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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

Primary Purpose

Clostridium Difficile Associated Diarrhea

Status
Completed
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Metronidazole
Metronidazole-DRF1
Metronidazole-DRF2
Sponsored by
Dr. Reddy's Laboratories Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clostridium Difficile Associated Diarrhea focused on measuring Clostridium difficile associated diarrhea, Metronidazole, CDAD

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dr. B.R. Ambedkar Medical College
  • St. John's Medical College and Hospital
  • PRS Hospitals
  • B.Y.L. Nair Hospital
  • Chopda Research and Medical Center Pvt
  • Ruby Hall Clinic
  • Deenanath Mangeshkar Hospital
  • S.P. Medical College and Hospital
  • Apex Medicical College
  • Meenakshi Mission Hospital and Research Center
  • SKS Hospital India Pvt. Ltd.
  • Heritage Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

Metronidazole

Metronidazole-DRF1

Metronidazole-DRF2

Arm Description

Immediate release metronidazole

Modified release metronidazole (DRF1)

Modified release metronidazole (DRF2)

Outcomes

Primary Outcome Measures

Tolerability
Tolerability as assessed by physical examination, ECG, clinical laboratory tests and adverse events
Pharmacokinetics
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
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
Recurrence defined as re-establishment of diarrhea after clinical cure.
30-Day Cure Rate
Clinical cure with no recurrence and no retreatment for 30 days after 14 days of metronidazole treatment (Day 44).

Full Information

First Posted
March 19, 2012
Last Updated
June 6, 2013
Sponsor
Dr. Reddy's Laboratories Limited
Collaborators
Reliance Clinical Research Services (Navi Mumbai, India)
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1. Study Identification

Unique Protocol Identification Number
NCT01559545
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dr. Reddy's Laboratories Limited
Collaborators
Reliance Clinical Research Services (Navi Mumbai, India)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile Associated Diarrhea
Keywords
Clostridium difficile associated diarrhea, Metronidazole, CDAD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Metronidazole
Arm Type
Active Comparator
Arm Description
Immediate release metronidazole
Arm Title
Metronidazole-DRF1
Arm Type
Experimental
Arm Description
Modified release metronidazole (DRF1)
Arm Title
Metronidazole-DRF2
Arm Type
Experimental
Arm Description
Modified release metronidazole (DRF2)
Intervention Type
Drug
Intervention Name(s)
Metronidazole
Other Intervention Name(s)
Flagyl®
Intervention Description
Immediate release metronidazole 500 mg orally three times a day for 14 days
Intervention Type
Drug
Intervention Name(s)
Metronidazole-DRF1
Other Intervention Name(s)
Metronidazole
Intervention Description
Modified release metronidazole (DRF1) 500 mg orally three times a day for 14 days.
Intervention Type
Drug
Intervention Name(s)
Metronidazole-DRF2
Other Intervention Name(s)
Metronidazole
Intervention Description
Modified release metronidazole (DRF2) 500 mg orally three times a day for 14 days.
Primary Outcome Measure Information:
Title
Tolerability
Description
Tolerability as assessed by physical examination, ECG, clinical laboratory tests and adverse events
Time Frame
44 Days
Title
Pharmacokinetics
Description
Systemic pharmacokinetics of metronidazole on Days 1 and 14. Intraluminal colonic concentration of metronidazole as reflected in excreted stool on Days 1 and 14.
Time Frame
14 Days
Secondary Outcome Measure Information:
Title
Clinical Cure
Description
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).
Time Frame
44 Days
Title
Recurrence Rate
Description
Recurrence defined as re-establishment of diarrhea after clinical cure.
Time Frame
44 Days
Title
30-Day Cure Rate
Description
Clinical cure with no recurrence and no retreatment for 30 days after 14 days of metronidazole treatment (Day 44).
Time Frame
44 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female patients 18 years of age or older Mild to moderate C.difficile associated diarrhea (CDAD) with a positive stool C.difficile toxin (by ELISA). Either a first episode of CDAD or a first recurrence (patients with more than 1 recurrence are not eligible) Greater than 3 watery or unformed bowel movements in the prior 24 hours Females of child bearing potential having a negative pregnancy test and taking adequate birth control measures. 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). Able to comprehend and give informed consent for the study and able to adhere to study schedules and protocol requirements. Exclusion Criteria: Known prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives Life expectancy ≤ 60 days Sepsis, severe sepsis, or septic shock Signs or symptoms of peritonitis, megacolon or ileus History of ulcerative colitis or Crohn's disease 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 Recent history of significant drug or alcohol abuse within 1 year 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 Patients with history of blood dyscrasias, porphyria and active non-infectious disease of the central nervous system Patients with history of rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption Pregnant or lactating female patients 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 Unable to participate in the study for any reason in the opinion of the Principal Investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dilip Pawar, MD
Organizational Affiliation
Dr. Reddy's Laboratories Limited
Official's Role
Study Director
Facility Information:
Facility Name
Dr. B.R. Ambedkar Medical College
City
Bangalore
State/Province
Karnataka
Country
India
Facility Name
St. John's Medical College and Hospital
City
Bangalore
State/Province
Karnataka
Country
India
Facility Name
PRS Hospitals
City
Trivandrum
State/Province
Kerala
Country
India
Facility Name
B.Y.L. Nair Hospital
City
Mumbai
State/Province
Maharashtra
Country
India
Facility Name
Chopda Research and Medical Center Pvt
City
Nashik
State/Province
Maharashtra
Country
India
Facility Name
Ruby Hall Clinic
City
Pune
State/Province
Maharashtra
Country
India
Facility Name
Deenanath Mangeshkar Hospital
City
Pune
State/Province
Maharastra
Country
India
Facility Name
S.P. Medical College and Hospital
City
Bikaner
State/Province
Rajasthan
Country
India
Facility Name
Apex Medicical College
City
Jaipur
State/Province
Rajasthan
Country
India
Facility Name
Meenakshi Mission Hospital and Research Center
City
Madurai
State/Province
Tamil Nadu
Country
India
Facility Name
SKS Hospital India Pvt. Ltd.
City
Salem
State/Province
Tamil Nadu
Country
India
Facility Name
Heritage Hospital
City
Lanka
State/Province
Varanasi
Country
India

12. IPD Sharing Statement

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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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