Trial Outcomes & Findings for Efficacy of Combination Therapies for Gonorrhea Treatment (NCT NCT00926796)

NCT ID: NCT00926796

Last Updated: 2015-08-19

Results Overview

Percentage of enrollees negative by culture at cervix/urethra 10-17 days after treatment, regardless of history of re-exposure, among those with positive gonococcal cultures at enrollment (microbiological cure)

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 614 participants
• Primary outcome timeframe: 10-17 days after treatment.
• Results posted on: 2015-08-19

Participant Flow

Participants were recruited in outpatient STD clinics located in 5 cities across the United States.

Since Gonorrhea lab results were not available at randomization, participants who were found to be negative for Gonorrhea were withdrawn after randomization as they did not meet one of the eligibility criteria.

Participant milestones

Measure	Regimen A: Gentamicin Plus Azithromycin Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
Overall Study STARTED	309	305
Overall Study COMPLETED	202	199
Overall Study NOT COMPLETED	107	106

Reasons for withdrawal

Measure	Regimen A: Gentamicin Plus Azithromycin Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
Overall Study Did not receive randomized treatment	4	7
Overall Study Ineligible, negative for gonorrhea	57	60
Overall Study Ineligible, but positive for gonorrhea	1	1
Overall Study Adverse Event	7	14
Overall Study Lost to Follow-up	22	13
Overall Study Protocol Violation	15	11
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Efficacy of Combination Therapies for Gonorrhea Treatment

Baseline characteristics by cohort

Measure	Regimen A: Gentamicin Plus Azithromycin n=202 Participants Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin n=199 Participants Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.	Total n=401 Participants Total of all reporting groups
Age, Categorical <=18 years	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	196 Participants n=5 Participants	196 Participants n=7 Participants	392 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	30 years STANDARD_DEVIATION 9.9 • n=5 Participants	30 years STANDARD_DEVIATION 9.6 • n=7 Participants	30 years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	21 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	183 Participants n=5 Participants	178 Participants n=7 Participants	361 Participants n=5 Participants
Region of Enrollment United States	202 participants n=5 Participants	199 participants n=7 Participants	401 participants n=5 Participants

PRIMARY outcome

Timeframe: 10-17 days after treatment.

Population: Per protocol population (all randomized participants who took study drug, positive for gonorrhea, completed follow up visit, and met additional protocol specific conditions such as key inclusion/exclusion, the 10-17 day Visit 2 window requirement, etc.)

Percentage of enrollees negative by culture at cervix/urethra 10-17 days after treatment, regardless of history of re-exposure, among those with positive gonococcal cultures at enrollment (microbiological cure)

Outcome measures

Measure	Regimen A: Gentamicin Plus Azithromycin n=202 Participants Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
Microbiological Efficacy of Gentamicin and Azithromycin for the Treatment of Uncomplicated Gonococcal Infection	100 percentage of participants	—

PRIMARY outcome

Timeframe: 10-17 days after treatment.

Population: Per protocol population (all randomized participants who took study drug, positive for gonorrhea, completed follow up visit, and met additional protocol specific conditions such as key inclusion/exclusion, the 10-17 day Visit 2 window requirement, etc.)

Percentage of enrollees negative by culture at cervix/urethra 10-17 days after treatment, regardless of history of re-exposure, among those with positive gonococcal cultures at enrollment (microbiological cure)

Outcome measures

Measure	Regimen A: Gentamicin Plus Azithromycin n=199 Participants Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
Microbiological Efficacy of Gemifloxacin and Azithromycin for the Treatment of Uncomplicated Gonococcal Infection	99.50 percentage of participants	—

SECONDARY outcome

Timeframe: 10-17 days after treatment.

Population: Participants who were positive for rectal gonorrhea at enrollment and were in the per protocol population (all randomized participants who took study drug, positive for gonorrhea, completed follow up visit, and met additional protocol specific conditions such as key inclusion/exclusion, the 10-17 day Visit 2 window requirement, etc.)

Number of enrollees with positive rectal culture at enrollment who have negative culture 10-17 days after treatment

Outcome measures

Measure	Regimen A: Gentamicin Plus Azithromycin n=1 Participants Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin n=5 Participants Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
Eradication of Rectal Infection	1 participants	5 participants

SECONDARY outcome

Timeframe: 10-17 days after treatment.

Population: Participants who were positive for pharyngeal gonorrhea at enrollment and were in the per protocol population (all randomized participants who took study drug, positive for gonorrhea, completed follow up visit, and met additional protocol specific conditions such as key inclusion/exclusion, the 10-17 day Visit 2 window requirement, etc.)

Number of enrollees with positive pharyngeal culture at enrollment who have negative culture 10-17 days after treatment

Outcome measures

Measure	Regimen A: Gentamicin Plus Azithromycin n=10 Participants Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin n=15 Participants Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
Eradication of Pharyngeal Infection	10 participants	15 participants

SECONDARY outcome

Timeframe: Isolates obtained at enrollment (Day 0).

Population: Participants in the per protocol population (all randomized participants who took study drug, positive for gonorrhea, completed follow up visit, and met additional protocol specific conditions such as key inclusion/exclusion, the 10-17 day Visit 2 window requirement, etc.) with treatment failure.

For treatment failures (i.e., participants with positive culture at cervix/urethra 10-17 days after treatment), the minimum inhibitory concentrations for various antimicrobial agents (Azithromycin, Cefixime, Ceftriaxone, Ciprofloxacin, Gemifloxacin, Gentamicin, Penicillin, Tetracycline).

Outcome measures

Measure	Regimen A: Gentamicin Plus Azithromycin Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin n=1 Participants Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
Antimicrobial Susceptibility Profile of Treatment Failures. Azithromycin	—	0.25 micrograms/milliliter Because data was available for only 1 participant, Measure of Dispersion could not be calculated.
Antimicrobial Susceptibility Profile of Treatment Failures. Cefixime	—	0.015 micrograms/milliliter Because data was available for only 1 participant, Measure of Dispersion could not be calculated.
Antimicrobial Susceptibility Profile of Treatment Failures. Ceftriaxone	—	0.004 micrograms/milliliter Because data was available for only 1 participant, Measure of Dispersion could not be calculated.
Antimicrobial Susceptibility Profile of Treatment Failures. Ciprofloxacin	—	0.002 micrograms/milliliter Because data was available for only 1 participant, Measure of Dispersion could not be calculated.
Antimicrobial Susceptibility Profile of Treatment Failures. Gemifloxacin	—	0.004 micrograms/milliliter Because data was available for only 1 participant, Measure of Dispersion could not be calculated.
Antimicrobial Susceptibility Profile of Treatment Failures. Gentamicin	—	4 micrograms/milliliter Because data was available for only 1 participant, Measure of Dispersion could not be calculated.
Antimicrobial Susceptibility Profile of Treatment Failures. Penicillin	—	0.5 micrograms/milliliter Because data was available for only 1 participant, Measure of Dispersion could not be calculated.
Antimicrobial Susceptibility Profile of Treatment Failures. Tetracycline	—	0.25 micrograms/milliliter Because data was available for only 1 participant, Measure of Dispersion could not be calculated.

SECONDARY outcome

Timeframe: 10-17 days

Population: Participants who had clinical symptoms at enrollment and were in the per protocol population (all randomized participants who took study drug, positive for gonorrhea, completed follow up visit, and met additional protocol specific conditions such as key inclusion/exclusion, the 10-17 day Visit 2 window requirement, etc.) with treatment failure.

For treatment failures (i.e., participants with positive culture at cervix/urethra 10-17 days after treatment), number participants with clinical symptoms (vaginal/urethral discharge, dysuria, dyspareunia) at 10-17 days.

Outcome measures

Measure	Regimen A: Gentamicin Plus Azithromycin Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin n=1 Participants Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
Clinical Profile of Treatment Failures. Vaginal/urethral discharge	—	0 participants
Clinical Profile of Treatment Failures. Dysuria	—	0 participants
Clinical Profile of Treatment Failures. Dyspareunia	—	0 participants

SECONDARY outcome

Timeframe: 10-17 days after treatment.

Population: Participants who had clinical symptoms at enrollment and were in the per protocol population (all randomized participants who took study drug, positive for gonorrhea, completed follow up visit, and met additional protocol specific conditions such as key inclusion/exclusion, the 10-17 day Visit 2 window requirement, etc.)

Number of participants whose gonorrhea-related symptoms (e.g. vaginal/urethral discharge, dysuria, dyspareunia) present at enrollment has resolved by visit 2.

Outcome measures

Measure	Regimen A: Gentamicin Plus Azithromycin n=188 Participants Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin n=182 Participants Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
Resolution of Symptoms and Signs (Clinical Cure)	179 participants	177 participants

SECONDARY outcome

Timeframe: Isolates obtained at enrollment (Day 0).

Population: Per protocol population (all randomized participants who too study drug, positive for gonorrhea, completed follow up visit, and met additional protocol specific conditions such as key inclusion/exclusion, the 10-17 day Visit 2 window requirement, etc.).

Minimum inhibitory concentration (micrograms/milliliter) of pretreatment gonorrhea isolates collected from participants

Outcome measures

Measure	Regimen A: Gentamicin Plus Azithromycin n=396 Participants Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
Antimicrobial Susceptibility Profile of Enrollment Isolates. Gemifloxacin	0.004 micrograms/milliliter Interval 0.001 to 8.0	—
Antimicrobial Susceptibility Profile of Enrollment Isolates. Azithromycin	0.25 micrograms/milliliter Interval 0.03 to 16.0	—
Antimicrobial Susceptibility Profile of Enrollment Isolates. Cefixime	0.015 micrograms/milliliter Interval 0.001 to 1.0	—
Antimicrobial Susceptibility Profile of Enrollment Isolates. Ceftriaxone	0.008 micrograms/milliliter Interval 0.001 to 0.125	—
Antimicrobial Susceptibility Profile of Enrollment Isolates. Ciprofloxacin	0.004 micrograms/milliliter Interval 0.002 to 32.0	—
Antimicrobial Susceptibility Profile of Enrollment Isolates. Gentamicin	4 micrograms/milliliter Interval 0.002 to 16.0	—
Antimicrobial Susceptibility Profile of Enrollment Isolates. Penicillin	0.5 micrograms/milliliter Interval 0.004 to 64.0	—
Antimicrobial Susceptibility Profile of Enrollment Isolates. Tetracycline	0.5 micrograms/milliliter Interval 0.03 to 32.0	—

SECONDARY outcome

Timeframe: Day 0 through Day 30

Population: All participants receiving study medication comprised the safety population. Of 614 participants randomized, 603 received study medication.

Number of treated participants experiencing mild, moderate, severe, or life-threatening adverse events (AEs) either temporarily associated or not associated with study product.

Outcome measures

Measure	Regimen A: Gentamicin Plus Azithromycin n=305 Participants Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin n=298 Participants Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
Number of Participants With Adverse Events for Each Regimen	157 participants	185 participants

Adverse Events

Regimen A: Gentamicin Plus Azithromycin

Serious events: 0 serious events

Other events: 124 other events

Deaths: 0 deaths

Regimen B: Gemifloxacin Plus Azithromycin

Serious events: 0 serious events

Other events: 164 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Regimen A: Gentamicin Plus Azithromycin n=305 participants at risk Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.	Regimen B: Gemifloxacin Plus Azithromycin n=298 participants at risk Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
Gastrointestinal disorders Diarrhea	17.4% 53/305 • Number of events 53 • Enrollment, at follow-up, which as targeted 10-17 days, and through 30 days. All participants who received study medication comprise the number of participants at risk.	22.1% 66/298 • Number of events 67 • Enrollment, at follow-up, which as targeted 10-17 days, and through 30 days. All participants who received study medication comprise the number of participants at risk.
Gastrointestinal disorders Nausea	25.9% 79/305 • Number of events 79 • Enrollment, at follow-up, which as targeted 10-17 days, and through 30 days. All participants who received study medication comprise the number of participants at risk.	40.3% 120/298 • Number of events 121 • Enrollment, at follow-up, which as targeted 10-17 days, and through 30 days. All participants who received study medication comprise the number of participants at risk.
Gastrointestinal disorders Vomiting	10.5% 32/305 • Number of events 32 • Enrollment, at follow-up, which as targeted 10-17 days, and through 30 days. All participants who received study medication comprise the number of participants at risk.	14.1% 42/298 • Number of events 44 • Enrollment, at follow-up, which as targeted 10-17 days, and through 30 days. All participants who received study medication comprise the number of participants at risk.

Additional Information

Shelly Lensing

University of Arkansas for Medical Sciences

Phone: 501-686-8203

Email: sylensing@uams.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place