CTRI/2025/09/095284 [Registered on: 23/09/2025] Trial Registered Prospectively
Last Modified On:
22/09/2025
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A Study to Compare the Bioequivalence of Two Metformin 1000 mg Extended-Release Tablets in Healthy Adults Under Fed Conditions
Scientific Title of Study
An open label, balanced, randomized, two-treatment, two-period, two-sequence,
single dose, crossover, oral bioequivalence study of Metformin 1000 mg XR Extended-Release Tablets of Laboratorios Leti, S.A.V with Glucophage XR 1000 mg tablets (Metformin Hydrochloride) of Bristsol-Myers Squibb Company in healthy adult human subjects under fed conditions.
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
ICBio/018/0125; Ver 01; 26 Apr 2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Lakshmikar B V
Designation
Principal Investigator
Affiliation
ICBio Clinical Research Private limited
Address
2, Survey 8/1/2 ICBio tower II, Devi Circle,
Yelahanka Main Road, Chikkabetahalli, Vidyaranyapu
Yalahanka, Bangalore
Bangalore KARNATAKA 560097 India
Phone
8069423000
Fax
Email
headcl@icbiocro.com
Details of Contact Person Scientific Query
Name
Dr Lakshmikar B V
Designation
Principal Investigator
Affiliation
ICBio Clinical Research Private limited
Address
2, Survey 8/1/2 ICBio tower II, Devi Circle,
Yelahanka Main Road, Chikkabetahalli, Vidyaranyapu
Yalahanka, Bangalore
Bangalore KARNATAKA 560097 India
Phone
8069423000
Fax
Email
headcl@icbiocro.com
Details of Contact Person Public Query
Name
Dr Lakshmikar B V
Designation
Principal Investigator
Affiliation
ICBio Clinical Research Private limited
Address
2, Survey 8/1/2 ICBio tower II, Devi Circle,
Yelahanka Main Road, Chikkabetahalli, Vidyaranyapu
Yalahanka, Bangalore
Bangalore KARNATAKA 560097 India
Phone
8069423000
Fax
Email
headcl@icbiocro.com
Source of Monetary or Material Support
ICBio Clinical Research Private limited
2, Survey, 8/1/2 ICBio tower II, Devi Circle,
Yelahanka Main Road, Chikkabetahalli, Vidyaranyapura, Bangalore-560097 India
Primary Sponsor
Name
Laboratorios Leti, S.A.V
Address
Zona Industrial del Este, Avenida 2, Manzana J, Edificio Leti, Guarenas, Estado Miranda
Postal code 1220. República Bolivariana de Venezuela
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
ICBio Clinical Research Private limited
2, Survey, 8/1/2 ICBio tower II, Devi Circle, Yelahanka Main Road, Chikkabetahalli, Vidyaranyapura, Bangalore-560097 India
Countries of Recruitment
India
Sites of Study
No of Sites = 1
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Lakshmikar B V
ICBio Clinical Research Pvt. Ltd.
2, Survey 8/1/2 ICBio tower II, Devi Circle,
Yelahanka Main Road, Chikkabetahalli, Vidyaranyapu Yalahanka, Bangalore Bangalore KARNATAKA
After an overnight fasting of at least 10.00 hours before scheduled time for dosing, high fat high calorie breakfast will be served to each subjects exactly 30 min before drug administration and subjects should eat this breakfast within 30 min and after completion of breakfast, a single dose of either the study drug Metformin Hydrochloride 1000 mg LP Tablets (Test Product) or Glucofage XR (Metformin Hydrochloride) 1000 mg LP tablets (Reference Product) will be allocated as per the randomization schedule and administered orally to each subject while in sitting position with 240ml ± 5 mL of 20%w/v glucose solution at ambient temperature under yellow monochromatic light. The subject will be instructed not to chew or crush the tablet but to swallow it whole.
Thereafter the subjects will be given 60 mL of 20% w/v glucose solution administered every 15 minutes for up to 4 hours after dosing in each period.
Intervention
Test Product - Metformin Hydrochloride 1000 mg LP Tablets of Laboratorios Leti, S.A.V
After an overnight fasting of at least 10.00 hours before scheduled time for dosing, high fat high calorie breakfast will be served to each subjects exactly 30 min before drug administration and subjects should eat this breakfast within 30 min and after completion of breakfast, a single dose of either the study drug Metformin Hydrochloride 1000 mg LP Tablets (Test Product) or Glucofage XR (Metformin Hydrochloride) 1000 mg LP tablets (Reference Product) will be allocated as per the randomization schedule and administered orally to each subject while in sitting position with 240ml ± 5 mL of 20%w/v glucose solution at ambient temperature under yellow monochromatic light. The subject will be instructed not to chew or crush the tablet but to swallow it whole.
Thereafter the subjects will be given 60 mL of 20% w/v glucose solution administered every 15 minutes for up to 4 hours after dosing in each period.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
55.00 Year(s)
Gender
Both
Details
1) Willing to provide written informed consent for participation in the study,
and an ability to comprehend the nature and purpose of the study.
2) Willing to be available for the entire study period and to comply with
protocol requirements.
3) Normal, healthy, adult, human subject of 18to 55 years (both inclusive) of age.
4) Body mass index in the range of 18.50 – 30.00 kg per m2
(both inclusive).
5) Healthy volunteers who are clinically non-anemic will be included as per the
discretion of PI, CI, Physician.
6) Normal health status as determined by baseline medical and medication
history, at the time of screening and vital signs (blood pressure, pulse rate,
respiratory rate and axillary temperature) measurements at the time screening
as well as throughout the study.
7) With normal or clinically non-significant laboratory values as determined by
hematological, biochemistry tests and urine analysis.
8) With a normal or clinically non-significant 12-lead ECG.
9) With a negative test for Human Immunodeficiency Virus (HIV) type I, II
antibodies or Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibodies.
10) Non-smokers and willing to abstain from smoking or chewing any tobacco
containing product at least 72.00 hours prior to dosing if have history of
smoking habit and throughout the sampling points.
11) Male volunteer willing to use appropriate contraceptive measures to ensure
that his female partner will not get pregnant for at least 15 days before 1st
dosing till 15 days post last-dose or entire study period.
12) In case of female subjects:
13) Negative urine pregnancy test during screening and negative serum Beta hCG test at check-in of each study period.
14) Female subjects with childbearing potential or those within their first two
years of onset of menopausal syndrome must either abstain from sexual
intercourse or using acceptable methods of birth control for at least 15
days before 1st dosing till 15 days post last-dose/ entire study period
[Acceptable birth control methods include barrier methods such as
diaphragm/condom with or without spermicide or who are surgically
sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)
has been performed].
15) Able to read and understand the Informed Consent Document as a whole and
communicate effectively if required.
ExclusionCriteria
Details
1) Incapable of understanding the informed consent information.
2) History or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological or psychiatric disease or disorder.
3) History or presence of severe renal dysfunction, including those receiving
dialysis and hepatic dysfunction.
4) History or presence of active liver disease, including those with primary
biliary cirrhosis and unexplained persistent liver function abnormalities.
5) History or presence of pre-existing gallbladder disease.
6) History or presence of mortality and coronary heart disease morbidity
7) Use of antihypertensive drugs and pressor Agents (e.g. dopamine,
dobutamine), use of CYP2D6 (e.g., paroxetine, fluoxetine, and quinidine),
use of monoamine oxidase Inhibitors in the previous 30 days before first
drug administration and till the completion of the study.
8) History or presence of asthma, urticaria and any other allergic reactions.
9) History or presence of gastric and/or duodenal ulceration.
10) History or presence of thyroid disease, adrenal dysfunction, organic
intracranial lesion.
11) History or presence of acute or chronic metabolic acidosis, including diabetic
ketoacidosis, with or without coma.
12) History or presence of cancer.
13) Difficulty with donating blood.
14) Difficulty in swallowing solids like tablets.
15) Use of any prescribed medication [including herbal medicines, vitamin
supplements, glyburide, furosemide, nifedipine, organic cationic transporter 2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as
ranolazine, vandetanib, dolutegravir, and cimetidine, thiazides and other
diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium
channel blocking drugs, and isoniazid and Topiramate or other carbonic
anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide)]
or vitamins, herbal products and OTC medicinal products during two weeks
prior to study initiation.
16) Subject chewed tobacco / consumed pan or pan masala, gutkha, masala
(containing beetle nut and tobacco), xanthine-containing foods or beverages
(coffee, tea, chocolate, and caffeine-containing sodas, colas, etc) for 48.00 hours prior to initiation of the study till the end of the study.
17) Subjects consumed grape fruit juice and poppy containing foods for 72.00
hours prior to initiation of the study till the end of the study.
18) Major illness during the 180 days before screening.
19) Participation in a drug research study within 90 days of screening.
20) Donation of blood within 90 days of screening.
21) Positive screening test result for any one or more of the following: HIV, Hepatitis B, Hepatitis C and VDRL.
22) Positive result for urinary screen test for drugs of abuse (amphetamines, morphine, benzodiazepines, marijuana, cocaine and barbiturate).
23) Subjects with positive test results for urine pregnancy test for female
subjects.
24) History or presence of easy bruising or bleeding.
25) Abnormal diet patterns (for any reason) during the four weeks preceding
the study, including fasting, high protein, low sodium diets etc.
26) Use of any hormone replacement therapy within 3 months prior to the first dose of study medication.
27) A depot injection or implant of any drug within 3 months prior to the first dose of study medication.
28) Pregnant woman and nursing mothers.
29) History of allergy or hypersensitivity intolerance to Metformin or its
formulation excipients which, in the opinion of the clinical investigator,
would compromise the safety of the subject or the study.
30) History of difficulty in accessibility of veins in arms.
31) Evidence of an uncooperative attitude.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pharmacy-controlled Randomization
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To compare the rate and extent of absorption Metformin Hydrochloride 1000 mg LP Tablets of Laboratorios Leti, S.A.V in comparison with Glucofage XR (Metformin Hydrochloride) 1000 mg LP tablets of Merck S.A., in healthy adult human subjects under fed conditions.
The venous blood samples were withdrawn at pre-dose
(00.000 hour) 00.500, 01.000, 01.500, 02.000, 02.500,
03.000, 03.500, 04.000, 05.000, 06.000, 07.000, 08.000,
10.000, 12.000, 16.000, 24.000, 48.000 and 72.000 hours
post-dose following drug administration in each period
Secondary Outcome
Outcome
TimePoints
To monitor the safety and tolerability of the study subjects after administration of Metformin Hydrochloride 1000 mg LP Tablets in healthy, adult, human subjects, under fed conditions
Vital signs (blood pressure, pulse rate, respiratory rate and axillary temperature) measurement station
Before check-in, at Pre-dose 0.00 (within 2.00 hrs before dosing), at 3.00, 7.00 and 11.00 hrs after dosing (within ± 60 min of scheduled time of recording), at the time of checkout and ambulatory visit in each period. The well-being of subjects will be ascertained at each vital sign measurement
Target Sample Size
Total Sample Size="32" Sample Size from India="32" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
N/A
Date of First Enrollment (India)
20/11/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="0" Months="0" Days="12"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Descriptive statistics of primary and secondary pharmacokinetic parameters will be computed and reported for Metformin. ANOVA, 90% confidence interval using schuirmann’s two one-sided tests for bioequivalence, power and ratio analysis, for ln-transformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf will be computed and reported for Metformin.
Based on the statistical results of 90% confidence interval for the ratio of the geometric least squares means for ln transformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf for Metformin, conclusion will be drawn for Test Product-T vs. Reference Product-R. Bioequivalence of the test product with that of the reference product will be concluded if 90% confidence interval falls within the acceptance range of 80.00-125.00% for ln transformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf for Metformin.