Study to Compare the Safety and Anti-HIV Effect of GSK1265744 Versus Placebo in HIV-1 Infected Adults (ITZ112929)

This study has been completed.
Sponsor:
Collaborator:
Shionogi
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00920426
First received: June 12, 2009
Last updated: March 10, 2011
Last verified: March 2011

June 12, 2009
March 10, 2011
June 2009
August 2009   (final data collection date for primary outcome measure)
  • Change from plasma HIV-1 ribonucleic acid (RNA) to Day 1 [ Time Frame: Day 1 to Day 11 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following dose administration on Day 1 and 10: AUC(0-24) [ Time Frame: Day 1 and Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following last repeat administration on Day 10:AUC(0-tau) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
  • Safety and tolerability: adverse events (AEs) [ Time Frame: Day 1 to Day 25 ] [ Designated as safety issue: No ]
  • Safety and tolerability: clinical laboratory results [ Time Frame: Day 1 to Day 25 ] [ Designated as safety issue: No ]
  • Safety and tolerability: vital signs [ Time Frame: Day 1 to Day 25 ] [ Designated as safety issue: No ]
  • Safety and tolerability: electrocardiogram (ECG) assessments [ Time Frame: Day 1 to Day 25 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following dose administration on Day 1 and 10: Cmax, [ Time Frame: Day 1 and Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following dose administration on Day 1 and 10: tmax [ Time Frame: Day 1 and Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following dose administration on Day 1 and 10: concentration at 24 hrs post dose(C24) [ Time Frame: Day 1 and Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following dose administration on Day 1 and 10: terminal half-life(t1/2) [ Time Frame: Day 1 and Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following dose administration on Day 1 and 10: absorption lag time(tlag) [ Time Frame: Day 1 and Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following last repeat administration on Day 10: predose concentration(C0) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following last repeat administration on Day 10: concentration at end of dosing interval(Ctau) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following last repeat administration on Day 10: minimum observed concentration during one dosing interval(Cmin) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following last repeat administration on Day 10: Cmax [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following last repeat administration on Day 10: tmax [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following last repeat administration on Day 10: t1/2 [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following last repeat administration on Day 10: Apparent clearance following oral dosing (CL/F) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
  • Change in plasma HIV-1 ribonucleic acid (RNA). [ Time Frame: From baseline to Day 11. ] [ Designated as safety issue: No ]
  • GSK1265744 PK parameters following dose administration. [ Time Frame: On Day 1 and 10. ] [ Designated as safety issue: No ]
  • Safety and tolerability parameters, including adverse events (AEs), clinical laboratory results, vital signs, and electrocardiogram (ECG) assessments. [ Time Frame: From Day 1 through 11. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00920426 on ClinicalTrials.gov Archive Site
  • Change from baseline in plasma HIV-1 RNA [ Time Frame: Day 1 to Day 25 ] [ Designated as safety issue: No ]
  • Change from baseline in plasma HIV-1 RNA to nadir (maximum change) over 11 days [ Time Frame: Day 1 to Day 11 ] [ Designated as safety issue: No ]
  • Plasma HIV-1 RNA rate of decline (slope) [ Time Frame: Day 1 to Day 11 ] [ Designated as safety issue: No ]
  • Proportion of subjects with HIV-1 RNA<400 copies/mL [ Time Frame: Day 1 to Day 25 ] [ Designated as safety issue: No ]
  • Proportion of subjects with HIV-1 RNA<50 copies/mL [ Time Frame: Day 1 to Day 25 ] [ Designated as safety issue: No ]
  • Change from baseline in CD4+ cell count to Day 11 [ Time Frame: Day 1 to Day 11 ] [ Designated as safety issue: No ]
  • Emergence of drug resistance mutations, if appropriate [ Time Frame: Day 1 to Day 25 ] [ Designated as safety issue: No ]
  • GSK1265744 Day 10 AUC(0-tau) compared to Day 1 AUC(0-24) to estimate accumulation ratios (R) for AUC [ Time Frame: Day 1 and Day 10 ] [ Designated as safety issue: No ]
  • Pre-morning dose concentrations (C0) on Day 2 through 10 to assess the achievement of steady state of GSK1265744 following repeat administration [ Time Frame: Day 2 to day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 Day 10 Cmax compared to Day 1 Cmax to estimate accumulation ratios (R) for Cmax [ Time Frame: Day 1 and Day 10 ] [ Designated as safety issue: No ]
  • GSK1265744 Day 10 Ctau compared to Day 1 C24 to estimate accumulation ratios (R) for Ctau [ Time Frame: Day 1 and Day 10 ] [ Designated as safety issue: No ]
  • Change from baseline in plasma HIV-1 RNA [ Time Frame: Baseline to Study Completion ] [ Designated as safety issue: No ]
  • Change from baseline in plasma HIV-1 RNA to nadir (maximum change) [ Time Frame: Baseline to Day 11 ] [ Designated as safety issue: No ]
  • Plasma HIV-1 RNA rate of decline (slope) [ Time Frame: Baseline to Day 11 ] [ Designated as safety issue: No ]
  • Proportion of subjects with HIV-1 RNA<400 copies/mL [ Time Frame: Baseline to Study Completion ] [ Designated as safety issue: No ]
  • Proportion of subjects with HIV-1 RNA<50 copies/mL [ Time Frame: Baseline to Study Completion ] [ Designated as safety issue: No ]
  • Change from baseline in CD4+ cell count [ Time Frame: Baseline to Day 11 ] [ Designated as safety issue: No ]
  • Emergence of drug resistance mutations, if appropriate [ Time Frame: Baseline to Study Completion ] [ Designated as safety issue: No ]
  • Estimate accumulation ratios for AUC, Cmax, and Ctau; assess the achievement of steady state of GSK1265744 following repeat administration [ Time Frame: Day 1 and Day 10; Day 2 through Day 10 ] [ Designated as safety issue: No ]
  • AUC, Cmax, Cmin, C24 at different doses for the assessment of dose proportionality. [ Time Frame: Day 1 and Day 10 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study to Compare the Safety and Anti-HIV Effect of GSK1265744 Versus Placebo in HIV-1 Infected Adults (ITZ112929)
A Phase 2a Study to Compare Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK1265744 Monotherapy Versus Placebo in HIV-1 Infected Adults (ITZ112929)

The purpose of this randomized, double-blinded study is to test the safety of GSK1265744 and how well it works on reducing the amount of HIV in the blood. It will also look at how people react to and how a human body uses GSK1265744. This study will compare the effects of GSK1265744 and placebo.

The study will consist of 1 or 2 parts to look at doses of GSK1265744. About 8 people will take part in Part 1 of the study receiving dose A. If additional dosing information is needed after Part 1, about 6 people will take part in Part 2 of the study receiving dose B.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Acquired Immunodeficiency Syndrome
  • Drug: GSK1265744
    Active drug
  • Drug: Placebo
    Placebo to match GSK1265744
  • Cohort 1
    Cohort 1 is the 5mg dose.
    Interventions:
    • Drug: GSK1265744
    • Drug: Placebo
  • Cohort 2
    Cohort 2 may be used to evaluate the next chosen dose.
    Interventions:
    • Drug: GSK1265744
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
9
August 2009
August 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

  • Male or female between 18 and 65 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, defined as:
  • Pre-menopausal females with a documented bilateral oophorectomy, tubal ligation or hysterectomy; or
  • Postmenopausal defined as 12 months of spontaneous amenorrhea. A follicle stimulating hormone level will be performed to confirm post-menopausal status. For this study, FSH levels > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory.
  • Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 14 days after the last dose of study medication.
  • CD4+ cell count greater than or equal to 200 cells/mm3 and plasma HIV-1 RNA greater than or equal to 5000 copies/mL at Screening.
  • No current antiretroviral therapy and have not received any in the 12 weeks prior to first dose.
  • For subjects who have received antiretroviral treatment in the past, adequate treatment options to construct HAART therapy with at least 3 active antiretrovirals for Optimized Therapy, as selected by the Investigator.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

  • A positive screening Hepatitis B surface antigen; positive screening hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid (RNA) on subsequent testing. If the hepatitis C antibody is positive but the HCV RNA is undetectable, the subject may be included in the study.
  • AST and ALT > 3ULN at Screening. A single repeat is allowed for eligibility determination.
  • Inadequate renal function at Screening, defined as either a serum creatinine >1.5 mg/dL or a calculated creatinine clearance (CrCl) ≤ 50 mL/min. A single repeat serum creatinine is allowed to determine eligibility.
  • Any acute laboratory abnormality at screening which, in the opinion of the investigator, should preclude the subject's participation in the study of an investigational compound. Any grade 4 laboratory abnormality at screening, with the exception of CPK, will exclude a subject from study participation unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat is allowed for eligibility determination.
  • A positive drug screen at screening and baseline. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine or PCP.
  • History of regular alcohol consumption, defined as an average weekly intake of >14 drinks for males or >7 drinks for females, within 6 months of Screening.

Note: One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.

  • Any condition (including alcohol or drug abuse) which, in the opinion of the investigator, could interfere with the subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject.
  • Prior treatment with an integrase inhibitor (greater than or equal to 1 dose).
  • Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or anticipated need for such treatment within the study.
  • Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration.
  • Treatment with any vaccine within 30 days prior to receiving study medication.
  • An active Center for Disease Control and Prevention (CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial.
  • Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
  • Lactating females.
  • Use of multivitamins or antacids within 24 hours prior to the first dose of investigational product.
  • 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. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.

Note: Study medications refer to GSK1265744 or placebo.

  • 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).
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • History of clinically relevant pancreatitis or hepatitis within the previous 6 months.
  • 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.
  • Exclusion Criteria for Screening ECG (A single repeat is allowed for eligibility determination):

Exclusion Criteria for Screening ECG:

Males Females Heart rate <45 and >100 bpm <50 and >100 bpm QRS duration >120 msec >120 msec QTc interval (Bazett) > 450 msec > 450 msec Non-sustained (≥ 3 consecutive beats) or sustained ventricular tachycardia. Sinus Pauses >3 seconds. 2nd degree (Type II) or higher AV block. Evidence of previous myocardial infarction (pathologic Q waves, S-T segment changes (except early repolarization)).

Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00920426
112929
No
Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
GlaxoSmithKline
Shionogi
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
March 2011

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