Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Safety, Tolerability and Pharmacokinetic Study of Two Formulations of Metronidazole Versus Immediate Release Metronidazole in Patient With C. Difficile Colitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01559545
Recruitment Status : Completed
First Posted : March 21, 2012
Last Update Posted : June 7, 2013
Sponsor:
Collaborator:
Reliance Clinical Research Services (Navi Mumbai, India)
Information provided by (Responsible Party):
Dr. Reddy's Laboratories Limited

Tracking Information
First Submitted Date  ICMJE March 19, 2012
First Posted Date  ICMJE March 21, 2012
Last Update Posted Date June 7, 2013
Study Start Date  ICMJE March 2012
Actual Primary Completion Date February 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2012)
  • Tolerability [ Time Frame: 44 Days ]
    Tolerability as assessed by physical examination, ECG, clinical laboratory tests and adverse events
  • Pharmacokinetics [ Time Frame: 14 Days ]
    Systemic pharmacokinetics of metronidazole on Days 1 and 14. Intraluminal colonic concentration of metronidazole as reflected in excreted stool on Days 1 and 14.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2012)
  • Clinical Cure [ Time Frame: 44 Days ]
    Response rate to treatment 2 days after completion of 14 days of metronidazole treatment with no recurrence 30 days after 14 days of metronidazole treatment (Day 44).
  • Recurrence Rate [ Time Frame: 44 Days ]
    Recurrence defined as re-establishment of diarrhea after clinical cure.
  • 30-Day Cure Rate [ Time Frame: 44 Days ]
    Clinical cure with no recurrence and no retreatment for 30 days after 14 days of metronidazole treatment (Day 44).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety, Tolerability and Pharmacokinetic Study of Two Formulations of Metronidazole Versus Immediate Release Metronidazole in Patient With C. Difficile Colitis
Official Title  ICMJE A Randomized, Open Label, Active Control, Safety, Tolerability and Pharmacokinetics Study of Two Dr. Reddy's Formulations of Metronidazole Versus Immediate Release Metronidazole (Flagyl) in Patients With Mild to Moderate C. Difficile Associated Diarrhea (CDAD)
Brief Summary

Clostridium difficile bacteria can be a cause of significant diarrheal disease, particularly in people who have taken potent antibiotics. When C. difficile multiplies within the colon, it produces two toxins that cause inflammation and resultant abdominal pain, fever and diarrhea. Current treatment of mild to moderate disease is with immediate release metronidazole, an antibiotic that kills C. difficile. Dr. Reddy's Laboratories has developed a delayed release form of metronidazole to release just before the colon to increase the concentration of antibiotic in the colon to improve the effectiveness of metronidazole treatment and potentially to allow less whole body exposure to the antibiotic.

This study will measure the amount of metronidazole in the blood and stool of patients with C. difficile associated diarrhea (CDAD) to confirm that the new formulations are releasing the antibiotic as designed, immediately before the colon.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Clostridium Difficile Associated Diarrhea
Intervention  ICMJE
  • Drug: Metronidazole
    Immediate release metronidazole 500 mg orally three times a day for 14 days
    Other Name: Flagyl®
  • Drug: Metronidazole-DRF1
    Modified release metronidazole (DRF1) 500 mg orally three times a day for 14 days.
    Other Name: Metronidazole
  • Drug: Metronidazole-DRF2
    Modified release metronidazole (DRF2) 500 mg orally three times a day for 14 days.
    Other Name: Metronidazole
Study Arms  ICMJE
  • Active Comparator: Metronidazole
    Immediate release metronidazole
    Intervention: Drug: Metronidazole
  • Experimental: Metronidazole-DRF1
    Modified release metronidazole (DRF1)
    Intervention: Drug: Metronidazole-DRF1
  • Experimental: Metronidazole-DRF2
    Modified release metronidazole (DRF2)
    Intervention: Drug: Metronidazole-DRF2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 20, 2012)
60
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2013
Actual Primary Completion Date February 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male and female patients 18 years of age or older
  2. Mild to moderate C.difficile associated diarrhea (CDAD) with a positive stool C.difficile toxin (by ELISA).
  3. Either a first episode of CDAD or a first recurrence (patients with more than 1 recurrence are not eligible)
  4. Greater than 3 watery or unformed bowel movements in the prior 24 hours
  5. Females of child bearing potential having a negative pregnancy test and taking adequate birth control measures.
  6. Patients should not consume alcohol at least 12 hours prior to dosing (i.e. in-house monitoring) and until 48 hours after the last dose of drug administration (until Day 14).
  7. Able to comprehend and give informed consent for the study and able to adhere to study schedules and protocol requirements.

Exclusion Criteria:

  1. Known prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives
  2. Life expectancy ≤ 60 days
  3. Sepsis, severe sepsis, or septic shock
  4. Signs or symptoms of peritonitis, megacolon or ileus
  5. History of ulcerative colitis or Crohn's disease
  6. Oral or parenteral antibiotic therapy with metronidazole or vancomycin or other drugs effective in treating DCAD (e.g., bacitracin, fusidic acid) within the 1 week prior to enrollment
  7. Recent history of significant drug or alcohol abuse within 1 year
  8. Any findings on physical examination, medical history, 12-lead ECG or clinical laboratory tests which, in the judgment of the Principal Investigator, would exclude patients from participating in the study
  9. Patients with history of blood dyscrasias, porphyria and active non-infectious disease of the central nervous system
  10. Patients with history of rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
  11. Pregnant or lactating female patients
  12. Participation within 30 days before the start of this study in any experimental drug or device study, or currently participating in a study in which the administration of investigational drug or device within 60 days is anticipated
  13. Unable to participate in the study for any reason in the opinion of the Principal Investigator
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE India
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01559545
Other Study ID Numbers  ICMJE DFA-03-CD-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr. Reddy's Laboratories Limited
Study Sponsor  ICMJE Dr. Reddy's Laboratories Limited
Collaborators  ICMJE Reliance Clinical Research Services (Navi Mumbai, India)
Investigators  ICMJE
Study Director: Dilip Pawar, MD Dr. Reddy's Laboratories Limited
PRS Account Dr. Reddy's Laboratories Limited
Verification Date June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP