Pharmacokinetic Interactions of Valsartan and Hydrochlorothiazide (PKVH)

Pharmacokinetic Interactions of Valsartan and Hydrochlorothiazide: An Open-Label, Randomized, Four-Period Crossover Study in Healthy Egyptian Male Volunteers

This study was conducted to compare the rate and extent of absorption of valsartan and hydrochlorothiazide following oral administration as a fixed dose combination tablet and concomitant administration of the individual drugs under fasting conditions in healthy Egyptian subjects. The study was extended to investigate any potential reaction between VAL and HCT.

Study Overview

• Status: Completed
• Conditions: Healthy Normotensive Participants
• Intervention / Treatment: Drug: Valsartan; Drug: Hydrochlorothiazide; Drug: Valsartan/Hydrochlorothiazide

Detailed Description

This study comprised 2 separate parts, I and II; each was a single-dose, open-label, 4-crossover periods separated by a 2 weeks washout, and 4-Treatments. Part I consisted of Treatments A (VAL 160 mg alone), B (HCT 12.5 mg alone), C (VAL 160 mg + HCT 12.5 mg) and D (VAL / HCT 160 mg/12.5mg) and Part II consisted of Treatments E (VAL 320 mg alone), F (HCT 25 mg alone), G (VAL 320 mg + HCT 25 mg) and H (VAL / HCT 320 mg/25 mg). Blood samples were collected up to 48 hours postdose and plasma was analyzed for VAL and HCT concentrations using HPLC. The pharmacokinetic properties of each drug after co-administration of VAL and HCT were compared with those of each drug administered alone.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Damanhour, Egypt
    • Pharmaceutics Department, Faculty of Pharmacy, Damanhour University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• At least 18 years old and not more than 45 healthy male volunteers
• Actual weight no more than ± 30% from ideal body weight based on sex, height, and body frame
• Who had passed all the screening parameters
• Free of any drug exposure known to interfere with the pharmacokinetics or assay of fexofenadine for at least 10 days prior to the study
• Who had to be able to communicate effectively with study personnel, be literate, and able to give consent.

Exclusion Criteria:

• A clinically significant abnormal physical exam, medical history, or laboratory studies
• If they showed a sitting SBP of >140 or <100 mmHg, DBP > 90 or <60mm Hg, or a pulse rate of > 95 or < 50 beats/min at screening
• A history of serious intolerance, allergy, or sensitivity to fexofenadine
• The use of any prescription drug within the previous month or use of any over-the-counter medication (with the exception of acetaminophen) within the past 14 days
• A history of blood dyscrasias
• A history of alcohol or drug abuse within the past year
• Donation of blood during the 8 weeks prior to the study or plans to donate blood during or within 8 weeks of completing the study
• Unable to tolerate vein puncture and multiple blood samplings
• Any surgical/medical condition that might alter drug absorption, distribution, metabolism, or excretion
• Cannot follow instructions, in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Valsartan 160 mg alone; Valsartan alone	Drug: Valsartan; Valsartan alone
Other: Hydrochlorothiazide 12.5 mg alone; Hydrochlorothiazide alone	Drug: Hydrochlorothiazide; Hydrochlorothiazide alone
Other: Valsartan160 mg + Hydrochlorothiazide12.5 mg; Concomitant administration of valsartan 160 mg + Hydrochlorothiazide 12.5 mg	Drug: Valsartan/Hydrochlorothiazide; Co-administration or fixed dose combination; Other Names: Fixed dose combination; Pharmacokinetic interaction
Other: Valsartan / Hydrochlorothiazide 160 mg/12.5mg; Fixed dose combination of valsartan 160 mg + Hydrochlorothiazide 12.5 mg	Drug: Valsartan/Hydrochlorothiazide; Co-administration or fixed dose combination; Other Names: Fixed dose combination; Pharmacokinetic interaction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability	Tolerability was assessed based on changes in vital signs (temperature, blood pressure, pulse, and heart rate), measured before dosing in each period and approximately every 4 hours thereafter, and laboratory tests (hematology, biochemistry, liver function, and urinalysis), and performed at baseline and at the end of the study. In addition, a physician questioned volunteers about any adverse events occurring during the study, addressed them as necessary, and recorded them on the appropriate form. This physician was not blinded to treatment, but had no involvement in the study.	Participants will be followed for the duration of study, an expected average of 6 weeks.

Collaborators and Investigators

• Sponsor: Damanhour University
• Investigators: Principal Investigator: Sally Helmy, PhD, CPHQ, Pharmaceutics Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: January 8, 2013
• First Submitted That Met QC Criteria: January 10, 2013
• First Posted (Estimate): January 14, 2013

Study Record Updates

• Last Update Posted (Estimate): January 15, 2013
• Last Update Submitted That Met QC Criteria: January 12, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Fixed dose combination; Valsartan; Hydrochlorothiazide
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Valsartan; Hydrochlorothiazide
• Other Study ID Numbers: PPT1