CTRI/2024/02/062871 [Registered on: 19/02/2024] Trial Registered Prospectively
Last Modified On:
19/02/2024
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioequivalence study of FDC Dapagliflozin 10 mg + Linagliptin 05 mg + Metformin Hydrochloride(as extended release) 1000 mg film coated Tablets
Scientific Title of Study
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.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
Protocol No.:S-23-821, Version no .01, dated 01.09.2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Harisha
Designation
Principal investigator
Affiliation
Notrox research Pvt ltd
Address
No 19 3, 2nd Floor, Bikasipura road, JC Industrial layout, off Kanakapura Road (Behind Metro Cash & carry) Bangalore-560062, Karnataka India.
Bangalore KARNATAKA 560062 India
Phone
8183086951
Fax
Email
harisha-c@notroxresearch.com
Details of Contact Person Scientific Query
Name
Dr Harisha
Designation
Principal investigator
Affiliation
Notrox research Pvt ltd
Address
No 19 3, 2nd Floor, Bikasipura road, JC Industrial layout, off Kanakapura Road (Behind Metro Cash & carry) Bangalore-560062, Karnataka India.
Bangalore KARNATAKA 560062 India
Phone
8183086951
Fax
Email
harisha-c@notroxresearch.com
Details of Contact Person Public Query
Name
Dr D Sharmilaa
Designation
Medical Affairs
Affiliation
Optimus Pharma Pvt Ltd
Address
Plot No. 73 B, 73 B 2, EPIP, Pashamylaram (Village), Patancheru (Mandal), Sangareddy (District), Hyderabad-502307, Telangana, India.
After an overnight fasting of at least 10.00 hours, a single dose of FDC of Linagliptin 05 mg, Dapagliflozin 10 mg and Metformin Hydrochloride 1000 mg extended release Tablets Manufactured by Optimus Pharma Pvt. Ltd., India along with 240±2 mL of 20% aqueous glucose solution, will be administered orally to the subjects in sitting posture at ambient temperature in the morning, as per the randomization schedule.
Subjects will receive the alternate ‘treatment’ in the subsequent periods, in such a way that each subject will have received all the ‘treatments’ by the end of the study
Comparator Agent
Trajenta® 5 mg (Linagliptin 05 mg)Tablet and Xigduo® XR (Dapagliflozin and Metformin HClExtended Release Tablets 10 mg + 1000 mg)
After an overnight fasting of at least 10.00 hours, a single dose of Trajenta® 5 mg (Linagliptin 05 mg) Tablet 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) Manufactured by AstraZeneca Pharmaceuticals LP, USA and Imported & Marketed by AstraZeneca Pharma India Ltd., Bangalore, India along with 240±2 mL of 20% aqueous glucose solution, will be administered orally to the subjects in sitting posture at ambient temperature in the morning, as per the randomization schedule.
Subjects will receive the alternate ‘treatment’ in the subsequent periods, in such a way that each subject will have received all the ‘treatments’ by the end of the study.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
45.00 Year(s)
Gender
Both
Details
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.
3. 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.
4. Able to comply with the study procedures, in the opinion of the principal
investigator.
5.Compliance with study specific restrictions and prohibitions.
6. Able to give voluntary written informed consent for participation in the trial.
In case of Female subjects:
7. 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.
8. Female subjects who are tested negative for serum pregnancy test at the time
of check-in.
9. Female subjects who are tested negative for urine pregnancy test at the time
of screening.
ExclusionCriteria
Details
If any subject is having any of the following conditions, then exclude him/her from
participation in this study
1. Known hypersensitivity or idiosyncratic reaction to the study drug or any
related drug.
2. 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.
3. 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.
4. Habit of consuming high caffeine (more than 5 cups of coffee or tea/day).
5. 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.
9. 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.
10. 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.
11. Difficulty in swallowing capsule/tablet.
12. Positive HIV, VDRL/RPR, Hepatitis B and C tests.
13. 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.
14. Pregnant and lactating women or those using hormonal contraceptives
(oral implants).
15. 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.
Method of Generating Random Sequence
Method of Concealment
Blinding/Masking
Primary Outcome
Outcome
TimePoints
Linagliptin: Cmax, and AUC (0-72)
Dapagliflozin and Metformin: Cmax, AUC(0-t) and AUC(0-inf)
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.
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 & post-dose blood samples will be collected in pre-labeled K2EDTA vacutainers.
Target Sample Size
Total Sample Size="24" Sample Size from India="24" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
Phase of Trial
Phase 2
Date of First Enrollment (India)
29/02/2024
Date of Study Completion (India)
Date Missing
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Date Missing
Estimated Duration of Trial
Years="0" Months="6" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Completed
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
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.