Clinical trial NCT01559545: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Clostridium Difficile Associated Diarrhea
Keywords: Clostridium difficile associated diarrhea
Metronidazole
CDAD
Lead sponsor: Dr. Reddy's Laboratories Limited
Sponsor class: INDUSTRY
Collaborators: name: Reliance Clinical Research Services (Navi Mumbai, India)
First posted: 2012-03-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Tolerability
timeFrame: 44 Days
measure: Pharmacokinetics
timeFrame: 14 Days
Secondary outcomes:
measure: Clinical Cure
timeFrame: 44 Days
measure: Recurrence Rate
timeFrame: 44 Days
measure: 30-Day Cure Rate
timeFrame: 44 Days
Other outcomes:
Locations:
city: Bangalore
country: India
facility: Dr. B.R. Ambedkar Medical College
state: Karnataka
city: Bangalore
country: India
facility: St. John's Medical College and Hospital
state: Karnataka
city: Trivandrum
country: India
facility: PRS Hospitals
state: Kerala
city: Mumbai
country: India
facility: B.Y.L. Nair Hospital
state: Maharashtra
city: Nashik
country: India
facility: Chopda Research and Medical Center Pvt
state: Maharashtra
city: Pune
country: India
facility: Ruby Hall Clinic
state: Maharashtra
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital
state: Maharastra
city: Bikaner
country: India
facility: S.P. Medical College and Hospital
state: Rajasthan
city: Jaipur
country: India
facility: Apex Medicical College
state: Rajasthan
city: Madurai
country: India
facility: Meenakshi Mission Hospital and Research Center
state: Tamil Nadu
city: Salem
country: India
facility: SKS Hospital India Pvt. Ltd.
state: Tamil Nadu
city: Lanka
country: India
facility: Heritage Hospital
state: Varanasi
Study officials:
affiliation: Dr. Reddy's Laboratories Limited
name: Dilip Pawar, MD
role: STUDY_DIRECTOR
References: