Single Dose, Two-period, Crossover, Fed Bioequivalence Study of Darifenacin Extended Release Oral Formulation (Darisec(R) 15 mg) vs. Enablex(R) 15 mg in Healthy Volunteers.
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Extent of Absorption.
研究概览
简要总结
The present study was designed to assess the bioequivalence and pharmacokinetic profiling of a brand generic formulation of darifenacin [Darisec(R)]vs. the innovator [Enablex(R)]in healthy volunteers after a high fat breakfast.
The bioequivalence will be evaluated using:
- the Area Under the Curve (AUC) and,
- the peak plasma concentration (Cmax).
Safety will be evaluated recording:
- vital signs
- adverse events,
- laboratory analysis.
- EKG and chest XRays.
Bioequivalence will be claimed if the drugs comply with local regulatory requirement, eg.:
- mean AUCt/AUCr and 90% confidence interval within 0.80-1.25
- mean Cmaxt/Cmaxr and 90% confidence interval within 0.80-1.25.
详细描述
Darifenacin is a muscarinic receptor antagonist drug used to treat overactive bladder. There is a new formulation of darifenacin extended release developed by an argentinian pharmaceutical company and, according to regional regulations, a bioequivalence study should be performed to put it in the market.
The purpose of this study is to evaluate the relative bioavailability and pharmacokinetic profiling of a brand generic formulation of darifenacin [Darisec(R) 15 mg] vs. the innovator [Enablex(R) 15 mg] in 24 healthy uruguayan volunteers after a high fat breakfast of 1000 calories (50% fat, 35% carbohydrates (sugar, flour, etc.) and 15& proteins) to establish their average bioequivalence.
The bioequivalence will be evaluated using outcome measures that will be described later.
The pharmacokinetic characteristics of the drugs will be described calculating:
- the time to Cmax (Tmax)
- the elimination constant (Ke),
- the elimination half-life (t1/2e)and,
- the systemic clearance (Cls.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female subjects 18 to 50 years of age (inclusive)
- •In good health, as determined by lack of clinically significant abnormalities at screening as judged by the physician.
- •Female subjects are required to use a medically accepted method of hormonal contraception or abstinence throughout the entire study period and for one week after the study is completed.
- •Body mass index within the range of 18.5 and 29.9 kg/m2 and weight at least 45 kg.
排除标准
- •Known hypersensitivity or severe adverse event to darifenacin or similar drugs.
- •Urinary retention, narrow-angle glucoma, myasthenia gravis, severe hepatic impairment, severe ulcerative colitis, toxic megacolon.
- •Symptomatic hiatus hernia, erosive or symptomatic gastroesophageal reflux disease/heartburn (>2 days in a week), severe constipation, gastrointestinal obstructive disorder, and gastric retention.
- •Clinically significant cardiac abnormalities, fainting, low blood pressure upon standing, irregular heartbeats.
- •Acute or chronic bronchospastic disease (including asthma and Chronic Obstructive Pulmonary Disease).
- •Clinically significant drug allergy or history of atopic allergy (asthma, urticaria, eczematous dermatitis).
- •Smokers of more than 5 cigarettes a week.
- •Regular use of any drugs known to induce or inhibit hepatic drug metabolism (particularly those that affect CYP2D6) within 30 days prior to each study drug administration.
- •Any surgical or medical condition wich might significantly alter the absorption, distribution, metabolism or excretion of drugs which may jeopardize participation in the study.
- •Immunodeficiency diseases, including a positive HIV (Elisa or Western blot) test result.
- •Positive hepatitis B Surface antigen (HBsAg) or Hepatitis C test result.
- •Drug or alcohol abuse within the 6 months prior to dosing.
- •Use of prescription drugs within 1 month prior to dosing, or over-the-counter medication (vitamine, herbal supplements, dietary supplements) within 2 weeks prior to dosing. Paracetamol and ibuprofen are acceptable.
- •Participation in any clinical investigation within 4 weeks prior to dosing.
- •Donation or loss of 400 ml or more of blood within 2 months prior to dosing.
- •significant illness within 2 weeks prior to dosing.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Enablex(R) 15 mg , single dose
干预措施: Darifenacin (Drug)
Darifenacin 15 mg tablets, single dose
干预措施: Darifenacin (Drug)
结局指标
主要结局
Extent of Absorption.
时间窗: 72 hours
Extent of absorption will be measured using the area under plasma concentrations of darifenacin vs. time from time 0 to the last sample point (AUC0-t) and from time 0 to infinity (AUC0-inf).
Rate of Absorption
时间窗: 72
Rate of abosrption will be measured using the peak concentration of darifenacin (Cmax).
次要结局
- Elimination Rate Constant (Ke)(72)
- Time to peak concentration (tmax)(72 hours)
- Absorption Rate Constant(Ka)(72 hours)