A Single Dose, Randomized, Open-label, Two-way Crossover Bioequivalence Study of a Fixed-dose Combination of Pioglitazone Hydrochloride and Metformin Hydrochloride 15 mg and 850 mg Tablets and Reference Product (actosmet®) in Healthy Thai Volunteers under Fed Conditions (BE18-012)
- Conditions
- Bioequivalence Study in Healthy Thai Volunteers under Fed Conditions
- Registration Number
- TCTR20181008005
- Lead Sponsor
- International Bio Service Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 56
1. Healthy Thai male or female subjects between the ages of 18 to 55 years.
2. Body mass index between 18.0 to 30.0 kg/m2.
3. Non-alcoholic, never drink alcohol and/or non-consumer of alcohol containing products
4. 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.
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 admission in Period 1. Injectable contraceptives e.g. Depo-Provera® will be discontinued at least 6 months prior to admission 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 admission in Period 1 until 7 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 admission in Period 1:
ï‚· Postmenopausal for at least 1 year or
ï‚· 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 admission in Period 1 until 7 days after the end of study in Period 2.
8. Have voluntarily given written informed consent (signed and dated) by the subject prior to participating in this study.
1. History of allergic reaction or hypersensitivity to pioglitazone, metformin or other component of pioglitazone and metformin combination
2. History or evidence of clinically significant renal, hepatic, gastrointestinal, hematological (e.g. anemia), endocrine (e.g. thyroid), pulmonary or respiratory (e.g. asthma), cardiovascular (e.g. coronary artery disease, myocardial infraction, heart failure), psychiatric, neurologic (e.g. convulsion), allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) or any significant ongoing chronic medical illness
3. History or evidence of diabetes mellitus or family history of diabetes mellitus
4. History of problems with swallowing tablet or capsule
5. History of sensitivity to heparin or heparin-induced thrombocytopenia
6. History of preceding diarrhea or vomiting within 24 hours prior to admission in each period
7. Any condition possibly affecting drug absorption e.g. gastrectomy, enterectomy, gastritis or duodenal or gastric ulceration other than appendectomy
8. History or evidence of drug addict or investigation with urine sample shows a positive test for drug of abuse (morphine, marijuana or methamphetamine)
9. 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.
10. Investigation with blood sample shows positive test for HBsAg.
11. Investigation with blood sample shows fasting blood glucose level less than 70 mg/dl or more than 99 mg/dl at screening laboratory test
12. Abnormal liver function, ≥ 1.5 times of upper normal limit of reference range for ALT, AST or bilirubin levels at screening laboratory test
13. Creatine kinase levels > 1.5 times of upper normal limit of reference range (unless explained by exercise) at screening laboratory test
14. History or evidence of habitual use of tobacco or nicotine containing products and cannot abstain for at least 7 days prior to admission and continued until last sample collection in each study period
15. History or evidence of habitual consume of tea, coffee, xanthine or caffeine containing products and cannot abstain for at least 7 days prior to admission and continued until last sample collection in each study period
16. Consume or drink juice of grapefruit or orange or pomelo or its supplement/containing products and cannot abstain for at least 7 days prior to admission and continued until last sample collection in each study period
17. Use of prescription (e.g., insulin) or nonprescription drugs (e.g. paracetamol, erythromycin, ketoconazole, phenformin, sulfonylureas, NSAIDs, coxibs), herbal medications or supplements (e.g. St. John's wort), vitamins or mineral (e.g. iron) or dietary supplements within 14 days prior to admission in Period 1 or during enrollment
18. Participated in other clinical trials within 90 days prior to admission in Period 1 (except for the subjects who drop out or withdrawn from the previous study prior to Period 1 dosing) or still participates in the clinical trial or participates in other clinical trials during enrollment in
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Metformin and Pioglitazone Plasama concentration 0-72 hr Cmax, AUC0-tlast and AUC0-∞
- Secondary Outcome Measures
Name Time Method Metformin and Pioglitazone Plasama concentration 0-72 hr Tmax, t1/2, λz, AUC0-tlast/AUC0-∞, AUC%extrapolate and MRT