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OXEMET™ 1000 mg Coated Tablets (Metformin Hydrochloride) Bioequivalence Study. OXEMET (TM) is a Trademark of the GlaxoSmithKline Group of Companies. GLAFORNIL(TM) is a Trademark of Merck.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01842620
First received: April 25, 2013
Last updated: September 25, 2014
Last verified: September 2014
  Purpose

This is an open-label, single-center, randomized, 2-way crossover study to evaluate the bioequivalence of OXEMET™ 1000 mg coated tablets, relative to 1000 mg of the reference product administered as two 500 mg tablets, under fasting conditions, in 24 healthy adult subjects. Each subject will receive two treatments (Treatment A and Treatment B). In Period 1, subjects will be dosed with either one OXEMET™ 1000 mg tablet (Treatment A, Test) or two 500 mg tablets of reference product (GLAFORNIL™ 500 mg) (Treatment B, Reference). Following a washout of at least 7 days, subjects will be crossed over in Period 2 to receive the treatment that they did not receive in Period 1.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Metformin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Oral Bioavailability Study Comparing OXEMET™ 1000 mg Coated Tablets Containing Metformin Hydrochloride With 1000 mg of the Reference Product (GLAFORNIL™) Administered as Two 500 mg Tablets, Through a Randomized, Single-dose, Open Label, Balanced, 2-way Crossover Study in Healthy Volunteers Under Fasting Conditions.OXEMET (TM) is a Trademark of the GlaxoSmithKline Group of Companies. GLAFORNIL(TM) is a Trademark of Merck.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • AUCTest/AUCRef: geometric means ratios for areas under the curve of Test product and Reference product [ Time Frame: 0-36 h ] [ Designated as safety issue: No ]
    AUCTest/AUCRef: geometric means ratios for areas under the curve of Test product and Reference product.The 90% confidence interval for AUCs geometric means ratio must be within bioequivalence range of 0.8 - 1.25. The 90% confidence interval for logarithmic transformation of the parameter will be assessed.

  • CmaxTest/CmaxRef: geometric means ratio for Cmax of Test product and Reference product. [ Time Frame: 0-36 h ] [ Designated as safety issue: No ]
    CmaxTest/CmaxRef: geometric means ratio for Cmax of Test product and Reference product. The 90% confidence interval for Cmax geometric means ratio must be within bioequivalence range of 0.8 - 1.25. The 90% confidence interval for logarithmic transformation of the parameter will be assessed.


Secondary Outcome Measures:
  • The elimination constant (kel) [ Time Frame: 0-36 h ] [ Designated as safety issue: No ]
    The elimination constant (kel)of Metformin will be determined for each subject, both for Test and Reference products.

  • terminal plasma half-life (t1/2) [ Time Frame: 0-36 h ] [ Designated as safety issue: No ]
    terminal plasma half-life (t1/2) of Metformin will be determined for each subject, both for Test and Reference products.


Enrollment: 25
Study Start Date: March 2013
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OXEMET 1000 mg coated tablets
Generic undergoing bioequivalence study against reference
Drug: Metformin
Oral antidiabetic agent
Active Comparator: GLAFORNIL 500 mg tablets
Reference drug for bioequivalence study
Drug: Metformin
Oral antidiabetic agent

  Eligibility

Ages Eligible for Study:   21 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • ALT, alkaline phosphatase and bilirubin > 1.5xULN (isolated bilirubin > 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
  • Single QTc < 450 msec.
  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Male or female between 21 and 55 years of age inclusive, at the time of signing the informed consent.
  • A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea.
  • A female subject is eligible to participate if she is of child-bearing potential and is abstinent or agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 7 days post-last dose.
  • Body weight > 50 kg and BMI within the range 19 - 27 kg/m2 (inclusive).
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
  • A positive test for HIV antibody.
  • History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of > 14 drinks for males or > 7 drinks for females. One drink is equivalent to 12 g of alcohol: 360 mL of beer, 150 mL of wine or 45 mL of 40% abv distilled spirits.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Subjects whose sitting blood pressure is less than 110/60 mmHg at screening or prior to dosing, or greater than 140/90 mmHg at screening.
  • Subjects whose pulse is lower than 50 beats per minute or higher than 99 beats per minute at screening or prior to dosing.
  • Subjects whose ECG PR interval is > 220 msec at screening or prior to dosing.
  • Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
  • Lactating females.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subject is mentally or legally incapacitated.
  • Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  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: NCT01842620

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01842620     History of Changes
Other Study ID Numbers: 117219
Study First Received: April 25, 2013
Last Updated: September 25, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Chile: Instituto de Salud Pública de Chile

Keywords provided by GlaxoSmithKline:
Metformin
Bioequivalence

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 19, 2014