared with that of perindopril monotherapy in patients with mild-to-moderate hypertension. After a 2-week, single-blind, placebo run-in period, 60 patients were randomised to double-blind, once-daily treatment with telmisartan 80 mg or perindopril 4 mg for 6 weeks. Clinic and ambulatory blood pressure measurements and clinical laboratory evaluation were performed at the end of the placebo run-in and active treatment phases. Both telmisartan and perindopril significantly (p < 0.0001) reduced clinic systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared with baseline values. Also, both drugs significantly (p < 0.0001) reduced 24-h mean ambulatory SBP and DBP compared with baseline. Comparison of the mean hourly antihypertensive activities showed that the reduction in mean ambulatory DBP for the last 8 h of the dosing interval was significantly greater (p < 0.05) in telmisartan-treated patients. A 24-h mean DBP of <85 mmHg was observed in 66.6% of the telmisartan-treated patients but in only 46.6% of the perindopril-treated patients (p < 0.05). It is concluded that telmisartan and perindopril both produce significant reductions in clinic SBP and DBP, but the mean reduction in ambulatory DBP during the last 8 h of the dosing interval is greater in patients treated with telmisartan. [source]

One-year treatment of chronic urticaria with mizolastine: efficacy and safety

G Lorette
Abstract Aim,To assess the long-term safety and efficacy of the H1-receptor antagonist mizolastine in the symptomatic treatment of chronic urticaria (CU). Background,Mizolastine is a novel second generation antihistamine with additional anti-inflammatory properties which has been shown to be effective in this condition as well as in allergic rhinitis. As the drug is used for chronic treatment, a detailed study of its efficacy and safety over a prolonged period was warranted. Methods,This open label multicentre trial recruited 211 patients suffering from CU (67% female; mean age 40 ± 13 years), with , 1 episode/week if untreated. After a 7-day placebo run-in period, patients received mizolastine (10 or 15 mg) for 12 months. Efficacy was assessed by the patient using daily diary cards and overall condition evaluation at study visits. Clinicians also assessed the same parameters at each visit, and gave a global assessment at study termination. Safety was assessed by monitoring adverse events and laboratory parameters. Cardiac safety was monitored every 4 months using 12-lead ECGs, with particular attention to QT intervals. Results,The trial was completed by 127 patients. Mizolastine reduced overall discomfort from the second week of therapy, and reduced itching and the number and size of wheals, as assessed by the patients. The clinician's assessment of the proportion of patients with > 10 wheals decreased from 42% to 28% after 2 months. Clinical assessment also indicated that itch intensity and angioedema were improved by mizolastine, and the improvement was sustained throughout the trial. The investigators estimated that 70% of patients benefited from therapy. There were no drug-related serious adverse events during the study. The cardiac repolarization assessed according to the QTc intervals was not modified during prolonged administration. Conclusion,Mizolastine improves CU symptoms, and these improvements are sustained over 12 months with no loss of drug sensitivity. No specific side-effects are associated with its long-term use in the current study. [source]

Desloratadine in combination with montelukast in the treatment of chronic urticaria: a randomized, double-blind, placebo-controlled study

E. Nettis
Summary Background Chronic urticaria (CU) is a common skin condition. It is frequently a disabling disease due to the persistency of clinical symptoms, the unpredictable course and negative influence on the quality of life. Objective The aim of this study is to determine whether montelukast, a LTD4 receptor antagonist, plus desloratadine, is more efficacious than desloratadine alone in the treatment of chronic urticaria. Materials A randomized, double-blind, placebo-controlled study was conducted on 81 patients with a diagnosis of CU. A 1-week single-blind placebo run-in period (baseline) was followed by a 6-weeks double blind active treatment period. The patients were randomized to receive the following treatment once daily: (a) oral desloratadine (5 mg) plus placebo; (b) desloratadine (5 mg) plus montelukast (10 mg); (c) oral placebo alone. The study ended after another 1-week single-blind placebo washout period. Results The evaluable population thus consisted of 76 patients. Both desloratadine alone and desloratadine plus montelukast administered once daily yielded improvements with respect to the baseline assessment as regards pruritus, number of separate episodes, size and number of weals, visual analogue score and patients' quality of life and with respect to the placebo group both in the active treatment period and in the run-out period. However, desloratadine plus montelukast was shown to improve the symptoms and patients' quality of life significantly more than desloratadine alone, although it did not have a significant effect on the number of urticarial episodes. Conclusion The combination of desloratadine plus montelukast is effective in the treatment of CU. It may therefore be a valid alternative in patients with relatively mild CU, in view of its efficacy and the lack of adverse events. [source]

Combination treatment with telmisartan and hydrochlorothiazide in black patients with mild to moderate hypertension

Janet B. Mcgill M.D.
Abstract Background: Hydrochlorothiazide (HCTZ) is commonly used to treat black patients with hypertension. To avoid the metabolic disturbances associated with high-dose HCTZ, blood pressure control may be achieved by combining low doses with another antihypertensive. Hypothesis: The study was undertaken to assess the tolerability and antihypertensive dose-response efficacy of telmisartan and HCTZ and their combination in black patients with mild to moderate hypertension (mean supine blood pressure 140/95-200/114 mmHg). Methods: Following a 4,week, single-blind, placebo run-in period, 222 black patients were randomized to once-daily treatment with one of 20 different double-blind combinations of telmisartan (0, 20, 40, 80, 160 mg) and HCTZ (0, 6.25, 12.5, 25 mg) for 8 weeks. Blood pressure was measured at baseline and after 2, 4, and 8 weeks. Results: Telmisartan 80 mg/HCTZ 12.5 mg reduced supine trough diastolic blood pressure (DBP),primary efficacy parameter,by 13.3 mmHg, and supine trough systolic blood pressure (SBP) by 21.5 mmHg. These reductions represented benefits of 13.7/8.7 mmHg over telmisartan 80 mg and 12.3/8.1 mmHg over HCTZ 12.5 mg(p<0.01). Telmisartan 40 mg/HCTZ 12.5 mg reduced supine trough SBP/DBP by 14.3/10.0 mmHg, amounting to 12.3/3.3 mmHg more than telmisartan 40 mg and 5.1/4.8 mmHg more than HCTZ 12.5 mg, This reached significance for the comparisons with telmisartan 40 mg for SBP and HCTZ 12.5 mg for DBP (p,0.05). A response surface analysis and therapeutic response rates confirmed the additive antihypertensive effects of telmisartan and HCTZ. All treatments were well tolerated, with side-effect profiles comparable with placebo. Adverse events were mainly transient and of mild to moderate severity. Conclusions: Telmisartan 80 mg combined with HCTZ 12.5 mg is effective and well tolerated in black patients with mild to moderate hypertension, providing greater antihypertensive activity than the corresponding monotherapies. [source]