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

January 15, 2018 updated by: Aziende Chimiche Riunite Angelini Francesco S.p.A

A Phase I Study of a Novel Intravaginal Antimycotic Cream (Econazole Nitrate 1% Plus Benzydamine HCl 0.12%) Administered Once Daily for 15 Days to Healthy Women

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Arzo, Switzerland, CH-6864
        • CROSS Research S.A., Phase I Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Econazole nitrate 1% plus Benzydamine HCl 0.12%
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
Active Comparator: Placebo plus Econazole nitrate 1%
5 grams of Placebo plus Econazole nitrate 1% intravaginal cream, once daily for 15 consecutive days
Drug: Placebo plus Econazole nitrate 1% intravaginal cream
Active Comparator: Placebo plus Benzydamine HCl 0.12%
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 Comparator: Placebo
5 grams of Placebo intravaginal cream, once daily for 15 consecutive days.
Drug: Placebo intravaginal cream

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Local Adverse Events (AEs)
Time Frame: 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
Up to 7 days after administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Econazole (free base), benzydamine (free base) and benzydamine N-oxide (free base) plasma concentrations
Time Frame: 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
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)
Time Frame: 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
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)
Time Frame: 15-16 days
15-16 days
Change from screening in vital signs
Time Frame: From screening (from day -21 to day -7) at days 1 and 15 at pre-dose (0), 12 and 24 hours post-dose
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
Time Frame: From screening (from day -21 to day -7) at final visit (from day 17 to day 20)
From screening (from day -21 to day -7) at final visit (from day 17 to day 20)
Change from screening in laboratory parameters
Time Frame: From screening (from day -21 to day -7) and at final visit (from day 17 to day 20)
From screening (from day -21 to day -7) and at final visit (from day 17 to day 20)
Change from screening in vaginal pH measurement
Time Frame: 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)
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 gynaecological examination findings
Time Frame: From screening (from day -21 to day -7) at final visit (from day 17 to day 20)
From screening (from day -21 to day -7) at final visit (from day 17 to day 20)
Overall tolerability assessment scale
Time Frame: At final visit (from day 17 to day 20)
At final visit (from day 17 to day 20)
Questionnaire for the comfort of use
Time Frame: At final visit (from day 17 to day 20)
At final visit (from day 17 to day 20)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Aziende Chimiche Riunite Angelini Francesco S.p.A

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Cross Research S.A.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 15, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 7, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 21, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 17, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 15, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 030(4A)HO14387
  • CRO-PK-14-289 (Other Identifier: CROSS Research S.A., Phase I Unit)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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