A Single Dose, Randomized, Open-label, Two-period, Two-sequence Crossover Bioequivalence Study of Generic Linagliptin/Metformin Hydrochloride Tablets 2.5 mg/1000 mg and Reference Product (TRAJENTA DUO) in Healthy Thai Volunteers under Fed Conditions
- Conditions
- Bioequivalence Study Healthy Thai Volunteers
- Registration Number
- TCTR20231012008
- Lead Sponsor
- International Bio Service Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending (Not yet recruiting)
- Sex
- All
- Target Recruitment
- 40
1. Healthy Thai male or female subjects between the ages of 18 to 55 years. Subject must meet age requirements at the time of signing the initial informed consent and at the dosing day in Period 1.
2. Body mass index between 18.5 to 30.0 kg/m
3. Normal laboratory values, including vital signs and physical examination, for all parameters in clinical laboratory tests at screening. Any abnormalities from the normal or reference range will be carefully considered clinically relevant by the physician as individual cases, documented in study files prior to enrolling the subject in this study.
4. Non-smoker and non-consumer of nicotine containing products Non-smoker or non-consumer of nicotine containing products means any subject who has never smoked/consumed or stopped for at least 90 days.
5. Non-pregnant woman (negative pregnancy test) and not currently breast feeding.
6. Female subjects abstain from either hormonal methods of contraception (including oral or transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone-releasing IUDs, postcoital contraceptive methods) or hormone replacement therapy for at least 28 days prior to check-in in Period 1. Injectable contraceptives e.g. Depo-Provera will be discontinued at least 6 months prior to check-in in Period 1. Subjects agree to use acceptable non-hormonal contraceptive methods such as condom, diaphragm, foams, jellies, or abstinence for at least 14 days prior to check-in in Period 1 until 14 days after the end of study in Period 2. Female subjects of non-childbearing potential must meet at least one of the following criteria prior to check-in in Period 1:
- Postmenopausal for at least 1 year or
- Surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)
at least 6 months
7. Male subjects who are willing or able to use effective contraceptive e.g. condom or abstinence after check-in in Period 1 until 14 days after the end of study in Period 2
8. Able to understand and voluntarily given written informed consent (signed and dated) by the subject prior to participating in this study.
9. Adequate venous access in both arms for the collection of a number of samples during the study
1.History of hypersensitivity to linagliptin or metformin HCl (with symptoms including asthma/bronchial hyperresponsiveness, urticaria or angioedema) or to any of the excipients
2. History or evidence of clinically significant renal, hepatic, gastrointestinal, hematological (e.g. anemia), endocrine (e.g. hyper-/hypothyroid, diabetes), pulmonary or respiratory (e.g. asthma), cardiovascular (e.g. hyper-/hypotension, heart failure), psychiatric (e.g. depression), neurologic (e.g. convulsant), allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) or any significant ongoing chronic medical illness
3. Have high risk for coronavirus infection based on risk assessment questionnaire or diagnosed as confirmed case of COVID-19
4. History about administration of COVID-19 vaccine within 30 days prior to check-in in each Period.
5. History or evidence of acute or chronic metabolic acidosis including diabetic ketoacidosis or lactic acidosis
6. History or evidence of acute pancreatitis
7. History or evidence of bullous pemphigoid
8. History or evidence of vitamin B12 deficiency
9. History or evidence of severe infection or severe accident or shock within 14 days prior to check-in in each period
10. Investigation with blood sample shows fasting blood glucose level less than 70 mg/dl or more than 99 mg/dl at screening.
11.History of sensitivity to heparin or heparin-induced thrombocytopenia
12.Any condition possibly affecting drug absorption e.g. gastrectomy, enterectomy, gastritis or duodenal or gastric ulceration other than appendectomy
13.History of dehydration, diarrhea or vomiting within 24 hours prior to check-in in each period
14.History of problems with swallowing tablet or capsule
15.History or evidence of drug addict or investigation with urine sample shows a positive test for drug of abuse (morphine, marijuana or methamphetamine)
16.12-lead ECG demonstrating QTc > 450 msec, a QRS interval > 120 msec or with an abnormality considered clinically significant at screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG will be repeated two more times and the average of the three QTc or QRS values will be used to determine the subject s eligibility.
17.Investigation with blood sample shows positive test for HBsAg
18.Abnormal liver function, is greater than or equal to 1.5 times of upper normal limit of reference range for ALT, AST or bilirubin levels at screening laboratory test
19.Have eGFR (CKD-EPI) < 30 mL/min/1.73 m2 based on serum creatinine results, at the screening laboratory test or during enrollment.
20.History or evidence of alcoholism or harmful use of alcohol (less than 2 years) i.e., alcohol consumption of more than 14 standard drinks per week for men and 7 standard drinks per week for women (A standard drink is defined as 360 mL of beer or 150 mL of wine or 45 mL of 40% distilled spirits, such as rum, whisky, brandy etc.)
21.History or evidence of alcohol consumption or alcohol-containing products and cannot abstain for at least 48 hours prior to check-in and continued for entire duration of the study or alcohol breath test shows positive result In case of alcohol breath test result represents the alcohol concentration range of 1 - 10 mg% BAC and the physician carefully considers that the value came from other reasons, not from the alcohol drinking behavior of subjects, the test will be repeated two times separately, not more tha
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Plasma Linagliptin concentrations 0-72 hrs Cmax, AUC0-tlast and AUC0-infinity for metformin,
- Secondary Outcome Measures
Name Time Method Plasma Linagliptin concentrations 0-72 hrs Tmax, t1/2, lambda z, AUC0-tlast/AUC0-infinity, AUC%extrapolate and MRT for metformin,