An open label, randomized, balanced, two treatment, two sequence, two period, truncated, two way cross-over, single-dose, oral bioequivalence study of FDC of Linagliptin 05 mg, Dapagliflozin 10 mg and Metformin Hydrochloride 1000 mg extended release Tablets (T) Manufactured by Optimus Pharma Pvt. Ltd., India with Trajenta® 5 mg (Linagliptin 05 mg) Tablet (R1) Manufactured by West-Ward Columbus Inc., USA and Marketed by Boehringer Ingelheim India Pvt. Ltd., Maharashtra, India and Xigduo® XR (Dapagliflozin and Metformin HCl Extended Release Tablets 10 mg + 1000 mg) (R2) Manufactured by AstraZeneca Pharmaceuticals LP, USA and Imported & Marketed by AstraZeneca Pharma India Ltd., Bangalore, India in normal healthy, adult human subjects under fasting condition.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Linagliptin: Cmax, and AUC (0-72)
研究概览
简要总结
An open label, randomized, balanced, two treatment, two sequence, two period, truncated, two way cross-over, single-dose, oral bioequivalence study of FDC of Linagliptin 05 mg, Dapagliflozin 10 mg and Metformin Hydrochloride 1000 mg extended release Tablets (T) Manufactured by Optimus Pharma Pvt. Ltd., India with Trajenta® 5 mg (Linagliptin 05 mg) Tablet (R1) Manufactured by West-Ward Columbus Inc., USA and Marketed by Boehringer Ingelheim India Pvt. Ltd., Maharashtra, India and Xigduo® XR (Dapagliflozin and Metformin HCl Extended Release Tablets 10 mg/ 1000 mg) (R2) Manufactured by AstraZeneca Pharmaceuticals LP, USA and Imported & Marketed by AstraZeneca Pharma India Ltd., Bangalore, India in normal healthy, adult human subjects under fasting condition. Dapagliflozin ,a Sodium-glucose cotransporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Dapagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, dapagliflozin reduces reabsorption of filtered glucose, and thereby promotes urinary glucose excretion. Dapagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule. This may influence several physiological functions including, but not restricted to, lowering both pre- and afterload of the heart and downregulation of sympathetic activity, and decreased intraglomerular pressure which is believed to be mediated by increased tubuloglomerular feedback. Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation. Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretin hormones are secreted at a low basal level throughout the day and levels rise immediately after meal intake. GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels. Furthermore, GLP-1 also reduces glucagon secretion from pancreatic alpha-cells, resulting in a reduction in hepatic glucose output.
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18.00 Year(s) 至 45.00 Year(s)（—）
- 性别
- All
入选标准
- •Volunteers who accept for participating in this study must: 1.Healthy, adult human, subjects aged between 18-45 years (both inclusive) at the time of screening.
- •2.Having a Body Mass Index (BMI) between 18.50 to 29.99 kg/m2 (both inclusive) at the time of screening.
- •Normal or clinically insignificant findings during screening, medical history, clinical examination including vital signs, laboratory evaluations, 12 lead ECG and X-ray chest (posterior-anterior view) recordings.
- •Able to comply with the study procedures, in the opinion of the principal investigator.
- •5.Compliance with study specific restrictions and prohibitions.
- •Able to give voluntary written informed consent for participation in the trial.
- •In case of Female subjects:
- •Female subjects who are of child bearing potential and are willing to use a suitable and effective double barrier contraceptive method or non-hormonal intra uterine device during the study.
- •Female subjects who are tested negative for serum pregnancy test at the time of check-in.
- •Female subjects who are tested negative for urine pregnancy test at the time of screening.
排除标准
- •If any subject is having any of the following conditions, then exclude him/her from participation in this study
- •Known hypersensitivity or idiosyncratic reaction to the study drug or any related drug.
- •History or presence of any disease or disorder known to influence bone metabolism, compromise the hemopoietin, renal, hepatic, endocrine, pulmonary, central nervous, cardiovascular, immunological, dermatological, gastrointestinal, musculoskeletal or any other body system.
- •Ingestion of any medicine at any time within 14 days prior to IP administration in period I.
- •In any such case subject selection will be at the discretion of the principal investigator.
- •Habit of consuming high caffeine (more than 5 cups of coffee or tea/day).
- •Smokers and Alcoholics.
- •History of dehydration from diarrhea, vomiting or any other reason within a period of 24.00 hours prior to study check-in.
- •6.An unusual or abnormal diet within 48.00 hours prior to study check-in, whatever reason e.g. because of fasting due to religious reasons.
- •7.The presence of clinically significant abnormal laboratory values during screening.
- •8.Use of any recreational drugs or history of drug addiction or testing positive in pre-study urine drug screening and Urine alcohol test.
- •A history of difficulty with donating blood or having donated blood in the preceding 90 days for males / 120 days for females prior to the start of the study.
- •Subject who has participated in any other clinical study involving drug administration and collection of blood samples in the 90 days for males / 120 days for females preceding the start of the study.
- •Difficulty in swallowing capsule/tablet.
- •Positive HIV, VDRL/RPR, Hepatitis B and C tests.
- •Subjects who have used any drugs or substances known to be strong inhibitors or inducers of Cytochrome P450 enzymes within 14 days prior to IP administration in period I.
- •Pregnant and lactating women or those using hormonal contraceptives (oral implants).
- •History of undiagnosed vaginal bleeding (for females only).
- •16.Female subjects who demonstrates a positive pregnancy during screening or currently breast-feeding.
- •17.Female volunteer who has used implanted or injected hormonal contraceptives anytime during the 6 months prior to study or used hormonal contraceptives within 14 days before dosing.
- •Prior to check-in of Period- I, complete the Inclusion and Exclusion Criteria for each volunteer.
- •Only suitable volunteers should be allowed to participate in the study.
结局指标
主要结局
Linagliptin: Cmax, and AUC (0-72)
时间窗: Total 27 blood samples in each period, a single pre-dose (-02.00 to 00.00) blood sample of 5.0 mL will be collected in Ice cold bath at each period. The pre-dose and post-dose blood samples will be collected in pre-labeled K2EDTA vacutainers.
Dapagliflozin and Metformin: Cmax, AUC(0-t) and AUC(0-inf)
时间窗: Total 27 blood samples in each period, a single pre-dose (-02.00 to 00.00) blood sample of 5.0 mL will be collected in Ice cold bath at each period. The pre-dose and post-dose blood samples will be collected in pre-labeled K2EDTA vacutainers.
次要结局
- Linagliptin: Tmax,(Dapagliflozin & Metformin: Tmax, Kel, t½ & AUCExtrapolated%)
研究者
Dr Harisha
Notrox research Pvt ltd