Drug-Drug Interaction Study With Metformin and Nizatidine

NCT01409395 | Completed Phase 1 DMC

• 2 other identifiers: 6968R01GM036780
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Drug drug interaction

Outcome Measures

Primary Outcomes (1)

• Composite of Pharmacokinetics of co-administration of nizatidine & metformin in healthy volunteers.

  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)

  24 hours

Study Arms (2)

Metformin

EXPERIMENTAL

Subjects will be dosed with Metformin alone (850 mg)

Drug: Metformin

Metformin and Nizatidine

EXPERIMENTAL

Subjects will be dosed with metformin in conjunction with nizatidine

Drug: Metformin and nizatidine

Interventions

Metformin and nizatidine DRUG

Subjects will be given a single oral dose of 850 mg of metformin and a single oral dose of 600 mg of nizatidine

Also known as: Metformin: Fortamet, Glucophage, Nizatidine: Axid

Metformin and Nizatidine

Metformin DRUG

Subjects will be given a single oral dose of 850 mg of metformin

Also known as: GLUCOPHAGE

Metformin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Pregnant or lactating woman (female subjects will have a urine pregnancy test at the screening visit)
• Abnormal bone marrow function (leukocyte, neutrophil, or platelet counts outside the normal range)
• History of hypersensitivity or allergic reaction to metformin or nizatidine
• Risk of congestive heart failure requiring pharmacologic treatment (medical history)
• History of renal or hepatic dysfunction (e.g., CLcr \<60mL/min, ALT \>80U/L, AST\>60 U/L)
• Anemic (hemoglobin \<12 g/dL)
• 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.
• Laboratory parameters that are more than 2 standard deviations from the laboratory mean
• Subject carries a MATE2K gene variant that is predicted to effect MATE2K protein expression

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

Ucsf Ctsi Crc

San Francisco, California, 94158, United States

Location

MeSH Terms

Interventions

Metformin; Nizatidine

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kathleen M Giacomini, Ph.D

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2011
• First Posted: August 4, 2011
• Study Start: September 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: April 10, 2014

Record last verified: 2014-04

Locations

US (1)