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

This study has been completed.
Sponsor:
Collaborator:
Reliance Clinical Research Services (Navi Mumbai, India)
Information provided by (Responsible Party):
Dr. Reddy's Laboratories Limited
ClinicalTrials.gov Identifier:
NCT01559545
First received: March 19, 2012
Last updated: June 6, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Clostridium Difficile Associated Diarrhea
Drug: Metronidazole
Drug: Metronidazole-DRF1
Drug: Metronidazole-DRF2
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Dr. Reddy's Laboratories Limited:

Primary Outcome Measures:
  • Tolerability [ Time Frame: 44 Days ] [ Designated as safety issue: Yes ]
    Tolerability as assessed by physical examination, ECG, clinical laboratory tests and adverse events

  • Pharmacokinetics [ Time Frame: 14 Days ] [ Designated as safety issue: Yes ]
    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:
  • Clinical Cure [ Time Frame: 44 Days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Recurrence defined as re-establishment of diarrhea after clinical cure.

  • 30-Day Cure Rate [ Time Frame: 44 Days ] [ Designated as safety issue: No ]
    Clinical cure with no recurrence and no retreatment for 30 days after 14 days of metronidazole treatment (Day 44).


Enrollment: 60
Study Start Date: March 2012
Study Completion Date: March 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01559545

Locations
India
St. John's Medical College and Hospital
Bangalore, Karnataka, India
Dr. B.R. Ambedkar Medical College
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)
Investigators
Study Director: Dilip Pawar, MD Dr Reddy's Laboratories Ltd.
  More Information

No publications provided

Responsible Party: Dr. Reddy's Laboratories Limited
ClinicalTrials.gov Identifier: NCT01559545     History of Changes
Other Study ID Numbers: DFA-03-CD-002
Study First Received: March 19, 2012
Last Updated: June 6, 2013
Health Authority: India: Drugs Controller General of India

Keywords provided by Dr. Reddy's Laboratories Limited:
Clostridium difficile associated diarrhea
Metronidazole
CDAD

Additional relevant MeSH terms:
Diarrhea
Signs and Symptoms, Digestive
Signs and Symptoms
Metronidazole
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Infective Agents
Therapeutic Uses
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on July 22, 2014