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

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ClinicalTrials.gov Identifier: NCT01559545
Recruitment Status : Completed
First Posted : March 21, 2012
Last Update Posted : June 7, 2013
Reliance Clinical Research Services (Navi Mumbai, India)
Information provided by (Responsible Party):
Dr. Reddy's Laboratories Limited

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.

Condition or disease Intervention/treatment Phase
Clostridium Difficile Associated Diarrhea Drug: Metronidazole Drug: Metronidazole-DRF1 Drug: Metronidazole-DRF2 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : March 2012
Actual Primary Completion Date : February 2013
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diarrhea

Arm Intervention/treatment
Active Comparator: Metronidazole
Immediate release metronidazole
Drug: Metronidazole
Immediate release metronidazole 500 mg orally three times a day for 14 days
Other Name: Flagyl®

Experimental: Metronidazole-DRF1
Modified release metronidazole (DRF1)
Drug: Metronidazole-DRF1
Modified release metronidazole (DRF1) 500 mg orally three times a day for 14 days.
Other Name: Metronidazole

Experimental: Metronidazole-DRF2
Modified release metronidazole (DRF2)
Drug: Metronidazole-DRF2
Modified release metronidazole (DRF2) 500 mg orally three times a day for 14 days.
Other Name: Metronidazole

Primary Outcome Measures :
  1. Tolerability [ Time Frame: 44 Days ]
    Tolerability as assessed by physical examination, ECG, clinical laboratory tests and adverse events

  2. 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.

Secondary Outcome Measures :
  1. 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).

  2. Recurrence Rate [ Time Frame: 44 Days ]
    Recurrence defined as re-establishment of diarrhea after clinical cure.

  3. 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).

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01559545

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Dr. B.R. Ambedkar Medical College
Bangalore, Karnataka, India
St. John's Medical College and Hospital
Bangalore, Karnataka, India
PRS Hospitals
Trivandrum, Kerala, India
B.Y.L. Nair Hospital
Mumbai, Maharashtra, India
Chopda Research and Medical Center Pvt
Nashik, Maharashtra, India
Ruby Hall Clinic
Pune, Maharashtra, India
Deenanath Mangeshkar Hospital
Pune, Maharastra, India
S.P. Medical College and Hospital
Bikaner, Rajasthan, India
Apex Medicical College
Jaipur, Rajasthan, India
Meenakshi Mission Hospital and Research Center
Madurai, Tamil Nadu, India
SKS Hospital India Pvt. Ltd.
Salem, Tamil Nadu, India
Heritage Hospital
Lanka, Varanasi, India
Sponsors and Collaborators
Dr. Reddy's Laboratories Limited
Reliance Clinical Research Services (Navi Mumbai, India)
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Study Director: Dilip Pawar, MD Dr. Reddy's Laboratories Limited
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Responsible Party: Dr. Reddy's Laboratories Limited
ClinicalTrials.gov Identifier: NCT01559545    
Other Study ID Numbers: DFA-03-CD-002
First Posted: March 21, 2012    Key Record Dates
Last Update Posted: June 7, 2013
Last Verified: June 2013
Keywords provided by Dr. Reddy's Laboratories Limited:
Clostridium difficile associated diarrhea
Additional relevant MeSH terms:
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Signs and Symptoms, Digestive
Anti-Infective Agents
Anti-Bacterial Agents
Antiprotozoal Agents
Antiparasitic Agents