Arzneimittel Forsch
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Arzneimittel Forsch · Jan 2009
Randomized Controlled Trial Comparative StudyEfficacy and safety of piroxicam patch versus piroxicam cream in patients with lumbar osteoarthritis. A randomized, placebo-controlled study.
In order to assess the efficacy and safety of a new patch containing 14 mg of piroxicam (CAS 36322-90-4) 1%, applied once daily, in comparison with a reference marketed formulation, piroxicam 1% cream applied three times a day, placebo patch applied once daily, a randomized, placebo-controlled, parallel-group clinical trial was carried out by general practitioners in patients with lumbar osteoarthritis aged between 18 and 75 years. Pain during daily activities scored on a 100 mm visual analogue scale was the primary outcome measure. Other secondary outcome measures were pain on isometric contraction, on full passive motion, and on pressure, and functional disability. Statistical analysis was performed on the differences between the three groups in the intention-to-treat population (ITT). One hundred and eighty patients were enrolled. The available ITT population comprised 179 patients. The compliance was very good. Decrease in pain score during daily activities after the eight days of study treatment (at the final visit, Vf) was 42.2%, 41.7% and 25.8% in the piroxicam patch, piroxicam cream and placebo groups, respectively. The difference between the pain scores in two active treatments arms was not statistically significant at the Vf whereas the differences between the pain scores of two active treatment arms vs the placebo arm were statistically significant validating the study design. All efficacy measures improved during the study, for both the active treatment groups, and the results for the secondary efficacy variables were generally consistent with those concerning the main efficacy criterion. The difference between the two active treatments in pain during daily activities were statistically significant at the final visit; in fact the 95% CI of the difference between the mean of responder rate of the piroxicam patch and piroxicam cream was -18.3%, +24.4% indicating a trend of superiority of the piroxicam patch versus the cream (per-protocol analysis). The data obtained during the intermediate visit (V2, day 4) allow us to assess that the piroxicam patch was on average better than the piroxicam cream in terms of fast pain reduction (change from baseline: - 29.1% for piroxicam patch in comparison to -24.6% for piroxicam cream). Moreover the piroxicam patch proved to be on average more effective than the piroxicam cream in terms of secondary efficacy endpoints. Safety was considered satisfactory in all groups. ⋯ The piroxicam patch is effective in the treatment of lumbar osteoarthritis and has demonstrated to be well tolerated and it improves patients compliance. The piroxicam patch offers a comparable alternative to the marketed piroxicam cream for the treatment of lumbar osteoarthritis with the advantage of a better compliance with the once a day application of the patch compared to three daily applications for the piroxicam cream.
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Arzneimittel Forsch · Jan 2009
Randomized Controlled TrialPharmacokinetics and bioequivalence study of a fixed dose combination of rabeprazole and itopride in healthy Indian volunteers.
The aim of the present study was to compare the pharmacokinetics of rabeprazole (CAS 117976-89-3) and itopride (CAS 122898-67-3) after oral administration of a rabeprazole (20 mg)-itopride (150 mg) fixed dose combination (FDC) in healthy human volunteers. The bioequivalence of two formulations (test and reference) was determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.69 years; weight: 60.50 +/- 5.04 kg) in a randomized, single-dose, two-period, two-treatment crossover study. Both formulations were administered orally as a single dose, with the treatments separated by a washout period of 1 week. ⋯ General linear model (GLM) procedures were used in which sources of variation were subject, treatment and period. The results indicated that there were no statistically significant differences (P > 0.05) between the logarithmically transformed AUC(0-infinity) and Cmax values between test and reference formulation. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limits of 0.8-1.25 and the relative bioavailability of rabeprazole and itopride test and reference formulations was 98.24 and 93.65%, respectively.
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Arzneimittel Forsch · Jan 2009
Randomized Controlled Trial Comparative StudyBioequivalence study of generic tablet formulations containing ethinylestradiol and chlormadinone acetate in healthy female volunteers.
The bioavailability and bioequivalence of two different film coated tablets containing ethinylestradiol (CAS 57-63-6) and chlormadinone acetate (CAS 302-22-7) (Bellissima as test and the respective preparation from the originator as reference) were investigated in 20 healthy female volunteers after oral single-dose administration. The study was performed according to a single-center, randomised, single-dose, 2-way cross-over design with a wash-out phase of 28 days. Blood samples for pharmacokinetic profiling were taken up to 168 h post-dose, and ethinylestradiol and chlormadinone acetate plasma concentrations were determined with a validated LC-MS/MS method. ⋯ Regarding the AUC(0-infinity) ratio of chlormadinone acetate, the point estimator is 91.60% and the 90% confidence interval 84.08%-99.79%. Furthermore, exchangeability of both formulations is also suggested by the point estimator and 90% confidence of Cmax of this active agent (104.72% [95.76%-114.53%]). Bioequivalence between test and reference formulation was demonstrated since for both ethinylestradiol and chlormadinone acetate all 90% confidence intervals of AUC(0-infinity) and Cmax fall into the generally accepted range of 80%-125%.
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Arzneimittel Forsch · Jan 2009
Randomized Controlled TrialPharmacokinetics and bioequivalence study of escitalopram oxalate formulations after single-dose administration in healthy Chinese male volunteers.
The aim of the present study was to compare the bioavailability of escitalopram (CAS 128196-01-0) from two escitalopram oxalate (CAS 219861-08-2) tablets (escitalopram 10 mg tablet as test preparation and 10 mg tablet commercially available original tablet of the drug as reference preparation) in 20 Chinese healthy male volunteers, aged between 19 and 27. The study was conducted according to an open, randomized, single blind, 2-way crossover study design with a wash-out phase of 14 d. Blood samples for pharmacokinetic profiling were taken up to 156 h post-dose, and escitalopram plasma concentrations were determined with a validated liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method. ⋯ Bioequivalence between test and reference preparation was demonstrated for both parameters, AUC(0-infinity) and AUC(0-t). The 90% confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80%-125%. That means that the test formulation is bioequivalent to the reference formulation for escitalopram.
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Arzneimittel Forsch · Jan 2009
Substitution of theophylline slow-release formulations according to the rebate contracts in the German statutory health insurance.
On the basis of the rebate contracts between individual statutory health insurance funds and pharmaceutical enterprises, the generic substitution of prescribed medications is economically attractive and is advocated for statutory health insurees in Germany. In addition to the drugs whose substitution can be considered to be uncritical, rebate contracts also include controversial substances such as the bronchodilator theophylline (CAS 58-55-9), which has a narrow therapeutic range and should only be substituted under certain conditions. The objective of this article was to check the safety of the substitution of theophylline by means of a comparative evaluation of bioequivalence studies carried out on theophylline slow-release preparations. ⋯ Because of the heterogeneity of study outcomes no metanalysis could be performed. On the basis of the studies analysed the conclusion can be drawn that a theophylline slow-release preparation should only be substituted under close monitoring by a physician because of the many factors which can adversely affect serum levels, such as the narrow therapeutic range of the active ingredient, the patient's metabolisation rate or the different galenics of the preparations. Nevertheless, the question remains as to whether the costs saved by the rebate contracts would not be significantly outweighed.