Nell H, Louw C M, Cyster H, Williams Z, Bardin P G, Joubert J R
Drug Research Unit, Department Internal Medicine and Pulmonology, University of Stellenbosch, Tygerberg, W Cape.
S Afr Med J. 2001 Jan;91(1):51-6.
To study the therapeutic equivalence of two formulations (innovator v. generic) of beclomethasone dipropionate (BDP) 400 micrograms twice daily administered per metered dose inhaler (MDI), in adults with moderate to severe asthma.
A double-blind randomised parallel-group trial was performed with a 2-week run-in and an 8-week treatment period. Thirty-six symptomatic adult asthmatics on a mean daily dose of 750 micrograms inhaled corticosteroids during run-in, a mean forced expiratory volume in 1 second (FEV1) of 70% predicted normal and a mean histamine concentration provoking a 20% reduction in FEV1 (histamine PC20) of 0.11 mg/l were randomised to one of the two treatment groups. Primary variables were morning peak expiratory flow (mPEF), FEV1 and histamine PC20. Secondary variables were beta 2-agonist use, symptom score and nocturnal awakening. The Schuirmann two one-sided tests procedure was used for the statistical analysis. Ninety-five per cent confidence intervals (CIs) were calculated for the differences in means.
The mean differences end of treatment to baseline for the two formulations (Becotide and Beclate) respectively were: mPEF 5.6 l/min (CI - 16.4-27.6) and -22.3 l/min (CI -35.6(-)-9); FEV1 -2.9% (CI -11-5.2) and 0.2% (CI -4.8-5.2); Histamine PC20 -0.04 mg/ml (CI -0.15-0.06) and 0.02 mg/ml (CI -0.37-0.4). Changes in clinical variables were not conclusive. The mean differences with CIs for primary variables were contained within the limits set for equivalence. The sample size was sufficient to differentiate the groups for mPEF, but this was not of clinical significance.
After 8 weeks of treatment the two formulations of BDP, delivered by MDI through a large-volume spacer, were therapeutically equivalent in moderate-to-severe asthmatic adults.
研究每日两次、每次400微克丙酸倍氯米松（BDP）的两种制剂（创新型与仿制药）通过定量吸入器（MDI）给药，在中度至重度哮喘成年患者中的治疗等效性。
进行了一项双盲随机平行组试验，有2周的导入期和8周的治疗期。36名有症状的成年哮喘患者在导入期平均每日吸入皮质类固醇剂量为750微克，1秒用力呼气容积（FEV1）平均为预测正常值的70%，组胺浓度激发FEV1降低20%（组胺PC20）平均为0.11毫克/升，被随机分配到两个治疗组之一。主要变量为早晨呼气峰值流速（mPEF）、FEV1和组胺PC20。次要变量为β2受体激动剂使用情况、症状评分和夜间觉醒。采用Schuirmann双单侧检验程序进行统计分析。计算均值差异的95%置信区间（CIs）。
两种制剂（必可酮和倍氯米松）治疗结束时与基线相比的平均差异分别为：mPEF 5.6升/分钟（CI -16.4 - 27.6）和 -22.3升/分钟（CI -35.6(-)-9）；FEV1 -2.9%（CI -11 - 5.2）和0.2%（CI -4.8 - 5.2）；组胺PC20 -0.04毫克/毫升（CI -0.15 - 0.06）和0.02毫克/毫升（CI -0.37 - 0.4）。临床变量的变化尚无定论。主要变量的均值差异及其CIs包含在等效性设定的限度内。样本量足以区分mPEF组，但这无临床意义。
经MDI通过大容量储雾罐给药8周后，两种BDP制剂在中度至重度哮喘成年患者中治疗等效。
