Bioequivalence Study of Valsartan 320mg Tablets Under Fasting Conditions

Tablet in healthy, adult human subjects under fasting condition, with a screening period of 28 days prior to dose administration in Period-I. In each study period, twenty-four (24) blood samples, including two (02) predose blood samples, each of 02 mL were collected from each subject except for the discontinued / withdrawn subjects to analyze the pharmacokinetic profile of the test as well as the reference product.

The pharmacokinetic parameters were calculated from the drug concentration vs. time profile by non-compartmental model using WinNonlin Professional Software-Version 5.3 (Pharsight Corporation, USA) for Valsartan. Statistical comparison of the pharmacokinetic parameters of the two formulations was carried out using PROC MIXED of SAS® Version 9.3 (SAS Institute Inc., USA) to assess the bioequivalence of both the formulations.

Inclusion criteria

• Healthy, adult, human volunteers between 18 to 45 years of age (both inclusive) living in and around Ahmedabad city or western part of India.
• Having a Body Mass Index (BMI) between 18.5-24.9 (both inclusive), calculated as weight in kg/height in meter2.
• Not having any significant disease in medical history or clinically significant abnormal findings during screening, medical history, physical examination, laboratory evaluations, 12- lead ECG and X-ray chest (P/A view) recordings.
• Able to understand and comply with the study procedures, in the opinion of the investigator.
• Able to give voluntary written informed consent for participation in the trial.
• In case of female subjects:

• Surgically sterilized at least 6 months prior to study participation; Or
• If of child bearing potential is willing to use a suitable and effective double barrier contraceptive method or intra uterine device during the study.

And

• Pregnancy test must be negative.

Exclusion criteria

• Known hypersensitivity or idiosyncratic reaction to valsartan or any of the formulation excipients or any related drug.
• History or presence of any disease or condition which might compromise the haemopoietic, renal, hepatic, endocrine, pulmonary, central nervous, cardiovascular, immunological, dermatological, gastrointestinal or any other body system.
• Sitting blood pressure less than 110 /70 mm Hg and pulse rate less than 60 or more than 100 beats per minute at the time of screening.
• Presence of orthostatic hypotension.
• If the QTc interval were to be more than 450 ms on ECG measurement at the time of screening.
• Inability to remain in an upright position at the time of dosing.
• Ingestion of a medicine (including herbal remedies) at any time within 14 days before dosing in period-I. In any such case subject selection were at the discretion of the Principal Investigator.
• Any history or presence of asthma (including aspirin induced asthma) or nasal polyp or NSAIDs induced urticaria.
• A recent history of harmful use of alcohol (less than 2 years), i.e. alcohol consumption of more than 14 standard drinks per week for men and more than 7 standard drinks per week for women (A standard drink is defined as 360 ml of beer or 150 ml of wine or 45 ml of 40% distilled spirits, such as rum, whisky, brandy etc) or consumption of alcohol or alcoholic products within 48 hours prior to receiving study medicine.
• Smokers, who smoke 10 or more than 10 cigarettes/day or inability to abstain from smoking during the study.
• The presence of clinically significant abnormal laboratory values during screening.
• Use of any recreational drugs or history of drug addiction or testing positive in pre study drug scans.
• History or presence of psychiatric disorders.
• A history of difficulty in donating blood.
• Donation of blood (1 unit or 350 mL) or receipt of an investigational medicinal product or participation in a drug research study within a period of 90 days prior to the first dose of study medication. Elimination half-life of the study drug should be taken into consideration for inclusion of the subject in the study.

Note: In case the blood loss is ≤ 200 mL; subject may be dosed 60 days after blood donation or last sample of the previous study.

• A positive hepatitis screen including hepatitis B surface antigen and/or HCV antibodies.
• A positive test result for HIV antibody.
• An unusual diet, for whatever reason (e.g. low-sodium), for four weeks prior to receiving the study medicine in period-I. In any such case subject selection were at the discretion of the Principal Investigator.
• Consumption of grapefruit or grapefruit products within 48 hours prior to dosing.
• Nursing mothers (females).