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.
Primary Purpose
Diabetes Mellitus, Type 2
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Metformin
Sponsored by
About this trial
This is an interventional other trial for Diabetes Mellitus, Type 2 focused on measuring Metformin, Bioequivalence
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
OXEMET 1000 mg coated tablets
GLAFORNIL 500 mg tablets
Arm Description
Generic undergoing bioequivalence study against reference
Reference drug for bioequivalence study
Outcomes
Primary Outcome Measures
Geometric Means of Area Under Plasma Concentration Time Curve of the Test Drug (Oxemet) to the Reference Drug (Glafornail) From Time Zero to the Time of Last Quantifiable Concentration of 36 Hours (h)
Area under plasma concentration-time curve of metformin was quantifiable from time 0 to 36 h. The parameter was calculated by non-compartmental methods with WinNonlin Version 6.02. The calculations were based on the actual sampling times recorded during the study. Period wise outcome data has been presented; however, the statistical analysis has been presented for overall period.
Geometric Means for Area Under Plasma Concentration Time Curve of the Study Drug (Oxemet) to the Reference Drug (Glafornail) Between Time Zero to Infinity (Inf) Over Period
Area under plasma concentration-time curve of metformin from time 0 to inf was calculated by non-compartmental methods with WinNonlin Version 6.02. The calculations were based on the actual sampling times recorded during the study. Period wise outcome data has been presented; however, the statistical analysis has been presented for overall period.
Geometric Means for Maximum Plasma Concentration of the Study Drug (Oxemet) to the Reference Drug (Glafornail) From 0 to 36 h
Cmax is maximum plasma concentration of metformin. Plasma concentration-time curve of metformin from time 0 to 36 h was calculated by non-compartmental methods with WinNonlin Version 6.02. The calculations were based on the actual sampling times recorded during the study. Period wise data has been presented; however, the statistical analysis has been presented for overall period.
Secondary Outcome Measures
The Elimination Constant (Kel) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) From 0 to 36 h
The elimination constant (kel) of Metformin was analyzed for each participant, both for Test and Reference products. The calculations were based on the actual sampling times recorded during the study.
Terminal Plasma Half-life (t1/2) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) From 0 to 36 h
Terminal phase half-life is the time required for the study drug to reduce to 50% of its concentration. t1/2 of Metformin was determined for each participant, both for Test and Reference products.
Time to Reach Maximum Plasma Concentration (Tmax) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) Over Period
Time to reach maximum plasma concentration is the time at which Cmax of metformin was obtained for test and reference products.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01842620
Brief Title
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.
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.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
March 13, 2013 (Actual)
Primary Completion Date
May 4, 2013 (Actual)
Study Completion Date
May 4, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
Metformin, Bioequivalence
7. Study Design
Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
OXEMET 1000 mg coated tablets
Arm Type
Experimental
Arm Description
Generic undergoing bioequivalence study against reference
Arm Title
GLAFORNIL 500 mg tablets
Arm Type
Active Comparator
Arm Description
Reference drug for bioequivalence study
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Oral antidiabetic agent
Primary Outcome Measure Information:
Title
Geometric Means of Area Under Plasma Concentration Time Curve of the Test Drug (Oxemet) to the Reference Drug (Glafornail) From Time Zero to the Time of Last Quantifiable Concentration of 36 Hours (h)
Description
Area under plasma concentration-time curve of metformin was quantifiable from time 0 to 36 h. The parameter was calculated by non-compartmental methods with WinNonlin Version 6.02. The calculations were based on the actual sampling times recorded during the study. Period wise outcome data has been presented; however, the statistical analysis has been presented for overall period.
Time Frame
From 0 to 36 hours (h)
Title
Geometric Means for Area Under Plasma Concentration Time Curve of the Study Drug (Oxemet) to the Reference Drug (Glafornail) Between Time Zero to Infinity (Inf) Over Period
Description
Area under plasma concentration-time curve of metformin from time 0 to inf was calculated by non-compartmental methods with WinNonlin Version 6.02. The calculations were based on the actual sampling times recorded during the study. Period wise outcome data has been presented; however, the statistical analysis has been presented for overall period.
Time Frame
From 0 to 36 h
Title
Geometric Means for Maximum Plasma Concentration of the Study Drug (Oxemet) to the Reference Drug (Glafornail) From 0 to 36 h
Description
Cmax is maximum plasma concentration of metformin. Plasma concentration-time curve of metformin from time 0 to 36 h was calculated by non-compartmental methods with WinNonlin Version 6.02. The calculations were based on the actual sampling times recorded during the study. Period wise data has been presented; however, the statistical analysis has been presented for overall period.
Time Frame
From 0 to 36 h
Secondary Outcome Measure Information:
Title
The Elimination Constant (Kel) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) From 0 to 36 h
Description
The elimination constant (kel) of Metformin was analyzed for each participant, both for Test and Reference products. The calculations were based on the actual sampling times recorded during the study.
Time Frame
From 0 to 36 h
Title
Terminal Plasma Half-life (t1/2) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) From 0 to 36 h
Description
Terminal phase half-life is the time required for the study drug to reduce to 50% of its concentration. t1/2 of Metformin was determined for each participant, both for Test and Reference products.
Time Frame
From 0 to 36 h
Title
Time to Reach Maximum Plasma Concentration (Tmax) of the Study Drug (Oxemet) and the Reference Drug (Glafornail) Over Period
Description
Time to reach maximum plasma concentration is the time at which Cmax of metformin was obtained for test and reference products.
Time Frame
From 0 to 36 h
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117219
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117219
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117219
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Annotated Case Report Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117219
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117219
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117219
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117219
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
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.
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