Clinical Trial Results:
Multicenter, randomized, double-blind, comparative with reference product clinical trial to evaluate the efficacy and safety of treatment with Clindamycin vaginal suppositories 100 mg in patients with bacterial vaginosis
Summary
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EudraCT number |
2011-002386-38 |
Trial protocol |
GR |
Global end of trial date |
19 Oct 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Feb 2017
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First version publication date |
04 Feb 2017
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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 |
CLVS100VER
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Verisfield (UK) Ltd
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Sponsor organisation address |
8 Vironos Street, Halandri/Athens, Greece,
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Public contact |
Clinical Research Scientist, Antonios Margaritis, VERISFIELD (UK) LTD, 0030 2107475196, info@verisfield.gr
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Scientific contact |
Clinical Trial Department, Verisfield (UK) Ltd, Greek Branch, VERISFIELD (UK) LTD, 0030 2107475196, info@verisfield.gr
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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 |
19 Oct 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Oct 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Oct 2015
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main objective of this study was the comparison of: (a) the efficiency, and (b) the safety of local treatment with clindamycin vaginal suppositories of Verisfield (UK) Ltd (Clindamycin/Verisfield, vaginal suppositories, 100 mg) and the therapeutic comparison with the reference product (Dalacin/Pfizer, vaginal suppositories, 100 mg), in women with bacterial vaginosis.
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Protection of trial subjects |
This study was conducted in accordance with International Conference of Harmonization (ICH) Good Clinical Practice (GCP) guidelines adopted by the European Medicines Agency (EMA). In accordance with local requirements, the study was submitted to the National Ethics Committee and the National Drug Organization for approval. The study begun only when Verisfield (UK) Ltd had received a copy of the written approval from the National Drug Organization. The conduct of the study was done in accordance with the relevant requirements of the National Drug Organization. Moreover, the involvement of patients in this study were reported to the Data Protection Authority in accordance with European Union Directive 95/46/EC and the Directives/laws of each country.Finally, the study has been designed according to the European Directives 2001/20/EC and 2005/28/EC and Directives ICH E1-E3 and E5-E11. Physical examination and an assessment of vital signs (blood pressure, pulse rate, temperature) were performed during the screening, as well as during all the study visits for all the participating volunteers. Moreover, adverse events (AEs) were observed during the entire study period and adequately handled and reported. Furthermore, a urine human chorionic gonadotropin (hCG) test was performed for all females of childbearing potential during all study Visits. Finally, all volunteers participating in this clinical study were covered by insurance on behalf of the sponsor.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
19 Jun 2012
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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 |
Greece: 6
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Worldwide total number of subjects |
6
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EEA total number of subjects |
6
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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) |
6
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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 |
The participants were selected among adult premenopausal female patients with bacterial vaginosis, volunteers, aged 18-54 years (including the limits) that attended/visited the hospitals of the study sites | |||||||||
Pre-assignment
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Screening details |
Adult premenopausal female patients with bacterial vaginosis, volunteers, aged 18-54 years (including the limits). Other inclusion and exclusion criteria applied. | |||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Test | |||||||||
Arm description |
The subjects were administered with the experimental medicinal product. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Clindamycin/Verisfield 100 mg vaginal suppositories
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suppository
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Routes of administration |
Vaginal use
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Dosage and administration details |
The route of administration, dosage, dosage regimen and duration of treatment was in accordance with the summary of product characteristics of the original formulation (reference product). The dosage regimen was one suppository for three consecutive days, before bedtime.
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Arm title
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Reference | |||||||||
Arm description |
The subjects were administered with the reference product. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Dalacin/Pfizer 100 mg vaginal suppositories
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suppository
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Routes of administration |
Vaginal use
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Dosage and administration details |
The dosage regimen was one suppository for three consecutive days, before bedtime.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Test
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Reporting group description |
The subjects were administered with the experimental medicinal product. | ||
Reporting group title |
Reference
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Reporting group description |
The subjects were administered with the reference product. |
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End point title |
Efficacy -The cure of the patients defined as the absence of three or four criteria of Amsel (existence of one or none criterion) in the 2nd visit. [1] | |||||||||
End point description |
The Amsel criteria are the following four:
1. Homogeneous, white, attaching vaginal discharge (often with fishy smell).
2. Positive amine check (characteristic odor of fish by applying 10% KOH - whiff test).
3. pH> 4.5.
4. Presence of clue cells (epithelial cells covered by coccobacillary organisms) in wet mount of vaginal secretion.
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End point type |
Primary
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End point timeframe |
The Amsel criteria for the primary endpoint were assessed in the 2nd visit (7-12 days after the beginning of the treatment)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: In the context of the present study, 10 volunteers were screened, of which 6 who met the eligibility criteria, were enrolled in the study and received one of the IMPs. Since the number of the enrolled volunteers was very low, no statistical analysis could be performed. |
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Notes [2] - Very low enrollment rate.No statistical analysis could be performed [3] - Very low enrollment rate.No statistical analysis could be performed |
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No statistical analyses for this end point |
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End point title |
IGII (Patient Global Improvement Index) | ||||||||||||
End point description |
Clinical evaluation of vaginitis based on the progression of symptoms by the investigator. The assessment is done using the following scale:
Serious deterioration (-2), Mild deterioration (-1), no change (0), mild improvement (1), moderate improvement (2), significant improvement (3), complete improvement (4).
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End point type |
Secondary
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End point timeframe |
The IGII (Patient Global Improvement Index) was assessed in the 2nd visit (7-12 days after the beginning of the treatment) and in the 3rd visit (21-30 days after the beginning of the treatment)
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Notes [4] - Very low enrollment rate. No statistical analysis could be performed. [5] - Very low enrollment rate. No statistical analysis could be performed. |
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No statistical analyses for this end point |
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End point title |
Efficacy_The cure of patients based to Amsel and Nugent criteria in the 2nd and 3rd visit | |||||||||
End point description |
The cure of patients was based on the absence of three or four Amsel criteria at Visit 3 and on the absence of three or four Amsel criteria and score <7 in Nugent scale in 2nd and 3rd visit.
The Amsel criteria are the following four:
1. Homogeneous, white, attaching vaginal discharge (often with fishy smell).
2. Positive amine check (characteristic odor of fish by applying 10% KOH - whiff test).
3. pH> 4.5.
4. Presence of clue cells (epithelial cells covered by coccobacillary organisms) in wet mount of vaginal secretion.
The Nugent method include:
1 loss of lactobacilli (score 0-4)
2 increase in the number of gram (+) and gram (-) coccobacillus (especially Gardnerella vaginalis, score 0-4)
3 Increase in the number of Mobi luncus spp (score 0-2)
These scores are added and based to their sum, the condition is assessed.
• The score of 0-3 is considered normal flora
• The score of 4-6 as intermediate
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End point type |
Secondary
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End point timeframe |
The Amsel and Nugent criteria were assessed in the 2nd (7-12 days after the beginning of the treatment) and 3rd visit (21-30 days after the beginning of the treatment).
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Notes [6] - Very low enrollment rate.No statistical analysis could be performed [7] - Very low enrollment rate.No statistical analysis could be performed |
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No statistical analyses for this end point |
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End point title |
PGII (Patient Global Improvement Index) | ||||||||||||
End point description |
Clinical evaluation of vaginitis by the patient, based on the progression of symptoms. The assessment is done using the following scale:
Serious deterioration (-2), Mild deterioration (-1), no change (0), mild improvement (1), moderate improvement (2), significant improvement (3), complete improvement (4).
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End point type |
Secondary
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End point timeframe |
The PGII (Patient Global Improvement Index) was assessed in the 2nd visit (7-12 days after the beginning of the treatment) and in the 3rd visit (21-30 days after the beginning of the treatment)
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Notes [8] - Very low enrollment rate. No statistical analysis could be performed. [9] - Very low enrollment rate. No statistical analysis could be performed. |
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No statistical analyses for this end point |
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End point title |
Efficacy -The cure of the patients defined as the absence of three or four criteria of Amsel (existence of one or none criterion) in the 3rd visit | |||||||||
End point description |
The Amsel criteria are the following four:
1. Homogeneous, white, attaching vaginal discharge (often with fishy smell).
2. Positive amine check (characteristic odor of fish by applying 10% KOH - whiff test).
3. pH> 4.5.
4. Presence of clue cells (epithelial cells covered by coccobacillary organisms) in wet mount of vaginal secretion.
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End point type |
Secondary
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End point timeframe |
The Amsel criteria were assessed in the 3rd visit (21-30 days after the beginning of the treatment).
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Notes [10] - Very low enrollment rate. No statistical analysis could be performed. [11] - Very low enrollment rate. No statistical analysis could be performed. |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
The duration of the overall study
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Assessment type |
Systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
14.1
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Frequency threshold for reporting non-serious adverse events: 0% | |||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: None of the enrolled volunteers (6 in total) developed any adverse event during their participation in the study. |
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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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06 Apr 2012 |
The modification was the addition of an extra visit 21-30 days after the start of the treatment (Visit 3), and the introduction of Nugent criteria on efficacy assessments in the 2nd and 3rd visit. This results in the addition of three additional secondary efficacy parameters:
1. The healing of patients under the Amsel criteria at Visit 3
2. The therapeutic effect based on the Amsel criteria and Nugent score at the second visit.
3. The therapeutic effect based on the Amsel criteria and Nugent score at the 3rd visit. |
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11 Feb 2014 |
This amendment included:
1. Amendment of the study protocol by 3rd Edition dated 08/03/2013 in 4th Edition dated 28/11/2013.
2. Modification of Informed Consent Form for volunteers participating in the study from 2nd Edition dated 14/03/2012 in 3rd Edition dated 28/11/2013.
3. Change of Principal Investigator in already existing Centre. More specifically, there was a replacement of the Principal Investigator of the already participating Centre (A Obstetrics-Gynecology Clinic, University of Athens, General Hospital of Athens "Alexandra") Professor Aristides Antsaklis by Associate Professor Alexandros Rodolakis.
4. Add of an additional center. More specifically, the study incorporated the VI Obstetrics-Gynecology Clinic Regional General Hospital-Maternity Hospital "Elena Venizelou" with Principal Investigator the obstetrician-gynecologist Mr. George Farmakides.
5. Extension of the study duration from 12 to 36 months. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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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 |