Clinical trial NCT03441841: Pharmacokinetic Study of Nanoencapsulated Gel of Lidocaine, Prilocaine and Combination of Lidocaine and Prilocaine
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Topical Anesthesia
Keywords: local anesthetics
pharmacokinetics
nanotechnology
Lead sponsor: Galeno Desenvolvimento de Pesquisas Clínicas
Sponsor class: OTHER_GOV
Collaborators: name: Biolab Sanus Farmaceutica
First posted: 2018-02-22
Enrollment: 48
Sex: ALL
Minimum age (years): 19
Maximum age (years): 53
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Measurement of lidocaine and prilocaine plasma levels
timeFrame: 0-24 h
measure: Maximum Plasma Concentration (Cmax) of lidocaine and prilocaine
timeFrame: 0-24 h
measure: Area Under the Curve (AUC) of lidocaine and prilocaine
timeFrame: 0-24 h
Secondary outcomes:
measure: Number of adverse events per participant
timeFrame: Up to 36 h after treatment
Other outcomes:
Locations:
city: Campinas
country: Brazil
facility: Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME
state: SP
Study officials:
References: