AzTrials
AzTrials

Healthy SubjectsPhase 1NCT00920088

Drug Interaction Study of Darunavir/Ritonavir and Lopinavir/Ritonavir on GSK2248761 PK and CYP450 Probe Drugs

A Phase 1 study testing darunavir/ritonavir, lopinavir/ritonavir and Midazolam in people with Healthy Subjects and Infection, Human Immunodeficiency Virus, run by GlaxoSmithKline at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the effect of GSK2448761 on CYP450 metabolic probes and to evaluate the 2-way interaction between GSK2448761 and two ritonavir-boosted protease inhibitors that are commonly used in HIV-infected subjects. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
What is being tested?
darunavir/ritonavir, lopinavir/ritonavir and Midazolam
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
Jun 2009to Nov 2009
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 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • Male or female between 18 and 50 years of age inclusive, at the time of signing the informed consent.
  • A female subject is eligible to participate if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant).
  • Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the follow-up visit.
  • Body weight >=50 kg for men and >=45 kg for women and body mass index (BMI) within the range 18.5-31.0 kg/m2 (inclusive).
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Who cannot join

  • As a result of the medical interview, physical examination, or screening investigations, the Investigator considers the subject unfit for the study.
  • The subject has a positive pre-study drug/alcohol screen.
  • Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated restrictions while participating in the study.
  • History of regular alcohol consumption within 6 months of the study.
  • Unwilling to abstain from alcohol for 48 hours prior to the start of dosing until collection of the final pharmacokinetic sample during each treatment period.
  • History or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
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  • History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PCTA) or any clinically significant cardiac disease.
  • History/evidence of clinically significant pulmonary disease.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy should be excluded.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • The subject has received GSK2248761 in a previous clinical trial.
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Has a known intolerance or hypersensitivity to aspirin, NSAIDS, or benzodiazepines, or a known intolerance to the active and/or inactive ingredients in dextromethorphan, midazolam and flurbiprofen (Cohort 1 only)
  • Has any condition or symptom contraindicated for administration of the study drugs: dextromethorphan, midazolam and flurbiprofen. The Investigator should reference the product information of each study drug. (Cohort 1 only)
  • History of sensitivity to heparin or heparin-induced thrombocytopenia (if heparin is used to maintain the patency of an intravenous cannula).
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • A positive test for HIV antibody.
  • AST, ALT, alkaline phosphatase and bilirubin >=1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
  • Lactating females.
  • The subject's systolic blood pressure is outside the range of 90-140mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 50-100bpm for female subjects or 45-100 bpm for male subjects at Screening and Day -1.
  • Cardiac conduction abnormalities denoted on a single 12-lead ECG at screening or Day -1

Trial locations and contacts

1 site in 1 country.

United States1 site

  • GSK Investigational Site

    Baltimore, Maryland, 21225

Other trials in United States

About this study

Official title: A Phase I Study to Evaluate the Effect of Darunavir/Ritonavir and Lopinavir/Ritonavir on GSK2248761 Pharmacokinetics and to Assess the Effect of GSK2248761 on CYP450 Probe Drugs in Healthy Adult Subjects

The purpose of this study is to evaluate the effect of GSK2448761 on CYP450 metabolic probes and to evaluate the 2-way interaction between GSK2448761 and two ritonavir-boosted protease inhibitors that are commonly used in HIV-infected subjects.

Being tested
darunavir/ritonavir, lopinavir/ritonavir, Midazolam, Dextromethorphan, Flurbiprofen
Keywords
probes, NNRTI, drug interaction, protease inhitibor
Medical subject headings
Infections, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • darunavir/ritonavirDrug

    DRV/RTV 600/100mg

  • lopinavir/ritonavirDrug

    LPV/RTV 400/100mg

  • MidazolamDrug

    Midazolam 3mg

  • DextromethorphanDrug

    Dextromethorphan 30mg

  • FlurbiprofenDrug

    Flurbiprofen 50mg

  • GSK2248761Drug

    NNRTI under investigation

Study groups in NCT00920088
Study groupRoleWhat they receive
Cohort 1ExperimentalGSK2248761 with LPV/RTV arm and probes
Receives: Drug: lopinavir/ritonavir; Drug: Midazolam; Drug: Dextromethorphan; Drug: Flurbiprofen; Drug: GSK2248761
Cohort 2ExperimentalGSK2248761 with DRV/RTV
Receives: Drug: darunavir/ritonavir; Drug: GSK2248761

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PK parameters

    Measured: 35 days

Secondary outcomes (4)

  1. 12-lead ECGs

    Measured: 35 days

  2. clinical laboratory assessments

    Measured: 35 days

  3. vital signs

    Measured: 35 days

  4. pharmacokinetic parameters

    Measured: 35 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2009 (estimated)
  2. Study startJun 2009
  3. Primary completionNov 2009
  4. Study completionNov 2009

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00920088
Sponsor's protocol ID
113045
Status last verified
Nov 2010
First submitted
12 Jun 2009
Last updated
3 Nov 2010
Results posted
No
Data monitoring committee
No

Publications

  • Piscitelli S, Kim J, Gould E, Lou Y, White S, de Serres M, Johnson M, Zhou XJ, Pietropaolo K, Mayers D. Drug interaction profile for GSK2248761, a next generation non-nucleoside reverse transcriptase inhibitor. Br J Clin Pharmacol. 2012 Aug;74(2):336-45. doi: 10.1111/j.1365-2125.2012.04194.x.

    PubMed 22288567

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing darunavir/ritonavir, lopinavir/ritonavir and Midazolam in people with Healthy Subjects and Infection, Human Immunodeficiency Virus, run by GlaxoSmithKline 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 6 inclusion and 25 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 3 Nov 2010. 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?

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?

PK parameters (time frame: 35 days). 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 NCT00920088, 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 3 Nov 2010.

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