Trial Outcomes & Findings for Mycoplasma Genitalium Antibiotic Susceptibility and Treatment (MEGA) (NCT NCT00358462)

NCT ID: NCT00358462

Last Updated: 2018-08-15

Results Overview

Microbiologic cure of M. genitalium at first follow-up visit (defined as a negative in-house PCR test performed on urine)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 606 participants
• Primary outcome timeframe: approximately 3 weeks after initial study visit (allowable window is 2-5 weeks after initial study visit)
• Results posted on: 2018-08-15

Participant Flow

Men were recruited from a sexually transmitted diseases clinic in Seattle, Washington from January 2007 to July 2011

Participant milestones

Measure	Active Azithromycin + Placebo Doxycycline Azithromycin : two 500mg tablets or four 250mg tablets administered as a single dose	Active Doxycycline + Placebo Azithromycin Doxycycline : one 100mg capsule administered twice daily for seven days
Overall Study STARTED	304	302
Overall Study COMPLETED	245	238
Overall Study NOT COMPLETED	59	64

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Mycoplasma Genitalium Antibiotic Susceptibility and Treatment (MEGA)

Baseline characteristics by cohort

Measure	Active Azithromycin + Placebo Doxycycline n=304 Participants Azithromycin : two 500mg tablets or four 250mg tablets administered as a single dose	Active Doxycycline + Placebo Azithromycin n=302 Participants Doxycycline : one 100mg capsule administered twice daily for seven days	Total n=606 Participants Total of all reporting groups
Age, Continuous	34.1 years STANDARD_DEVIATION 9.8 • n=5 Participants	33.3 years STANDARD_DEVIATION 10.1 • n=7 Participants	33.7 years STANDARD_DEVIATION 10.0 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	304 Participants n=5 Participants	302 Participants n=7 Participants	606 Participants n=5 Participants
Region of Enrollment United States	304 participants n=5 Participants	302 participants n=7 Participants	606 participants n=5 Participants

PRIMARY outcome

Timeframe: approximately 3 weeks after initial study visit (allowable window is 2-5 weeks after initial study visit)

Population: mITT population (defined as urethral symptoms or visible discharge plus \>=5PMNs/HPF at baseline) who tested positive for M. genitalium at baseline

Microbiologic cure of M. genitalium at first follow-up visit (defined as a negative in-house PCR test performed on urine)

Outcome measures

Measure	Active Azithromycin + Placebo Doxycycline n=38 Participants Azithromycin : two 500mg tablets or four 250mg tablets administered as a single dose	Active Doxycycline + Placebo Azithromycin n=27 Participants Doxycycline : one 100mg capsule administered twice daily for seven days	Moxifloxacin Cultivated U. urealyticum biovar 2 isolates that successfully underwent in vitro MICs for moxifloxacin
mITT Analysis of Eradication of M. Genitalium at First Follow-up Study Visit	15 participants	8 participants	—

PRIMARY outcome

Timeframe: 3 weeks (allowable window 2-5)

Population: mITT population (defined as urethral symptoms or visible discharge plus \>=5PMNs/HPF at baseline) who tested positive for U. urealyticum at baseline

Microbiologic cure, defined as negative PCR for U. urealyticum (if cultured), or negative culture at first follow-up visit

Outcome measures

Measure	Active Azithromycin + Placebo Doxycycline n=52 Participants Azithromycin : two 500mg tablets or four 250mg tablets administered as a single dose	Active Doxycycline + Placebo Azithromycin n=55 Participants Doxycycline : one 100mg capsule administered twice daily for seven days	Moxifloxacin Cultivated U. urealyticum biovar 2 isolates that successfully underwent in vitro MICs for moxifloxacin
mITT Analysis of Eradication of U. Urealyticum at First Follow-up Visit	39 participants	38 participants	—

SECONDARY outcome

Timeframe: approximately 3 weeks after initial study visit (allowable window is 2-5 weeks after initial study visit)

Population: mITT population

Proportion of men with M. genitalium at the initial study visit who had clinical cure, defined as <5 PMNs/HPF (with or without urethral symptoms) on a urethral Gram stain and absence of urethral discharge at follow-up.

Outcome measures

Measure	Active Azithromycin + Placebo Doxycycline n=38 Participants Azithromycin : two 500mg tablets or four 250mg tablets administered as a single dose	Active Doxycycline + Placebo Azithromycin n=27 Participants Doxycycline : one 100mg capsule administered twice daily for seven days	Moxifloxacin Cultivated U. urealyticum biovar 2 isolates that successfully underwent in vitro MICs for moxifloxacin
Clinical Cure Among Case Subjects Who Were Positive for M. Genitalium at the Initial Study Visit	24 participants	13 participants	—

SECONDARY outcome

Timeframe: approximately 3 weeks after initial study visit (allowable window is 2-5 weeks after initial study visit)

Population: mITT population

Proportion of men with Ureaplasma urealyticum at the initial study visit who had clinical cure, defined as <5 PMNs/HPF (with or without urethral symptoms) on a urethral Gram stain and absence of urethral discharge at follow-up.

Outcome measures

Measure	Active Azithromycin + Placebo Doxycycline n=52 Participants Azithromycin : two 500mg tablets or four 250mg tablets administered as a single dose	Active Doxycycline + Placebo Azithromycin n=55 Participants Doxycycline : one 100mg capsule administered twice daily for seven days	Moxifloxacin Cultivated U. urealyticum biovar 2 isolates that successfully underwent in vitro MICs for moxifloxacin
Clinical Cure Among Case Subjects Who Were Positive for Ureaplasmas at the Initial Study Visit	43 participants	40 participants	—

SECONDARY outcome

Timeframe: baseline

Population: Participants with recovered isolates that successfully underwent in vitro assessment of antibiotic susceptibilities

In vitro susceptibiities of M. genitalium to azithromycin

Outcome measures

Measure	Active Azithromycin + Placebo Doxycycline n=56 Participants Azithromycin : two 500mg tablets or four 250mg tablets administered as a single dose	Active Doxycycline + Placebo Azithromycin Doxycycline : one 100mg capsule administered twice daily for seven days	Moxifloxacin Cultivated U. urealyticum biovar 2 isolates that successfully underwent in vitro MICs for moxifloxacin
Minimum Inhibitory Concentrations (MIC) of M. Genitalium for Azithromycin MIC range <=0.001 - 0.004 ug/ml	31 Participants	—	—
Minimum Inhibitory Concentrations (MIC) of M. Genitalium for Azithromycin MIC range >8 ug/ml	25 Participants	—	—

SECONDARY outcome

Timeframe: baseline

In vitro susceptibilities of M. genitalium to doxycycline

Outcome measures

Measure	Active Azithromycin + Placebo Doxycycline n=61 Participants Azithromycin : two 500mg tablets or four 250mg tablets administered as a single dose	Active Doxycycline + Placebo Azithromycin Doxycycline : one 100mg capsule administered twice daily for seven days	Moxifloxacin Cultivated U. urealyticum biovar 2 isolates that successfully underwent in vitro MICs for moxifloxacin
Minimum Inhibitory Concentrations (MIC) of M. Genitalium for Doxycycline	0.5 MIC (ug/mL) Interval 0.125 to 2.0	—	—

SECONDARY outcome

Timeframe: baseline

Population: isolates

In vitro susceptibilities of U. urealyticum biovar 2

Outcome measures

Measure	Active Azithromycin + Placebo Doxycycline n=22 Participants Azithromycin : two 500mg tablets or four 250mg tablets administered as a single dose	Active Doxycycline + Placebo Azithromycin n=22 Participants Doxycycline : one 100mg capsule administered twice daily for seven days	Moxifloxacin n=22 Participants Cultivated U. urealyticum biovar 2 isolates that successfully underwent in vitro MICs for moxifloxacin
Minimum Inhibitory Concentrations (MIC) of U. Ureaplasma Biovar 2	1.00 MIC (ug/mL) Interval 0.25 to 2.0	0.5 MIC (ug/mL) Interval 0.125 to 1.0	0.5 MIC (ug/mL) Interval 0.25 to 1.0

SECONDARY outcome

Timeframe: baseline

Population: isolates

In vitro susceptibilities of U. parvum

Outcome measures

Measure	Active Azithromycin + Placebo Doxycycline n=8 Participants Azithromycin : two 500mg tablets or four 250mg tablets administered as a single dose	Active Doxycycline + Placebo Azithromycin n=8 Participants Doxycycline : one 100mg capsule administered twice daily for seven days	Moxifloxacin n=8 Participants Cultivated U. urealyticum biovar 2 isolates that successfully underwent in vitro MICs for moxifloxacin
Minimum Inhibitory Concentrations (MIC) of U. Parvum	0.5 MIC (ug/mL) Interval 0.125 to 2.0	0.25 MIC (ug/mL) Interval 0.125 to 0.5	0.25 MIC (ug/mL) Interval 0.125 to 0.5

Adverse Events

Active Azithromycin + Placebo Doxycycline

Serious events: 1 serious events

Other events: 53 other events

Deaths: 0 deaths

Active Doxycycline + Placebo Azithromycin

Serious events: 3 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Measure	Active Azithromycin + Placebo Doxycycline n=304 participants at risk Azithromycin : two 500mg tablets or four 250mg tablets administered as a single dose	Active Doxycycline + Placebo Azithromycin n=302 participants at risk Doxycycline : one 100mg capsule administered twice daily for seven days
Injury, poisoning and procedural complications Gun shot wound	0.00% 0/304	0.33% 1/302 • Number of events 1
Injury, poisoning and procedural complications Broken leg	0.00% 0/304	0.33% 1/302 • Number of events 1
Psychiatric disorders Unstable mental status	0.33% 1/304 • Number of events 1	0.00% 0/302
Eye disorders Optic neuritis	0.00% 0/304	0.33% 1/302 • Number of events 1

Other adverse events

Measure	Active Azithromycin + Placebo Doxycycline n=304 participants at risk Azithromycin : two 500mg tablets or four 250mg tablets administered as a single dose	Active Doxycycline + Placebo Azithromycin n=302 participants at risk Doxycycline : one 100mg capsule administered twice daily for seven days
Gastrointestinal disorders Nausea	9.2% 28/304 • Number of events 73	11.9% 36/302 • Number of events 68
Gastrointestinal disorders Diarrhea	10.2% 31/304 • Number of events 74	11.6% 35/302 • Number of events 47
General disorders Vomiting	2.0% 6/304 • Number of events 7	2.3% 7/302 • Number of events 7
General disorders Rash	2.0% 6/304 • Number of events 7	2.3% 7/302 • Number of events 7
Gastrointestinal disorders Other	3.9% 12/304 • Number of events 32	5.6% 17/302 • Number of events 32

Additional Information

Lisa E. Manhart, PhD - PI

University of Washington

Phone: 206-744-3646

Email: lmanhart@uw.edu

Results disclosure agreements

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