HIV InfectionsPhase 4NCT00630734
Genetic Predictors of Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin
A Phase 4 study testing Pravastatin, Darunavir and Ritonavir in people with HIV Infections and Hyperlipidemia, run by University of Colorado, Denver at 1 site in United States.
Trial summary
Pravastatin (Pravachol) is approved by the Food and Drug Administration (FDA) and is used to treat high cholesterol. Darunavir (Prezista) and ritonavir (Norvir) are approved by the Food and Drug Administration (FDA) to treat HIV infection. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infections, Hyperlipidemia
- What is being tested?
- Pravastatin, Darunavir and Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to Sep 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy, HIV-negative volunteers
Who cannot join
- Currently active or chronic cardiovascular, hepatic, renal, pancreatic, gastrointestinal, neurologic, hematologic, psychiatric, metabolic, respiratory, inflammatory, or infectious disease
- Chronic pancreatitis
- History of rhabdomyolysis
- History of statin-associated myopathy
- Active malignancy
- History of significant skin disease, food allergy, drug allergy, dermatitis, eczema, psoriasis
Show all 17Show fewer
- Pregnancy/breastfeeding
- HIV positive and/or AIDS
- serum creatinine grade 1 or greater (≥ 1.1 x upper limit of laboratory normal range [ULN]);
- hemoglobin grade 1 or greater (≤ 10.9 g/dL);
- platelet count grade 1 or greater (≤ 124.999 x 109/L);
- absolute neutrophil count grade 1 or greater (≤ 1.3 x 109/L);
- aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater (≥ 1.25 x ULN);
- total bilirubin grade 1 or greater (≥ 1.1 x ULN)
- serum lipase grade 1 or greater (≥ 1.1 x ULN)
- serum amylase grade 1 or greater (≥ 1.1 x ULN)
- any other laboratory abnormality of grade 2 or above
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: Genetic Predictors of Pharmacokinetic Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin: the Role of SLCO1B1 Polymorphisms.
Pravastatin (Pravachol) is approved by the Food and Drug Administration (FDA) and is used to treat high cholesterol. Darunavir (Prezista) and ritonavir (Norvir) are approved by the Food and Drug Administration (FDA) to treat HIV infection. When darunavir and ritonavir are given with pravastatin, they can increase the blood levels of pravastatin. The degree of this interaction varies from person to person. The way that darunavir and ritonavir interact with pravastatin may be affected by a person's genetic make-up. Genetic factors (or DNA) are those that people are born with and that make each person unique. Genetic differences are the reason why one person's body traits such as height and hair color are different from another person's body traits. Genetic differences can also affect the way a medication works in the body or the way two medications interact in the body. The purpose of this clinical study is to determine if a person's genetic make-up affects the way darunavir and ritonavir interact with pravastatin in the body.
- Conditions
- HIV Infections, Hyperlipidemia
- Being tested
- Pravastatin, Darunavir, Ritonavir, Washout
- Keywords
- HIV, Pravastatin, Darunavir, Ritonavir, Genetic
- Medical subject headings
- HIV Infections, Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PravastatinDrug
Also called Pravachol
Pravastatin 40 mg by mouth daily on days 1-4
DarunavirDrug
Also called Prezista
Darunavir 600mg by mouth twice daily on days 12-18
RitonavirDrug
Also called Norvir
Ritonavir 100mg by mouth twice daily on days 12-18
PravastatinDrug
Also called Pravachol
Pravastatin 40 mg by mouth daily on days 15-18
WashoutOther
Washout (no medication) on days 5-11.
| Study group | Role | What they receive |
|---|---|---|
| SLCO1B1 Group 1 | Experimental | Participants with the SLCO1B1 *1A/*1A diplotype; Interventions: pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18. Receives: Drug: Pravastatin; Drug: Darunavir; Drug: Ritonavir; Other: Washout |
| SLCO1B1 Group 2 | Experimental | Participants with the SLCO1B1 *1A/*1B or *1B/*1B diplotype; Interventions: Pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18. Receives: Drug: Pravastatin; Drug: Darunavir; Drug: Ritonavir; Other: Washout |
| SLCO1B1 Group 3 | Experimental | Participants who carry at least one SLCO1B1 *5, *15, or *17 diplotype; Interventions: Pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18. Receives: Drug: Pravastatin; Drug: Darunavir; Drug: Ritonavir; Other: Washout |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
AUC of pravastatin when administered with darunavir/ritonavir divided by AUC of pravastatin when administered alone. The AUC was measured over a 24-hour dosing interval.
Measured: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Relative Change in Pravastatin Maximum Plasma Concentration (Cmax)
Cmax of pravastatin when administered with darunavir/ritonavir divided by the Cmax of pravastatin when administered alone.
Measured: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Secondary outcomes (4)
Pravastatin Alone: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Dosing interval of 24 hours
Measured: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Pravastatin Alone: Pravastatin Maximum Plasma Concentration (Cmax)
Measured: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Pravastatin + Darunavir/Ritonavir: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Dosing interval of 24 hours
Measured: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Pravastatin + Darunavir/Ritonavir: Pravastatin Maximum Plasma Concentration (Cmax)
Measured: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2008 (estimated)
- Study startFeb 2008
- Primary completionOct 2009
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
- Responsible party
- Sponsor
- Investigators
- Christina L Aquilante, PharmD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00630734
- Sponsor's protocol ID
- 07-0272
- Other IDs
- TMC114HIV4003
- Status last verified
- May 2014
- First submitted
- 28 Feb 2008
- Last updated
- 22 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Predictors of Pharmacokinetic Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin: the Role of SLCO1B1 Polymorphisms.
- ClinicalTrials.gov ID
- NCT00630734
- Acronym / sponsor ID
- 07-0272
- Conditions
- HIV Infections, Hyperlipidemia
- Keywords
- HIV, Pravastatin, Darunavir, Ritonavir, Genetic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
- Study start
- Feb 2008
- Primary completion
- Oct 2009 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 7 Mar 2008 (estimated)
- Results
- Posted 15 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pravastatin (Pravachol) is approved by the Food and Drug Administration (FDA) and is used to treat high cholesterol. Darunavir (Prezista) and ritonavir (Norvir) are approved by the Food and Drug Administration (FDA) to treat HIV infection. When darunavir and ritonavir are given with pravastatin, they can increase the blood levels of pravastatin. The degree of this interaction varies from person to person. The way that darunavir and ritonavir interact with pravastatin may be affected by a person's genetic make-up. Genetic factors (or DNA) are those that people are born with and that make each person unique. Genetic differences are the reason why one person's body traits such as height and hair color are different from another person's body traits. Genetic differences can also affect the way a medication works in the body or the way two medications interact in the body. The purpose of this clinical study is to determine if a person's genetic make-up affects the way darunavir and ritonavir interact with pravastatin in the body.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SLCO1B1 Group 1 | Experimental | Drug: Pravastatin, Drug: Darunavir, Drug: Ritonavir, Other: WashoutParticipants with the SLCO1B1 *1A/*1A diplotype; Interventions: pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18. |
| SLCO1B1 Group 2 | Experimental | Drug: Pravastatin, Drug: Darunavir, Drug: Ritonavir, Other: WashoutParticipants with the SLCO1B1 *1A/*1B or *1B/*1B diplotype; Interventions: Pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18. |
| SLCO1B1 Group 3 | Experimental | Drug: Pravastatin, Drug: Darunavir, Drug: Ritonavir, Other: WashoutParticipants who carry at least one SLCO1B1 *5, *15, or *17 diplotype; Interventions: Pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy, HIV-negative volunteers
Key exclusion criteria (17 listed)
- Currently active or chronic cardiovascular, hepatic, renal, pancreatic, gastrointestinal, neurologic, hematologic, psychiatric, metabolic, respiratory, inflammatory, or infectious disease
- Chronic pancreatitis
- History of rhabdomyolysis
- History of statin-associated myopathy
- Active malignancy
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 |
|---|---|---|
| PravastatinAlso: PravacholPravastatin 40 mg by mouth daily on days 1-4 | Drug | SLCO1B1 Group 1, SLCO1B1 Group 2, SLCO1B1 Group 3 |
| DarunavirAlso: PrezistaDarunavir 600mg by mouth twice daily on days 12-18 | Drug | SLCO1B1 Group 1, SLCO1B1 Group 2, SLCO1B1 Group 3 |
| RitonavirAlso: NorvirRitonavir 100mg by mouth twice daily on days 12-18 | Drug | SLCO1B1 Group 1, SLCO1B1 Group 2, SLCO1B1 Group 3 |
| PravastatinAlso: PravacholPravastatin 40 mg by mouth daily on days 15-18 | Drug | SLCO1B1 Group 1, SLCO1B1 Group 2, SLCO1B1 Group 3 |
| WashoutWashout (no medication) on days 5-11. | Other | SLCO1B1 Group 1, SLCO1B1 Group 2, SLCO1B1 Group 3 |
Primary outcome
Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
AUC of pravastatin when administered with darunavir/ritonavir divided by AUC of pravastatin when administered alone. The AUC was measured over a 24-hour dosing interval.
Relative Change in Pravastatin Maximum Plasma Concentration (Cmax)
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Cmax of pravastatin when administered with darunavir/ritonavir divided by the Cmax of pravastatin when administered alone.
4 secondary outcomes
Pravastatin Alone: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Pravastatin Alone: Pravastatin Maximum Plasma Concentration (Cmax)
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Pravastatin + Darunavir/Ritonavir: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Pravastatin + Darunavir/Ritonavir: Pravastatin Maximum Plasma Concentration (Cmax)
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Christina L Aquilante, PharmD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pravastatin, Darunavir and Ritonavir in people with HIV Infections and Hyperlipidemia, run by University of Colorado, Denver at 1 site in United States.
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 1 inclusion and 17 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 22 May 2014. 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 United States. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval (time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose). The study lists 2 primary outcomes in all. 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 22 May 2014.