Trial Outcomes & Findings for Efficacy and Safety Study of SPL7013 Gel to Prevent the Recurrence of Bacterial Vaginosis (BV) (NCT NCT02237950)

NCT ID: NCT02237950

Last Updated: 2019-07-22

Results Overview

Number of participants with a recurrence of BV, where a diagnosis of BV is defined as the presence of at least 3 clinical findings (Amsel criteria)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 586 participants
• Primary outcome timeframe: At or by the Week 16 visit
• Results posted on: 2019-07-22

Participant Flow

Participant milestones

Measure	1% SPL7013 Gel Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Overall Study STARTED	295	291
Overall Study COMPLETED	247	243
Overall Study NOT COMPLETED	48	48

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety Study of SPL7013 Gel to Prevent the Recurrence of Bacterial Vaginosis (BV)

Baseline characteristics by cohort

Measure	1% SPL7013 Gel n=294 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel n=291 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks	Total n=585 Participants Total of all reporting groups
Age, Continuous	31.6 years STANDARD_DEVIATION 7.23 • n=5 Participants	31.6 years STANDARD_DEVIATION 6.99 • n=7 Participants	31.6 years STANDARD_DEVIATION 7.11 • n=5 Participants
Sex: Female, Male Female	294 Participants n=5 Participants	291 Participants n=7 Participants	585 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: At or by the Week 16 visit

Population: Analysis population is the modified intent-to-treat analysis population. One patient was excluded compared with the intent-to-treat population because they were dispensed medication but returned all unused.

Number of participants with a recurrence of BV, where a diagnosis of BV is defined as the presence of at least 3 clinical findings (Amsel criteria)

Outcome measures

Measure	1% SPL7013 Gel n=294 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel n=291 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings	130 Participants	158 Participants

SECONDARY outcome

Timeframe: At or by the Week 16 visit

Population: Analysis population is the modified intent-to-treat analysis population. One patient was excluded compared with the intent-to-treat population because they were dispensed medication but returned all unused.

Time to recurrence of BV (days), where a diagnosis of BV is defined as the presence of at least 3 clinical findings (Amsel criteria)

Outcome measures

Measure	1% SPL7013 Gel n=294 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel n=291 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Time to Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings	105 days Interval 98.0 to 111.0	99 days Interval 87.0 to 106.0

SECONDARY outcome

Timeframe: At or by the Week 16 visit

Population: Modified Intent-to-Treat, excluding patients with missing values.

Number of participants with self-reported BV symptoms (vaginal discharge and/or odor)

Outcome measures

Measure	1% SPL7013 Gel n=269 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel n=266 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Recurrence of Patient-reported BV Symptoms	75 Participants	108 Participants

SECONDARY outcome

Timeframe: At or by the Week 16 visit

Population: Modified Intent-to-Treat, excluding patients with missing values.

Number of participants with positive individual Amsel criterion

• Clue cells representing at least 20% of total epithelial cells

Outcome measures

Measure	1% SPL7013 Gel n=274 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel n=273 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Recurrence of Individual Amsel Criteria	104 Participants	132 Participants

SECONDARY outcome

Timeframe: At or by the Week 16 visit

Population: Modified Intent-to-Treat, excluding patients with missing values.

Number of participants with a recurrence of BV as determined by presence of a Nugent score of 7-10 (BV), where 0-3 is normal, and 4-6 is intermediate.

Outcome measures

Measure	1% SPL7013 Gel n=247 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel n=273 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Recurrence of BV as Determined by Presence of a Nugent Score of 7-10	95 Participants	135 Participants

SECONDARY outcome

Timeframe: At or by the Week 24 visit

Population: Analysis population is the modified intent-to-treat analysis population. One patient was excluded compared with the intent-to-treat population because they were dispensed medication but returned all unused.

Number of participants with a recurrence of BV, where a diagnosis of BV is defined as the presence of at least 3 clinical findings (Amsel criteria)

Outcome measures

Measure	1% SPL7013 Gel n=294 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel n=291 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Recurrence of BV Where a Diagnosis of BV is Defined as the Presence of at Least 3 Clinical Findings	194 Participants	213 Participants

SECONDARY outcome

Timeframe: At or by the Week 16 visit

Population: Modified Intent-to-Treat, excluding patients with missing values.

Number of participants with a recurrence of BV according to the composite definition of at least 3 clinical findings (Amsel criteria) and a Nugent score of 4-10 (intermediate to BV), where 0-3 is normal.

Outcome measures

Measure	1% SPL7013 Gel n=276 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel n=276 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Recurrence of BV According to the Composite Definition of at Least 3 Clinical Findings (Amsel Criteria) and a Nugent Score of 4-10.	81 Participants	111 Participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Analysis population includes only those participants who completed the survey, which was optional.

Change from baseline in brief index of sexual functioning for women (BISF-W) questionnaire composite score. The composite score includes scores from dimensions (D) of thoughts/desire (D1, 0-12), arousal (D2, 0-12), frequency of sexual activity (D3, 0-12), receptivity/initiation (D4, 0-12), pleasure (D5, 0-12), relationship satisfaction (D6, 0-12), and any problems affecting sexual functioning (D7, 0-16). The composite score is calculated as D1+D2+D3+D4+D5+D6-D7 with a range of -16 to +75. A positive change in composite score from baseline to Week 16 reflects an improvement in sexual functioning, with a greater change in score indicating a greater improvement in sexual functioning.

Outcome measures

Measure	1% SPL7013 Gel n=163 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel n=166 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Change From Baseline in Brief Index of Sexual Functioning for Women Questionnaire Composite Score	1.6 change in score on a scale Interval -0.5 to 3.7	0.1 change in score on a scale Interval -2.0 to 2.1

SECONDARY outcome

Timeframe: From Baseline to end of Week 28

Population: Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.

Number of participants with genitourinary AEs considered potentially related to study treatment

Outcome measures

Measure	1% SPL7013 Gel n=294 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel n=291 Participants Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Adverse Events (AEs)	37 Participants	33 Participants

Adverse Events

1% SPL7013 Gel

Serious events: 4 serious events

Other events: 92 other events

Deaths: 0 deaths

Placebo Gel

Serious events: 3 serious events

Other events: 80 other events

Deaths: 0 deaths

Serious adverse events

Measure	1% SPL7013 Gel n=294 participants at risk Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel n=291 participants at risk Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Cardiac disorders Tachycardia	0.34% 1/294 • Number of events 1 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.	0.00% 0/291 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.
Infections and infestations Bartholin's abscess	0.00% 0/294 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.	0.34% 1/291 • Number of events 1 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.
Infections and infestations Klebsiella bacteremia	0.00% 0/294 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.	0.34% 1/291 • Number of events 1 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.
Nervous system disorders Hemiplegic migraine	0.00% 0/294 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.	0.34% 1/291 • Number of events 1 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.
Pregnancy, puerperium and perinatal conditions Blighted ovum	0.34% 1/294 • Number of events 1 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.	0.34% 1/291 • Number of events 1 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.
Psychiatric disorders Suicidal ideation	0.34% 1/294 • Number of events 1 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.	0.00% 0/291 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.
Reproductive system and breast disorders Menorrhagia	0.34% 1/294 • Number of events 1 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.	0.00% 0/291 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.

Other adverse events

Measure	1% SPL7013 Gel n=294 participants at risk Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days 1% SPL7013 Gel: 5g inserted in to the vaginal on alternate days (i.e. every other day) for 16 consecutive weeks.	Placebo Gel n=291 participants at risk Inserted in to the vagina on alternate days (i.e. every other day) for 16 weeks Metronidazole oral tablets 500mg: One tablet taken orally twice daily for seven consecutive days Placebo gel: 5g inserted in to the vagina on alternate days (i.e. every other day) for 16 consecutive weeks
Infections and infestations Nasopharyngitis	3.1% 9/294 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.	5.2% 15/291 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.
Infections and infestations UTI	9.5% 28/294 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.	3.4% 10/291 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.
Infections and infestations Vulvovaginal candidiasis	16.0% 47/294 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.	12.0% 35/291 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.
Infections and infestations Vulvovaginal mycotic infection	4.8% 14/294 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.	5.5% 16/291 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.
Nervous system disorders Headache	5.8% 17/294 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.	6.9% 20/291 Safety population was all patients in the Intent-to-Treat population, but excluding those who later returned all the study medication unused.

Additional Information

Dr Jeremy Paull

Starpharma

Email: jeremy.paull@starpharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee For multicenter studies, PIs can publish data only after study data are published collectively.
• Publication restrictions are in place

Restriction type: OTHER