Efficacy Of Fixed-dose Combination Research Articles

Comparative efficacy and safety of glycopyrronium/formoterol fixed-dose combination versus glycopyrronium monotherapy in patients with moderate-to-severe COPD.

The safety and efficacy of fixed-dose combination (FDC) of glycopyrronium bromide 12.5 μg/formoterol fumarate 12 μg (GB/FF) twice daily as dry powder inhalers (DPIs) compared to glycopyrronium 50 μg monotherapy (GLY) once daily as DPI in subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD) were evaluated. This was a phase-3, randomized, double-blind, active-controlled, parallel-group, superiority study conducted in India. COPD patients aged ≥40 to ≤65 years, current or ex-smokers with FEV1/FVC <0.70, using ICS, LAMA, or LABA for ≥1 month were included. Subjects were randomized (1:1) to GB/FF or GLY for 12 weeks. The primary efficacy endpoint was the change from baseline in peak FEV1 at the end of 12 weeks. The study is registered with the Clinical Trials Registry of India (CTRI/2017/02/007814). Between March 2017 and July 2018, 331 patients were enrolled and randomized into GB/FF FDC (165 patients) and GLY monotherapy (166 patients) groups. At week 12, the difference in change from baseline in the peak FEV1 for GB/FF DPI versus GLY was 0.115 L (SE = 0.02; 95% CI = 0.061, 0.170; P < 0.0001). Trough FEV1 increased significantly in the GB/FF group compared to the GLY group with a treatment difference of 0.078 L (SE = 0.02; 95% CI = 0.015, 0.14; P = 0.01). There were no significant differences in adverse events between the groups. FDC of GB/FF (12.5/12 μg twice daily) as a DPI provides superior bronchodilation and lung function improvement over GLY (50 μg once daily) monotherapy. It is safe and well tolerated in symptomatic COPD patients.

2206-PUB: Efficacy of Fixed-Dose Combination of Empagliflozin and Linagliptin in Addition to the Ongoing Treatment in Type 2 Diabetes: Real-World Observational Study

Empagliflozin (SGLT2 inhibitor) and linagliptin (DPP-4 inhibitor) is a Fixed Dose Combination (FDC) with limited real-world evidence. We assessed the efficacy of this novel FDC in the real world Indian setting by analyzing the mean change in 12-week values of the glycemic (HbA1c and FPG) and extra-glycemic parameters (SBP, DBP, eGFR and body weight) as compared to the baseline values at the point of initiation of FDC in 498 patients. (Table). The patients enrolled were independently naïve to both DPP IV inhibitor and SGLT2 inhibitor therapy. Unpaired t test and ANOVA were utilised for statistical analysis. The mean age was 61 years (SD ± 7.6). The ongoing treatment in 20% (n=100), 43% (n=214), 38% (n=189), 26% (n=127) were metformin (M), combination of M and sulfonylureas (SU), combination of M, SU and voglibose, and insulin, respectively. The mean change in HbA1c, FPG, SBP, DBP, eGFR and body weight was -1.1%, -45 mg/dl, -12 mmHg, -5 mmHg, 5 mL/min/1.73m2, -5 kg (p&amp;lt;0.0001), respectively. 23.9 % patients (n=119) achieved HbA1c &amp;lt; 7%. 36.8% (n=183) patients achieved FPG reductions ≥100mg/dl. Six patients reported clinically evident hypoglycaemia which was managed symptomatically. There was a meaningful change and a substantial quantum of improvement in glycemic, metabolic and renal parameters. The results need to be validated through a long-term larger study. Disclosure A. Gupta: None. M. Khalse: None. A. Bhargava: None.

Comparison of the efficacy of fixed-dose combination of mitiglinide/voglibose with repaglinide on glycemic variability in hospitalized patients with type 2 diabetes

Comparison of the efficacy of fixed-dose combination of mitiglinide/voglibose with repaglinide on glycemic variability in hospitalized patients with type 2 diabetes

Comparison of Efficacy and Safety of Fixed Dose Combination of Rosuvastatin and Choline Fenofibrate to Fixed Dose Combination of Rosuvastatin and Fenofibrate in Patients of Mixed Dyslipidemia: A Randomized, Open-label, Multicentre Clinical Trial in Indian Population.

Introduction:This study was conducted to evaluate the safety and efficacy of fixed-dose combination (FDC) of rosuvastatin and choline fenofibrate in comparison to rosuvastatin and fenofibrate FDC among Indian patients of mixed dyslipidemia. This would be a first study evaluating FDC of rosuvastatin and choline fenofibrate in Indian population.Methods:A multicenter, open-label, randomized, active controlled, comparative, parallel-design study was conducted at 12 centers spread all across India. Mixed dyslipidemic patients aged 18–70 years were randomized to FDC of rosuvastatin 10 mg and choline fenofibrate 135 mg (RCF group) and FDC of rosuvastatin 10 mg and fenofibrate 160 mg (RF group) once daily for approximately 180 days. The primary endpoint of study was percentage change in serum triglyceride level at the end of study from baseline.Results:Of 290 patients screened, 240 patients were enrolled in this study (120 patients in each group). At the end of 180 days, there was a significant reduction in triglyceride level in both the groups (−37.7% in RCF group and −37.8% reduction in RF group; P < 0.0001 for both); however, the difference between both the groups was not statistically significant (P = 0.94). Similarly, there was significant increase (P < 0.0001 for both) in high-density lipoprotein cholesterol (HDL-C) in both groups (+17.8% in RCF group and +14.9% in rosuvastatin fenofibrate RF group). Low-density lipoprotein cholesterol (LDL-C), very low-LDL (VLDL-C), and total cholesterol were also reduced significantly in both groups (P < 0.0001). However, the difference between two groups for increase in HDL-C and decrease in LDL-C, VLDL-C, and total cholesterol was not significant. Both the treatments were safe and well tolerated.Conclusion:Overall, FDC of rosuvastatin and choline fenofibrate is as safe and effective as rosuvastatin and fenofibrate combination in Indian patients with mixed dyslipidemia with added advantage improved patient compliance as it can be taken irrespective of intake of food.

Treatment outcomes of fixed-dose combination versus separate tablet regimens in pulmonary tuberculosis patients with or without diabetes in Qatar

BackgroundTuberculosis is considered the second most common cause of death due to infectious agent. The currently preferred regimen for treatment of pulmonary tuberculosis (PTB) is isoniazid, rifampin, pyrazinamide, and ethambutol, which has been used either as separate tablets (ST) or as fixed-dose combination (FDC). To date, no studies have compared both regimens in Qatar. We aim to evaluate the safety and effectiveness of FDC and ST regimen for treating PTB, in addition to comparing safety and efficacy of FDC and ST regimens in patients with diabetes treated for TB.MethodsA retrospective observational study was conducted in two general hospitals in Qatar. Patients diagnosed with PTB received anti-tuberculosis medications (either as FDC or ST) administered by the nurse. Sputum smears were tested weekly. We assessed the time to negative sputum smear and incidence of adverse events among FDC and ST groups.ResultsThe study included 148 patients. FDC was used in 90 patients (61%). Effectiveness was not different between FDC and ST regimens as shown by mean time to sputum conversion (29.9 ± 18.3 vs. 35.6 ± 23 days, p = 0.12). Similarly, there was no difference in the incidence of adverse events, except for visual one that was higher in ST group. Among the 33 diabetic patients, 19 received the FDC and had faster sputum conversion compared to those who received ST (31 ± 12 vs. 49.4 ± 30.9 days, p = 0.05). Overall, diabetic patients needed longer time for sputum conversion and had more hepatotoxic and gastric adverse events compared to non-diabetics.ConclusionST group had higher visual side effects compared to FDC. FDC may be more effective in diabetic patients; however, further studies are required to confirm such finding.

Оцінка впливу фіксованої комбінації периндоприл + амлодипін на ураження органів-мішеней у пацієнтів з артеріальною гіпертензією (первинні результати дослідження EPHES)

Дослідження EPHES (Evaluation of influence of fixed dose combination Рerindopril/Amlodipine on target organ damage in patients with arterial HypErtension with or without iSchemic heart disease) мало за мету оцінити ефективність фіксованої комбінації периндоприл + амлодипін щодо зниження артеріального тиску (АТ) та динаміки вираженості ураження органів-мішеней у хворих на артеріальну гіпертензію (АГ) з ішемічною хворобою серця (ІХС) та без такої. У первинний аналіз включено дані 30 пацієнтів з АГ без ІХС віком понад 30 років. Рівень систолічного (САТ) і/або діастолічного (ДАТ) АТ у хворих, що до цього не лікувалися, на момент включення мав бути ≥ 160 та/або 100 мм рт.ст., але &lt; 200/120 мм рт.ст.; у тих, хто знаходився на монотерапії або подвійній комбінованій терапії, — ≥ 140/90 мм рт.ст., але &lt; 200/120 мм рт.ст. Усім пацієнтам у день рандомізації призначали фіксовану комбінацію периндоприл + амлодипін у початковій дозі 5/5 мг один раз на добу. При необхідності (АТ &gt; 140/90 мм рт.ст.) дози компонентів фіксованої комбінації збільшували поступово кожні 2 тижні до 10/10 мг, а після 6 тижнів лікування додавали індапамід 1,5 мг, бета-адреноблокатори або альфа-адреноблокатори. Усім пацієнтам проводили: вимірювання маси тіла та зросту, офісних рівнів САТ, ДАТ та частоти серцевих скорочень, добове моніторування АТ, визначення швидкості поширення пульсової хвилі в артеріях еластичного (ШППХе) та м’язового типів, центрального САТ, біохімічне дослідження крові, електрокардіографію, ехокардіографію з Д-графією, вимірювання гомілково-плечового індексу, визначення товщини комплексу інтима-медіа. Тривалість спостереження становила 12 місяців.Лікування за допомогою фіксованої комбінації периндоприл + амлодипін забезпечувало досягнення цільового рівня і САТ, і ДАТ у 60 % випадків на етапі 6 тижнів. Додавання індапаміду 1,5 мг на добу (n = 12) та бісопрололу (n = 1) забезпечило контроль офісного САТ і ДАТ у 100 % пацієнтів на етапі 6 місяців лікування. Зниження офісного АТ супроводжувалося достовірним зменшенням середньодобового, денного та нічного АТ відповідно на 22,3 ± 0,1 мм рт.ст., 19,6 ± 0,4 мм рт.ст., 26,1 ± 0,2 мм рт.ст. та 8,2 ± 0,2 мм рт.ст., 8,4 ± 0,1 мм рт.ст., 7,9 ± 0,1 мм рт.ст. і досягненням цільового середньодобового АТ у 98,7 % пацієнтів. Достовірно зменшилася частка пацієнтів, які характеризувалися як «нон-діппери», з 50 до 23,3 % та варіабельність денних САТ/ДАТ та нічного САТ. Частка пацієнтів із величиною ранкового підйому САТ понад 55 мм рт.ст. достовірно зменшилася з 60 до 20 %. Центральний САТ достовірно знизився з 142,8 ± 2,5 мм рт.ст. до 118,3 ± 2,7 мм рт.ст. (Р &lt; 0,001). Паралельно відбулося достовірне (Р &lt; 0,001) зменшення індексу приросту з 26,8 ± 1,9 % до 11,2 ± 1,7 %. Ефективна щодо зниження АТ терапія протягом року призводила до достовірного регресу ураження органів-мішеней: зменшення гіпертрофії лівого шлуночка (індекс маси міокарда зменшився з 108,8 ± 5,5 г/м2 до 88,3 ± 5,3 г/м2, індекс Корнелла — з 2440,1 ± 67,9 мм • мс до 1987,2 ± 66,8 мм • мс, розмір лівого передсердя — з 41,1 ± 0,2 мм до 38,1 ± 0,3 мм), рівня альбумінурії (з 53,3 ± 5,6 мг/добу до 15,8 ± 3,2 мг/добу), покращенню діастолічної функції лівого шлуночка та пружно-еластичних властивостей аорти (­ШППХе зменшилася з 11,9 ± 0,7 м/с до 9,4 ± 0,8 м/с). Зміни діастолічної функції лівого шлуночка та рівня альбумінурії достовірно та незалежно від змін рівня АТ (і офісного, і центрального) корелювали зі змінами ШППХе та індексу приросту. Проведена антигіпертензивна терапія на основі фіксованої комбінації периндоприл + амлодипін добре переносилася хворими (частота побічних реакцій 6,5 %).

772 Patient satisfaction with the safety and efficacy of fixed-dose combinations of solifenacin and tamsulosin OCAS™: Results from the NEPTUNE II study

772 Patient satisfaction with the safety and efficacy of fixed-dose combinations of solifenacin and tamsulosin OCAS™: Results from the NEPTUNE II study

Central aortic pressure indices and their correlation with brachial pressure in hypertensive subjects on newer angiotensin receptor blockers olmesartan and telmisartan

Background: Efficacy of Fixed-dose combination of olmesartan and amlodipine on central aortic pressure and Aortic pulse wave velocity (PWV), which are independent predictors of adverse cardiovascular events in hypertension is lacking. Aim of this study was to correlate the effects of fixed-dose combination therapy with olmesartan 20mg and amlodipine 5mg on central aortic blood pressure (CBP) indices in mild to moderate hypertensive subjects with controlled office BP. Methods: Twenty seven patients with brachial systolic BP 140 mmHg and/or diastolic BP 90 mmHg on three office readings who received fixed-dose combination therapy with olmesartan 20mg and amlodipine 5mg for atleast 12 weeks were included. CBP was measured with Periscope using standard cuff BP measurements and proprietary software utilizing a validated transfer function to convert the brachial waveform. Statistical analysis was done with SPSS version 10. Results: Average age of the study group was 47 years. Carotid femoral pulse wave velocity was 1210.2 454.5 cm/sec. Average brachial SBP, DBP and pulse pressure (PP) at the end of the study was 138.8 11.5, 75.9 9.6 and 62.1 12.8 mm of Hg. Average aortic SBP, DBP and pulse pressure (PP) at the end of the study was 121.5 13.8, 75.6 6.0 and 45.4 12.3 mm of Hg. Aortic augmentation pressure and aortic augmentation index noted were 13.7 9.1 mm of Hg and 28.1 10.7 respectively. A significant positive correlation was noted between brachial SBP and aortic SBP (r1⁄40.603, p < 0.001), brachial DBP and aortic DBP (r1⁄40.775, p < 0.001), brachial PP and aortic PP (r1⁄40.622, p<0.001). Conclusions: Combination therapy with fixed-dose olmesartan 20mg and amlodipine 5mg were shown to substantially benefit pulsatile hemodynamics (i.e. CBP and indices, AIx and PWV) and have beneficial effects on central aortic BP beyond brachial BP lowering with excellent correlation between the two BP parameters.

Correction of vitamin D insufficiency with combined strontium ranelate and vitamin D3 in osteoporotic patients

This study aims to investigate the efficacy and safety of oral fixed-dose combination of strontium ranelate 2 g/vitamin D₃ 1000 IU daily vs strontium ranelate 2 g daily for correcting vitamin D insufficiency in osteoporosis. A 6-month international, randomized, double-blind, parallel-group, phase 3 study. A total of 518 men and postmenopausal women aged ≥50 years with primary osteoporosis (T-score ≤-2.5 s.d.) and serum 25-hydroxyvitamin D (25(OH)D) >22.5 nmol/l were included. Patients were allocated to strontium ranelate 2 g/vitamin D₃ 1000 IU daily (n=413) or strontium ranelate 2 g daily (n=105). The participants received calcium 1 g daily. The primary endpoint was serum 25(OH)D at last post-baseline evaluation during 3 months. Both groups were comparable at baseline. Mean baseline of 25(OH)D was 44.1 ± 14.6 nmol/l. After 3 months, the percentage of patients with 25(OH)D ≥50 nmol/l was higher with strontium ranelate/vitamin D₃ vs strontium ranelate (84 vs 44%, P<0.001; adjusted between-group odds ratio=6.7; 95% CI, 4.2-10.9). The efficacy of the fixed-dose combination on 25(OH)D was maintained at 6 months (86 vs 40%, P<0.001). Mean 25(OH)D was 65.1 and 49.5 nmol/l, respectively, after 3 months and 66.9 and 45.4 nmol/l after 6 months. Physical performance improved in both groups. Falls were 17 and 20% in the strontium ranelate/vitamin D₃ and strontium ranelate groups respectively. Parathyroid hormone levels were inversely correlated with 25(OH)D. No clinically relevant differences in safety were observed. This study confirms the efficacy and safety of fixed-dose combination of strontium ranelate 2 g/vitamin D₃ 1000 IU for correction of vitamin D insufficiency in osteoporotic patients.

Blood pressure and metabolic efficacy of fixed-dose combination of perindopril and indapamide in everyday practice

The aim of the PICASSO study was to evaluate the efficacy and safety of fixed-dose perindopril 10 mg/indapamide 2.5 mg in everyday medical practice. In this 3-month, open-label, observational study, outpatients with primary hypertension who did not reach the blood pressure goal (< 140/90 mmHg) with antihypertensive treatment were enrolled if their treating physician had planned, as part of their ongoing therapy, to switch them to fixed-dose perindopril 10 mg/indapamide 2.5 mg. Blood pressure, heart rate, and metabolic parameters and – optionally – ambulatory blood pressure were measured. Data from 9257 patients were evaluated. Over the course of 3 months, mean blood pressure decreased from 159/93 mmHg to 132/80 mmHg (p < 0.001) and heart rate decreased from 79 to 73 beats/min (p < 0.001). The target blood pressure was reached by 72.7% of patients. Reductions in total cholesterol, low-density lipoprotein-cholesterol (LDL-c), triglycerides, fasting glucose and uric acid levels were clinically significant. Blood levels of high-density lipoprotein-cholesterol (HDL-c), sodium and potassium remained unchanged. Beneficial changes in metabolic parameters were primarily attributed to the reduction in therapy with drugs with unfavourable metabolic profiles (thiazides and beta-blockers). Perindopril/indapamide is an effective and safe antihypertensive treatment in everyday medical practice.