Trial record 20 of 30 for:    " May 27, 2009":" June 26, 2009"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

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
  Purpose

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.


Condition Intervention Phase
Acquired Immunodeficiency Syndrome
Drug: GSK1265744
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2a Study to Compare Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK1265744 Monotherapy Versus Placebo in HIV-1 Infected Adults (ITZ112929)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 9
Study Start Date: June 2009
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Cohort 1
Cohort 1 is the 5mg dose.
Drug: GSK1265744
Active drug
Drug: Placebo
Placebo to match GSK1265744
Cohort 2
Cohort 2 may be used to evaluate the next chosen dose.
Drug: GSK1265744
Active drug
Drug: Placebo
Placebo to match GSK1265744

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00920426

Locations
United States, Florida
GSK Investigational Site
Fort Lauderdale, Florida, United States, 33308
GSK Investigational Site
Orlando, Florida, United States, 32803
GSK Investigational Site
Vero Beach, Florida, United States, 32960
United States, North Carolina
GSK Investigational Site
Charlotte, North Carolina, United States, 28209
Sponsors and Collaborators
GlaxoSmithKline
Shionogi
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00920426     History of Changes
Other Study ID Numbers: 112929
Study First Received: June 12, 2009
Last Updated: March 10, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
HIV
HIV Infections
naive
Phase II
integrase inhibitor
GSK1265744
newly diagnosed
pharmacokinetics
AIDS
integrase
Treatment naive

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014