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

Phase 2

Completed

• Conditions: Clostridium Difficile Associated Diarrhea
• Interventions: Drug: Metronidazole-DRF1; Drug: Metronidazole-DRF2; Drug: Metronidazole

• Registration Number: NCT01559545
• Lead Sponsor: Dr. Reddy's Laboratories Limited

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 available

Study Timeline

• Study Start: 2012-03
• Study First Submitted: 2012-03-19
• Study First Submitted QC: 2012-03-20
• Study First Posted: 2012-03-21
• Primary Completion: 2013-02
• Study Completion: 2013-03
• Status Verified: 2013-06
• Last Update Submitted: 2013-06-06
• Last Update Posted: 2013-06-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metronidazole-DRF1	Metronidazole-DRF1	Modified release metronidazole (DRF1)
Metronidazole-DRF2	Metronidazole-DRF2	Modified release metronidazole (DRF2)
Metronidazole	Metronidazole	Immediate release metronidazole

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics	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.
Tolerability	44 Days	Tolerability as assessed by physical examination, ECG, clinical laboratory tests and adverse events

Secondary Outcome Measures

Name	Time	Method
Clinical Cure	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	44 Days	Recurrence defined as re-establishment of diarrhea after clinical cure.
30-Day Cure Rate	44 Days	Clinical cure with no recurrence and no retreatment for 30 days after 14 days of metronidazole treatment (Day 44).

Trial Locations

Locations (12)

Apex Medicical College; 🇮🇳 Jaipur, Rajasthan, India

SKS Hospital India Pvt. Ltd.; 🇮🇳 Salem, Tamil Nadu, India

Meenakshi Mission Hospital and Research Center; 🇮🇳 Madurai, Tamil Nadu, India

St. John's Medical College and Hospital; 🇮🇳 Bangalore, Karnataka, India

Deenanath Mangeshkar Hospital; 🇮🇳 Pune, Maharastra, India

Heritage Hospital; 🇮🇳 Lanka, Varanasi, India

Dr. B.R. Ambedkar Medical College; 🇮🇳 Bangalore, Karnataka, India

Chopda Research and Medical Center Pvt; 🇮🇳 Nashik, Maharashtra, India

B.Y.L. Nair Hospital; 🇮🇳 Mumbai, Maharashtra, India

PRS Hospitals; 🇮🇳 Trivandrum, Kerala, India

S.P. Medical College and Hospital; 🇮🇳 Bikaner, Rajasthan, India

Ruby Hall Clinic; 🇮🇳 Pune, Maharashtra, India