NCT01561976

Evaluation of Food Effect on the Pharmacokinetics of Sustained Release Metformin in Healthy Indian Volunteers

Completed NA Results posted Last updated 16 October 2017

What this trial tests

NA trial testing Metformin hydrochloride prolonged release in Diabetes Mellitus, Type 2 in 30 participants. Completed in 21 February 2012.

Timeline

30 January 2012

Primary endpoint
21 February 2012

21 February 2012

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	other
Enrollment	30
Start date	30 January 2012
Primary completion	21 February 2012
Estimated completion	21 February 2012

Drugs / interventions tested

• Metformin hydrochloride prolonged release — full drug profile →
• metformin hydrochloride prolonged release — full drug profile →
• Metformin hydrochloride sustained release/Glimepiride — full drug profile →

Conditions studied

• Diabetes Mellitus, Type 2 — all drugs for Diabetes Mellitus, Type 2 →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 50, male only, with Diabetes Mellitus, Type 2. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Observed Concentration (Cmax) Primary · 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

Pharmacokinetic (PK) blood samples for estimation of Cmax were collected at 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. Point estimates and corresponding 90% confidence interval was constructed for the ratio of the geometric mean of the test treatment (fed condition) to the geometric mean of the reference treatment (fasting condition).

Group	Value	95% CI
METLEAD ForteSR-Fasting	884.297	± 28.10
METLEAD ForteSR-Fed	963.384	± 26.13
METLEAD G2 Forte	942.653	± 27.16

Area Under Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC (0-infinity)] Primary · 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 blood samples for estimation of AUC (0-infinity) were collected at 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. Point estimates and corresponding 90% confidence interval was constructed for the ratio of the geometric mean of the test treatment (fed condition) to the geometric mean of the reference treatment (fasting condition).

Group	Value	95% CI
METLEAD ForteSR-Fasting	10099.285	± 30.31
METLEAD ForteSR-Fed	11765.202	± 24.99
METLEAD G2 Forte	10751.895	± 29.76

AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments [AUC (0-t)] Secondary · 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 blood samples for estimation of AUC (0-t) were collected at 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. Point estimates and corresponding 90% confidence interval was constructed for the ratio of the geometric mean of the test treatment (fed condition) to the geometric mean of the reference treatment (fasting condition).

Group	Value	95% CI
METLEAD ForteSR-Fasting	9894.580	± 30.48
METLEAD ForteSR-Fed	11563.589	± 25.02
METLEAD G2 Forte	10546.905	± 29.87

Time of Occurrence of Cmax (Tmax) Secondary · 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 blood samples for estimation of Tmax were collected at 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. Point estimates and corresponding 90% confidence interval was constructed for the ratio of the geometric mean of the test treatment (fed condition) to the geometric mean of the reference treatment (fasting condition).

Group	Value	95% CI
METLEAD ForteSR-Fasting	8.00	1.00 – 12.00
METLEAD ForteSR-Fed	8.00	4.50 – 12.00
METLEAD G2 Forte	8.00	4.50 – 12.00

PK Lag Time (Tlag) Secondary · 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 blood samples for estimation of Tlag were collected at 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. Point estimates and corresponding 90% confidence interval was constructed for the ratio of the geometric mean of the test treatment (fed condition) to the geometric mean of the reference treatment (fasting condition).

Group	Value	95% CI
METLEAD ForteSR-Fasting	0.00	0.00 – 0.00
METLEAD ForteSR-Fed	0.00	0.00 – 0.52
METLEAD G2 Forte	0.50	0.00 – 0.52

Elimination Constant (Kel) Secondary · 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 blood samples for estimation of Kel were collected at 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. Point estimates and corresponding 90% confidence interval was constructed for the ratio of the geometric mean of the test treatment (fed condition) to the geometric mean of the reference treatment (fasting condition).

Group	Value	95% CI
METLEAD ForteSR-Fasting	0.162	0.088 – 0.192
METLEAD ForteSR-Fed	0.167	0.144 – 0.209
METLEAD G2 Forte	0.165	0.135 – 0.192

Terminal Phase Half Life (t1/2) Secondary · 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 blood samples for estimation of t1/2 were collected at 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. Point estimates and corresponding 90% confidence interval was constructed for the ratio of the geometric mean of the test treatment (fed condition) to the geometric mean of the reference treatment (fasting condition).

Group	Value	95% CI
METLEAD ForteSR-Fasting	4.281	3.604 – 7.915
METLEAD ForteSR-Fed	4.155	3.321 – 4.804
METLEAD G2 Forte	4.199	3.610 – 5.153

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Secondary · Up to approximately 24 days (during treatment and washout) after initiation of study

An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A serious adverse event is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity

Any AEs

Group	Value	95% CI
METLEAD ForteSR-Fasting	0
METLEAD ForteSR-Fed	1
METLEAD G2 Forte	2

Any SAEs

Group	Value	95% CI
METLEAD ForteSR-Fasting	0
METLEAD ForteSR-Fed	0
METLEAD G2 Forte	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 24 days (during treatment and washout) after initiation of study. On treatment SAEs and non-serious AEs have been presented.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

METLEAD ForteSR-Fasting

Serious: 0/24 (0%)

Deaths: 0/24

METLEAD ForteSR-Fed

Serious: 0/24 (0%)

Deaths: 0/24

METLEAD G2 Forte

Serious: 0/24 (0%)

Deaths: 0/24

Other adverse events (3 terms — click to expand)

Reaction	System	METLEAD ForteSR-Fasting	METLEAD ForteSR-Fed	METLEAD G2 Forte
Fever	General disorders	—	—	—
Upper abdominal pain	Gastrointestinal disorders	—	—	—
Loose motions	Gastrointestinal disorders	—	—	—

Data from ClinicalTrials.gov NCT01561976 adverse events section.

Sponsor's own 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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.