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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00920088
First received: June 12, 2009
Last updated: November 2, 2010
Last verified: November 2010

June 12, 2009
November 2, 2010
June 2009
November 2009   (final data collection date for primary outcome measure)
PK parameters [ Time Frame: 35 days ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00920088 on ClinicalTrials.gov Archive Site
  • 12-lead ECGs [ Time Frame: 35 days ] [ Designated as safety issue: Yes ]
  • clinical laboratory assessments [ Time Frame: 35 days ] [ Designated as safety issue: Yes ]
  • vital signs [ Time Frame: 35 days ] [ Designated as safety issue: Yes ]
  • pharmacokinetic parameters [ Time Frame: 35 days ] [ Designated as safety issue: No ]
  • 12-lead ECGs [ Time Frame: 35 days ] [ Designated as safety issue: Yes ]
  • clinical laboratory assessments [ Time Frame: 35 days ] [ Designated as safety issue: Yes ]
  • vital signs [ Time Frame: 35 days ] [ Designated as safety issue: Yes ]
  • PK parameters [ Time Frame: 35 days ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Drug Interaction Study of Darunavir/Ritonavir and Lopinavir/Ritonavir on GSK2248761 PK and CYP450 Probe Drugs
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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
  • Healthy Subjects
  • Infection, Human Immunodeficiency Virus
  • Drug: darunavir/ritonavir
    DRV/RTV 600/100mg
  • Drug: lopinavir/ritonavir
    LPV/RTV 400/100mg
  • Drug: Midazolam
    Midazolam 3mg
  • Drug: Dextromethorphan
    Dextromethorphan 30mg
  • Drug: Flurbiprofen
    Flurbiprofen 50mg
  • Drug: GSK2248761
    NNRTI under investigation
  • Experimental: Cohort 1
    GSK2248761 with LPV/RTV arm and probes
    Interventions:
    • Drug: lopinavir/ritonavir
    • Drug: Midazolam
    • Drug: Dextromethorphan
    • Drug: Flurbiprofen
    • Drug: GSK2248761
  • Experimental: Cohort 2
    GSK2248761 with DRV/RTV
    Interventions:
    • Drug: darunavir/ritonavir
    • Drug: GSK2248761
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
November 2009
November 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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
Both
18 Years to 50 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00920088
113045
No
E.D. Derilus; Clinical Disclosure Advisor, GSK Clinical Disclosure
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
November 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP