A Trial Comparing Moxifloxacin Versus Levofloxacin Plus Metronidazole In Uncomplicated Pelvic Inflammatory Disease

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00453349
• Collaborator: (none)
• Enrollment: 460
• Locations: 13
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 35.4
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

To assess the efficacy and safety of oral moxifloxacin compared to oral levofloxacin plus oral metronidazole in uncomplicated pelvic inflammatory disease (PID)

Condition or Disease	Intervention/Treatment	Phase
Pelvic Inflammatory Disease	Drug: Moxifloxacin (Avelox, BAY12-8039); Drug: Levofloxacin & Metronidazole	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 460 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized, Double Dummy, Double Blind, Multi-center Multinational Trial Comparing the Efficacy and Safety of Moxifloxacin 400 mg PO QD 24 Hours for 14 Days to That of Levofloxacin 500 mg PO QD 24 Hours Plus Metronidazole 500 mg BID for 14 Days in Subjects With an Uncomplicated Pelvic Inflammatory Disease (PID). Moxifloxacin, Metronidazole, and Levofloxacin in Asia (MONALISA Study)
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Moxifloxacin Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Drug: Moxifloxacin (Avelox, BAY12-8039); Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days
Active Comparator: Levofloxacin plus Metronidazole Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days	Drug: Levofloxacin & Metronidazole; Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days

Outcome Measures

Primary Outcome Measures

1. Clinical Response 7 to 14 Days After Completion of Study Drug Therapy in Per Protocol (PP) Population [7 - 14 days after completion of study drug therapy]

   Clinical cure was defined as: Reduction of the tenderness score (modified McCormack) by > 70% and apyrexia (rectal/tympanic/oral temperature value < 38.0°C or axillary temperature value < 37.5°C) and white blood cell count < 10,500/mm^3.

Secondary Outcome Measures

1. Clinical Response 7 to 14 Days After Completion of Study Drug Therapy on Intent To Treat (ITT) Population [7 - 14 days after completion of study drug therapy]

   For any subject in the ITT population also valid for the PP analysis, same clinical response as in the PP analysis was applied to the ITT analysis. For those subjects in the ITT population invalid for the PP analysis, any clinical response different from clinical cure was set to "non-success".

2. Clinical Response on Treatment for Per Protocol Population [4 - 7 days after start of therapy]

   At the During Therapy (Day 4 to 7) assessment, the clinical response was graded as clinical Improvement (severity score reduced by >30% with improvement in temperature, clinical failure (reduction in severity score of < or equal 30% and/or no improvement in temperature) or indeterminate (clinical assessment not possible to determine).

3. Clinical Response on Treatment for Intent To Treat Population [4 - 7 days after start of therapy]

   Clinical response during treatment was analyzed exploratively in the same way as the primary efficacy variable. At the During Therapy (Day 4 to 7) assessment, the clinical response was graded as clinical Improvement, clinical failure or indeterminate accordingly. Clinical improvement was considered success, all other outcomes as non-success.

4. Bacteriological Response at Test Of Cure (TOC) Visit Microbiologically Valid [7 - 14 days at TOC visit]

   The bacteriological responses was based on the results of appropriate cultures taken before and, if necessary, during treatment, at the TOC visit and within the follow-up period. Bacteriological response at the TOC visit would also be based on repeated PCR tests for N. gonorrhoeae and C. trachomatis.

5. Bacteriological Response at Test Of Cure (TOC) Visit in Intent To Treat Population With Causative Organism [7 - 14 days at TOC visit]

   Bacteriological response at the TOC was analyzed exploratively in the same way as the primary efficacy variable based on the subgroup of microbiologically valid subjects. At the TOC visit, eradication was considered a bacteriological success, and persistence, presumed persistence and superinfection were considered bacteriological failures.

6. Clinical Response at Follow-up Visit on Per Protocol Population [28 - 42 days after completion of study drug therapy]

   Clinical response at follow up was analyzed exploratively in the same way as the primary efficacy variable. At Follow-up, the clinical response was graded as continued cure, clinical relapse, or indeterminate, of which only continued cure was considered success. Failures from end of treatment were carried forward.

7. Clinical Response at Follow-up Visit on Intent To Treat Population [28 - 42 days after completion of study drug therapy]

   All successfully treated subjects and subjects evaluated as"indeterminate" at TOC, who were not administered an additional antibiotic therapy would have their clinical response rate assessed at the follow-up visit. Patients with missing or indeterminate outcome were treated as non-successes.

8. Bacteriological Response at Follow-up Visit Microbiologically Valid [28 - 42 days after completion of study drug therapy]

   Subjects with at least one causative organism identified in the pre-therapy culture or a positive pre-therapy PCR result and an appropriate post-therapy bacteriological evaluation available were analyzed. Bacteriological responses at follow-up visit was analyzed exploratively in the same way as the primary efficacy variable.

9. Bacteriological Response at Follow-up Visit in Intent To Treat Population With Causative Organism [28 - 42 days after completion of study drug therapy]

   Subjects with at least one causative organism identified in the pre-therapy culture or a positive pre-therapy PCR result and an appropriate post-therapy bacteriological evaluation available were analyzed. Bacteriological responses at follow-up visit was analyzed exploratively in the same way as the primary efficacy variable.

10. Number of Subjects Who Received Alternative Medicine [Up to 42 days after end of treatment]

    As alternative medicine any systemic antibacterial medication was considered.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of uncomplicated PID based on the absence of pelvic or tubo-ovarian abscess at pelvic ultrasound and/or laparoscopic examination.

Exclusion Criteria:

• Subjects with impaired liver and renal function; known hypersensitivity to study drugs, related compounds or any of the excipients.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Shenyang	Liaoning	China	110004
2		Chengdu	Sichuan	China	610041
3		Beijing		China	100034
4		Beijing		China	100083
5		Chongqing		China	400010
6		Shanghai		China	200011
7		Jakarta		Indonesia
8		Seoul		Korea, Republic of	133792
9		Karachi		Pakistan
10		Manila		Philippines
11		Taipei		Taiwan	10002
12		Taizung		Taiwan	402
13		Bangkok		Thailand	10700

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00453349
• Other Study ID Numbers: 11981; 2006-000874-56
• First Posted: Mar 28, 2007
• Last Update Posted: Sep 8, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by Bayer: Uncomplicated pelvic inflammatory disease
• Additional relevant MeSH terms: Pelvic Inflammatory Disease; Pelvic Infection; Moxifloxacin; Metronidazole; Levofloxacin; Ofloxacin; Norgestimate, ethinyl estradiol drug combination

Study Results

Participant Flow

Recruitment Details	A total of 463 females with uncomplicated PID were enrolled on the basis of a complete evaluation (interview, medical history and physical examination and laboratory tests). 460 subjects were randomized, 412 completed study treatment (whole medication), and 384 subjects were valid for the primary efficacy analysis.
Pre-assignment Detail	The efficacy results in ITT are consistent with those in PP, supporting that this is a non-inferiority study and the primary efficacy population was PP not ITT. 76 subjects were excluded from primary efficacy analysis mainly due to essential data missing or invalid, violation of inclusion/exclusion criteria and insufficient duration of therapy.

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Period Title: Randomized
STARTED	228	232
COMPLETED	203	209
NOT COMPLETED	25	23
Period Title: Randomized
STARTED	225	230
Valid for Primary Efficacy Analysis	194	190
COMPLETED	215	219
NOT COMPLETED	10	11
Period Title: Randomized
STARTED	228	232
Completed Study Treatment	203	209
COMPLETED	201	198
NOT COMPLETED	27	34

Baseline Characteristics

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole	Total
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days	Total of all reporting groups
Overall Participants	228	232	460
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.2 (8.4)	35.4 (8.7)	35.2 (8.6)
Sex: Female, Male (Count of Participants)
Female	228 100%	232 100%	460 100%
Male	0 0%	0 0%	0 0%
Microbiology recovery (number of participants with pathogenes) [Number]
Number [number of participants with pathogenes]	36 15.8%	36 15.5%	72 15.7%
Total pelvic pain score (using modified McCormack score) (points on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [points on a scale]	11.3 (3.8)	11.6 (3.8)	11.5 (3.8)

Outcome Measures

1. Primary Outcome

Title	Clinical Response 7 to 14 Days After Completion of Study Drug Therapy in Per Protocol (PP) Population
Description	Clinical cure was defined as: Reduction of the tenderness score (modified McCormack) by > 70% and apyrexia (rectal/tympanic/oral temperature value < 38.0°C or axillary temperature value < 37.5°C) and white blood cell count < 10,500/mm^3.
Time Frame	7 - 14 days after completion of study drug therapy

Outcome Measure Data

Analysis Population Description

The number of subjects in the PP population was slightly higher than the planned number of subjects (184 subjects per treatment group). The most common reasons for exclusion from the population valid for efficacy in both the Moxifloxacin and Comparator were essential data missing/invalid, followed by violation of inclusion/exclusion criteria.

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Measure Participants	194	190
Clinical cure	152 66.7%	155 66.8%
Clinical non-success	42 18.4%	35 15.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin, Levofloxacin Plus Metronidazole
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The non-inferiority margin was set to 15% in the protocol. Sample size was estimated using the method as described in Farrington-Manning (STATISTICS IN MEDICINE, Vol. 9; Farrington CP, Manning G: "Test statistics and sample size formulae for comparative binomial trials with null hypothesis of non-zero risk difference...", pg.1447-1454 [1990]). Estimation was performed to achieve 90% power, based on the equivalence delta of 15%, and a clinical success rate of 87% in the per protocol population
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.2
	Confidence Interval	() 95%; -10.7 to 4.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference denotes the difference of clinical cure rates in percent between the two treatment groups. A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

2. Secondary Outcome

Title	Clinical Response 7 to 14 Days After Completion of Study Drug Therapy on Intent To Treat (ITT) Population
Description	For any subject in the ITT population also valid for the PP analysis, same clinical response as in the PP analysis was applied to the ITT analysis. For those subjects in the ITT population invalid for the PP analysis, any clinical response different from clinical cure was set to "non-success".
Time Frame	7 - 14 days after completion of study drug therapy

Outcome Measure Data

Analysis Population Description

Subjects who were randomized, had received at least one dose of study medication and had at least one observation after drug intake would be included in the ITT analysis.

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Measure Participants	225	230
Clinical cure	163 71.5%	171 73.7%
Clinical non-success	62 27.2%	59 25.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin, Levofloxacin Plus Metronidazole
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variables.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.9
	Confidence Interval	() 95%; -9.9 to 6.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference denotes the difference of clinical cure rates in percent between the two treatment groups. A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

3. Secondary Outcome

Title	Clinical Response on Treatment for Per Protocol Population
Description	At the During Therapy (Day 4 to 7) assessment, the clinical response was graded as clinical Improvement (severity score reduced by >30% with improvement in temperature, clinical failure (reduction in severity score of < or equal 30% and/or no improvement in temperature) or indeterminate (clinical assessment not possible to determine).
Time Frame	4 - 7 days after start of therapy

Outcome Measure Data

Analysis Population Description

Analysis was performed for the per protocol population.

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Measure Participants	188	186
Clinical Improvement	177 77.6%	181 78%
Clinical failure	11 4.8%	5 2.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin, Levofloxacin Plus Metronidazole
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variables.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.2
	Confidence Interval	() 95%; -7.4 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference denotes the difference of clinical improvement rates in percent between the two treatment groups. A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

4. Secondary Outcome

Title	Clinical Response on Treatment for Intent To Treat Population
Description	Clinical response during treatment was analyzed exploratively in the same way as the primary efficacy variable. At the During Therapy (Day 4 to 7) assessment, the clinical response was graded as clinical Improvement, clinical failure or indeterminate accordingly. Clinical improvement was considered success, all other outcomes as non-success.
Time Frame	4 - 7 days after start of therapy

Outcome Measure Data

Analysis Population Description

Subjects who were randomized, had received at least one dose of study medication and had at least one observation after drug intake would be included in the ITT analysis. For any subject in the ITT population also valid for the PP analysis, same clinical response as in the PP analysis was applied to the ITT analysis.

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Measure Participants	225	230
Clinical improvement	166 72.8%	170 73.3%
Failure, indeterminate, missing	59 25.9%	60 25.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin, Levofloxacin Plus Metronidazole
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variables.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	() 95%; -8.1 to 7.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference denotes the difference of clinical improvement rates in percent between the two treatment groups. A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

5. Secondary Outcome

Title	Bacteriological Response at Test Of Cure (TOC) Visit Microbiologically Valid
Description	The bacteriological responses was based on the results of appropriate cultures taken before and, if necessary, during treatment, at the TOC visit and within the follow-up period. Bacteriological response at the TOC visit would also be based on repeated PCR tests for N. gonorrhoeae and C. trachomatis.
Time Frame	7 - 14 days at TOC visit

Outcome Measure Data

Analysis Population Description

All subjects for whom a specific bacterial pathogen was isolated/identified from any pre-treatment culture and which was considered responsible for the infection would be assessed for bacteriological efficacy.

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Measure Participants	30	26
Eradication	27 11.8%	22 9.5%
Persistence	3 1.3%	4 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin, Levofloxacin Plus Metronidazole
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variables.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.4
	Confidence Interval	() 95%; -12.7 to 20.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference denotes the difference of eradication rates in percent between the two treatment groups. A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

6. Secondary Outcome

Title	Bacteriological Response at Test Of Cure (TOC) Visit in Intent To Treat Population With Causative Organism
Description	Bacteriological response at the TOC was analyzed exploratively in the same way as the primary efficacy variable based on the subgroup of microbiologically valid subjects. At the TOC visit, eradication was considered a bacteriological success, and persistence, presumed persistence and superinfection were considered bacteriological failures.
Time Frame	7 - 14 days at TOC visit

Outcome Measure Data

Analysis Population Description

Patients were included in this analysis if a causative organism could be established pre-therapy by culture or PCR, and if the patient was valid for intent-to-treat.

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Measure Participants	36	34
Eradication	28 12.3%	25 10.8%
Persistence, indeterminate, missing	8 3.5%	9 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin, Levofloxacin Plus Metronidazole
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variables.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.3
	Confidence Interval	() 95%; -19.4 to 17.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference denotes the difference of eradication rates in percent between the two treatment groups. A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

7. Secondary Outcome

Title	Clinical Response at Follow-up Visit on Per Protocol Population
Description	Clinical response at follow up was analyzed exploratively in the same way as the primary efficacy variable. At Follow-up, the clinical response was graded as continued cure, clinical relapse, or indeterminate, of which only continued cure was considered success. Failures from end of treatment were carried forward.
Time Frame	28 - 42 days after completion of study drug therapy

Outcome Measure Data

Analysis Population Description

All successfully treated subjects and subjects evaluated as "indeterminate" at TOC, who were not administered an additional antibiotic therapy would have their clinical response rate assessed at the follow up visit. Patients with missing or indeterminate outcome were omitted.

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Measure Participants	184	180
Continued clinical cure	157 68.9%	158 68.1%
Continued failure, clinical recurrence/relapse	27 11.8%	22 9.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin, Levofloxacin Plus Metronidazole
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variables.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.5
	Confidence Interval	() 95%; -8.6 to 4.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference denotes the difference of clinical cure rates in percent between the two treatment groups. A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

8. Secondary Outcome

Title	Clinical Response at Follow-up Visit on Intent To Treat Population
Description	All successfully treated subjects and subjects evaluated as"indeterminate" at TOC, who were not administered an additional antibiotic therapy would have their clinical response rate assessed at the follow-up visit. Patients with missing or indeterminate outcome were treated as non-successes.
Time Frame	28 - 42 days after completion of study drug therapy

Outcome Measure Data

Analysis Population Description

At the follow-up visit, the clinical response in subjects who were non-failures at the TOC visit were graded as Continued cure, Clinical relapse or Indeterminate.

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Measure Participants	225	230
Continued clinical cure	166 72.8%	170 73.3%
Failure, relapse, indeterminate, missing	59 25.9%	60 25.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin, Levofloxacin Plus Metronidazole
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variables.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	() 95%; -8.1 to 7.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference denotes the difference of clinical cure rates in percent between the two treatment groups. A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

9. Secondary Outcome

Title	Bacteriological Response at Follow-up Visit Microbiologically Valid
Description	Subjects with at least one causative organism identified in the pre-therapy culture or a positive pre-therapy PCR result and an appropriate post-therapy bacteriological evaluation available were analyzed. Bacteriological responses at follow-up visit was analyzed exploratively in the same way as the primary efficacy variable.
Time Frame	28 - 42 days after completion of study drug therapy

Outcome Measure Data

Analysis Population Description

At the follow-up visit, the bacteriological success response was classified as eradication, and recurrence/persistence as bacteriological failures.

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Measure Participants	28	26
Eradication	23 10.1%	22 9.5%
Eradication with recurrence, persistence	5 2.2%	4 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin, Levofloxacin Plus Metronidazole
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variables.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.9
	Confidence Interval	() 95%; -24.9 to 15.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference denotes the difference of eradication rates in percent between the two treatment groups. A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

10. Secondary Outcome

Title	Bacteriological Response at Follow-up Visit in Intent To Treat Population With Causative Organism
Description	Subjects with at least one causative organism identified in the pre-therapy culture or a positive pre-therapy PCR result and an appropriate post-therapy bacteriological evaluation available were analyzed. Bacteriological responses at follow-up visit was analyzed exploratively in the same way as the primary efficacy variable.
Time Frame	28 - 42 days after completion of study drug therapy

Outcome Measure Data

Analysis Population Description

At the follow-up visit, the bacteriological success response was classified as Eradication, and recurrence/persistence as bacteriological failures.

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Measure Participants	36	34
Eradication	23 10.1%	23 9.9%
Eradication with recurrence, persistence	13 5.7%	11 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moxifloxacin, Levofloxacin Plus Metronidazole
	Comments	Calculated were 95% confidence intervals for the difference in success rates between treatment groups (moxifloxacin minus comparator). Method as described in Koch et al. ('Categorical Data Analysis' in Statistical methodology in the pharmaceutical sciences / edited by D. A. Berry, p. 415 ff., Marcel Dekker, 1990)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size estimation was based on the primary efficacy variables.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.7
	Confidence Interval	() 95%; -30.5 to 11.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference denotes the difference of eradication rates in percent between the two treatment groups. A positive value indicates an advantage for the treatment group of moxifloxacin, a negative value an advantage for the comparator group.

11. Secondary Outcome

Title	Number of Subjects Who Received Alternative Medicine
Description	As alternative medicine any systemic antibacterial medication was considered.
Time Frame	Up to 42 days after end of treatment

Outcome Measure Data

Analysis Population Description

The number of subjects who received alternative medicine in the PP population was analyzed. The clinical response was graded as alternative medicine (clinical cure, improvement, continued clinical cure) versus no alternative medicine.

Arm/Group Title	Moxifloxacin	Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Measure Participants	194	190
Receiving alternative medicine	4 1.8%	1 0.4%
Not receiving alternative medicine	190 83.3%	189 81.5%

Adverse Events

Arm/Group Title	Moxifloxacin		Levofloxacin Plus Metronidazole
Arm/Group Description	Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days		Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
All Cause Mortality
	Moxifloxacin		Levofloxacin Plus Metronidazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Moxifloxacin		Levofloxacin Plus Metronidazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/225 (1.3%)		1/230 (0.4%)
Gastrointestinal disorders
Colitis	1/225 (0.4%)		0/230 (0%)
Infections and infestations
Pyelonephrits acute	0/225 (0%)		1/230 (0.4%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/225 (0.4%)		0/230 (0%)
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome	1/225 (0.4%)		0/230 (0%)
Other (Not Including Serious) Adverse Events
	Moxifloxacin		Levofloxacin Plus Metronidazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	83/225 (36.9%)		94/230 (40.9%)
Gastrointestinal disorders
Abdominal pain upper	10/225 (4.4%)		14/230 (6.1%)
Nausea	43/225 (19.1%)		54/230 (23.5%)
Vomiting	7/225 (3.1%)		15/230 (6.5%)
Nervous system disorders
Dizziness	39/225 (17.3%)		36/230 (15.7%)
Psychiatric disorders
Insomnia	7/225 (3.1%)		14/230 (6.1%)

Limitations/Caveats

Out of the 460 randomized subjects, 5 subjects (3 moxifloxacin subjects, 2 placebo subjects) did not receive any study medication. Only one of these patients had an adverse event (stomachache, randomized to Moxifloxacin).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.