Drug Interaction PotentiationPhase 1NCT01146483
Drug-drug Interaction Study in Healthy Male Volunteers Following the Administration of Pantoprazole and Rosuvastatin
A Phase 1 study testing Rosuvastatin, Pantoprazole in people with Drug Interaction Potentiation, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
Trial summary
This is a single-center, randomized, 2-period, 2-sequence, cross-over study. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Drug Interaction Potentiation
- What is being tested?
- Rosuvastatin, Pantoprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2010to Dec 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Centre hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, H2W1T7
About this study
This is a single-center, randomized, 2-period, 2-sequence, cross-over study.
Read the 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
- Being tested
- Rosuvastatin, Pantoprazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rosuvastatin, PantoprazoleDrug
Also called Crestor 10 mg, Pantoloc 40 mg
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.
| Study group | Role | What they receive |
|---|---|---|
| Pantoprazole | Active comparator | two-arm study: 2-period, 2-sequence, cross-over study.Volunteers will be administered either sequence 1 or sequence 2 randomly. Receives: Drug: Rosuvastatin, Pantoprazole |
| Placebo | Placebo comparator | Not described Receives: Drug: Rosuvastatin, Pantoprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine changes induced by pantoprazole administration on the pharmacokinetics of rosuvastatin in healthy volunteers.
Rosuvastatin will be administered with and without pantoprazole.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2010 (estimated)
- Study startApr 2010
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug Interaction PotentiationStudies of the same condition, open and under way.
- More trials run by Centre hospitalier de l'Université de Montréal (CHUM)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal
- Responsible party
- Sponsor
- Investigators
- Pavel Hamet, M.D., Ph.D., Principal investigator, Centre hospitalier de l'Université de Montréal (CHUM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01146483
- Sponsor's protocol ID
- CE 09.252
- Status last verified
- Dec 2011
- First submitted
- 25 May 2010
- Last updated
- 15 Dec 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Drug-drug Interaction Study in Healthy Male Volunteers Following the Administration of Pantoprazole and Rosuvastatin
- ClinicalTrials.gov ID
- NCT01146483
- Acronym / sponsor ID
- CE 09.252
- Conditions
- Drug Interaction Potentiation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)University, hospital or other
- Collaborators
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal
- Study start
- Apr 2010
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 17 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pantoprazole | Active comparator | Drug: Rosuvastatin, Pantoprazoletwo-arm study: 2-period, 2-sequence, cross-over study.Volunteers will be administered either sequence 1 or sequence 2 randomly. |
| Placebo | Placebo comparator | Drug: Rosuvastatin, Pantoprazole |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rosuvastatin, PantoprazoleAlso: Crestor 10 mg, Pantoloc 40 mgRosuvastatin, 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. | Drug | Pantoprazole, Placebo |
Primary outcome
To determine changes induced by pantoprazole administration on the pharmacokinetics of rosuvastatin in healthy volunteers.
Time frame: 2 weeks
Rosuvastatin will be administered with and without pantoprazole.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2011.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pavel Hamet, M.D., Ph.D. principal investigator
Centre hospitalier de l'Université de Montréal (CHUM)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Rosuvastatin, Pantoprazole in people with Drug Interaction Potentiation, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine changes induced by pantoprazole administration on the pharmacokinetics of rosuvastatin in healthy volunteers. (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2011.