Thomasius Friederike, Keung Nip Tsz, Ivan Paul
a Synexus Clinical Research , Frankfurt , Germany.
b Takeda Development Centre Europe Ltd , London , UK.
Curr Med Res Opin. 2016 Oct;32(10):1623-1631. doi: 10.1080/03007995.2016.1202817. Epub 2016 Jun 29.
INTRODUCTION/OBJECTIVES: Preference for supplement formulation helps determine an individual's adherence to long-term medication and can improve clinical benefit for chronic illnesses such as osteoporosis. This study compared the preference, acceptability and tolerability of a reformulation of Calcichew D3 500 mg/400 IU and Calcichew D3 500 mg/800 IU (Takeda UK Ltd, Wobrun Green, UK) with Adcal-D3 500 mg/400 IU (ProStrakan Ltd, Galashiels, UK) and Kalcipos-D 500 mg/800 IU (Meda Pharmaceuticals Ltd, Bishop's Stortford, UK), respectively.
This phase IV, randomized, open-label, two-period, cross-over study was conducted at nine sites in the UK and Germany. Eligible subjects (≥65 years requiring calcium/vitamin D supplementation for prevention/treatment of deficiencies, or ≥18 years requiring supplementation as an adjunct to osteoporosis treatment) were randomly assigned to one of two 2 week treatment sequences - Group 1: Calcichew D3 500/400 then Adcal-D3 500/400 (or vice versa), or Group 2: Calcichew D3 500/800 then Kalcipos-D 500/800 (or vice versa). After each treatment period, patients rated the treatment for acceptability using 100 mm visual analogue scales. After the second treatment period, patients indicated their treatment preference. The primary endpoint, the percentage of patients with a preference for each treatment, was analyzed with a logistic regression model.
Two hundred and seventy-six patients were randomly assigned by treatment sequence, 138 to each group. Preference questionnaires among patients who preferred Calcichew or comparator revealed the odds for patients preferring Calcichew 500/400 (77.6%) over Adcal-D3 was 3.46 ([95% CI 2.24, 5.36], p < 0.001) in Group 1, and Calcichew D3 500/800 (63.2%) over Kalcipos-D was 1.72 ([1.19, 2.47], p = 0.004) in Group 2. Adverse events were mostly gastrointestinal and were comparable between groups. The new formulation of Calcichew D3 is acceptable and consistent with its known tolerability profile.
In this short-term 30 day study, patients preferred Calcichew D3 500/400 and Calcichew D3 500/800 over respective comparators. A trend towards better compliance with Calcichew D3 preference observed in Group 1 warrants a longer term study to identify treatment compliance.
Clinicaltrials.gov: NCT02457247.
引言/目的：对补充剂配方的偏好有助于确定个体对长期药物治疗的依从性，并可改善骨质疏松症等慢性疾病的临床疗效。本研究比较了钙尔奇D3 500毫克/400国际单位和钙尔奇D3 500毫克/800国际单位（英国武田制药有限公司，英国沃本格林）的重新配方与阿法迪三500毫克/400国际单位（英国ProStrakan有限公司，加拉希尔斯）和卡奇泊D 500毫克/800国际单位（英国Meda制药有限公司，主教城斯特福德）的偏好、可接受性和耐受性。
本IV期、随机、开放标签、两阶段、交叉研究在英国和德国的9个地点进行。符合条件的受试者（≥65岁因预防/治疗缺乏症需要补充钙/维生素D，或≥18岁作为骨质疏松症治疗辅助需要补充）被随机分配到两个为期2周的治疗序列之一——第1组：先服用钙尔奇D3 500/400，然后服用阿法迪三500/400（或反之），或第2组：先服用钙尔奇D3 500/800，然后服用卡奇泊D 500/800（或反之）。在每个治疗期后，患者使用100毫米视觉模拟量表对治疗的可接受性进行评分。在第二个治疗期后，患者表明他们对治疗的偏好。主要终点，即对每种治疗有偏好的患者百分比，采用逻辑回归模型进行分析。
276名患者按治疗序列随机分配，每组138名。在偏好钙尔奇或对照产品的患者中进行的偏好问卷调查显示，在第1组中，患者偏好钙尔奇500/400（77.6%）而非阿法迪三的优势比为3.46（[95%置信区间2.24，5.36]，p<0.001），在第2组中，患者偏好钙尔奇D3 500/800（63.2%）而非卡奇泊D的优势比为1.72（[1.19，2.47]，p = 0.004）。不良事件大多为胃肠道事件，两组之间相当。钙尔奇D3重新配方是可接受的，且与其已知的耐受性特征一致。
在这项为期30天的短期研究中，患者更偏好钙尔奇D3 500/400和钙尔奇D3 500/800而非各自的对照产品。在第1组中观察到的对钙尔奇D3偏好的依从性更好的趋势值得进行长期研究以确定治疗依从性。
Clinicaltrials.gov：NCT02457247。
