Pharmacokinetic Drug-Drug Interaction Between Bisoprolol and Ivabradine in Healthy Volunteers

Pharmacokinetic Drug-Drug Interaction Between Bisoprolol and Ivabradine in Healthy Volunteers: An Open-Label, Randomized, Crossover Clinical Study

The purpose of the study was to investigate the potential interaction between ivabradine and bisoprolol in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases
• Intervention / Treatment: Drug: Ivabradine; Drug: Bisoprolol; Drug: combination of Ivabradine and bisoprolol

Detailed Description

The aim of this study is to undergo a pharmacokinetic study to investigate the incidence of potential pharmacokinetic interaction between Ivabradine and Bisoprolol through the Assessment of the drug-drug interactions of Ivabradine and Bisoprolol by determination of pharmacokinetic parameters of both drugs administered alone and in combination. The pharmacokinetic parameters will include; The maximum plasma concentration (Cmax),the time to reach the peak concentration (tmax), area under the concentration-time curve (AUC0-t) and (AUC0-∞) during the treatment periods, the absorption and elimination rate constants (ka and kel), the half-life and mean residence time (MRT).

Study design A comparative randomized open-label three-period crossover study of ivabradine/ bisoprolol in male healthy human volunteers

Methodology

Eighteen healthy volunteer will be recruited in the study and will be divided into three groups each consisting of six volunteers as follows:

Period I:

• Group A: Six Volunteers will receive single 10 mg oral dose of ivabradin (Procoralan®, Les Laboratoires Servier Industrie-France).
• Group B: Six Volunteers will receive single oral dose of bisoprolol 5mg (Concor®).
• Group C: Six Volunteers will receive a single dose of ivabradine 10 mg and bisoprolol 5 mg

Period II:

• Group A: Six Volunteers will receive a single dose of ivabradine 10 mg and bisoprolol 5 mg
• Group B: Six Volunteers will receive single 10 mg oral dose of ivabradin.
• Group C: Six Volunteers will receive single oral dose of bisoprolol 5mg.

Period III:

• Group A: Six Volunteers will receive single oral dose of bisoprolol 5mg.
• Group B: Six Volunteers will receive a single dose of ivabradine 10 mg and bisoprolol 5 mg
• Group C: Six Volunteers will receive single 10 mg oral dose of ivabradin

All drug administration will be followed by 240 ml of water after at least 10 h fasting prior to administration. The three treatment periods will be separated by a one week washout period. Standardized meals will be served at 2, 5, and 10 h after drug dosing. All subjects should abstain from the consumption of fruit juices during the study period.

Subject Selection Criteria Eighteen adult male volunteers will be enrolled. Subjects should understand the procedures and are willing to participate and give their final written consent prior to the commencement of the study procedures.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Faculty of Pharmacy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Subjects should be healthy adult volunteers with age between (18-45 years) with normal body weight. Subjects should understand the procedures and are willing to participate and gave their final written consent prior to the commencement of the study procedures. The volunteers will be asked to provide a complete medical history, and complete a physical examination, laboratory tests [hematology, clinical chemistry, urinalysis, serology (including hepatitis B surface antigen, anti-hepatitis C virus and antihuman immunodeficiency virus antibody).

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. Subjects who have taken any medication less than two weeks of the trials starting date.
3. Susceptibility to allergic reactions to study drugs.
4. Any prior surgery of the gastrointestinal tract that may interfere with drug absorption.
5. Gastrointestinal diseases.
6. Renal diseases.
7. Cardiovascular diseases.
8. Pancreatic disease including diabetes.
9. Hepatic diseases.
10. Hematological disease or pulmonary disease
11. Abnormal laboratory values.
12. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group Ivabradine; six healthy volunteers will administer Ivabradin tablet only once single 10 mg oral dose	Drug: Ivabradine; Ivabradine 10 mg tablet; Other Names: Procorloan
Experimental: Group Bisoprolol; six healthy volunteers will administer bisoprolol tablet only once single oral dose of 5mg	Drug: Bisoprolol; bisoprolo 5 mg tablets; Other Names: Concor
Experimental: Group combination; six healthy volunteers will administer only once a combination of a single dose of ivabradine 10 mg and bisoprolol 5 mg	Drug: combination of Ivabradine and bisoprolol; combination of 10 mg ivabradine and 5 mg bisoprolol; Other Names: concor plus procorolan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters	AUC0→∞	48 hours
Pharmacokinetic parameters	AUC0→t	48 hours
Bioavailability parameters	Cmax	48 hours
Bioavailability parameters	t max	48 hours

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: Sara Shaheen, Ass. Prof, Faculty of pharamacy, Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): March 23, 2018
• Study Completion (Actual): March 23, 2018

Study Registration Dates

• First Submitted: March 24, 2018
• First Submitted That Met QC Criteria: March 30, 2018
• First Posted (Actual): April 2, 2018

Study Record Updates

• Last Update Posted (Actual): April 2, 2018
• Last Update Submitted That Met QC Criteria: March 30, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: bisoprolol; Pharmacokinetic drug interaction; ivabtadine
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Bisoprolol
• Other Study ID Numbers: PHCL36

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No