Chronopharmacology of Valsartan in Normotensive Subjects

A Comparative Pharmacokinetic and Pharmacodynamic Study of Morning Versus Evening Administration of Valsartan in Healthy Adults

The choice of drug administration time may affect the pharmacokinetics and/or drug response, and knowledge of any such circadian rhythm-dependent effects may help to reduce side effects or to enhance efficacy. This study designed to investigate the potential influence of the time of drug administration on the pharmacokinetics and pharmacodynamics of the valsartan in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Normotensive Volunteers
• Intervention / Treatment: Drug: Valsartan

Detailed Description

International guidelines recommend the use of long acting, once-daily medications that provide 24h efficacy; they improve adherence to therapy and minimize BP variability with smoother and more consistent BP control.

Valsartan has been approved to be used once-daily, without any specification of treatment-time in package insert. Several trials have investigated the differential effects of morning versus evening administration of valsartan in hypertensive patients, however, the results of these studies were contradicting. Furthermore, the specific administration time dependent dose response curve have not been previously investigated. So, this study designed to investigate the potential influence of the time of drug administration on the pharmacokinetics and pharmacodynamics of the valsartan in healthy subjects.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11566
    • Ain Shams University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. At least 18 years old and not more than 45 healthy male volunteers
2. Actual weight no more than ± 30% from ideal body weight based on sex, height, and body frame
3. Who had passed all the screening parameters including physical examination, laboratory tests.
4. Who had to be able to communicate effectively with study personnel, be literate, and able to give consent.
5. diurnal active subjects with eight hour night sleep.
6. free of any drug exposure known to interfere with the pharmacokinetics/pharmacodynamics or assay of valsartan for at least 10 days prior to the study

Exclusion Criteria:

1. Treatment with any known enzyme-inducing/inhibiting agents within 30 days prior to the start of the study and throughout the study.
2. Susceptibility to allergic reactions to valsartan.
3. Any prior surgery of the gastrointestinal tract that may interfere with drug absorption.
4. Gastrointestinal diseases.
5. Renal diseases.
6. Cardiovascular diseases.
7. Pancreatic disease including diabetes.
8. Hepatic diseases.
9. Hematological disease or pulmonary disease
10. Abnormal laboratory values.
11. Subjects who have donated blood or who have been involved in multiple dosing study requiring a large volume of blood (more than 500 ml) to be drawn within 6 weeks preceding the start of the study.
12. Nocturnal active subjects

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: morning administration; administration of single oral dose valsartan (160 mg) in the morning	Drug: Valsartan; single oral dose of 160 mg valsartan under fasting conditions; Other Names: Diovan
Other: evening administration; administration of single oral dose valsartan (160 mg) in the evening	Drug: Valsartan; single oral dose of 160 mg valsartan under fasting conditions; Other Names: Diovan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters	Maximum plasma concentration (Cmax),	blood samples will be collected for 48 hour after drug administration
Pharmacokinetic parameters	Area under the curve (AUC).	blood samples will be collected for 48 hour after drug administration
Pharmacokinetic parameters	elimination half life (T1/2)	blood samples will be collected for 48 hour after drug administration
pharmacodynamic parameter	systolic blood pressure (mm Hg) ,diastolic blood pressure (mm Hg)	Blood samples will be measured at prespecified time points for 48 hour after drug administration
pharmacodynamic parameter	Heart rate (beat/min)	Blood samples will be measured at prespecified time points for 48 hour after drug administration

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: December 4, 2015
• First Submitted That Met QC Criteria: December 11, 2015
• First Posted (Estimate): December 15, 2015

Study Record Updates

• Last Update Posted (Actual): August 16, 2017
• Last Update Submitted That Met QC Criteria: August 14, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: valsartan; Chronokinetics; chronodynamics; chronopharmacology
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan
• Other Study ID Numbers: Ph.D (No.26)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO