Tolerability and Pharmacokinetic Study of Econazole Nitrate Plus Benzydamine HCl Vaginal Pessary

NCT02720783 | Completed Phase 1

• 2 other identifiers: 030(4C)HO15323CRO-PK-15-302
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study is to evaluate the local tolerability of the new Econazole/Benzydamine pessary, in comparison with Econazole and Benzydamine stand-alone products and placebo. Pharmacokinetics of the study products after single and multiple applications o.d. for 3 days, overall local and general tolerability, safety and comfort of use will also be evaluated.

Conditions

Healthy Women

Keywords

Pharmacokinetics; Econazole nitrate 150mg; Benzydamine HCl 6mg; Vaginal pessary; Tolerability

Outcome Measures

Primary Outcomes (1)

• Local Adverse Drug Reactions (ADRs)

  Occurence of local ADRs reported by the subjects as 1-3 scores for pruritus, burning sensation, pain, stinging and dryness; occurrence of all the other local Adverse Events (AEs) referred by the subjects; occurrence of all the local ADRs revealed by the Investigator/ Gynaecologist

  Up to 7 days after administration

Secondary Outcomes (6)

• 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 (day 1) and the last dose (day 3)

• 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 (day 1) and the last dose (day 3)

• Overall local tolerability assessment scale

  At final visit (from day 5 to day 8)

• Occurrence of all AEs and ADRs

  5-8 days

• Change from screening in laboratory parameters

  From screening (from day -21 to day -7) at final visit (from day 5 to day 8)

Study Arms (4)

Econazole nitrate 150 mg plus Benzydamine HCl 6 mg

EXPERIMENTAL

One vaginal pessary (2.7 g) of Econazole nitrate 150 mg plus Benzydamine HCl 6 mg, once daily, for 3 consecutive days

Drug: Econazole nitrate 150 mg plus Benzydamine HCl 6 mg vaginal pessary

Placebo plus Econazole nitrate 150 mg

ACTIVE COMPARATOR

One vaginal pessary (2,7 g) of Placebo plus Econazole nitrate 150 mg, once daily, for 3 consecutive days

Drug: Placebo plus Econazole nitrate 150 mg vaginal pessary

Placebo plus Benzydamine HCl 6 mg

ACTIVE COMPARATOR

One vaginal pessary (2,7 g) of Placebo plus Benzydamine HCl 6 mg, once daily, for 3 consecutive days

Drug: Placebo plus Benzydamine HCl 6 mg vaginal pessary

Placebo

PLACEBO COMPARATOR

One vaginal pessary (2.7 g) of Placebo, once daily, for 3 consecutive days

Drug: Placebo vaginal pessary

Interventions

Econazole nitrate 150 mg plus Benzydamine HCl 6 mg vaginal pessary DRUG

Econazole nitrate 150 mg plus Benzydamine HCl 6 mg vaginal pessary

Econazole nitrate 150 mg plus Benzydamine HCl 6 mg

Placebo plus Econazole nitrate 150 mg vaginal pessary DRUG

Placebo plus Econazole nitrate 150 mg

Placebo plus Benzydamine HCl 6 mg vaginal pessary DRUG

Placebo plus Benzydamine HCl 6 mg

Placebo vaginal pessary 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: healthy women, 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 on day 1.
• PAP test: negative PAP test result (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.
• Allergies: ascertained or presumptive hypersensitivity (including allergies) to the active ingredients (econazole nitrate and/or benzydamine HCl) 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 diseases: 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 or fungal vaginal infections for 3 weeks before the screening visit.
• Systemic and/or local infections: bacterial or fungal infections that may interfere with the aim of the study or affect the subject's safety. If the results of the microbiological analyses concerning Ureaplasma/Mycoplasma and Actinomyces are positive, the subject can be enrolled only if asymptomatic and without any clinical evidence (gynaecological visit, PAP test and vaginal pH measurement) of vaginal infections.
• Gynaecological findings: clinically significant abnormal findings at the gynaecological visit performed by the study Gynaecologist.
• Mucosa conditions: altered mucosa conditions affecting the site of insertion (e.g. open lesions or other).
• Habits: 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, acenocoumarol and rivaroxaban, 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

Related Publications (1)

• Di Stefano AFD, Radicioni MM, Vaccani A, Caccia G, Focanti F, Salvatori E, Pelacchi F, Picollo R, Rosignoli MT, Olivieri S, Bovi G, Comandini A. Phase I Study in Healthy Women of a Novel Antimycotic Vaginal Ovule Combining Econazole and Benzydamine. Infect Dis Obstet Gynecol. 2020 May 2;2020:7201840. doi: 10.1155/2020/7201840. eCollection 2020.

  PMID: 32410819 DERIVED

MeSH Terms

Interventions

Econazole; Benzydamine; Suppositories

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indazoles; Pyrazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Milko Radicioni, MD

  CROSS Research S.A. Phase I Unit

  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: March 22, 2016
• First Posted: March 28, 2016
• Study Start: March 4, 2016
• Primary Completion: October 12, 2016
• Study Completion: October 12, 2016
• Last Updated: February 7, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)