Drug-Drug Interaction Study With Metformin and Nizatidine

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01409395
First received: July 29, 2011
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

This study will address the following question: Does nizatidine affect the pharmacokinetics of metformin in healthy volunteers? Recent studies in the Giacomini laboratory have indicated that nizatidine may block metformin elimination from the kidney by inhibiting organic cation transporter efflux of metformin. The investigators hypothesize that the co-administration of metformin and nizatidine will reduce the renal clearance (CLR) of metformin leading to increased plasma concentrations and potential risk for toxicities. Knowledge of the pharmacokinetic interaction profile of metformin with organic transporter inhibitors, such as nizatidine, is important to help develop safer more effective drug therapy with reduced side effects.


Condition Intervention Phase
Healthy
Drug: Metformin and nizatidine
Drug: Metformin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Pharmacokinetic Interaction Between Metformin and Nizatidine in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Composite of Pharmacokinetics of co-administration of nizatidine & metformin in healthy volunteers. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Cmax and Tmax will be determined from AUC-time curve Glomerular filtration rate (GFR) will be approximated by measured creatinine clearance using the following equation:GFR calculation: GFR = CLcreatinine = (Urinary creatinine * V) / (Plasma creatinine)


Enrollment: 10
Study Start Date: September 2011
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
Subjects will be dosed with Metformin alone (850 mg)
Drug: Metformin
Subjects will be given a single oral dose of 850 mg of metformin
Other Name: GLUCOPHAGE
Experimental: Metformin and Nizatidine
Subjects will be dosed with metformin in conjunction with nizatidine
Drug: Metformin and nizatidine
Subjects will be given a single oral dose of 850 mg of metformin and a single oral dose of 600 mg of nizatidine
Other Names:
  • Metformin: Fortamet, Glucophage
  • Nizatidine: Axid

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age 18-45 years
  2. Male or female
  3. If female, using appropriate contraception
  4. Healthy as judged by medical examination, medical history and normal biochemical and hematological measures
  5. Normal urinalysis and renal function
  6. Understand the nature and purpose of the study and provide informed consent

Exclusion Criteria:

  1. Pregnant or lactating woman (female subjects will have a urine pregnancy test at the screening visit)
  2. Abnormal bone marrow function (leukocyte, neutrophil, or platelet counts outside the normal range)
  3. History of hypersensitivity or allergic reaction to metformin or nizatidine
  4. Risk of congestive heart failure requiring pharmacologic treatment (medical history)
  5. History of renal or hepatic dysfunction (e.g., CLcr <60mL/min, ALT >80U/L, AST>60 U/L)
  6. Anemic (hemoglobin <12 g/dL)
  7. Use of any medications (including over the counter products, herbal products, or mineral supplements) with the exception of a daily vitamin or oral contraceptives. In particular use of medications that are known to interfere with the pharmacokinetics of metformin and nizatidine such as cimetidine, cetirizine, ketoconazole, procainamide, St. John's Wort, and testosterone are prohibited.
  8. Laboratory parameters that are more than 2 standard deviations from the laboratory mean
  9. Subject carries a MATE2K gene variant that is predicted to effect MATE2K protein expression
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01409395

Locations
United States, California
Ucsf Ctsi Crc
San Francisco, California, United States, 94158
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Kathleen M Giacomini, Ph.D University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01409395     History of Changes
Other Study ID Numbers: 6968, R01GM036780
Study First Received: July 29, 2011
Last Updated: April 9, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
Drug drug interaction

Additional relevant MeSH terms:
Metformin
Nizatidine
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014