Crossover Study to Evaluate the Comparative Bioavailability of Two Fixed Dose Combination Tablet Formulations of Extended Release Metformin and Extended Release Glimepiride in Health Volunteers
Overview[ - collapse ][ - ]
Purpose | This is a an open-label, randomized, single dose, four-way crossover, multi-stage study enrolling 20 healthy adult male and female subjects per part. This study consists of two separate parts (Part A and B) with each part comprising four treatment periods. Each subject will participate in all four treatment periods per part; Subjects may not enrol in both Parts A and B. This study is being conducted to compare the pharmacokinetics (PK) of two extended release fixed dose combinations (FDC) oral formulations of metformin and glimepiride at two doses, 500mg/1mg and 1000mg/2mg, with each FDC formulation to be administered orally as a single dose and compared with the commercially available formulations of metformin extended release (XR) (GLUCOPHAGE ™ Sustained Release [SR]) and glimepiride immediate release (IR) (AMARYL ™). Part A of study will evaluate the bioavailability of a formulation comprising a film coated tablet containing release controlling polymers; and Part B will evaluate the bioavailability of a formulation comprising a tablet coated with release controlling polymers. In each part there will be 4 treatment periods. During each period, subjects will be randomized sequentially to receive a single dose of a reference treatment of 500 mg metformin XR / 1 mg glimepiride IR; and a reference treatment of 1000 mg metformin XR / 2 mg glimepiride IR; and an FDC tablet containing 500 mg metformin XR and 1 mg glimepiride XR; and an FDC tablet containing 1000 mg metformin XR and 2 mg glimepiride XR.Serial PK sampling for up to 36 hours and safety assessments will be performed. Each period will be separated by a washout period of at least 5 days and a follow-up visit will occur 14 days after the last dose of study drug. |
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Condition | Diabetes Mellitus, Type 2 |
Intervention | Drug: Metformin, 500 mg extended release tablet Drug: Metformin, 1000 mg extended release tablet Drug: Glimepiride, 1 mg immediate release tablet Drug: Glimepiride, 2 mg immediate release tablet Drug: Metformin, 500 mg and Glimepiride, 1 mg extended release film coated tablet containing release controlling polymers Drug: Metformin, 1000 mg and Glimepiride, 2 mg extended release film coated tablet containing release controlling polymers Drug: Metformin, 500 mg and Glimepiride, 1 mg extended release tablet coated with release controlling polymers Drug: Metformin, 1000 mg and Glimepiride, 2 mg extended release tablet coated with release controlling polymers |
Phase | Phase 1 |
Sponsor | GlaxoSmithKline |
Responsible Party | GlaxoSmithKline |
ClinicalTrials.gov Identifier | NCT01725672 |
First Received | November 1, 2012 |
Last Updated | November 27, 2013 |
Last verified | November 2013 |
Tracking Information[ + expand ][ + ]
First Received Date | November 1, 2012 |
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Last Updated Date | November 27, 2013 |
Start Date | September 2012 |
Estimated Primary Completion Date | December 2012 |
Current Primary Outcome Measures |
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Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
Brief Title | Crossover Study to Evaluate the Comparative Bioavailability of Two Fixed Dose Combination Tablet Formulations of Extended Release Metformin and Extended Release Glimepiride in Health Volunteers |
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Official Title | An Open-Label, Randomized, Single Dose, Four-way Crossover, Multi-stage Study to Determine the Comparative Bioavailability of Two Fixed Dose Combination Tablet Formulations, 500 mg or 1000 mg Extended Release Metformin and 1 mg or 2 mg Extended Release Glimepiride, in Healthy Adult Male and Female Subjects in the Fed State |
Brief Summary | This is a an open-label, randomized, single dose, four-way crossover, multi-stage study enrolling 20 healthy adult male and female subjects per part. This study consists of two separate parts (Part A and B) with each part comprising four treatment periods. Each subject will participate in all four treatment periods per part; Subjects may not enrol in both Parts A and B. This study is being conducted to compare the pharmacokinetics (PK) of two extended release fixed dose combinations (FDC) oral formulations of metformin and glimepiride at two doses, 500mg/1mg and 1000mg/2mg, with each FDC formulation to be administered orally as a single dose and compared with the commercially available formulations of metformin extended release (XR) (GLUCOPHAGE ™ Sustained Release [SR]) and glimepiride immediate release (IR) (AMARYL ™). Part A of study will evaluate the bioavailability of a formulation comprising a film coated tablet containing release controlling polymers; and Part B will evaluate the bioavailability of a formulation comprising a tablet coated with release controlling polymers. In each part there will be 4 treatment periods. During each period, subjects will be randomized sequentially to receive a single dose of a reference treatment of 500 mg metformin XR / 1 mg glimepiride IR; and a reference treatment of 1000 mg metformin XR / 2 mg glimepiride IR; and an FDC tablet containing 500 mg metformin XR and 1 mg glimepiride XR; and an FDC tablet containing 1000 mg metformin XR and 2 mg glimepiride XR.Serial PK sampling for up to 36 hours and safety assessments will be performed. Each period will be separated by a washout period of at least 5 days and a follow-up visit will occur 14 days after the last dose of study drug. |
Detailed Description | Not Provided |
Study Type | Interventional |
Study Phase | Phase 1 |
Study Design | Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment |
Condition | Diabetes Mellitus, Type 2 |
Intervention | Drug: Metformin, 500 mg extended release tablet In Part A and Part B of the study, Metformin 500 mg XR tablet will be administered with 240 millilitre (mL) water ; 125 mL of LUCOZADE was administered every 30 mins for 4 hours after dosing. Drug: Metformin, 1000 mg extended release tablet In Part A and Part B of the study, Metformin 1000 mg XR tablet will be administered with 240mL water; 125 mL of LUCOZADE was administered every 30 mins for 4 hours after dosing. Drug: Glimepiride, 1 mg immediate release tablet In Part A and Part B of the study, Glimepiride 1 mg IR tablet will be administered with 240mL water; 125 mL of LUCOZADE was administered every 30 mins for 4 hours after dosing. Drug: Glimepiride, 2 mg immediate release tablet In Part A and Part B of the study, Glimepiride 2 mg IR tablet will be administered with 240mL water; 125 mL of LUCOZADE was administered every 30 mins for 4 hours after dosing. Drug: Metformin, 500 mg and Glimepiride, 1 mg extended release film coated tablet containing release controlling polymers In Part A of the study, 1 XR film coated tablet combination of Metformin 500 mg and Glimepiride 1 mg will be administered with 240 mL water; 125 mL of LUCOZADE was administered every 30 mins for 4 hours after dosing. Drug: Metformin, 1000 mg and Glimepiride, 2 mg extended release film coated tablet containing release controlling polymers In Part A of the study, 1 XR film coated tablet combination of Metformin 1000 mg and Glimepiride 2 mg will be administered with 240 mL water; 125 mL of LUCOZADE was administered every 30 mins for 4 hours after dosing. Drug: Metformin, 500 mg and Glimepiride, 1 mg extended release tablet coated with release controlling polymers In Part B of the study, 1 XR tablet combination of Metformin 500 mg and Glimepiride 1 mg will be administered with 240 mL water; 125 mL of LUCOZADE was administered every 30 mins for 4 hours after dosing. Drug: Metformin, 1000 mg and Glimepiride, 2 mg extended release tablet coated with release controlling polymers In Part B of the study, 1 XR tablet combination of Metformin 1000 mg and Glimepiride 2 mg will be administered with 240 mL water; 125 mL of LUCOZADE was administered every 30 mins for 4 hours after dosing. |
Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
Recruitment Status | Terminated |
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Estimated Enrollment | 20 |
Estimated Completion Date | December 2012 |
Estimated Primary Completion Date | December 2012 |
Eligibility Criteria | Inclusion Criteria: - Healthy male or female subjects between 18 and 65 years of age inclusive with body weight >= 50 kg and body mass index (BMI) within the range 19 to 32 kilogram/meter squared - Alanine aminotransferase (ALT) alkaline phosphatase and bilirubin - Normal ECG measurements. Average QT duration corrected for heart rate by Fridericia's formula (QTcF) <450 millisecond or QTcF <480 msec in subjects with Bundle Branch Block based on an average from three electrocardiograms (ECGs) obtained over a brief recording period. - Female subjects of non-child bearing potential. Females of child bearing potential are eligible to enter if they are not pregnant and willing to use protocol-specified methods of contraception to prevent pregnancy until 14 days post-last dose of metformin/glimepiride. - Capable of giving written informed consent Exclusion Criteria: - The subject has a positive: drug/alcohol screen, Hepatitis, HIV screen - Abuse of alcohol - Current or chronic history of liver disease, or known hepatic or biliary abnormalities - Exposure to more than four new investigational chemical entities within 12 months prior to the first dosing day - 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) - 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 - Donation of more than 500 mL blood within a 56 day period - Pregnant or lactating females - Unwillingness or inability to follow the procedures outlined in the protocol - Subject is mentally or legally incapacitated - Subject having positive urinary cotinine levels indicative of use of tobacco or nicotine-containing products within 6 months prior to screening. - Unable to refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose - Subjects having asthma or are positive carbon monoxide (CO) on admission to the Unit - Unable to refrain from the use of prescription or non-prescription drugs within 7 days prior to first dose of study medication, unless approved by the Investigator and GSK Medical Monitor. |
Gender | Both |
Ages | 18 Years |
Accepts Healthy Volunteers | Accepts Healthy Volunteers |
Contacts | Not Provided |
Location Countries | Australia |
Administrative Information[ + expand ][ + ]
NCT Number | NCT01725672 |
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Other Study ID Numbers | 116806 |
Has Data Monitoring Committee | Not Provided |
Information Provided By | GlaxoSmithKline |
Study Sponsor | GlaxoSmithKline |
Collaborators | Not Provided |
Investigators | Study Director: GSK Clinical Trials GlaxoSmithKline |
Verification Date | November 2013 |
Locations[ + expand ][ + ]
GSK Investigational Site | Randwick, New South Wales, Australia, 2031 |
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