Tolerability and Pharmacokinetic Study of Econazole Nitrate and Benzydamine HCl Intravaginal Cream

NCT02713893 | Completed Phase 1

• 2 other identifiers: 030(4A)HO14387CRO-PK-14-289
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study is to evaluate local tolerability of the new Econazole/Benzydamine product, in comparison with the Econazole and Benzydamine stand-alone products and placebo. Pharmacokinetics of the study products after single and repeated applications once a day for 15 days, safety of the investigational products and comfort of use will also be evaluated as secondary objectives.

Conditions

Healthy

Keywords

Pharmacokinetics; Econazole nitrate 1%; Benzydamine HCl 0.12%; Intravaginal cream; Antimycotic; Tolerability

Outcome Measures

Primary Outcomes (1)

• Local Adverse Events (AEs)

  Occurrence of local Adverse Events (AEs) reported in the subject's diary as 1-3 scores for pruritus, burning sensation, pain, stinging, dryness; occurrence of all the other local AEs referred by the subject; occurrence of all the local Adverse Drug Reactions (ADRs) revealed by the Investigator

  Up to 7 days after administration

Secondary Outcomes (10)

• Econazole (free base), benzydamine (free base) and benzydamine N-oxide (free base) plasma concentrations

  At pre-dose (0), 1, 2, 3, 4, 6, 8, 12, 24 hours after the first (days 1-2) and the last dose (days 15-16) and at pre-dose (0) on day 6±1, day 9±1 and day 12±1

• Area under the plasma concentration versus time curve [AUC(0-t)] of econazole (free base), benzydamine (free base) and benzydamine N-oxide (free base)

  At pre-dose (0), 1, 2, 3, 4, 6, 8, 12, 24 hours after the first (days 1-2) and the last dose (days 15-16) and at pre-dose (0) on day 6±1, day 9±1 and day 12±1

• Treatment Emergent Adverse Events (TEAEs)

  15-16 days

• Change from screening in vital signs

  From screening (from day -21 to day -7) at days 1 and 15 at pre-dose (0), 12 and 24 hours post-dose

• Change from screening in 12-leads ECG

  From screening (from day -21 to day -7) at final visit (from day 17 to day 20)

Study Arms (4)

Econazole nitrate 1% plus Benzydamine HCl 0.12%

EXPERIMENTAL

5 grams of Econazole nitrate 1% plus Benzydamine HCl 0.12% intravaginal cream, once daily for 15 consecutive days

Drug: Econazole nitrate 1% plus Benzydamine HCl 0.12% intravaginal cream

Placebo plus Econazole nitrate 1%

ACTIVE COMPARATOR

5 grams of Placebo plus Econazole nitrate 1% intravaginal cream, once daily for 15 consecutive days

Drug: Placebo plus Econazole nitrate 1% intravaginal cream

Placebo plus Benzydamine HCl 0.12%

ACTIVE COMPARATOR

5 grams of Placebo plus Benzydamine HCl 0.12% intravaginal cream, once daily for 15 consecutive days.

Drug: Placebo plus Benzydamine HCl 0.12% intravaginal cream

Placebo

PLACEBO COMPARATOR

5 grams of Placebo intravaginal cream, once daily for 15 consecutive days.

Drug: Placebo intravaginal cream

Interventions

Econazole nitrate 1% plus Benzydamine HCl 0.12% intravaginal cream DRUG

Econazole nitrate 1% plus Benzydamine HCl 0.12%

Placebo plus Econazole nitrate 1% intravaginal cream DRUG

Placebo plus Econazole nitrate 1%

Placebo plus Benzydamine HCl 0.12% intravaginal cream DRUG

Placebo plus Benzydamine HCl 0.12%

Placebo intravaginal cream DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Sex and age: females, aged 18-55 years old inclusive;
• Body Mass Index (BMI): 18.5-30 kg/m2 inclusive;
• Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 50-90 bpm, measured after 5 min at rest (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;
• Sexual abstinence: agreement to sexual abstinence during the study;
• hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit;
• a non-hormonal intrauterine device \[IUD\] for at least 2 months before the screening visit;
• a male sexual partner who agrees to use a male condom;
• a vasectomised sexual partner. Female participants of non-child-bearing potential will be admitted. For all female subjects, pregnancy test result must be negative at screening and at each scheduled evaluation;
• PAP test: negative result at PAP test (i.e. normal PAP test result without atypical cells) at screening.

You may not qualify if:

• ECG (12-leads, supine position): clinically significant abnormalities;
• Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study as judged by the investigator;
• Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness;
• Allergy: ascertained or presumptive hypersensitivity (including allergies) to the active ingredients (econazole and/ or benzydamine) and/or formulations' excipients or related drugs, e.g. other azoles; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study;
• Diseases: relevant history of renal, hepatic, gastrointestinal, genitourinary, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study or affect the subject's safety;
• Genitourinary disease: presence of any specific genitourinary symptoms detected at Visit 2 with the relevant questionnaire (genitourinary symptoms questionnaire);
• Infection history: history of bacterial urinary tract or bacterial and fungal vaginal infections for 3 weeks before the screening visit;
• Infections: bacterial or fungal infections (microbiology assessment);
• Gynaecological findings: clinically significant abnormal findings at the gynaecological visit performed by the study gynaecologist;
• Mucosa conditions: altered mucosa conditions affecting the site of application (e.g. open lesion or other);
• Vaginal conditions: use of vaginal detergents, soaps and washes that, in the investigator's opinion, may have an influence on vaginal pH and/or change the vaginal flora;
• Medications: any medication (topical or systemic), including over the counter, herbal medication, topical drugs on the application area and anticoagulants, such as warfarin and acenocoumarol, for 2 weeks before the start of the study. Hormonal contraceptives and hormonal replacement therapies are allowed. Paracetamol will be allowed as a counter-measure for adverse events, on a case by case basis, if deemed appropriate by the investigator;
• Investigative drug studies: participation in the evaluation of any drug for 3 months before this study, calculated from the first day of the month following the last visit of a previous study and the first day of the present study (date of the informed consent signature);
• Blood donation: blood donations for 3 months before this study;
• Drug, alcohol, caffeine, tobacco: history of drug, alcohol (\> 1 drink/day, defined according to USDA Dietary Guidelines 2010), tobacco (≥ 10 cigarettes/day) or caffeine (\> 5 cups coffee/tea/day) abuse;

Sponsors & Collaborators

• Aziende Chimiche Riunite Angelini Francesco S.p.A: lead
• Cross Research S.A.: collaborator

Study Sites (1)

CROSS Research S.A., Phase I Unit

Arzo, CH-6864, Switzerland

Location

MeSH Terms

Interventions

Econazole; Benzydamine

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indazoles; Pyrazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Milko Radicioni, MD

  Cross Research S.A.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2015
• First Posted: March 21, 2016
• Study Start: September 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: June 15, 2016
• Last Updated: January 17, 2018

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)