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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Placebo plus Benzydamine HCl 0.12% intravaginal cream; Drug: Placebo plus Econazole nitrate 1% intravaginal cream; Drug: Econazole nitrate 1% plus Benzydamine HCl 0.12% intravaginal cream; Drug: Placebo intravaginal cream

• Registration Number: NCT02713893
• Lead Sponsor: Aziende Chimiche Riunite Angelini Francesco S.p.A

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-08-07
• Study Start: 2015-09
• Study First Submitted QC: 2016-03-18
• Study First Posted: 2016-03-21
• Primary Completion: 2016-06
• Study Completion: 2016-06-15
• Status Verified: 2016-08
• Last Update Submitted: 2018-01-15
• Last Update Posted: 2018-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 48

Inclusion Criteria

1. Informed consent: signed written informed consent before inclusion in the study;

2. Sex and age: females, aged 18-55 years old inclusive;

3. Body Mass Index (BMI): 18.5-30 kg/m2 inclusive;

4. 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);

5. 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;

6. Sexual abstinence: agreement to sexual abstinence during the study;

7. Contraception and fertility: women of child-bearing potential, even if sexual abstinent during the study as required by the study inclusion criteria, must be using at least one reliable method of contraception, as follows:

   1. hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit;
   2. a non-hormonal intrauterine device [IUD] for at least 2 months before the screening visit;
   3. a male sexual partner who agrees to use a male condom;
   4. 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;

8. PAP test: negative result at PAP test (i.e. normal PAP test result without atypical cells) at screening.

Exclusion Criteria

1. ECG (12-leads, supine position): clinically significant abnormalities;
2. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study as judged by the investigator;
3. Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness;
4. 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;
5. 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;
6. Genitourinary disease: presence of any specific genitourinary symptoms detected at Visit 2 with the relevant questionnaire (genitourinary symptoms questionnaire);
7. Infection history: history of bacterial urinary tract or bacterial and fungal vaginal infections for 3 weeks before the screening visit;
8. Infections: bacterial or fungal infections (microbiology assessment);
9. Gynaecological findings: clinically significant abnormal findings at the gynaecological visit performed by the study gynaecologist;
10. Mucosa conditions: altered mucosa conditions affecting the site of application (e.g. open lesion or other);
11. 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;
12. 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;
13. 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);
14. Blood donation: blood donations for 3 months before this study;
15. 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;
16. Diet: Abnormal diets (< 1600 or > 3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians
17. Pregnancy: positive or missing pregnancy test at screening or day 1, pregnant or lactating women or females of child-bearing potential not following adequate contraceptive procedures;
18. Non-compliance: subjects suspected to have a high potential for non-compliance to the study procedures according to the investigator's judgement, including non-compliance to sexual abstinence during the study;
19. Drug test (cocaine, amphetamine, methamphetamine, cannabinoids, opiates and ecstasy): positive result at the drug test at screening
20. Alcohol test: positive alcohol breath test at day 1

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Local Adverse Events (AEs)	Up to 7 days after administration	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

Secondary Outcome Measures

Name	Time	Method
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
Treatment Emergent Adverse Events (TEAEs)	15-16 days
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
Change from screening in vaginal pH measurement	From screening (from day -21 to day -7), before the application on days 1, 2, 15, on days 6±1, 9±1, 12±1 at final visit (from day 17 to day 20)
Change from screening in laboratory parameters	From screening (from day -21 to day -7) and at final visit (from day 17 to day 20)
Questionnaire for the comfort of use	At final visit (from day 17 to day 20)
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
Change from screening in 12-leads ECG	From screening (from day -21 to day -7) at final visit (from day 17 to day 20)
Change from screening in gynaecological examination findings	From screening (from day -21 to day -7) at final visit (from day 17 to day 20)
Overall tolerability assessment scale	At final visit (from day 17 to day 20)

Trial Locations

Locations (1)

CROSS Research S.A., Phase I Unit; 🇨🇭 Arzo, Switzerland