Cardiovascular Diseases, Type 2 Diabetes Mellitus (T2DM)
Conditions
Brief summary
An open label, randomized, two-period, two treatment, two-sequence, crossover, balanced, single dose oral bioequivalence study to compare Empagliflozin/ Linagliptin/ Metformin HCl 25 mg/5 mg/1000 mg Extended Release Tablet versus Trijardy® XR (Empagliflozin/linagliptin/metformin hydrochloride extended-release tablets 25 mg/5 mg/1000 mg) in healthy subject in fed condition.
Interventions
DRUGEmpagliflozin/Linagliptin/Metformin HCl Extended Release Tablet
1 extended Release tablet of Empagliflozin/Linagliptin/Metformin HCl 25 mg/5 mg/1000 mg
DRUGTrijardy® XR Tablets
1 extended Release tablet of Empagliflozin/Linagliptin/Metformin HCl 25 mg/5 mg/1000 mg
Sponsors
Humanis Saglık Anonim Sirketi
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Age: 18 to 55 years old, both inclusive. * Gender: Male and/or non-pregnant, non-lactating female. A. Female of child-bearing potential had a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test performed within 28 days of the first dose of study medication. They used an acceptable form of contraception. For female of child-bearing potential, acceptable forms of contraception included the following: i. Non hormonal intrauterine device in place for at least 3 months prior to the start of the study and remaining in place during the study period, or ii. Barrier methods containing or used in conjunction with a spermicidal agent, or iii. Surgical sterilization or iv. Practicing sexual abstinence throughout the course of the study. B. Females were not considered of child-bearing potential if one of the following was reported and documented on the medical history: i. Postmenopausal with spontaneous amenorrhea for at least 12 consecutive months without other medical explanation, or ii. Bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or iii. Total hysterectomy and an absence of bleeding for at least 3 months. * 18.5 to 30.0 kg/m2, both inclusive; BMI values were rounded off to one significant digit after decimal point (e.g. 30.04 rounded down to 30.0, while 18.45 rounded up to 18.5). * Able to communicate effectively with study personnel. * Non-alcoholic, non-smoker and non-tobacco user (i.e. had no past history of drinking alcohol, smoking and tobacco consuming for at least one year prior to study). * Normal or clinically non-significant ECG recording during screening. * Willing to provide written informed consent to participate in the study. * All participants were judged by the principal or sub-investigator or physician as normal and healthy during a pre-study safety assessment performed within 28 days of the first dose of study medication which included: a) A physical examination (clinical examination) with no clinically significant finding.
Exclusion criteria
* History of allergic responses to Empagliflozin, Linagliptin, Metformin or other related drugs, or any of its formulation ingredients. * Had significant diseases or clinically significant abnormal findings during screening \[medical history, physical examination (clinical examination), laboratory evaluations, ECG recording, gynecological history and examination (including pelvic examination and routine breast examination) (for female participants)\]. * Any disease or condition like diabetes, psychosis or others, which compromised the haemopoietic, gastrointestinal, renal, hepatic, cardiovascular, respiratory, Central nervous system or any other body system. * History or presence of bronchial asthma. * Used any hormone replacement therapy within 3 months prior to the first dose of study medication. * Used any depot injection or implant of any drug within 3 months prior to the first dose of study medication. * Used CYP enzyme inhibitors or inducers within 30 days prior to the first dose of study medication (see https://drug-interactions.medicine.iu.edu/MainTable.aspx). * History or evidence of drug dependence. * History of difficulty with donating blood or difficulty in accessibility of veins. * A positive hepatitis screen (included subtypes B \& C). * A positive test result for HIV antibody. * Participant who had received a known investigational drug within seven elimination half-life of the administered drug prior to the first dose of study medication. * Participant who had donated blood or loss of blood 50 ml to 100 ml within 30 days or 101 ml to 200 ml within 60 days or \>200 ml within 90 days (excluding volume drawn at screening for this study) prior to first dose of study medication, whichever was greater. * History of difficulty in swallowing or of any gastrointestinal disease, which affected drug absorption. * Intolerance to venipuncture. * Any food allergy, intolerance, restriction or special diet that, in the opinion of the principal investigator or sub-investigator, could contraindicate the participant's participation in this study. * Institutionalized participant. * Used any prescribed medications within 14 days prior to the first dose of study medication. * Used any OTC products, vitamin and herbal products, etc., within 7 days prior to the first dose of study medication. * Used grapefruit and grapefruit containing products within 7 days prior to the first dose of study medication. * Ingested any caffeine or xanthine products (i.e. coffee, tea, chocolate, and caffeinecontaining sodas, colas, etc.), recreational drugs within 48 hours prior to the first dose of study medication. * Ingested any unusual diet, for whatever reason (e.g.: low sodium) for three weeks prior to the first dose of study medication. * Presence of ketone during urine analysis. * History or presence of cardiovascular disorders. * Participant with Serum Lactate higher than upper limit of normal range. * Participant with Estimated Glomerular Filtration Rate was less than 60 ml/min/1.73 m2 during screening. * History or presence of hypoglycemia. * Participant with Serum Creatinine higher than upper limit of normal range. * History of acute and chronic metabolic acidosis. * History or sign and symptoms of pancreatitis. * History of genital mycotic infections. * History of severe and disabling arthralgia. * History of bullous pemphigoid. * History of recurrent urinary tract infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| For Empagliflozin & Linagliptin & Metformin; Maximum concentration obtained (Cmax) | Empagliflozin & Metformin; 48 hours, Linagliptin; 72 hours | two-sides 90% CI for the test to reference ratio of the population means is within 80.00-125.00% for each of the Ln-transformed data Cmax |
| For Empagliflozin & Metformin; AUC from time 0 to last collection time (AUC0 - t) | Empagliflozin & Metformin: 48 hours | two-sides 90% CI for the test to reference ratio of the population means is within 80.00-125.00% for each of the Ln-transformed data AUC |
| For Linagliptin; Area under the plasma concentration-time curve from 0 to 72 hours (AUC72) | 72 hours | two-sides 90% CI for the test to reference ratio of the population means is within 80.00-125.00% for each of the Ln-transformed data AUC |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| For Empagliflozin & Linagliptin & Metformin; Time to reach maximum concentration Cmax (Tmax) | Empagliflozin & Metformin: 48 hours, Linagliptin: 72 hours | Descriptive Statistics |
| For Metformin : Area under the plasma concentration versus time curve from the zero time point to the last quantifiable concentration(AUCt) | 48 hours | Descriptive Statistics |
| For Empagliflozin: Area under the plasma concentration versus time curve from zero to infinity (AUCi) | 48 hours | Descriptive Statistics |
Countries
India
Outcome results
None listed