Clinical trial NCT03485482: Pharmacokinetic Drug-Drug Interaction Between Bisoprolol and Ivabradine in Healthy Volunteers
Official title: Pharmacokinetic Drug-Drug Interaction Between Bisoprolol and Ivabradine in Healthy Volunteers: An Open-Label, Randomized, Crossover Clinical Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiovascular Diseases
Keywords: Pharmacokinetic drug interaction
ivabtadine
bisoprolol
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2018-04-02
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: open label, randomized, single-dose, three-period, crossover design
Primary purpose: OTHER

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic parameters
timeFrame: 48 hours
measure: Pharmacokinetic parameters
timeFrame: 48 hours
measure: Bioavailability parameters
timeFrame: 48 hours
measure: Bioavailability parameters
timeFrame: 48 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Faculty of Pharmacy
Study officials:
affiliation: Faculty of pharamacy, Ain Shams University
name: Sara Shaheen, Ass. Prof
role: PRINCIPAL_INVESTIGATOR
References: