Generic Formulations of Commonly-used Oral Drugs in Saudi Arabia:Interchangeability & Post-marketing Quality
Generic Formulations of Commonly-Used, Immediate-Release, Solid, Oral, Drugs in Saudi Arabia: Interchangeability & Post-Marketing Quality
Generic formulations of prescription drugs can, through their relatively lower cost, improve healthcare as long as they maintain their registration-quality and public trust. On the other hand, the market availability of several generic formulations raises a concern regarding their interchangeability, despite being proven to be individually therapeutically interchangeable with their corresponding innovator formulation.
The investigators propose to assess the quality and therapeutic interchangeability of generic formulations in the drug market of Saudi Arabia, using fifteen, commonly-used, oral, solid, immediate-release, and non-combinational drugs.
研究概览
地位
详细说明
Generic formulations of prescription drugs can, through their relatively lower cost, improve healthcare as long as they maintain their registration-quality and public trust. On the other hand, the market availability of several generic formulations raises a concern regarding their interchangeability, despite being proven to be individually therapeutically interchangeable with their corresponding innovator formulation.
The investigators propose to assess the quality and therapeutic interchangeability of generic formulations in the drug market of Saudi Arabia, using fifteen, commonly-used, oral, solid, immediate-release, and non-combinational drugs.
The following drugs have been identified from the Saudi National Formulary (September 2006) as having, among oral, immediate-release, non-combinational drugs, the highest number of formulations (they have each 15 to 47): ciprofloxacin, ranitidine, amoxicillin, paracetamol, atenolol, cephalexin, ibuprofen, diclofenac, metformin, omeprazole, metronidazole, enalapril, clarithromycin, amlodipine, and fluconazole. In the first set of studies and for each drug, a four-treatment, four-period, four-sequence, crossover bioequivalence study will be conducted on the innovator and three randomly-selected generic formulations. Each study will be designed to have a power of 0.9 to detect bioequivalence, and sampling and wash-out periods of at least 5 and 7 half lives, respectively. Individuals who are identified in the first set of studies as having the large intra-subject variation (bioequivalence parameters ratios of less the 80% or more than 120% for AUC) will be subjected to a second set of studies, in which 2 batches of the reference formulation (including the batch used in the first set of studies) and the generic formulation will be compared in a two-treatment, four-period, two-sequence, replicate design crossover bioequivalence study. Drug levels will be determined by an HPLC or LC-MS-MS method, locally-validated according to international guidelines. After log transformation, AUC and Cmax (non-compartmental model) of the formulations will be compared pair-wise by ANOVA. Pair-wise bioequivalence will be tested by 90% (and 95%) confidence interval of ratios and Schuirmann's two one sided t-tests for the 70-143, 80-125%, and 90-112% ranges. The following will be determined: 1) the prevalence of generic formulations that are not bioequivalent to their innovator formulation, 2) the prevalence of the phenomena that two generics of the same innovator formulation are not bioequivalent to each other, 3) the percentage of individuals with large intra-subject variation despite the presence of average bioequivalence between the two formulations, and 4) how much of the large intra-subject variation in 3 above is true or related, in part, to product failure, random error, or subject-by-formulation interaction; and how it compares to intra-subject variability when two batches of the innovator formulation are compared.
研究类型
注册 (预期的)
阶段
- 不适用
联系人和位置
学习地点
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Riyadh、沙特阿拉伯、11211
- King Faisal Specialist Hospital & Research Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- No evidence of clinically important deviation from normal health as indicated by a recent physical examination, medical history, and clinical laboratory tests (complete blood count, renal and hepatic profiles, and routine urinalysis.
- Body Mass Index (BMI) should be less than 35 kg/m2.
- Acceptance to abstain from taking any medication (including over-the-counter [OTC] drugs) for at least 2 weeks prior to, and during the study; and from smoking and taking alcohol or caffeine or related xanthenes-containing beverages or food for 48 hours before taking the study drug and throughout each of the two blood sampling periods.
Exclusion Criteria:
- any contraindication to use the drug.
- any history of hypersensitivity to the drug to be tested or related compounds.
学习计划
研究是如何设计的?
设计细节
- 分配:随机化
- 介入模型:交叉作业
- 屏蔽:四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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有源比较器:Reference formulation of each drug
Innovator formulation
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single, oral, immediate-release, non-combinational innovator formulation
single, oral, immediate-release, non-combinational generic formulation a
single, oral, immediate-release, non-combinational generic formulation b
single, oral, immediate-release, non-combinational generic formulation c
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有源比较器:generic formulation a
one of the several generic formulations in the market, randomly selected for each drug
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single, oral, immediate-release, non-combinational innovator formulation
single, oral, immediate-release, non-combinational generic formulation a
single, oral, immediate-release, non-combinational generic formulation b
single, oral, immediate-release, non-combinational generic formulation c
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有源比较器:generic formulation b
second of the several generic formulations in the market, randomly selected for each drug
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single, oral, immediate-release, non-combinational innovator formulation
single, oral, immediate-release, non-combinational generic formulation a
single, oral, immediate-release, non-combinational generic formulation b
single, oral, immediate-release, non-combinational generic formulation c
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有源比较器:generic formulation c
third of the several generic formulations in the market, randomly selected for each drug
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single, oral, immediate-release, non-combinational innovator formulation
single, oral, immediate-release, non-combinational generic formulation a
single, oral, immediate-release, non-combinational generic formulation b
single, oral, immediate-release, non-combinational generic formulation c
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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bioequivalence
大体时间:ciprofloxacin 24hrs,ranitidine 14hrs,amoxicillin 10hrs,paracetamol 14hrs,atenolol 36hrs,cephalexin 6hrs,ibuprofen 10hrs,diclofenac 14hrs,metformin 32hrs,omperazole 12hrs,metronidazole 48hrs,enalapril 8hrs,clarithromycin 24hrs,amlodipine 240hrs
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Bioequivalence between marketed generic formulations and their corresponding innovator formulations and between 2 marketed generic formulations.
Bioequivalence will be assessed by the ratio of the area under the curve (AUC) (drug level vs time)and maximum levels (cmax) of two formulations and analyzed by the 90% confidence interval method.
The time is 3-5 plasma half-life of each drug.
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ciprofloxacin 24hrs,ranitidine 14hrs,amoxicillin 10hrs,paracetamol 14hrs,atenolol 36hrs,cephalexin 6hrs,ibuprofen 10hrs,diclofenac 14hrs,metformin 32hrs,omperazole 12hrs,metronidazole 48hrs,enalapril 8hrs,clarithromycin 24hrs,amlodipine 240hrs
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Intra-subject variation despite average bioequivalence
大体时间:ciprofloxacin 24hrs,ranitidine 14hrs,amoxicillin 10hrs,paracetamol 14hrs,atenolol 36hrs,cephalexin 6hrs,ibuprofen 10hrs,diclofenac 14hrs,metformin 32hrs,omperazole 12hrs,metronidazole 48hrs,enalapril 8hrs,clarithromycin 24hrs,amlodipine 240hrs
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Large intra-subject variation (a ratio of the test to reference formulation of AUC that is less than 80% or more than 120%) between innovator and generic formulation, despite showing average bioequivalence between the two formulations
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ciprofloxacin 24hrs,ranitidine 14hrs,amoxicillin 10hrs,paracetamol 14hrs,atenolol 36hrs,cephalexin 6hrs,ibuprofen 10hrs,diclofenac 14hrs,metformin 32hrs,omperazole 12hrs,metronidazole 48hrs,enalapril 8hrs,clarithromycin 24hrs,amlodipine 240hrs
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合作者和调查者
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
- 生物等效性
- interchangeability
- innovator formulations
- generic formulations
- inter-patch variation
- quality of generic drug formulations on the market
- Interchangeability between marketed generic formulations
- prevalence of large intrasubject variability despite average bioequivalence
- Causes of large intrasubject variability
其他研究编号
- RAC 2101100
- project 10-BIO961-20 (其他赠款/资助编号:Saudi National Comprehensive Plan for Science & Technology)
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