Effect of Omeprazole on Metformin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Xijing Hospital
ClinicalTrials.gov Identifier:
NCT01711320
First received: October 5, 2012
Last updated: March 16, 2013
Last verified: March 2013
  Purpose

In this study, investigators hypothesized that the plasma concentration of metformin and its glucose-lowering action would be affected by omeprazole, probably by altering the expression or function of OCTs in the liver, its primary target organ, as well as in the kidney.


Condition Intervention Phase
Healthy
Drug: Placebo
Drug: Omeprazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Effect of Omeprazole, an OCT Inhibitor, on the Pharmacodynamics and Pharmacokinetics of Metformin, Involved the Mechanism of Attenuating AMPK Phosphorylation

Resource links provided by NLM:


Further study details as provided by Xijing Hospital:

Primary Outcome Measures:
  • Whether the pharmacokinetics of metformin would be effected by omeprazole [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Pharmacokinetic parameters such as the area under the concentration-time curve (AUC), the elimination half-life(t½) and maximum metformin concentration (Cmax)


Secondary Outcome Measures:
  • Whether the pharmacodynamics of metformin would be effected by omeprazole [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    oral glucose tolerance tests (OGTTs) before and after receiving two doses of metformin


Enrollment: 20
Study Start Date: September 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
oral dose of Placebo combined with two dose of Metformin (OGTTs)
Drug: Placebo
Experimental: Omeprazole
oral dose of Omeprazole (80 mg) combined with two dose of Metformin (OGTTs)
Drug: Omeprazole
Other Name: PPI

Detailed Description:

Metformin is the most widely used drug for the treatment of type 2 diabetes. This insulin-sensitizing agent has well known beneficial effects not only on glycemic control, but also on the cardiovascular system. The antihyperglycemic effect of metformin is mainly based on suppression of hepatic gluconeogenesis by activation of AMP-activated protein kinase (AMPK), which suppresses glucagon-stimulated glucose production and causes an increase in glucose uptake in muscle and in hepatic cells. Metformin is actively transported across membranes. The organic cation transporter 1 (OCT1) is responsible for uptake of metformin in hepatocytes, which is an essential step in reducing hepatic glucose production. , which is closely associated with its pharmacological action/adverse reactions.

However, metformin alone is thought to be insufficient for achieving good metabolic control. Thus, treatment in addition to metformin is often required. Sitagliptin attenuates metformin-mediated AMPK phosphorylation through inhibition of organic cation transporters PPIs are frequently used in metformin-treated patients with metabolic syndrome and cardiovascular diseases. Moreover, gastroesophageal reflux disease (GERD) is commonly seen in patients with type 2 diabetes and proton-pump inhibitors (PPIs) are the drugs of best choice in treatment of GERD. These data support the hypothesis that proton pump inhibitors can be used to treat type II diabetes. Moreover, PPIs itself appears to has significant glucose-lowering effects in an animal model of type 2 diabetes regardless of whether metformin is administered concurrently.

A recent in-vitro study found that PPI inhibit metformin uptake by organic cation transporters (OCTs). This drug-drug interaction the clinical has the potential relevance of consequences on metformin disposition and/or efficacy. Since there is a possibility for the combined use of metformin and omeprazole in chronic diabetics, the study is planned to investigate the effect of nicorandil on the activity of gliclazide in normal and diabetic rats to evaluate effectiveness of the combination.

The study is planned to find the pharmacodynamics and pharmacokinetics of metformin in the presence of omeprazole in healthy subjects and to evaluate the mechanisms of the interaction if occurs.

  Eligibility

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

Inclusion Criteria:

  • age: 18 - 45 years
  • sex: male
  • body weight: 18 kg/m² to 26 kg/m²
  • good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state
  • body weight: 18 kg/m² to 26 kg/m²
  • written informed consent

Exclusion Criteria:

  • existing cardiac or hematological diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of metformin
  • existing hepatic and renal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of metformin
  • existing gastrointestinal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of metformin
  • acute or chronic diseases which could affect drug absorption or metabolism
  • history of any serious psychological disorder
  • drug or alcohol dependence
  • smokers of 10 or more cigarettes per day
  • positive screening results for HIV, HBV and HCV
  • volunteers who are on a diet which could affect the pharmacokinetics of the drug
  • heavy tea or coffee drinkers (more than 1L per day)
  • lactation and pregnancy test positive or not performed
  • volunteers suspected or known not to follow instructions
  • blood donation or other blood loss of more than 400 ml within the last 12 weeks prior to the start of the study
  • participation in a clinical trial during the last 3 months prior to the start of the study
  • less than 14 days after last acute disease
  • intake of grapefruit containing food or beverages within 7 days prior to administration
  • any systemically available medication within 4 weeks prior to the intended first administration unless, because of the terminal elimination half-life, complete elimination from the body can be assumed for the drug and/or its primary metabolites (except oral contraceptives)
  • repeated use of drugs during the last 4 weeks prior to the intended first administration, which can influence hepatic biotransformation (e.g. barbiturates, cimetidine, phenytoin, rifampicin)
  • repeated use of drugs during the last 2 weeks prior to the intended first administration which affect absorption (e.g. laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists)
  • known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparation
  • subjects with severe allergies or multiple drug allergies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01711320

Locations
China, Shaanxi
Department of pharmacy, Xijing Hospital, Fourth Military Medical University
Xi'an, Shaanxi, China
Sponsors and Collaborators
Xijing Hospital
Investigators
Study Chair: AiDong Wen, Pro Department of pharmacy, Xijing Hospital, Fourth Military Medical University
  More Information

No publications provided

Responsible Party: Xijing Hospital
ClinicalTrials.gov Identifier: NCT01711320     History of Changes
Other Study ID Numbers: 20120925XJYYYJK
Study First Received: October 5, 2012
Last Updated: March 16, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Xijing Hospital:
Omeprazole
Metformin

Additional relevant MeSH terms:
Metformin
Omeprazole
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 14, 2014