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