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

NCT00920088 | Completed Phase 1

• 1 other identifier: 113045
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Subjects; Infection, Human Immunodeficiency Virus

Keywords

probes; NNRTI; drug interaction; protease inhitibor

Outcome Measures

Primary Outcomes (1)

• PK parameters

  35 days

Secondary Outcomes (4)

• 12-lead ECGs

  35 days

• clinical laboratory assessments

  35 days

• vital signs

  35 days

• pharmacokinetic parameters

  35 days

Study Arms (2)

Cohort 1

EXPERIMENTAL

GSK2248761 with LPV/RTV arm and probes

Drug: lopinavir/ritonavir; Drug: Midazolam; Drug: Dextromethorphan; Drug: Flurbiprofen; Drug: GSK2248761

Cohort 2

EXPERIMENTAL

GSK2248761 with DRV/RTV

Drug: darunavir/ritonavir; Drug: GSK2248761

Interventions

darunavir/ritonavir DRUG

DRV/RTV 600/100mg

Cohort 2

lopinavir/ritonavir DRUG

LPV/RTV 400/100mg

Cohort 1

Midazolam DRUG

Midazolam 3mg

Cohort 1

Dextromethorphan DRUG

Dextromethorphan 30mg

Cohort 1

Flurbiprofen DRUG

Flurbiprofen 50mg

Cohort 1

GSK2248761 DRUG

NNRTI under investigation

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

Related Publications (1)

• 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.

  PMID: 22288567 DERIVED

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

Interventions

Darunavir; Ritonavir; Lopinavir; Midazolam; Dextromethorphan; Flurbiprofen; IDX 899

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Pyrimidinones; Pyrimidines; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Propionates; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 12, 2009
• First Posted: June 15, 2009
• Study Start: June 1, 2009
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: November 3, 2010

Record last verified: 2010-11

Locations

US (1)