Vaginosis, Bacterial
Conditions
Keywords
Vaginosis, Bacterial, Colposeptine, Metronidazole
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.
Interventions
DRUGColposeptine
Colposeptine will be administered transvaginally at a dose of 1 capsule every day for 12 consecutive days
DRUGMetronidazole
Metronidazole will be administered orally at a dose of 400 mg twice a day for 7 days
Sponsors
Merck Serono Co., Ltd., China
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Colposeptine Colposeptine 1 capsule transvaginally daily for 12 consecutive days. | 66 |
| Metronidazole Metronidazole 400 milligram (mg) orally twice daily for 7 consecutive days | 67 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study Terminated | 36 | 32 |
Baseline characteristics
| Characteristic | Colposeptine | Metronidazole | Total |
|---|---|---|---|
| Age, Continuous | 32.11 years STANDARD_DEVIATION 8.78 | 30.72 years STANDARD_DEVIATION 7.06 | 31.41 years STANDARD_DEVIATION 7.95 |
| Sex: Female, Male Female | 66 Participants | 67 Participants | 133 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 66 | 10 / 67 |
| serious Total, serious adverse events | 0 / 66 | 0 / 67 |
Outcome results
Primary
Percentage of Participants With Relapse 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.
Time frame: 2 months post-treatment
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Colposeptine | Percentage of Participants With Relapse 2 Months Post-treatment | 23.3 percentage of participants |
| Metronidazole | Percentage of Participants With Relapse 2 Months Post-treatment | 17.2 percentage of participants |
Secondary
Change From Baseline in Nugent Score at 2 Months 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.
Time frame: Baseline and Month 2 post-treatment
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Colposeptine | Change From Baseline in Nugent Score at 2 Months Post-treatment | Baseline (n= 66, 67) | 7.86 units on a scale | Standard Deviation 0.58 |
| Colposeptine | Change From Baseline in Nugent Score at 2 Months Post-treatment | Change at Month 2 (n= 25, 29) | 3.20 units on a scale | Standard Deviation 2.12 |
| Metronidazole | Change From Baseline in Nugent Score at 2 Months Post-treatment | Baseline (n= 66, 67) | 8.01 units on a scale | Standard Deviation 0.59 |
| Metronidazole | Change From Baseline in Nugent Score at 2 Months Post-treatment | Change at Month 2 (n= 25, 29) | 4.03 units on a scale | Standard Deviation 2.71 |
Secondary
Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months 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.
Time frame: Baseline and Month 2 post-treatment
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Colposeptine | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment | Baseline, Grade 1 (n= 66, 66) | 0 participants |
| Colposeptine | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment | Baseline, Grade 2 (n= 66, 66) | 3 participants |
| Colposeptine | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment | Baseline, Grade 3 (n= 66, 66) | 63 participants |
| Colposeptine | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment | Month 2, Grade 1 (n= 25, 29) | 11 participants |
| Colposeptine | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment | Month 2, Grade 2 (n= 25, 29) | 7 participants |
| Colposeptine | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment | Month 2, Grade 3 (n= 25, 29) | 7 participants |
| Metronidazole | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment | Month 2, Grade 2 (n= 25, 29) | 14 participants |
| Metronidazole | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment | Baseline, Grade 1 (n= 66, 66) | 0 participants |
| Metronidazole | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment | Month 2, Grade 1 (n= 25, 29) | 9 participants |
| Metronidazole | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment | Baseline, Grade 2 (n= 66, 66) | 1 participants |
| Metronidazole | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment | Month 2, Grade 3 (n= 25, 29) | 6 participants |
| Metronidazole | Change From Baseline in Number of Participants With Each Grade of Lactobacilli at 2 Months Post-treatment | Baseline, Grade 3 (n= 66, 66) | 65 participants |
Secondary
Number of Participants With Adverse Events (AEs)
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
Population: Safety population included all randomized participants who used the investigational product at least once.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Colposeptine | Number of Participants With Adverse Events (AEs) | 8 participants |
| Metronidazole | Number of Participants With Adverse Events (AEs) | 8 participants |
Secondary
Percentage of Participants Cured
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Colposeptine | Percentage of Participants Cured | 22.9 percentage of participants |
| Metronidazole | Percentage of Participants Cured | 17.8 percentage of participants |
Secondary
Percentage of Participants With Relapse 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.
Time frame: 1 month post-treatment
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Colposeptine | Percentage of Participants With Relapse 1 Month Post-treatment | 16.0 percentage of participants |
| Metronidazole | Percentage of Participants With Relapse 1 Month Post-treatment | 10.7 percentage of participants |