A Cross-over Study of Pharmacokinetic Interaction Comparing Nanoencapsulated Gel of Prilocaine (2.5%), Lidocaine (2.5%) and Association of Prilocaine + Lidocaine 2.5% (Nanorap®) Topically in Healthy Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Measurement of lidocaine and prilocaine plasma levels
研究概览
简要总结
This trial evaluated the pharmacokinetic interaction between fixed doses of lidocaine (2.5%), prilocaine (2.5%) or the association of both (Nanorap®) in healthy volunteers. The drug safety and tolerability was also evaluated.
详细描述
This study was performed as a monocentric, open, randomized, double-blind, with 3 treatment regimen (lidocaine, prilocaine, or Nanorap®) in 3 periods design. Volunteers were submitted to clinical and laboratory examination before enrollment. Treatments were carried out on 3 different days with a washout period of 7 days between each dose.
After a fasting period (8 h), volunteers received topically 2g of the formulation in a delimited area of 16 cm2 in the volar surface of the forearm. The product was applied to the left arm and venous blood was collected from the right arm. The remaining product was removed with a cotton swab 10 minutes after application. Blood samples (3.5 mL) were collected into heparinized tubes before (0:00) and at 1.0, 2.0, 3.0, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 10.5, 11.0, 12.0, 14.0, 16.0 and 24.0 h after the hydrogel application.
Blood samples were centrifuged at 2000 g (4 ⁰C) for 10 minutes and the obtained plasma samples were stored at -20 °C until analysis.
Following dosing, volunteers were monitored for 36 h in a clinical setting safety and tolerability (signs, symptoms, adverse events, and laboratory parameters). The vital signs (blood pressure and pulse rate) were evaluated. ECGs were obtained before (30 min) and at drug Cmax (6 h) for each product application. QT interval corrected by heart rate (QTc) data were obtained from a Bionet Cardiocare 2000 and BMS-Plus software program, using Bazett's formula: QTc = QT/(sqrt RR Interval).
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
- 19 Years 至 53 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers over 18 years old
- •Body mass index (BMI) ≥ 19.0 kg/m² and ≤ 28.75 kg/m²
- •No evidence of significant diseases, that, at the investigator's discretion, may affect the participation in the clinical trial, in accordance with the protocol requirements
- •Ability to understand the nature and the objective of the clinical trial,including the risks and possible side effects; intention to cooperate with the investigator and act in accordance with the protocol requirements, as confirmed by the informed consent form signature.
排除标准
- •Subjects with known hypersensitivity to the compounds of the investigational products, severe allergies or multiple drug allergies
- •Existing diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the drug
- •Screening laboratory tests presenting deviations deemed as clinically significant, which, due to possible risks, prevents the participation in clinical trial.
- •Use of maintenance therapy with any drug
- •Drug or alcohol dependence
- •Volunteers who ingests more than 5 cups of coffee or tea per day and/or smoke
- •Volunteers with unusual eating habits, e.g, vegetarian
- •Treatment, within 3 months prior to the initiation of the clinical trial treatment, with any drug known to have a well-established toxic potential to major organs.
- •Use of regular medication within 2 weeks before the start of treatment and the date of evaluation, or made use of any medication within one week, except for oral contraceptives or cases where, based on the half-life of the drug and/or active metabolites, complete elimination can be assumed
- •Treatment within 6 months prior to the study with any known drug of have a well-defined toxic potential in large organs
- •Hospitalization for any reason up to 8 weeks before the start of the treatment of this study
- •Participation in a clinical trial during the last 6 months
- •Blood donation or other blood loss of more than 450 mL within the last 3 months
- •Pregnant, delivery or abortion in the 12 weeks prior to the planned hospitalization
- •The volunteer who has any condition that prevents him from participating in the study by judgment of the investigator
研究组 & 干预措施
Lidocaine + prilocaine
Single topical dose of a combination of nanoencapsulated lidocaine (2.5%) and prilocaine (2.5%) formulation in a delimited area of 16 cm2 in the volar surface of the forearm.
干预措施: Lidocaine + Prilocaine (Drug)
Lidocaine
Single topical dose of lidocaine nanoencapsulated gel (2.5 %) formulation in a delimited area of 16 cm2 in the volar surface of the forearm.
干预措施: Lidocaine (Drug)
Prilocaine
Single topical dose of prilocaine (2.5 %) nanoencapsulated gel formulation in a delimited area of 16 cm2 in the volar surface of the forearm.
干预措施: Prilocaine (Drug)
结局指标
主要结局
Measurement of lidocaine and prilocaine plasma levels
时间窗: 0-24 h
Blood sampling for the determination of plasma levels of lidocaine and prilocaine in participants of each treatment group.
Area Under the Curve (AUC) of lidocaine and prilocaine
时间窗: 0-24 h
Determination of AUC for lidocaine and prilocaine based on plasma concentrations of samples obtained.
Maximum Plasma Concentration (Cmax) of lidocaine and prilocaine
时间窗: 0-24 h
Determination of Cmax for lidocaine and prilocaine based on plasma concentrations of samples obtained.
次要结局
- Number of adverse events per participant(Up to 36 h after treatment)
研究者
Gilberto De Nucci
Doctor
Galeno Desenvolvimento de Pesquisas Clínicas