This study will be performed to compare the pharmacokinetics and invivo parameters of Losartan / Hydrochlorothiazide 50/12.5 mg formulation as a test product with HYZAAR® tablet formulation as a reference product and to evaluate the biocompatibility of these two formulations.
Design
Randomized, single-dose, crossover comparative bioequivalence study of Losartan / Hydrochlorothiazide 50/12.5 mg tablet of Razak. and MSD. in 24 healthy male under fasting.
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 18 – 45 years of age and Body Mass Index (BMI) between 18.5 and 30 (inclusive), calculated as kg/m2.
Subjects with no significant diseases or clinically significant abnormal findings during screening, medical history, clinical examination and laboratory evaluations.
Exclusion Criteria:
Known hypersensitivity to losartan, hydrochlorothiazide, or any other components of the FDC tablet.
Systolic blood pressure less than 100 mm Hg or more than 140 mm Hg and diastolic blood pressure less than 60 mm Hg or more than 90 mm Hg.
Intervention groups
Intervention group (test): Losartan / Hydrochlorothiazide 50/12.5 mg tablet , produced by َRazak is the test product. In each period, 12 of 24 subjects will be given a single oral dose of this product. Intervention group (Reference): HYZAAR® Tablet, produced by MSD 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:IRCT20180620040164N47
Registration date:2023-07-17, 1402/04/26
Registration timing:prospective
Last update:2023-07-17, 1402/04/26
Update count:0
Registration date
2023-07-17, 1402/04/26
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
2023-09-02, 1402/06/11
Expected recruitment end date
2023-09-16, 1402/06/25
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Comparative bioequivalence study of Losar H® 50/12.5 mg of Razak and MSD in 24 healthy male under fasting
Public title
Bioequivalence study of Losar H® 50/12.5 mg in 24 healthy male under fasting conditions
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Healthy subjects (male) between 18 – 45 years of age and Body Mass Index (BMI) between 18.5 and 30 (inclusive), calculated as kg/m2.
Subjects with no significant diseases or clinically significant abnormal findings during screening, medical history, clinical examination and laboratory evaluations.
Subjects with normal vital signs.
Subjects who agree with patient consent form.
Exclusion criteria:
Known hypersensitivity to losartan, hydrochlorothiazide, or any other components of the FDC tablet.
Systolic blood pressure less than 100 mm Hg or more than 140 mm Hg and diastolic blood pressure less than 60 mm Hg or more than 90 mm Hg.
Pulse rate less than 50/minute or more than 100/minute.
Oral temperature less than 95°P or more than 98.6°P.
Respiratory rate less than 12/minute or more than 20/minute.
Smoking more than 10 cigarettes per day and could not tolerate cigarette cessation during each clinical period.
Subjects who have used any drug including prescription or Over-The-Counter (OTC) drugs within 14 days prior to the start of the study and might need drug intake during study period.
Subjects who have a history of alcohol or substance abuse within the last 5 years.
Heavy drinker of alcohol, grapefruit juice or caffeinated drinks or who are on special diet (such as vegetarians) or do exertional physical activity.
Subject intends to be hospitalized within 3 months after first study drug administration.
Subjects who, through completion of this study, would have donated more than 500 ml of blood in 7 days.
Age
From 18 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's number (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
Ethics committee of Shahid Beheshti University of Medical Sciences
Street address
Niayesh Highway, Valiasr Ave, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1996835113
Approval date
2023-05-23, 1402/03/02
Ethics committee reference number
IR.SBMU.PHARMACY.REC.1402.030
Health conditions studied
1
Description of health condition studied
Secondary hypertension
ICD-10 code
I15
ICD-10 code description
Secondary hypertension
Primary outcomes
1
Description
Peak Plasma Concentration (Cmax)
Timepoint
20 blood samples will be withdrawn pre-dose and at 0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 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
20 blood samples will be withdrawn pre-dose and at 0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 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 group1: Losar/ H 50/ 12.5 mg tablet , produced by Razak. is the test product. In each period, 12 of 24 subjects will be given single oral dose of this product. After 7-day wash-out period the intervention 2 will be given to these subjects.
Category
Treatment - Drugs
2
Description
Intervention group2: HYZAAR® 50/12.5 Tablet, produced by MSD is the reference product. In each period, 12 of 24 subjects will be given single oral dose of this product. After 7-day wash-out period the intervention 1 will be given to these subjects.