Drug-drug Interaction Study in Healthy Male Volunteers Following the Administration of Pantoprazole and Rosuvastatin

NCT ID: NCT01146483

Last Updated: 2011-12-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2011-12-31

Brief Summary

This is a single-center, randomized, 2-period, 2-sequence, cross-over study.

Detailed Description

Background:

Notions used to describe drug disposition are being reviewed as the roles of drug membrane transporters are being discovered. In the near past, simple biophysical principles - lipophilicity and passive diffusion - were used to explain drug absorption, distribution and elimination. Today, with more than 367 genes known in humans, membrane transporters occupy a much central role.

Rational:

Drug influx/efflux transporters are expressed in various organs with variable activities and their presence increases (influx) or decreases (efflux) the intracellular concentration of a drug in a specific organ. Therefore, intersubject variability in the activity of these transporters due to genetic polymorphisms or concomitant drug treatments can explain intersubject variability in drug actions.

Rosuvastatin is an HMG-CoA reductase inhibitor and a substrate of OATPs and BCRP. There is not much information on the transporter-mediated disposition of rosuvastatin. Literature suggests that rosuvastatin is a transporter substrate of the influx OATP1B1, 1B3 and 2B1 as well as the efflux BCRP. The efflux of rosuvastatin by BCRP would be of major importance in the hepatocytes. BCRP would be responsible of the excretion of 30% of the unchanged drug in the bile. To confirm this hypothesis and identify patients at risk of toxicity with rosuvastatin, we want to perform a drug-drug interactions study with an inhibitor of BCRP namely, pantoprazole. With this approach, we will confirm if rosuvastatin is a real substrate of BCRP as suggested in the literature.

Methodology:

To determine changes induced by the administration of pantoprazole on the pharmacokinetics of rosuvastatin in healthy volunteers 16 healthy volunteers will be administered a single dose of rosuvastatin with and without (placebo) pantoprazole.

Urine and plasma analysis will be performed by LC-MSMS. Pharmacokinetics analysis will be performed. Plasma and urine concentrations of rosuvastatin will be analysed using a noncompartmental method. Pharmacokinetic parameters calculated in this study will be Cmax, Tmax, AUC0-72, AUC0-∞, Kel, T1/2β, CL/F, CLr, and Ae.

Conditions

Drug Interaction Potentiation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Pantoprazole

two-arm study: 2-period, 2-sequence, cross-over study.Volunteers will be administered either sequence 1 or sequence 2 randomly.

Group Type: ACTIVE_COMPARATOR

Rosuvastatin, Pantoprazole

Intervention Type: DRUG

Rosuvastatin, 10 mg tablets, single dose on the morning

Concomitant drug: Pantoprazole; 40 mg tablets, 2 single doses administered 1 hour before rosuvastatin and 23 hours after rosuvastatin administration. A placebo is given on the other period as a crossover design study.

Placebo

Group Type: PLACEBO_COMPARATOR

Rosuvastatin, Pantoprazole

Intervention Type: DRUG

Rosuvastatin, 10 mg tablets, single dose on the morning

Concomitant drug: Pantoprazole; 40 mg tablets, 2 single doses administered 1 hour before rosuvastatin and 23 hours after rosuvastatin administration. A placebo is given on the other period as a crossover design study.

Interventions

Rosuvastatin, Pantoprazole

Rosuvastatin, 10 mg tablets, single dose on the morning

Concomitant drug: Pantoprazole; 40 mg tablets, 2 single doses administered 1 hour before rosuvastatin and 23 hours after rosuvastatin administration. A placebo is given on the other period as a crossover design study.

Intervention Type: DRUG

Other Intervention Names

Crestor 10 mg; Pantoloc 40 mg

Eligibility Criteria

Inclusion Criteria

• Vital Signs, EKG and Clinical Laboratory Values within the normal range
• Body mass index (BMI) [20-29kg/m2]
• Caucasian male
• Age between [18-55]
• Healthy by physical exam
• Non or ex-smoker

Exclusion Criteria

• Presence or history of intolerance or hypersensibility to proton pump inhibitors or HMG-CoA reductase inhibitors.
• Significant illness. History of cardiovascular, kidney, liver or gastrointestinal disease. Presence of cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic disease.
• consumption of an investigational product or donation of blood in the previous 28 days preceding the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Centre de Recherche du Centre Hospitalier de l'Université de Montréal

OTHER

Sponsor Role: collaborator

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pavel Hamet, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Centre hospitalier de l'Université de Montréal (CHUM)

Locations

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

CE 09.252

Identifier Type: -

Identifier Source: org_study_id