Comparative bioequivalence study of Dapagliflozin/ Metformin 5/ 1000 mg Tablet of ActoverCo. and Xigdue ® of Astera Zeneca as reference in 24 healthy male under fasting condition
This study will be performed to compare the pharmacokinetics and invivo parameters of Dapagliflozin/ Metformin 5/1000 mg Tablet formulation as a test product with Xigdue 5/1000 mg Tablet formulation as a reference product and to evaluate the bioequivalence of these two formulations.
Design
n-blinded, randomized, crossover in vivo bioequivalence study on 24 healthy males under fasting conditions. Block randomization for a treatment sequence of Test/Reference or Reference/Test is used.
Settings and conduct
In each period, volunteers will receive a single dose of the treatment in the Noor Research and Development Institute (Tarasht, Tehran). 2 dosing periods will be separated by a 7-day washout period.
Participants/Inclusion and exclusion criteria
Inclusion Criteria: Healthy subjects (male) between 20 – 45 years of age.
Body Mass Index (BMI) within 15% of normal range according to the accepted normal values between 18.5 and 30(inclusive), calculated as kg/m2.
Exclusion: Sensitivity to the pharmaceutical substance being studied.
Cardiovascular, pulmonary, acute or chronic hormonal nervous system disease, gastrointestinal disease, and visual impairments on ophthalmology examinations.
Intervention groups
Intervention group 1: Dapagliflozin/ Metformin 5/ 1000 mg Tablet, produced by ActoverCo. is the test product. In each period, 12 of 24 subjects will be given a single oral dose of this product. Intervention group 2: Dapagliflozin/ Metformin 5/ 1000 mg Tablet (Xigdue®), produced by Astera Zeneca is the reference product. In each period, 12 of 24 subjects will be given a single oral dose of this product.
Main outcome variables
Peak Plasma Concentration
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20180620040164N76
Registration date:2025-01-08, 1403/10/19
Registration timing:prospective
Last update:2025-01-08, 1403/10/19
Update count:0
Registration date
2025-01-08, 1403/10/19
Registrant information
Name
Behzad Montaha Sangari
Name of organization / entity
Noor research and educational institute (Tavan)
Country
Iran (Islamic Republic of)
Phone
+98 21 6600 7026
Email address
info@tavaninstitute.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2025-01-31, 1403/11/12
Expected recruitment end date
2025-02-19, 1403/12/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Comparative bioequivalence study of Dapagliflozin/ Metformin 5/ 1000 mg Tablet of ActoverCo. and Xigdue ® of Astera Zeneca as reference in 24 healthy male under fasting condition
Public title
Comparative in vivo evaluation of 2 Dapagliflozin/ Metformin 5/ 1000 mg Tablet and Xigdue® 5/ 1000 mg Tablet formulations.
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Healthy subjects (male) between 20 – 45 years of age.
Body Mass Index (BMI) within 15% of normal range according to the accepted normal values between 18.5 and 30(inclusive), calculated as kg/m2.
Subjects with no significant diseases or abnormal findings during laboratory evaluations and clinical examination.Subjects with normal vital signs.
Candidates must have normal vital signs.
The consent of the candidates to all the requirements of the clinical study based on the instructions of the clinical study, which has been confirmed by accepting the informed consent form.
Exclusion criteria:
Sensitivity to the pharmaceutical substance being studied.
Cardiovascular, pulmonary, acute or chronic hormonal nervous system disease, gastrointestinal disease, and visual impairments on ophthalmology examinations.
A history of mental illness, water loss due to diarrhea or vomiting that lasts 24 hours before the medication is given.
Systolic blood pressure greater than 130 or less than 100 mmHg.
Diastolic blood pressure greater than 85 or less than 60 mmHg.
Smokers who smoke more than 10 cigarettes a day and have problems with not smoking during each clinical study period.
People who have used over the counter or doctor-prescribed medications 14 days before the start of the first period will need to take the medication at the same time during the study.
People who have a history of alcoholism or alcohol consumption within the past 2 years.
Volunteers who are heavy drinkers of caffeinated beverages, fruit juices (grapefruit juice) or follow a special diet (vegetarianism) or do heavy physical activity.
A history of difficulty donating blood or donating more than 500 mL of blood less than seven days before the start of the study.
Age
From 20 years old to 45 years old
Gender
Male
Phase
Bioequivalence
Groups that have been masked
No information
Sample size
Target sample size:
24
Randomization (investigator's opinion)
Randomized
Randomization description
The randomization schedule will be generated with https://www.sealedenvelope.com/simple-randomiser/v1/lists. A 2*2 block randomization list is created. We have 12 blocks and within each two volunteer numbers (allocated after screening) for all 24 volunteers. According to this list, a treatment sequence of Test/Reference or Reference/Test will be given to each volunteer.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Crossover
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics committees of school of pharmacy and nursing Midwifery-Shahid Beheshti University of
Street address
Niayesh Highway, Valiasr Ave
City
Tehran
Province
Tehran
Postal code
1996835113
Approval date
2024-12-30, 1403/10/10
Ethics committee reference number
IR.SBMU.PHARMACY.REC.1403.236
Health conditions studied
1
Description of health condition studied
Diabetes mellitus due to underlying condition
ICD-10 code
E08
ICD-10 code description
Diabetes mellitus due to underlying condition
Primary outcomes
1
Description
Peak Plasma Concentration (Cmax)
Timepoint
14 blood samples will be withdrawn pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 11, 24 and 48 hours after intervention.
Method of measurement
Using non-compartmental model of Win-Nonlin Professional software version 3.2.A (Pharsight Corporation, USA)
Secondary outcomes
1
Description
AUC (Area Under the Concentration-Time Curve)
Timepoint
14 blood samples will be withdrawn pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 11, 24 and 48 hours after intervention.
Method of measurement
Using non-compartmental model of Win-Nonlin Professional software version 3.2.A (Pharsight Corporation, USA)
Intervention groups
1
Description
Intervention group 1: Dapagliflozin/ Metformin 5/ 1000 mg Tablet, produced by ActoverCo. is the test product. In each period, 12 of 24 subjects will be given a single oral dose of this product.
Category
Treatment - Drugs
2
Description
Intervention group 2: Dapagliflozin/ Metformin 5/ 1000 mg Tablet (Xigdue®), produced by Astera Zeneca is the reference product. In each period, 12 of 24 subjects will be given a single oral dose of this product.