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

NCT01559545 | Completed Phase 2

• 1 other identifier: DFA-03-CD-002
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 12

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.

Conditions

Clostridium Difficile Associated Diarrhea

Keywords

Clostridium difficile associated diarrhea; Metronidazole; CDAD

Outcome Measures

Primary Outcomes (2)

• Tolerability

  Tolerability as assessed by physical examination, ECG, clinical laboratory tests and adverse events

  44 Days

• 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.

  14 Days

Secondary Outcomes (3)

• Clinical Cure

  44 Days

• Recurrence Rate

  44 Days

• 30-Day Cure Rate

  44 Days

Study Arms (3)

Metronidazole

ACTIVE COMPARATOR

Immediate release metronidazole

Drug: Metronidazole

Metronidazole-DRF1

EXPERIMENTAL

Modified release metronidazole (DRF1)

Drug: Metronidazole-DRF1

Metronidazole-DRF2

EXPERIMENTAL

Modified release metronidazole (DRF2)

Drug: Metronidazole-DRF2

Interventions

Metronidazole DRUG

Immediate release metronidazole 500 mg orally three times a day for 14 days

Also known as: Flagyl®

Metronidazole

Metronidazole-DRF1 DRUG

Modified release metronidazole (DRF1) 500 mg orally three times a day for 14 days.

Also known as: Metronidazole

Metronidazole-DRF1

Metronidazole-DRF2 DRUG

Modified release metronidazole (DRF2) 500 mg orally three times a day for 14 days.

Also known as: Metronidazole

Metronidazole-DRF2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Dr. Reddy's Laboratories Limited: lead
• Reliance Clinical Research Services (Navi Mumbai, India): collaborator

Study Sites (12)

Dr. B.R. Ambedkar Medical College

Bangalore, Karnataka, India

Location

St. John's Medical College and Hospital

Bangalore, Karnataka, India

Location

PRS Hospitals

Trivandrum, Kerala, India

Location

B.Y.L. Nair Hospital

Mumbai, Maharashtra, India

Location

Chopda Research and Medical Center Pvt

Nashik, Maharashtra, India

Location

Deenanath Mangeshkar Hospital

Pune, Maharashtra, India

Location

Ruby Hall Clinic

Pune, Maharashtra, India

Location

S.P. Medical College and Hospital

Bikaner, Rajasthan, India

Location

Apex Medicical College

Jaipur, Rajasthan, India

Location

Meenakshi Mission Hospital and Research Center

Madurai, Tamil Nadu, India

Location

SKS Hospital India Pvt. Ltd.

Salem, Tamil Nadu, India

Location

Heritage Hospital

Lanka, Varanasi, India

Location

MeSH Terms

Interventions

Metronidazole

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dilip Pawar, MD

  Dr. Reddy's Laboratories Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2012
• First Posted: March 21, 2012
• Study Start: March 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: March 1, 2013
• Last Updated: June 7, 2013

Record last verified: 2013-06

Locations

IN (12)