Last updated: 11/03/2018 19:16:05
Evaluation of food effect on the pharmacokinetics of sustained release metformin in healthy Indian volunteers
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: The effect of food on the pharmacokinetics of metformin given either as metformin hydrochloride SR 1000mg tablet or as a fixed dose combination of metformin hydrochloride SR 1000mg/glimepiride 2mg tablet in healthy Indian volunteers.
Trial description: Metformin hydrochloride in its immediate release (IR) form has been successfully used for decades in the treatment of type 2 diabetes; however the IR formulation may be associated with gastrointestinal side effects (especially nausea, diarrhea) in 20-30% patients, which can limit the tolerated dose, reduce adherence and result in discontinuation of therapy. Metformin hydrochloride extended release formulations have been developed to overcome these problems. In India, extended release formulations of metformin hydrochloride include metformin SR 1000mg tablet and combination of metformin hydrochloride SR 1000mg/glimepiride 2mg tablet. In the combination tablet, only metformin hydrochloride is in the extended release form. In view of the fact that extended release metformin hydrochloride is usually recommended with a meal, that food is known to affect the pharmacokinetic (PK) parameters of metformin and that there is a potential for dose dumping with extended release formulations that may lead to side effects similar to IR formulations, a study to estimate the magnitude of the food effect for these formulations in fed state compared to the fasting state is warranted. This study will be a randomized, single-center, open-label, single-dose, three-period, 6 sequence crossover study in 30 healthy adult volunteers to estimate the bioavailability of metformin from metformin hydrochloride 1000mg SR tablet given in fasting condition relative to metformin hydrochloride 1000mg SR tablet and a fixed dose combination of metformin hydrochloride 1000mg SR /glimepiride 2mg tablet, each given in fed condition. The safety and tolerability profile of metformin SR 1000mg tablet and metformin hydrochloride SR 1000mg/glimepiride 2mg tablet will also be evaluated in this study. The primary PK endpoints will be Cmax and AUC (0-∞). The secondary PK endpoints will include AUC (0-t), Tmax , T lag, Kel and t1/2. Safety endpoints will include vital signs, ECG, physical examination, clinical laboratory tests and adverse event reporting.
Primary purpose:
Other
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Maximum observed concentration (Cmax)
Timeframe: 0.0 (pre-dose) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24 and 30 hours after dosing
Area under concentration-time curve from time zero (pre-dose) extrapolated to infinite time [AUC (0-infinity)]
Timeframe: 0.0 (pre-dose) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24 and 30 hours after dosing
Secondary outcomes:
AUC from time zero (pre-dose) to last time of quantifiable concentration within a participant across all treatments [AUC (0-t)]
Timeframe: 0.0 (pre-dose) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24 and 30 hours after dosing
Time of occurrence of Cmax (Tmax)
Timeframe: 0.0 (pre-dose) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24 and 30 hours after dosing
PK lag time (Tlag)
Timeframe: 0.0 (pre-dose) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24 and 30 hours after dosing
Elimination constant (Kel)
Timeframe: 0.0 (pre-dose) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24 and 30 hours after dosing
Terminal phase half life (t1/2)
Timeframe: 0.0 (pre-dose) and 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24 and 30 hours after dosing
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Timeframe: Up to approximately 24 days (during treatment and washout) after initiation of study
Interventions:
Drug: Metformin hydrochloride prolonged release
Drug: Metformin hydrochloride sustained release/Glimepiride
Enrollment:
30
Observational study model:
Not applicable
Primary completion date:
2012-21-02
Time perspective:
Not applicable
Clinical publications:
LIESEL DSILVA, JONATHAN PALMER, VISHWANATH SUDERSHAN, SANMAN GHORPADE, SADHNA JOGLEKAR . Effect of food on the absorption of metformin from sustained release metformin hydrochloride formulations in healthy Indian volunteers. Asian J Pharmaceut Clin Res. 2013;6(1):95-99.
Medical condition
Diabetes Mellitus, Type 2
Product
metformin
Collaborators
Not applicable
Study date(s)
January 2012 to February 2012
Type
Interventional
Phase
Not applicable
Participation criteria
Sex
Male
Age
18 - 50 years
Accepts healthy volunteers
Yes
- 1.Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests, 12 lead ECG and chest-x-ray. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Medical Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- 2.Males between 18 and 50 years of age (both inclusive), who are willing to participate in the study and provide a written signed and dated informed consent.
- 1.A positive pre-study urine drug screen.
- 2.A positive test for HIV antibody.
Inclusion and exclusion criteria
Inclusion criteria:
- 1.Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests, 12 lead ECG and chest-x-ray. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Medical Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. 2.Males between 18 and 50 years of age (both inclusive), who are willing to participate in the study and provide a written signed and dated informed consent. 3.Body weight more than or equal to 60 kg and BMI within the range 18.5-24.9 kg/m2 (inclusive). 4.Availability of a study volunteer for the entire study period and willingness to adhere to protocol requirements as evidenced by written informed consent.
Exclusion criteria:
- 1.A positive pre-study urine drug screen. 2.A positive test for HIV antibody. 3.Subject has clinically significant abnormal values of laboratory parameters. 4.Regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits (CTRI, 2010). 5.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). 6.Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 7.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 the medication will not interfere with the study procedures or compromise subject safety. 8.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 contraindicates their participation. 9.Where participation in another study would result in donation of blood or blood products in excess of 350 ml within a 90 day period prior to this study. 10.Unwillingness or inability to follow the procedures outlined in the protocol. 11.Subject is mentally or legally incapacitated or the subject is incapable of understanding the informed consent. 12.Subject has any evidence of impaired renal, hepatic, cardiac, lung or gastrointestinal function. Study volunteers with a history of tuberculosis, epilepsy, asthma (during past 5 years), diabetes, psychosis or glaucoma will not be eligible for the study. 13.History of sensitivity to heparin or heparin-induced thrombocytopenia. 14.Regular use of tobacco- or nicotine-containing products within 6 months prior to screening. 15.Subject is intolerant to venipuncture. 16.Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice [and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices] from 7 days prior to the first dose of study medication.
Trial location(s)
No location data available.
Study documents
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2012-21-02
Actual study completion date
2012-21-02
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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