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. Moxifloxacin, Metronidazole, and Levofloxacin in Asia (MONALISA Study)”

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. Moxifloxacin, Metronidazole, and Levofloxacin in Asia (MONALISA Study).

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study

TIME FRAMES

Primary outcomes: TOC: 7-14 days after the end of treatment. Secondary outcomes:During-therapy: 4-7 days after start / 1st dose, TOC: 7-14 days after the end of treatment, FU: 28-42 days after the end of treatment

Number of arms: 2 (Treatment Group 1: Moxifloxacin 400 mg PO once daily for 14 days, Treatment Group 2:

Levofloxacin 500 mg PO once daily for 14 days plus Metronidazole 500 mg twice daily for 14 days)

Intervention(s) in this Clinical Trial

• Drug: Avelox (Moxifloxacin, BAY12-8039)

Primary Measures

• TOC visit (7-14 days after EOT). The primary efficacy analysis will be performed on the per protocol population.
  • Time Frame: see below
    
• Subjects will be included in the per protocol analysis if they satisfy the following criteria of a valid course: The diagnosis of uncomplicated pelvic inflammatory disease must have been confirmed.
  • Time Frame: see below
    
• No other systemic antimicrobial agent (with the exception of one single dose of ceftriaxone in subjects with a gonococcal infection) was administered concomitantly with the study drug unless the subject was a treatment failure.
  • Time Frame: see below
    
• The study drug was given for a minimum of 72 hours (in case of clinical failure) or 8 full days (in case of success) Compliance with ≥80 % of study medication administered, must be documented.
  • Time Frame: see below
    
• No protocol violations influencing the treatment efficacy must have been observed. The clinical evaluation at TOC visit must be available and different from indeterminate.
  • Time Frame: see below
    
• The subject was not given an immunosuppressive therapy, and had no neutropenia (<1000/mm3), no HIV infection with CD4 count < 200/mm3, no AIDS-defining event, and was not under HAART. Study blind must have been maintained
  • Time Frame: see below
    

Secondary Measures

• Clinical response during treatment (4 to 7 days after start of treatment) and FU visit(28-42 days after the end of treatment)
  • Time Frame: see below
    
• Bacteriological response at the TOC visit (7-14 days after the end of treatment)
  • Time Frame: see below
    
• Clinical and bacteriological response at the Follow-up visit (28 to 42 days post-therapy)
  • Time Frame: see below
    
• Clinical response at the TOC visit in subjects with bacteriologically documented infection
  • Time Frame: see below
    

Inclusion Criteria:

• 1. Women aged 18 years or above
• 2. Diagnosis of PID based on:

All of the following symptoms:

• Pelvic discomfort
• Direct lower abdominal tenderness with or without rebound tenderness
• Adnexal tenderness on bimanual vaginal examination
• Cervical motion tenderness on bimanual vaginal examination

And one or more of the following signs:

• Rectal/tympanic/oral temperature value > 38.0°C or axillary temperature value >
• 37.5°C
• Elevated C-reactive protein value (above the upper limit of normal value for the respective laboratory)
• White blood cell count (WBC) >= 10,500/mm3
• Laparoscopic evidence of PID
• Signs suggestive of cervical infection including mucopurulent cervical discharge or positive Gram stain for Gram-negative intracellular diplococci from the endocervix
• Untreated, recent (less than 14 days) documented gonococcal or chlamydial cervicitis
• Note: The diagnosis of uncomplicated PID will be based on the absence of pelvic or tubo-ovarian abscess at pelvic ultrasound and/or at laparoscopic examination performed within 48 hours prior to start of therapy or within 24 hours after start of therapy.
• 3. Endocervical cultures and PCR tests performed within 48 hours prior to start of therapy
• 4. Subjects who are willing to use condoms as barrier contraception until the completion of the Test-of-Cure (or alternative antibiotic) visit
• 5. Subjects who are willing to have a physical examination at the different assessment visits
• 6. Subjects must have signed an informed consent form prior to study entry
• If WBC count and/or C-reactive protein are performed at baseline at a local laboratory for selection of the subject, only these variables are to be entered into the CRF to document subject eligibility. No other local baseline laboratory tests will be entered.

Exclusion Criteria:

Subjects with any of the following will be excluded from participation in the study:

• 1. Subjects who are pregnant or lactating (Note: A negative urine pregnancy test must be obtained prior to randomization and will be confirmed by a serum test; however, the subject can be randomized before results of the serum test are available)
• 2. Known hypersensitivity to either of the study drugs, related compounds or any of the excipients
• 3. Previous history of tendon disorders associated with quinolones
• 4. Clinically relevant bradycardia
• 5. Clinically relevant heart failure with reduced left-ventricular ejection fraction
• 6. Previous history of symptomatic arrhythmias
• 7. Known to have congenital or documented acquired QT prolongation or receiving concomitant medication reported to increase the QT interval (e.g. antiarrhythmics class IA, antiarrhythmics class III, neuroleptics, tricyclic antidepressive agents, certain antimicrobials, certain antihistaminics, cisapride, bepridil, vincamine IV, diphemanil)
• 8. Subjects with known electrolyte disturbances, particularly uncorrected hypokalaemia
• 9. Subjects with a history of epilepsy.
• 10. Subjects with a known defect in glucose-6-phosphate dehydrogenase
• 11. Subjects likely to require concomitant systemic antibacterial therapy up to the Day
• +28/+42 Follow-up visit (Note: subjects with a documented gonococcal infection will receive one single administration of ceftriaxone at the during therapy visit)
• 12. Surgical intervention within the next 24 hours is anticipated (Note: diagnostic laparoscopy is not considered as a surgical intervention)
• 13. Subjects receiving any systemic antibacterial agents within 7 days prior to enrolment
• 14. Subjects with a history of uterine or pelvic or abdominal surgery within 30 days prior to treatment (Note: subjects with a PID occurring after delivery or abortion can be enrolled in the study)
• 15. Vomiting subjects or subjects unable to follow or tolerate an oral antibiotic regimen
• 16. Subjects receiving immunosuppressive therapy, defined as chronic treatment (>= 2 weeks) with a known immunosuppressive medication, including treatment with > 10 mg/day of systemic prednisone or equivalent
• 17. Subjects with known impaired liver function (Child Pugh C), and/or known transaminases increase > 5 fold the upper limit of normal (ULN)
• 18. Subjects with known impaired renal function (creatinine clearance <= 50 mL/min)
• 19. Subjects with known neutropenia (<1000/mm3), or having HIV infection with a CD4 count of <200/mm3, or presenting with an AIDS-defining event, or under an highly active antiretroviral therapy (HAART) (Note: HIV testing is not required for this study protocol)
• 20. Diagnosis of rapidly fatal illness with a life expectancy of less than 6 months
• 21. Subjects who have been previously enrolled in this clinical study
• 22. Subjects who have taken investigational drugs within the last 30 days

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Bayer

Overall Clinical Trial Officials and Contacts

Bayer Study Manager Study Director Bayer  

Overall Contact: Bayer Clinical Trials Contact  clinical-trials-contact@bayerhealthcare.com

Information obtained from ClinicalTrials.gov on October 07, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00453349

Study ID Number: 11981

ClinicalTrials.gov Identifier: NCT00453349

Health Authority: Thailand: Food and Drug Administration

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