Metronidazole Drug Interaction Study With MMX® Mesalazine/Mesalamine

A Phase 1, Randomized, Open-label, Crossover, Drug Interaction Study Evaluating the Pharmacokinetic Profiles of Metronidazole Administered Alone and in Combination With MMX® Mesalazine/Mesalamine in Healthy Adult Subjects

Drug interaction study evaluating the pharmacokinetic profiles of Metronidazole administered alone & in combination with MMX® Mesalazine/mesalamine

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Metronidazole + MMX Mesalazine/mesalamine placebo; Drug: Metronidazole + MMX Mesalazine/mesalamine

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States
      • PRA International

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Age 18-55 years inclusive at the time of consent. The date of signing informed consent is defined as the beginning of the Screening Period.

2. Subject is willing to comply with any applicable contraceptive requirements of the protocol and is:

   • Male, or
   • Non-pregnant, non-lactating female
   • Females must be at least 90 days post-partum or nulliparous.

Exclusion Criteria

1. A history of current or recurrent disease that could affect the colon. This includes gastrointestinal disease, peptic ulceration, gastrointestinal bleeding, celiac disease, lactose intolerance, ulcerative colitis, Crohn's disease, or Irritable Bowel Syndrome. Subjects who have a history of chronic constipation, which is physician diagnosed and treated, will also be excluded from the study (frequency of bowel movements >48 hours between samples).
2. A history of current or relevant serious, severe, or unstable (acute or progressive) physical or psychiatric illness.
3. A history of gastrointestinal surgery performed within the past 12 months prior to the first dose of investigational product, with the exception of an appendectomy.
4. A history of or current clinically relevant moderate or severe renal or hepatic impairment.
5. A history of asthma or bronchospasm associated with the use of 5-ASA or other non-steroidal anti-inflammatory drugs.
6. Known or suspected intolerance or hypersensitivity to the investigational product or metronidazole, closely related compounds, or any of the stated ingredients
7. A history of, or current, pancreatitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metronidazole + MMX placebo	Drug: Metronidazole + MMX Mesalazine/mesalamine placebo; Metronidazole 750 mg twice daily + MMX Mesalazine/mesalamine placebo once daily for 3 days orally, then Metronidazole 750 mg single dose + MMX Mesalazine/mesalamine placebo single dose on Day 4 orally
Experimental: Metronidazole + MMX Mesalazine/mesalamine	Drug: Metronidazole + MMX Mesalazine/mesalamine; Metronidazole 750 mg twice daily + MMX Mesalazine/mesalamine 4.8 g once daily for 3 days orally, then Metronidazole 750 mg single dose + MMX Mesalazine/mesalamine 4.8 g single dose on Day 4 orally; Other Names: Lialda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration Curve (AUC) at Steady State for Metronidazole	AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.	Assessed over a 24-hour period starting post-dose on day 4
Maximum Plasma Concentration (Cmax) at Steady State for Metronidazole	Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.	Assessed over a 24-hour period starting post-dose on day 4

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Pierce D, Corcoran M, Martin P, Barrett K, Inglis S, Preston P, Thompson TN, Willsie SK. Effect of MMX(R) mesalamine coadministration on the pharmacokinetics of amoxicillin, ciprofloxacin XR, metronidazole, and sulfamethoxazole: results from four randomized clinical trials. Drug Des Devel Ther. 2014 May 14;8:529-43. doi: 10.2147/DDDT.S55373. eCollection 2014.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2011
• Primary Completion (Actual): October 5, 2011
• Study Completion (Actual): October 5, 2011

Study Registration Dates

• First Submitted: August 15, 2011
• First Submitted That Met QC Criteria: August 16, 2011
• First Posted (Estimate): August 17, 2011

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole; Mesalamine
• Other Study ID Numbers: SPD476-116