Randomized, double-blind, cross-over efficacy and safety study based on the pharmacodynamic model of topical use of the new combination gel containing diphenhydramine hydrochloride 20 mg/g and lidocaine hydrochloride 10 mg/g versus placebo in the treatment of local skin inflammatory and allergic lesions induced by the provocative test with histamine in healthy subjects.

Phase 1

• Conditions: Skin inflamatory and allergic lesions inducted by insects bites (i.e. mosquitos) and after contact with plants (i.e.urtica). Decreasing redness, edema, papular urticaria, analgesic, antipriuritic and anaestetic locally.; MedDRA version: 20.0Level: LLTClassification code 10038198Term: RednessSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders; MedDRA version: 20.0Level: LLTClassification code 10014210Term: EdemaSystem Organ Class: 10018065 - General disorders and administration site conditions; MedDRA version: 20.0Level: PTClassification code 10033474Term: Pain of skinSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders; MedDRA version: 20.0Level: LLTClassification code 10018069Term: General pruritusSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders; MedDRA version: 20.0Level: PTClassification code 10061218Term: InflammationSystem Organ Class: 10018065 - General disorders and administration site conditions; MedDRA version: 20.0Level: PTClassification code 10015150Term: ErythemaSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders; Therapeutic area: Not possible to specify

• Registration Number: EUCTR2018-004502-26-PL
• Lead Sponsor: Przedsiebiorstwo Produkcji Farmaceutycznej (P.P.F.)HASCO-LEK S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-04-01
• Last Update Posted: 2 June 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

All Subjects must meet the following criteria:
1.The Subject is healthy male or female. Healthy Subjects are defined as individuals who are free from clinically significant illness or disease as determined by their medical history, physical examination, vital signs, laboratory screening (hematology). Medical history check will also include verification of data concerning special precautions for study drug use.
2.If males: male Subjects who are willing to use an acceptable method of contraception from the first dosing until completion of the study (barrier methods with spermicide and sexual abstinence are allowed).
3.If females: female Subjects are eligible to enter and participate in the study if they are of:
a.Non-childbearing potential (i.e. physiologically incapable of becoming pregnant) including females who: have had a hysterectomy or a bilateral oophorectomy, or a bilateral tubal ligation, or are post-menopausal (a demonstration of total cessation of menses for = 12 months on the day of screening). Performing of urine pregnancy test is not required for non-childbearing potential females.
b.Childbearing potential and have a negative result of urine pregnancy test at screening and on prior to each dose administration and agree to use one of the following contraception methods: complete abstinence from sexual intercourses or double barrier method (condom or occlusive cap used with spermicidal foam) from at least 6 days prior to administration of the study products until completion of the study or use of intrauterine non-hormonal device within at least 4 weeks prior to the first study product administration until completion of the study.
4.The Subject is = 18 and = 55 years of age (on the day of screening).
5.BMI = 18.5 to = 30.0 kg/m2 (on the day of screening).
6.Clear and normal (unchanged) skin at both forearms.
7.Caucasian race.
8.Signed and dated written informed consent of the Subject to participate in the clinical study prior to screening evaluations.
9.Non-smoker and non-tobacco user for at least 3 months before the day of screening.
10.The Subject is willing to refrain from the use of illicit drugs, nicotine containing products and alcohol and to adhere to other protocol-stated restrictions while participating in the study as well as refrain from eating chocolate, tomatoes, blue cheese, cabbage, spinach, sausage, tuna, pickled cucumbers, citrus fruits, products containing gluten, sea food, vit. C and acerola at the day of skin prick tests performed.
11.The Subject is able to understand and comply with the protocol requirements and instructions and is likely to complete the study as planned.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 44
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Each of the following is a criterion of exclusion:
1.A significant abnormality in the past and/or at screening that influences present general health condition and requires pharmacological treatment during the study.
2.Any current or past medical condition, including active atopic dermatitis, psoriasis, chronic eczema, or any other dermatologic condition, which might significantly affect response to study products application.
3.Current changes of the skin on forearms.
4.Any condition that impairs the patient's ability to overcome a rare anaphylactic reaction (e.g. hypertension or unstable coronary heart disease, reduced lung function).
5.An anaphylactic reaction (especially after insect bites) in the history.
6.Hypersensitivity to anesthetics.
7.Poorly controlled, moderate or severe bronchial asthma.
8.Patients with dermatography.
9.Any confirmed allergic reaction to any drug including allergy to active substances of test product and to excipients of both study products or multiple allergies, as clinically significant in the judgement of the Investigator.
10.Negative result at histamine skin prick test (on the day of screening).
11.Presence of cardiac disease, such as angina pectoris, conduction disorders (including those associated with prolongation of the QT interval, or AV blocks of different degree, recent myocardial infarction).
12.Presence of psychiatric conditions, such as depression, schizophrenia, episodes of mania or other psychotic disorders and suicide-related events in medical history.
13.History of drug addiction and/or alcohol abuse (alcohol consumption of more than 500 mL of beer/day or 200 mL of wine/day or 50 mL of liquor/day) during last year preceding the day of screening.
14.Blood pressure: systolic > 140 mmHg or < 90 mmHg, diastolic < 60 mmHg or > 90 mmHg during screening.
15.Any other current or past disease or condition that may influence on the course of the study in the opinion of the Investigator.
16.Pregnant or breast-feeding females.
17.Heart rate < 50 or > 100 bpm at screening and on the evening prior to the first dose administration.
18.Body temperature < 36.0°C or > 37.4°C at screening.
19.Clinically significant abnormal laboratory values at screening (hematology).
20.Use of any over-the-counter medication (except for paracetamol at dose = 1 g daily) including vitamins, lozenges, herbal and dietary supplements within 7 days before the screening visit.
21.Use of any prescription drugs (especially antihistamine and sedative drugs, Ca preparations and tricylic antidepressants) as well as topical use of ointments and creams with steroids in the studies forearms in the 28 days prior to the screening Visit.
22.Alcohol consumption within 72 hours prior to the first product administration.
23.Participation in other clinical trials where at least one dose of study product was administered within 30 days prior to the first dose administration.
24.Any reason for which the Subject is considered by the Investigator to be an unsuitable candidate to participate in the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate efficacy and safety of the new combination topical gel containing diphenhydramine hydrochloride 20 mg/g and lidocaine hydrochloride 10 mg/g versus placebo in the treatment of local skin inflammatory and allergic lesions induced in the provocative test with histamine (skin prick test).;Secondary Objective: not applicable;Primary end point(s): The difference in area under the curve (AUC) calculated from the intensity of itch for test product and placebo product assessed using visual analogue scale (VAS) at each estimation time point<br><br><br>;Timepoint(s) of evaluation of this end point: In each Period the evaluation of itch using VAS scale will be performed after histamine administration (time 0”) and at: 2, 4, 6, 8, 10, 15, 20, 30, 60 and 90 minutes after test product/placebo administration.<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Change in diameter of the wheal and the erythema<br>• Rate of decrease in itching.<br>• Safety of study products<br>• Peak itch intensity<br>;Timepoint(s) of evaluation of this end point: Change in diameter of the wheal and the erythema<br>Rate of decrease in itching.<br>Peak itch intensity<br>In each Period the evaluation will be performed after histamine administration (time 0”) and at: 2, 4, 6, 8, 10, 15, 20, 30, 60 and 90 minutes after test product/placebo administration.<br><br>Safety:<br>•Medical history (at scr).<br>•Hematology (at screening): hemoglobin, hematocrit, RBC count, WBC count with differential, and platelet count. <br>•Vital signs (heart rate, blood pressure, body temperature) measured at screening, and at Visit I and II. <br>•Pregnancy urine test (at screening and at Visit I and Visit II) childbearing potential females only.<br>•Breath alcohol test (at Visit I and Visit II).<br>•AE monitoring (from the study products administration until the end of the study).