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

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

Tracking Information

• First Submitted Date: March 19, 2012
• First Posted Date: March 21, 2012
• Last Update Posted Date: June 7, 2013
• Study Start Date: March 2012
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Clostridium Difficile Associated Diarrhea

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 20, 2012): 60
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: March 2013
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: India

Administrative Information

• NCT Number: NCT01559545
• Other Study ID Numbers: DFA-03-CD-002
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Dr. Reddy's Laboratories Limited
• Original Responsible Party: Same as current
• Current Study Sponsor: Dr. Reddy's Laboratories Limited
• Original Study Sponsor: Same as current
• Collaborators: Reliance Clinical Research Services (Navi Mumbai, India)

Investigators

• Study Director: Dilip Pawar, MD; Dr. Reddy's Laboratories Limited

• PRS Account: Dr. Reddy's Laboratories Limited
• Verification Date: June 2013