Colposeptine for the Treatment of Bacterial Vaginosis
Study Details
Study Description
Brief Summary
This is a prospective, randomized, controlled and multi-center trial to assess the use of colposeptine in female subjects with bacterial vaginosis. A total of 480 subjects were planned to be enrolled in various centers in China.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Colposeptine (A)
|
Drug: Colposeptine
Colposeptine will be administered transvaginally at a dose of 1 capsule every day for 12 consecutive days
Other Names:
|
| Active Comparator: Metronidazole (B)
|
Drug: Metronidazole
Metronidazole will be administered orally at a dose of 400 mg twice a day for 7 days
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Relapse 2 Months Post-treatment [2 months post-treatment]
Relapse: recurrence of the symptoms of bacterial vaginosis [BV] (Nugent score greater than or equal to 7, symptoms of vaginal irritation for example, pain, burning, odour or abnormal vaginal discharge) after a period of improvement. Nugent score was calculated by assessing for presence of large Gram-positive rods (Lactobacillus morphotypes; decrease in Lactobacillus scored as 0-4), small Gram-variable rods (Gardnerella vaginalis morphotypes; scored as 0-4), and curved Gram-variable rods (Mobiluncus species morphotypes; scored as 0-2). Total score range: 0-10. Score of 7-10 indicated BV.
Secondary Outcome Measures
- Percentage of Participants With Relapse 1 Month Post-treatment [1 month post-treatment]
Relapse: recurrence of the symptoms of bacterial vaginosis [BV] (Nugent score greater than or equal to 7, symptoms of vaginal irritation for example, pain, burning, odour or abnormal vaginal discharge) after a period of improvement. Nugent score was calculated by assessing for presence of large Gram-positive rods (Lactobacillus morphotypes; decrease in Lactobacillus scored as 0-4), small Gram-variable rods (Gardnerella vaginalis morphotypes; scored as 0-4), and curved Gram-variable rods (Mobiluncus species morphotypes; scored as 0-2). Total score range: 0-10. Score of 7-10 indicated BV.
- Change From Baseline in Nugent Score at 2 Months Post-treatment [Baseline and Month 2 post-treatment]
Nugent score was calculated by assessing for presence of large Gram-positive rods (Lactobacillus morphotypes; decrease in Lactobacillus scored as 0-4), small Gram-variable rods (Gardnerella vaginalis morphotypes; scored as 0-4), and curved Gram-variable rods (Mobiluncus species morphotypes; scored as 0-2). Total score range: 0-10. Score of 7-10 indicate bacterial vaginosis.
- Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment [Baseline and Month 2 post-treatment]
The grades of Lactobacilli in vaginal discharge were Grade 1 (Normal): Lactobacillus morphotypes predominate; Grade 2 (Intermediate): Mixed flora with some Lactobacilli present, but Gardnerella or Mobiluncus morphotypes also present; Grade 3 (Bacterial Vaginosis): Predominantly Gardnerella and/or Mobiluncus morphotypes, few or absent Lactobacilli.
- Number of Participants With Adverse Events (AEs) [Up to 2 months post-treatment]
An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
- Percentage of Participants Cured [1 week post-treatment]
Cure was defined as Nugent score less than 7, no symptoms of vaginal irritation (for example, pain, burning, odour or abnormal vaginal discharge). Nugent score was calculated by assessing for presence of large Gram-positive rods (Lactobacillus morphotypes; decrease in Lactobacillus scored as 0-4), small Gram-variable rods (Gardnerella vaginalis morphotypes; scored as 0-4), and curved Gram-variable rods (Mobiluncus species morphotypes; scored as 0-2). Total score range: 0-10. Score of 7-10 indicated bacterial vaginosis.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Female subjects in reproductive age and older than 18 year
-
Subjects with normal sexual activity
-
Subjects with symptoms such as vulva-vaginal irritation or abnormal vaginal discharge
-
Subjects with Nugent Score greater than or equal to 7
-
Subjects who are willing to use contraception
-
Subjects who are willing to refrain from the use of other vaginal products throughout the study
-
Subjects who sign informed consent form and agree to follow-up on time
Exclusion Criteria:
-
Subjects without sexual activity
-
Pregnant or lactating female subjects
-
Subjects with a history of recurrent bacterial vaginosis
-
Subjects diagnosed with trichomonas vaginitis，vulvovaginal candidiasis，chlamydia or gonococcus infection.
-
Subjects who are unwilling to refrain from the ingestion of any alcoholic beverages during the 7 day course of oral metronidazole therapy
-
Subjects who are under treatment by lithium, phenobarbitone, coumadine anticoagulant, cyclosporine or disulfiram by the time of inclusion (interactions with other products and metronidazole)
-
Subjects who are undergoing systemic or topical treatment with antibiotics, steroids, immunosuppressive, cytostatic or antimetabolic agents by the time of inclusion
-
Female subjects with a history of peripheral neuropathy
-
Female subjects who have participated in another clinical trial or have taken an experimental drug within the past 30 days
-
Subjects who are unable to give written informed consent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking University People's Hospital | Beijing | China | ||
| 2 | Second Hospital of West China Medical School, Sichuan University | Chengdu | China | ||
| 3 | Obstetrics & Gynaecology Hospital of Fudan University | Shanghai | China | ||
| 4 | Peking University Shenzhen Hospital | Shenzhen | China | ||
| 5 | Wuhan Union Hospital of China | Wuhan | China |
Sponsors and Collaborators
- Merck KGaA, Darmstadt, Germany
- Merck Serono Co., Ltd., China
Investigators
- Study Director: Study Director, Merck Serono Co., Ltd., China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EMR200059-504
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Colposeptine | Metronidazole |
|---|---|---|
| Arm/Group Description | Colposeptine 1 capsule transvaginally daily for 12 consecutive days. | Metronidazole 400 milligram (mg) orally twice daily for 7 consecutive days |
| Period Title: Overall Study | ||
| STARTED | 66 | 67 |
| COMPLETED | 30 | 35 |
| NOT COMPLETED | 36 | 32 |
Baseline Characteristics
| Arm/Group Title | Colposeptine | Metronidazole | Total |
|---|---|---|---|
| Arm/Group Description | Colposeptine 1 capsule transvaginally daily for 12 consecutive days. | Metronidazole 400 milligram (mg) orally twice daily for 7 consecutive days | Total of all reporting groups |
| Overall Participants | 66 | 67 | 133 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
32.11
(8.78)
|
30.72
(7.06)
|
31.41
(7.95)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
66
100%
|
67
100%
|
133
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Percentage of Participants With Relapse 2 Months Post-treatment |
|---|---|
| Description | Relapse: recurrence of the symptoms of bacterial vaginosis [BV] (Nugent score greater than or equal to 7, symptoms of vaginal irritation for example, pain, burning, odour or abnormal vaginal discharge) after a period of improvement. Nugent score was calculated by assessing for presence of large Gram-positive rods (Lactobacillus morphotypes; decrease in Lactobacillus scored as 0-4), small Gram-variable rods (Gardnerella vaginalis morphotypes; scored as 0-4), and curved Gram-variable rods (Mobiluncus species morphotypes; scored as 0-2). Total score range: 0-10. Score of 7-10 indicated BV. |
| Time Frame | 2 months post-treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) population included all enrolled participants who used investigational product. 'N' (number of participants analyzed) signifies those participants who were evaluated for this measure. |
| Arm/Group Title | Colposeptine | Metronidazole |
|---|---|---|
| Arm/Group Description | Colposeptine 1 capsule transvaginally daily for 12 consecutive days. | Metronidazole 400 milligram (mg) orally twice daily for 7 consecutive days |
| Measure Participants | 30 | 35 |
| Number [percentage of participants] |
23.3
35.3%
|
17.2
25.7%
|
| Title | Percentage of Participants With Relapse 1 Month Post-treatment |
|---|---|
| Description | Relapse: recurrence of the symptoms of bacterial vaginosis [BV] (Nugent score greater than or equal to 7, symptoms of vaginal irritation for example, pain, burning, odour or abnormal vaginal discharge) after a period of improvement. Nugent score was calculated by assessing for presence of large Gram-positive rods (Lactobacillus morphotypes; decrease in Lactobacillus scored as 0-4), small Gram-variable rods (Gardnerella vaginalis morphotypes; scored as 0-4), and curved Gram-variable rods (Mobiluncus species morphotypes; scored as 0-2). Total score range: 0-10. Score of 7-10 indicated BV. |
| Time Frame | 1 month post-treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS population included all enrolled participants who used investigational product. 'N' (number of participants analyzed) signifies those participants who were evaluated for this measure. |
| Arm/Group Title | Colposeptine | Metronidazole |
|---|---|---|
| Arm/Group Description | Colposeptine 1 capsule transvaginally daily for 12 consecutive days. | Metronidazole 400 milligram (mg) orally twice daily for 7 consecutive days |
| Measure Participants | 25 | 28 |
| Number [percentage of participants] |
16.0
24.2%
|
10.7
16%
|
| Title | Change From Baseline in Nugent Score at 2 Months Post-treatment |
|---|---|
| Description | Nugent score was calculated by assessing for presence of large Gram-positive rods (Lactobacillus morphotypes; decrease in Lactobacillus scored as 0-4), small Gram-variable rods (Gardnerella vaginalis morphotypes; scored as 0-4), and curved Gram-variable rods (Mobiluncus species morphotypes; scored as 0-2). Total score range: 0-10. Score of 7-10 indicate bacterial vaginosis. |
| Time Frame | Baseline and Month 2 post-treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS population included all enrolled participants who used investigational product. 'n' signifies those participants who were evaluated for this measure at the time point. |
| Arm/Group Title | Colposeptine | Metronidazole |
|---|---|---|
| Arm/Group Description | Colposeptine 1 capsule transvaginally daily for 12 consecutive days. | Metronidazole 400 milligram (mg) orally twice daily for 7 consecutive days |
| Measure Participants | 66 | 67 |
| Baseline (n= 66, 67) |
7.86
(0.58)
|
8.01
(0.59)
|
| Change at Month 2 (n= 25, 29) |
3.20
(2.12)
|
4.03
(2.71)
|
| Title | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment |
|---|---|
| Description | The grades of Lactobacilli in vaginal discharge were Grade 1 (Normal): Lactobacillus morphotypes predominate; Grade 2 (Intermediate): Mixed flora with some Lactobacilli present, but Gardnerella or Mobiluncus morphotypes also present; Grade 3 (Bacterial Vaginosis): Predominantly Gardnerella and/or Mobiluncus morphotypes, few or absent Lactobacilli. |
| Time Frame | Baseline and Month 2 post-treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS population included all enrolled participants who used investigational product. 'N' (number of participants analyzed) signifies those participants who were evaluated for this measure. 'n' signifies those participants who were evaluated for this measure at the time point. |
| Arm/Group Title | Colposeptine | Metronidazole |
|---|---|---|
| Arm/Group Description | Colposeptine 1 capsule transvaginally daily for 12 consecutive days. | Metronidazole 400 milligram (mg) orally twice daily for 7 consecutive days |
| Measure Participants | 66 | 66 |
| Baseline, Grade 1 (n= 66, 66) |
0
0%
|
0
0%
|
| Baseline, Grade 2 (n= 66, 66) |
3
4.5%
|
1
1.5%
|
| Baseline, Grade 3 (n= 66, 66) |
63
95.5%
|
65
97%
|
| Month 2, Grade 1 (n= 25, 29) |
11
16.7%
|
9
13.4%
|
| Month 2, Grade 2 (n= 25, 29) |
7
10.6%
|
14
20.9%
|
| Month 2, Grade 3 (n= 25, 29) |
7
10.6%
|
6
9%
|
| Title | Number of Participants With Adverse Events (AEs) |
|---|---|
| Description | An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. |
| Time Frame | Up to 2 months post-treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomized participants who used the investigational product at least once. |
| Arm/Group Title | Colposeptine | Metronidazole |
|---|---|---|
| Arm/Group Description | Colposeptine 1 capsule transvaginally daily for 12 consecutive days. | Metronidazole 400 milligram (mg) orally twice daily for 7 consecutive days |
| Measure Participants | 66 | 67 |
| Number [participants] |
8
12.1%
|
8
11.9%
|
| Title | Percentage of Participants Cured |
|---|---|
| Description | Cure was defined as Nugent score less than 7, no symptoms of vaginal irritation (for example, pain, burning, odour or abnormal vaginal discharge). Nugent score was calculated by assessing for presence of large Gram-positive rods (Lactobacillus morphotypes; decrease in Lactobacillus scored as 0-4), small Gram-variable rods (Gardnerella vaginalis morphotypes; scored as 0-4), and curved Gram-variable rods (Mobiluncus species morphotypes; scored as 0-2). Total score range: 0-10. Score of 7-10 indicated bacterial vaginosis. |
| Time Frame | 1 week post-treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS population included all enrolled participants who used investigational product. 'N' (number of participants analyzed) signifies those participants who were evaluated for this measure. |
| Arm/Group Title | Colposeptine | Metronidazole |
|---|---|---|
| Arm/Group Description | Colposeptine 1 capsule transvaginally daily for 12 consecutive days. | Metronidazole 400 milligram (mg) orally twice daily for 7 consecutive days |
| Measure Participants | 48 | 45 |
| Number [percentage of participants] |
22.9
34.7%
|
17.8
26.6%
|
Adverse Events
| Time Frame | Baseline up to 2 months post-treatment | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered. | |||
| Arm/Group Title | Colposeptine | Metronidazole | ||
| Arm/Group Description | Colposeptine 1 capsule transvaginally daily for 12 consecutive days. | Metronidazole 400 milligram (mg) orally twice daily for 7 consecutive days | ||
All Cause Mortality |
||||
| Colposeptine | Metronidazole | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Colposeptine | Metronidazole | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/66 (0%) | 0/67 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Colposeptine | Metronidazole | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/66 (12.1%) | 10/67 (14.9%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Pain | 1/66 (1.5%) | 1 | 0/67 (0%) | 0 |
| Abdominal Pain Upper | 0/66 (0%) | 0 | 2/67 (3%) | 2 |
| Nausea | 0/66 (0%) | 0 | 3/67 (4.5%) | 3 |
| General disorders | ||||
| Pyrexia | 1/66 (1.5%) | 2 | 0/67 (0%) | 0 |
| Infections and infestations | ||||
| Vulvovaginal Candidiasis | 2/66 (3%) | 2 | 0/67 (0%) | 0 |
| Vulvovaginitis Trichomonal | 1/66 (1.5%) | 1 | 0/67 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Bone Pain | 0/66 (0%) | 0 | 1/67 (1.5%) | 1 |
| Nervous system disorders | ||||
| Dizziness | 0/66 (0%) | 0 | 1/67 (1.5%) | 1 |
| Reproductive system and breast disorders | ||||
| Vulvovaginal Pruritus | 1/66 (1.5%) | 1 | 0/67 (0%) | 0 |
| Pelvic Pain | 1/66 (1.5%) | 1 | 0/67 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 0/66 (0%) | 0 | 1/67 (1.5%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 1/66 (1.5%) | 1 | 2/67 (3%) | 2 |
| Surgical and medical procedures | ||||
| Endodontic Procedure | 1/66 (1.5%) | 1 | 0/67 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Merck KGaA Communication Center |
|---|---|
| Organization | Merck Serono, a division of Merck KGaA |
| Phone | +49-6151-72-5200 |
| service@merckgroup.com |
- EMR200059-504