Clinical Trial Results:
A prospective, multicentre, uncontrolled study of Geonistin vaginal tablets effectiveness with pharmacokinetic evaluation for unspecific and mixed vulvovaginal infections characterized by vaginal discharge
Summary
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EudraCT number |
2016-000078-39 |
Trial protocol |
HR |
Global end of trial date |
13 Dec 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Feb 2020
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First version publication date |
28 Feb 2020
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GEO-2014/01-HR
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
PLIVA Croatia Ltd.
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Sponsor organisation address |
Prilaz baruna Filipovića 25, Zagreb, Croatia, 10000
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Public contact |
Mirjana Matrapazovski Kukuruzović, MD, PLIVA Croatia Ltd., 385 13724962, Mirjana.Matrapazovski-Kukuruzovic@pliva.com
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Scientific contact |
Mirjana Matrapazovski Kukuruzović, MD, PLIVA Croatia Ltd., 385 13724962, Mirjana.Matrapazovski-Kukuruzovic@pliva.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Mar 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Dec 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Dec 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to evaluate the clinical effectiveness of Geonistin vaginal tablets administered in empirical treatment of female adult patients with unspecific and mixed vulvovaginal infections characterized by vaginal discharge.
The secondary objectives of the study were to evaluate the: (1) systemic exposure to oxytetracycline in local treatment of vulvovaginal infections with Geonistin vaginal tablets; (2) cure rate according to the Nugent score (where applicable); (3) microbiology and microscopy results (outcome); and (4) safety of Geonistin vaginal tablets.
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Protection of trial subjects |
The study was conducted according to Helsinki Declaration, in compliance with local regulations and in accordance with PLIVA Croatia Ltd. standard procedures.
This study was conducted in full accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6) and any applicable national and local laws and regulations, European Union [EU] Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of GCP in the conduct of clinical trials on medicinal products for human use).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Sep 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Croatia: 192
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Worldwide total number of subjects |
192
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EEA total number of subjects |
192
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
192
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Physicians were asked to recruit patients that require Geonistin vaginal tablets treatment from their everyday practice during regular office visit, according to predefined inclusion and exclusion criteria. In total 194 patients were assessed for eligibility, 192 patients were enrolled and 189 completed the study. | ||||||||||
Pre-assignment
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Screening details |
2 subjects were assessed for eligibility but they were excluded per exclusion criteria. | ||||||||||
Period 1
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Period 1 title |
Geonistin (Baseline)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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Period 1 | ||||||||||
Arm description |
- | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Geonistin vaginal tablets
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Investigational medicinal product code |
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Other name |
Geonistin
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Pharmaceutical forms |
Tablet
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Routes of administration |
Vaginal use
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Dosage and administration details |
One vaginal tablet containing 100 mg oxytetracycline and 100,000 IU nystatin was self-administered by a patient once daily over 6 consecutive days.
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Period 2
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Period 2 title |
Geonistin End of Study
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Is this the baseline period? |
No | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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Period 1 | ||||||||||
Arm description |
- | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Geonistin vaginal tablets
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Investigational medicinal product code |
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Other name |
Geonistin
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Pharmaceutical forms |
Tablet
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Routes of administration |
Vaginal use
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Dosage and administration details |
One vaginal tablet containing 100 mg oxytetracycline and 100,000 IU nystatin was self-administered by a patient once daily over 6 consecutive days.
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Baseline characteristics reporting groups
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Reporting group title |
Geonistin (Baseline)
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Reporting group description |
Geonistin tablets administered for 6 day open label treatment period. One tablet containing 100 mg oxytetracycline and 100,000 IU nystatin was self-administered once daily. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Period 1
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Reporting group description |
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Reporting group title |
Period 1
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Reporting group description |
- |
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End point title |
Clinical cure rate after 6 days of treatment | |||||||||
End point description |
Clinical effectiveness was evaluated on Day 13 (Visit 2) after 6 days of treatment. Signs and symptoms such as vaginal discharge, odor, itching, were rated as present or absent. Clinical cure was defined as signs or symptoms identified on Day 1 that were absent on Day 13. Signs and symptoms were also rated by severity. Severity was rated as mild, moderate, or severe. Cure rate was defined as absent or improved from severe to mild.
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End point type |
Primary
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End point timeframe |
Day 13
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Notes [1] - All participants were assessed at end of the study. [2] - Of 189 participants counted, 154 were considered cured. |
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Statistical analysis title |
Confidence interval of a binomial proportion | |||||||||
Statistical analysis description |
95% two-sided Clopper-Pearson confidence interval for clinical cure rate
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Comparison groups |
Period 1 v Period 1
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Number of subjects included in analysis |
378
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | |||||||||
P-value |
< 0.025 [4] | |||||||||
Method |
Clopper-Pearson | |||||||||
Parameter type |
Percentage | |||||||||
Point estimate |
81.5
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
75.2 | |||||||||
upper limit |
86.7 | |||||||||
Notes [3] - Single arm assessed at end of the study (189 participants, not 378 as shown below). 154 out of 189 participants counted were considered cured (154 out of 189 = 81.5%). [4] - Statistically significant clinical effect implied by lower limit of 95% confidence interval for cure rate above 60% |
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End point title |
Steady-state serum concentrations of oxytetracycline | ||||||||||
End point description |
Steady-state serum concentrations were calculated from pharmacokinetic measurements on Day 7.
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End point type |
Secondary
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End point timeframe |
Day 7
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Notes [5] - Number of subjects analyzed equals number of participants with quantifiable data available |
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No statistical analyses for this end point |
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End point title |
Number of participants clinically cured based on Nugent score | ||||||
End point description |
Effectiveness was assessed based on improvement in Nugent scores from Day 1 to Day 13. Nugent scores of 4-6 (intermediate flora) and greater than or equal to 7 (bacterial vaginosis) were included in the analysis. Cured was defined as a Nugent score of 0-3 on Day 13.
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End point type |
Secondary
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End point timeframe |
Day 13 after 6 days of treatment
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Notes [6] - 138 participants had countable data. 67 out of 138 were considered cured. |
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No statistical analyses for this end point |
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End point title |
Number of participants cured according to microbiological results | ||||||
End point description |
Microbiological cure rate was assessed for participants with microorganisms identified at Day 1 visit. Cure was defined as a negative culture (no growth) for baseline pathogens or 1+ if the baseline value was greater than 1+.
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End point type |
Secondary
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End point timeframe |
Day 13 after 6 days of treatment
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Notes [7] - Of 151 participants assessed, 119 were considered cured. |
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No statistical analyses for this end point |
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End point title |
Number of participants who reported at least one adverse event | ||||||
End point description |
Adverse events were collected from signing the informed consent form through Day 13 (Visit 2) and were self-reported until the end of the follow up period (Day 30).
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End point type |
Secondary
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End point timeframe |
Up to Day 30
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Notes [8] - 13 participants experienced at least one adverse event. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events (AEs) were collected from the signature of the informed consent form through Day 13 (Visit 2) and were self-reported until the follow up period, Day 30.
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Adverse event reporting additional description |
Reported adverse events (AEs) are adverse events that are treatment emergent. Treatment emergent adverse events were AEs reported between the first dose of Geonistin up until the follow up period, Day 30.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
Geonistin
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Reporting group description |
Received at least one dose of Geonistin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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07 Nov 2016 |
Protocol amendment 1 was prepared to clarify exclusion criteria 13 (ongoing use of vaginal probiotics) |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |