Comparative Bioavailability Study of a New Riluzole Orodispersible Film vs. a Marketed Oral Reference (Rilutek® Tablets) in Healthy Male and Female Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Evaluation of the Bioequivalent Rate of Absorption (Cmax) of Riluzole After Replicate Single Dose Administration of Test and Reference
研究概览
简要总结
The objective of the study is to compare the pharmacokinetic profile of riluzole after replicate single dose of the novel orodispersible film test formulation and of the marketed reference Rilutek® tablets and to evaluate their bioequivalence.
详细描述
The new formulation riluzole orodispersible film is expected to fill an important medical need, since the medication can be easily administered without water and may improve patient care. Riluzole orodispersible film is easily administered, because the patient or caregiver needs only to place the film on the tongue, where it can immediately dissolve into the saliva and be ingested with intentional swallowing or during the normal reflex of swallowing, thus eliminating the need for swallowing a tablet with liquid or crushing it into soft food.
Zambon S.p.A., Italy, is sponsoring the present bioequivalence study in order to investigate the bioequivalence of the novel unit-dose product versus Rilutek® tablets, commercially available in Europe as 50 mg tablets. The dose strength for the test formulation is 50 mg, matching the 50 mg strength of the reference formulation.
The subjects will receive single oral doses of 50 mg of riluzole, as test orodispersible film and reference film-coated tablets, under fasting conditions, in each of 4 subsequent periods separated by wash-out intervals of at least 7 days between consecutive administrations, according to a 2-treatment, 4-period, replicate cross-over design.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Informed consent: signed written informed consent before inclusion in the study
- •Sex and Age: men/women, 18-55 years old inclusive
- •Tobacco: non-smokers for at least 6 months prior to study screening
- •Body Mass Index (BMI): 18.5-29 kg/m2 inclusive
- •Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, heart rate 50-90 bpm, measured after 5 min at rest in the sitting position
- •Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
- •Contraception and fertility (women only): women of child-bearing potential must be using at least one of the following reliable methods of contraception:
- •A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit
- •A male sexual partner who agrees to use a male condom with spermicide
- •A sterile sexual partner Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all women, pregnancy test result must be negative at screening.
排除标准
- •Electrocardiogram (ECG) 12-leads: (supine position) clinically significant abnormalities; corrected QT interval > 450 msec
- •Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
- •Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
- •Cotinine: positive cotinine test at screening
- •Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study
- •Diseases: clinically significant history or presence of renal, hepatic, gastrointestinal, cardiovascular, cerebrovascular, immunological, musculoskeletal, respiratory, skin, haematological, endocrine, psychiatric or neurological diseases or surgeries that may interfere with the aim of the study. Gastrointestinal pathologies include any clinically significant disorder of the mouth, e.g. impairment of swallowing, lesions, ulcerations, deformities, untreated dental caries
- •Dentures: presence of mouth jewellery, dentures, braces, piercings that may interfere with successful completion of the dosing
- •Medications: medications, including over the counter medications and herbal remedies for 2 weeks before study screening; central nervous system depressants, including opioids, benzodiazepines, general anaesthetics and anticonvulsants, or cytochrome C inhibitors, including cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and antiretroviral agents, or strong cytochrome C inducers, including barbiturates, carbamazepine, glucocorticoids, phenytoin, St John's wort and rifampin, or hormonal oral or transdermal contraceptives for 30 days before study screening; implanted, injected, intravaginal or intrauterine hormonal contraceptives for 6 months before study screening
- •Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study
- •Blood donation: blood donations for 3 months before this study
- •Drug, alcohol, caffeine, tobacco: history of drug, alcohol [>1 drink/day for females and >2 drinks/day for males, defined according to the Dietary Guidelines 2015 ], caffeine (>5 cups coffee/tea/day) or tobacco use including any tobacco product like e-cigarettes and vamping products
- •Drug test: positive result at the drug test at screening or Day -1
- •Alcohol test: positive alcohol breath test at Day -1
- •Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians and vegans
- •Pregnancy (women only): positive or missing pregnancy test at screening or Day -1, pregnant or lactating women
研究组 & 干预措施
Reference/Test/Reference/Test
Riluzole orodispersible film (test): The subjects will be treated with one orodispersible film containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence Rilutek® (reference): The subjects will be treated with one film-coated tablet containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
干预措施: Riluzole 50 mg orodispersible film (Drug)
Reference/Test/Reference/Test
Riluzole orodispersible film (test): The subjects will be treated with one orodispersible film containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence Rilutek® (reference): The subjects will be treated with one film-coated tablet containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
干预措施: Rilutek® 50 mg riluzole tablets (Drug)
Test/Reference/Test/Reference
Riluzole orodispersible film (test): The subjects will be treated with one orodispersible film containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence Rilutek® (reference): The subjects will be treated with one film-coated tablet containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
干预措施: Riluzole 50 mg orodispersible film (Drug)
Test/Reference/Test/Reference
Riluzole orodispersible film (test): The subjects will be treated with one orodispersible film containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence Rilutek® (reference): The subjects will be treated with one film-coated tablet containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
干预措施: Rilutek® 50 mg riluzole tablets (Drug)
结局指标
主要结局
Evaluation of the Bioequivalent Rate of Absorption (Cmax) of Riluzole After Replicate Single Dose Administration of Test and Reference
时间窗: 0 h (pre-dose) and 15, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h after the drug administration
For each individual, the maximum plasma concentration (Cmax) of riluzole after replicate single dose administration of Test and Reference was measured. The Cmax 90% confidence interval of the ratio Test/Reference of the population means was calculated. The bioequivalence is demonstrated when the 90% confidence Interval of this ratio lies within the range 80.00-125.00% (acceptance interval).
Evaluation of the Bioequivalent Extent of Absorption (AUC0-t) of Riluzole After Replicate Single Dose Administration of Test and Reference.
时间窗: 0 h (pre-dose), 15, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h after drug administration
For each individual, the area under the concentration-time curve from single dose Test and Reference administration to the last observed concentration time t (AUC0-t) of riluzole was measured. The AUC0-t 90% confidence interval of the ratio Test/Reference of the population means was calculated. The bioequivalence is demonstrated when the 90% confidence Interval of this ratio lies within the range 80.00-125.00% (acceptance interval).
次要结局
- Evaluation of the Test Product Palatability(Immediately after 2nd Test product administration, approximately within 5 minutes after administration)
- To Describe the t1/2 (Half-life) of Riluzole After Replicate Single Dose Administration of Test and Reference(0 h (pre-dose), 15, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h after drug administration)
- To Describe the AUC0-∞ of Riluzole After Replicate Single Dose Administration of Test and Reference(0 h (pre-dose), 15, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h after drug administration)
- Description Tmax: Time to Achieve Cmax Reference(0 h (pre-dose), 15, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h after drug administration)
- Number of Participants With Mucosal Irritation(pre-dose (0), 0.5 and 1 h after the drug administration)
- Haematology, Blood Chemistry and Urinalysis Laboratory Tests Interpretation(At screening (initial visit) and at final visit (approximately 1 month))
研究者
Milko Radicioni
Principal Investigator
Cross Research S.A.