HyperlipidemiaPhase 1NCT01695954
Pharmacokinetic Study of Pitavastatin and Ritonavir-Boosted Darunavir or Efavirenz
A Phase 1 study testing Pitavastatin, Darunavir and Ritonavir in people with Hyperlipidemia and HIV, run by NYU Langone Health at 1 site in United States.
Trial summary
The main goal of this study is to determine how taking efavirenz affects the levels of pitavastatin in the bloodstream when both drugs are taken together and to see how darunavir with ritonavir affects the levels of pitavastatin in the bloodstream. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperlipidemia, HIV
- What is being tested?
- Pitavastatin, Darunavir and Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- May 2012to Jan 2013
- Phase
- Phase 1
- 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
- Absence of HIV-1 infection as documented by any licensed ELISA test kit within 21 days prior to study entry.
- Male or female aged 18-60 years.
- Able and willing to provide informed consent.
- All men and women of reproductive potential must practice adequate birth control to prevent pregnancy from start of the study until completion of the study.
- Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to study entry and day of entry.
- Hemoglobin > 12.5 g/dL for men; > 11.5 g/dL for women;
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- Absolute neutrophil count >1,500 cells/mm3;
- Platelet count > 100,000 platelets/mm3;
- AST (SGOT)/ALT (SGPT) <1.5X ULN;
- Creatinine <1.5 X ULN
- Subject is within 20% (+/-) of ideal body weight and must weigh at least 50 kg
Who cannot join
- Use of illicit drugs or alcohol which would interfere with the completion of this study.
- Pregnancy or breast-feeding.
- History of chronic illnesses such as hypertension, coronary artery disease, arthritis, diabetes, or any chronic gastrointestinal conditions which might interfere with drug absorption.
- Any medical condition which, in the opinion of the investigator, would interfere with the subjects ability to participate in this protocol.
- Use of prohibited protocol-specified drugs, prescription or over-the-counter within 14 days prior to study entry.
- Participation in any investigational drug studies within 30 days prior to study entry.
Trial locations and contacts
1 site in 1 country.
United States1 site
Bellevue/NYU AIDS Clinical Trials Unit
New York, New York, 10016
About this study
Official title: The Effect of Efavirenz and Ritonavir-boosted Darunavir on the Pharmacokinetics of the HMG CoA Reductase Inhibitor Pitavastatin
The main goal of this study is to determine how taking efavirenz affects the levels of pitavastatin in the bloodstream when both drugs are taken together and to see how darunavir with ritonavir affects the levels of pitavastatin in the bloodstream. Secondary goals are to see how taking pitavastatin affects the levels in the blood of efavirenz when both drugs are taken together and to see how taking pitavastatin affects the levels in the blood of darunavir.
Read the detailed description
HIV infected persons are at risk for coronary heart disease due to chronic inflammation associated with the virus itself, the side effects of the antiretroviral (ARV) therapies which can cause elevated cholesterol, and the risk factors such as smoking, high blood pressure and family history of heart disease.
The most commonly prescribed ARVs for treatment of HIV are efavirenz and drugs in the protease inhibitor (PI) class such as darunavir with ritonavir. To treat elevated cholesterol in patients infected with HIV, guidelines recommend the use of statins (a class of lipid lowering drugs). PIs and efavirenz can increase the levels of some statins and reduce the levels of others in the bloodstream. Pitavastatin (Livalo) is a statin approved by the Food and Drug Administration (FDA) for the treatment of high cholesterol.
In order to be able to use pitavastatin safely in HIV-infected patients taking either darunavir with ritonavir or efavirenz, it is important to study how taking pitavastatin with darunavir and ritonavir or pitavastatin with efavirenz affect the levels of each of these drugs in the bloodstream.
Twenty-eight participants will be enrolled in one of two study arms: 14 in Arm A and 14 in Arm B.
Arm A:
Participants will start taking pitavastatin 2 mg tablets every night at bedtime. On day 4 participants will come in for a 14-hour pharmacokinetic (PK) overnight visit and will have about 9 tablespoons of blood drawn. Participants will return 12 hours after the last blood draw for a final blood draw. They will then stop taking pitavastatin. Participants will then start taking one efavirenz 600 mg tablet at bedtime.
On day 14, participants will come in for a second 14-hour visit and will have about 9 tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final blood draw. Participants will then start taking both pitavastatin and efavirenz at bedtime.
On day 18, participants will come in for a third 14-hour PK visit and will have about 9 tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final blood draw. They will then stop taking all study drugs and will either come in or receive a final phone call on day 25.
Arm B:
Participants will start taking one pitavastatin 2 mg tablet every morning. On day 4 participants will come in for a 14-hour pharmacokinetic (PK) daytime visit and will have about 9 tablespoons of blood drawn. Participants will return 12 hours after the last blood draw for a final blood draw. They will then stop taking pitavastatin. Participants will then start taking darunavir 400 mg tablets (2) and ritonavir 100 mg tablets (1) every morning.
On day 14, participants will come in for a second 14-hour visit and will have about 9 tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final blood draw. Participants will then start taking one pitavastatin 2mg tablet, two darunavir 400 mg tablets and one ritonavir 100 mg tablet.
On day 18, participants will come in for a third 14-hour PK visit and will have about 9 tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final blood draw. They will then stop taking all study drugs and will either come in or receive a final phone call on day 25.
- Conditions
- Hyperlipidemia, HIV
- Being tested
- Pitavastatin, Darunavir, Ritonavir, Efavirenz
- Keywords
- HIV, Hyperlipidemia, Pharmacokinetics, Statins, Darunavir, Efavirenz, Pitavastatin
- Medical subject headings
- Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PitavastatinDrug
Also called Livalo
Pitavastatin 2 mg tablets taken at bedtime in Arm A and in the morning in Arm B.
DarunavirDrug
Also called Prezista
Darunavir 400 mg tablets x 2 taken daily in Arm B
RitonavirDrug
Also called Norvir
Ritonavir 100 mg tablets taken daily in Arm B
EfavirenzDrug
Also called Sustiva
Efavirenz 600 mg tablets taken at bedtime in Arm A
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime. Receives: Drug: Pitavastatin; Drug: Efavirenz |
| Arm B | Experimental | Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily. Receives: Drug: Pitavastatin; Drug: Darunavir; Drug: Ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC
24-hour area under the curve (AUC) for pitavastatin when coadministered with efavirenz and with darunavir/ritonavir and 24-hour AUC for efavirenz or darunavir when coadministered with pitavastatin
Measured: 0 to 24 hours
GMR of 24- Hour AUC of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir Over 24 Hour AUC of Pitavastatin
Geometric Mean Ratio (GMR) of 24- Hour Area under the plasma drug concentration-time curve (AUC) of pitavastatin when coadministered with efavirenz or with darunavir/ritonavir over 24 Hour (AUC) of pitavastatin
Measured: 0 to 24 hours
Secondary outcomes (1)
GMR of Cmax of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir
Geometric Mean Ratio (GMR) of Cmax for pitavastatin with Efavirenz vs. alone and GMR of Cmax for pitavastatin with darunavir/ritonavir vs. alone was reported.
Measured: Day 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2012 (estimated)
- Study startMay 2012
- Primary completionJan 2013
- Study completionJan 2013
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HyperlipidemiaStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- New York City Health and Hospitals Corporation, Kowa Pharmaceuticals America, Inc., University at Buffalo
- Responsible party
- Sponsor
- Investigators
- Judith Aberg, M.D., Principal investigator, NYU School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01695954
- Sponsor's protocol ID
- 11-01787
- Status last verified
- Jul 2020
- First submitted
- 26 Sep 2012
- Last updated
- 11 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Malvestutto CD, Ma Q, Morse GD, Underberg JA, Aberg JA. Lack of pharmacokinetic interactions between pitavastatin and efavirenz or darunavir/ritonavir. J Acquir Immune Defic Syndr. 2014 Dec 1;67(4):390-6. doi: 10.1097/QAI.0000000000000333.
PubMed 25202920
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Efavirenz and Ritonavir-boosted Darunavir on the Pharmacokinetics of the HMG CoA Reductase Inhibitor Pitavastatin
- ClinicalTrials.gov ID
- NCT01695954
- Acronym / sponsor ID
- 11-01787
- Conditions
- Hyperlipidemia, HIV
- Keywords
- HIV, Hyperlipidemia, Pharmacokinetics, Statins, Darunavir, Efavirenz, Pitavastatin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- New York City Health and Hospitals Corporation, Kowa Pharmaceuticals America, Inc., University at Buffalo
- Study start
- May 2012
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 28 Sep 2012 (estimated)
- Results
- Posted 11 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main goal of this study is to determine how taking efavirenz affects the levels of pitavastatin in the bloodstream when both drugs are taken together and to see how darunavir with ritonavir affects the levels of pitavastatin in the bloodstream. Secondary goals are to see how taking pitavastatin affects the levels in the blood of efavirenz when both drugs are taken together and to see how taking pitavastatin affects the levels in the blood of darunavir.
Detailed description
HIV infected persons are at risk for coronary heart disease due to chronic inflammation associated with the virus itself, the side effects of the antiretroviral (ARV) therapies which can cause elevated cholesterol, and the risk factors such as smoking, high blood pressure and family history of heart disease.
The most commonly prescribed ARVs for treatment of HIV are efavirenz and drugs in the protease inhibitor (PI) class such as darunavir with ritonavir. To treat elevated cholesterol in patients infected with HIV, guidelines recommend the use of statins (a class of lipid lowering drugs). PIs and efavirenz can increase the levels of some statins and reduce the levels of others in the bloodstream. Pitavastatin (Livalo) is a statin approved by the Food and Drug Administration (FDA) for the treatment of high cholesterol.
In order to be able to use pitavastatin safely in HIV-infected patients taking either darunavir with ritonavir or efavirenz, it is important to study how taking pitavastatin with darunavir and ritonavir or pitavastatin with efavirenz affect the levels of each of these drugs in the bloodstream.
Twenty-eight participants will be enrolled in one of two study arms: 14 in Arm A and 14 in Arm B.
Arm A:
Participants will start taking pitavastatin 2 mg tablets every night at bedtime. On day 4 participants will come in for a 14-hour pharmacokinetic (PK) overnight visit and will have about 9 tablespoons of blood drawn. Participants will return 12 hours after the last blood draw for a final blood draw. They will then stop taking pitavastatin. Participants will then start taking one efavirenz 600 mg tablet at bedtime.
On day 14, participants will come in for a second 14-hour visit and will have about 9 tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final blood draw. Participants will then start taking both pitavastatin and efavirenz at bedtime.
On day 18, participants will come in for a third 14-hour PK visit and will have about 9 tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final blood draw. They will then stop taking all study drugs and will either come in or receive a final phone call on day 25.
Arm B:
Participants will start taking one pitavastatin 2 mg tablet every morning. On day 4 participants will come in for a 14-hour pharmacokinetic (PK) daytime visit and will have about 9 tablespoons of blood drawn. Participants will return 12 hours after the last blood draw for a final blood draw. They will then stop taking pitavastatin. Participants will then start taking darunavir 400 mg tablets (2) and ritonavir 100 mg tablets (1) every morning.
On day 14, participants will come in for a second 14-hour visit and will have about 9 tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final blood draw. Participants will then start taking one pitavastatin 2mg tablet, two darunavir 400 mg tablets and one ritonavir 100 mg tablet.
On day 18, participants will come in for a third 14-hour PK visit and will have about 9 tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final blood draw. They will then stop taking all study drugs and will either come in or receive a final phone call on day 25.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Pitavastatin, Drug: EfavirenzSubjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime. |
| Arm B | Experimental | Drug: Pitavastatin, Drug: Darunavir, Drug: RitonavirSubjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Absence of HIV-1 infection as documented by any licensed ELISA test kit within 21 days prior to study entry.
- Male or female aged 18-60 years.
- Able and willing to provide informed consent.
- All men and women of reproductive potential must practice adequate birth control to prevent pregnancy from start of the study until completion of the study.
- Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to study entry and day of entry.
Key exclusion criteria (6 listed)
- Use of illicit drugs or alcohol which would interfere with the completion of this study.
- Pregnancy or breast-feeding.
- History of chronic illnesses such as hypertension, coronary artery disease, arthritis, diabetes, or any chronic gastrointestinal conditions which might interfere with drug absorption.
- Any medical condition which, in the opinion of the investigator, would interfere with the subjects ability to participate in this protocol.
- Use of prohibited protocol-specified drugs, prescription or over-the-counter within 14 days prior to study entry.
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 |
|---|---|---|
| PitavastatinAlso: LivaloPitavastatin 2 mg tablets taken at bedtime in Arm A and in the morning in Arm B. | Drug | Arm A, Arm B |
| DarunavirAlso: PrezistaDarunavir 400 mg tablets x 2 taken daily in Arm B | Drug | Arm B |
| RitonavirAlso: NorvirRitonavir 100 mg tablets taken daily in Arm B | Drug | Arm B |
| EfavirenzAlso: SustivaEfavirenz 600 mg tablets taken at bedtime in Arm A | Drug | Arm A |
Primary outcome
AUC
Time frame: 0 to 24 hours
24-hour area under the curve (AUC) for pitavastatin when coadministered with efavirenz and with darunavir/ritonavir and 24-hour AUC for efavirenz or darunavir when coadministered with pitavastatin
GMR of 24- Hour AUC of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir Over 24 Hour AUC of Pitavastatin
Time frame: 0 to 24 hours
Geometric Mean Ratio (GMR) of 24- Hour Area under the plasma drug concentration-time curve (AUC) of pitavastatin when coadministered with efavirenz or with darunavir/ritonavir over 24 Hour (AUC) of pitavastatin
1 secondary outcome
GMR of Cmax of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir
Time frame: Day 18
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25202920Malvestutto CD, Ma Q, Morse GD, Underberg JA, Aberg JA. Lack of pharmacokinetic interactions between pitavastatin and efavirenz or darunavir/ritonavir. J Acquir Immune Defic Syndr. 2014 Dec 1;67(4):390-6. doi: 10.1097/QAI.0000000000000333.
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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.
Judith Aberg, M.D. principal investigator
NYU School of Medicine
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 Pitavastatin, Darunavir and Ritonavir in people with Hyperlipidemia and HIV, run by NYU Langone Health 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 11 inclusion and 6 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 11 Aug 2020. 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 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?
Yes. Results are posted in the registry (first posted 11 Aug 2020). 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?
AUC (time frame: 0 to 24 hours). 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?
On the ClinicalTrials.gov record for NCT01695954, which also lists 1 linked publication.
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 11 Aug 2020.