Safety and Tolerability Study to Evaluate Lower Dose of GSK2248761 in Antiretroviral Treatment-Naive HIV-1 Infected Adults.

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00945282
First received: July 23, 2009
Last updated: May 30, 2013
Last verified: March 2012
  Purpose

GSK has in-licensed a novel NNRTI-class candidate (GSK2248761, IDX12899) for the treatment of subjects with HIV-1 infection from Idenix Pharmaceuticals. Idenix Pharmaceuticals completed a proof-of-concept study evaluating GSK2248761 monotherapy over seven days in forty treatment-naïve subjects infected with HIV-1. GSK2248761 doses sequentially evaluated were 800 mg QD, 400 mg QD, 200 mg QD and 100mg QD.

This study will evaluate a lower dose, or doses, of GSK2248761 to better characterize the dose-response and concentration-response curves. The results from this study will be used to select doses for future clinical studies in HIV-1 infected subjects.


Condition Intervention Phase
Infection, Human Immunodeficiency Virus
Drug: GSK2248761
Drug: Lopinavir/ritonavir
Drug: HAART
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 Proof of Concept Study for GSK2248761 (An Extension of NV-05A-002: A Phase I/IIa Double-Blind Study to Evaluate the Safety and Tolerability, Antiretroviral Activity, Pharmacokinetics and Pharmacodynamics of IDX12899 in Antiretroviral Treatment-Naive HIV-1 Infected Subjects, Completed by Idenix)

Resource links provided by NLM:


Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:
  • Safety and tolerability parameters, including adverse event, clinical laboratory, electrocardiogram (EGC) and vital sign assesssments. [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Change from baseline through Day 8 in plasma HIV-1 RNA. [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  • GSK2248761 PK parameters following dose administration on Day 1 and Day 7. [ Time Frame: 8 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in reverse transcriptase sequences of HIV-1 at Day 8. [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  • Change from baseline CD4+ and CD8+ T-Lymphocyte cell count and percentages at Day 8. [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  • GSK2248761 PK parameters on Day 2 through Day 7. [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  • Day 1 and Day 7 PK data at different doses for the assessment of dose proportionality. [ Time Frame: 8 days ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: October 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
In Cohort 1 subjects will receive either GSK2248761 30 mg or placebo once a day for 7 days. On Day 8 subjects will receive either Kaletra or HAART for 28 days. The doctor will choose the most appropriate medications for HAART.
Drug: GSK2248761
GSK2248761 30 mg capsule once a day for 7 days. GSK2248761 is an investigational (not approved by the FDA) HIV drug in the class of non-nucleoside reuptake inhibitor class.
Drug: Lopinavir/ritonavir
Lopinavir 400 mg and ritonovir 100 mg every 12 hours for 28 days. Lopinavir/ritonavir is approved by the FDA as an HIV medication in the protease inhibitor class. Kaletra is a trademark of Abbott Laboratories.
Other Name: Kaletra
Drug: HAART
Highly Active Antiretroviral therapy of the doctor's choice.
Drug: Placebo
Placebo is a capsule with no drug in it.
Experimental: Cohort 2
In Cohort 2 subjects will receive either GSK2248761 in the range of 10 mg - 20 mg or 40 mg - 90 mg or placebo once a day for 7 days. On Day 8 subjects will receive either Kaletra or HAART for 28 days. The doctor will choose the most appropriate medications for HAART. The dose for Cohort 2 will be determined following evaluation of results from Cohort 1. Cohort 2 may not be done.
Drug: Lopinavir/ritonavir
Lopinavir 400 mg and ritonovir 100 mg every 12 hours for 28 days. Lopinavir/ritonavir is approved by the FDA as an HIV medication in the protease inhibitor class. Kaletra is a trademark of Abbott Laboratories.
Other Name: Kaletra
Drug: HAART
Highly Active Antiretroviral therapy of the doctor's choice.
Drug: Placebo
Placebo is a capsule with no drug in it.
Drug: GSK2248761
GSK2248761 10 mg -20 mg or 40 mg - 90 mg once a day for 7 days. GSK2248761 is an investigational (not approved by the FDA) HIV drug in the class of non-nucleoside reuptake inhibitor class.

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or Female, 21 to 65 years of age.
  • Female of non-childbearing potential defined as: being post-menopausal, defined as 12 months of spontaneous amenorrhea and having a serum FSH level >40 MIU/ml at Screening OR have had a documented bilateral tubal ligation or hysterectomy of at least 6 months prior to study initiation, bilateral oophorectomy or bilateral tubal ligation.
  • Plasma HIV-1 RNA value >= 5000 copies/mL.
  • CD4+ count >= 200 cells/mm3.
  • Is antiretroviral treatment-naïve and agrees not to start antiretroviral therapy prior to clinic check-in (Day-1).
  • Subject agrees to start a standard HAART regimen on Day 8 of the study or Kaletra monotherapy for 28 days within 24 hours after the last dose of study medication.
  • Capable of giving written informed consent, which includes being willing and able to comply with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

  • Subject is pregnant as determined by a positive urine/serum pregnancy test at Screening and Day -1.
  • Lactating females.
  • Male subjects of reproductive potential and unwilling to use double barrier method of contraception (e.g., condom plus spermicide) and continue to use an adequate method of birth control for at least 30 days after the last dose of the study drug.
  • Has 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.
  • History of regular alcohol consumption within 6 months of Screening as defined as: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits
  • Has a positive pre-study drug screen. Drugs that will be screened for include amphetamines, barbiturates, cocaine and PCP.
  • 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 Principal Investigator, 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 drugs include GSK2248761 placebo or the follow-up HAART or Kaletra therapy.

  • Received an immunomodulating agent (e.g., interleukin-2) or immunotherapeutic vaccine within 30 days before Day -1.
  • Requires a medication that is a known substrate, inhibitor and/or inducer of CYP3A4.
  • Has received an investigational drug or participated in any other research trial within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dosing day.
  • Has ever had an AIDS-defining illness.
  • Has a history of or has a currently active clinically important disease other than HIV-1 infection that, in the opinion of the Investigator, may put the subject at risk because of participation in this study (including renal and hepatic impairment, active infections including tuberculosis or opportunistic infection, malignancy and cardiac dysfunction).
  • Has an intestinal malabsorption (e.g., structural defects, digestive failure, enzyme deficiencies, etc).
  • Has a pre-existing NNRTI drug resistance based on genotyping at Screening.
  • Where participation in the study would result in donation of blood or blood products in excess of 500mL within a 56 day period.
  • Subject has any of the following laboratory parameters at Screening (a single repeat is allowed for eligibility determination): Hemoglobin <8.5 g/dL, Neutrophil count <1000 cells/mm3, Platelet count <100,000 cells/mm3, Serum creatinine > the upper limit of normal (ULN), AST or ALT <= 2.5 x ULN.
  • Exclusion Criteria for Screening ECG (A single repeat is allowed for eligibility determination): Exclusion Criteria for Screening ECG: Heart rate: (males) <45 and >100 bpm (females) <50 and >100 bpm, QRS duration: >120 msec, QTc interval (Bazett): > 450 msec. Non-sustained (>= 3 consecutive beats) or sustained ventricular tachycardia. Sinus Pauses >2.5 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: NCT00945282

Sponsors and Collaborators
ViiV Healthcare
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare
  More Information

No publications provided

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00945282     History of Changes
Other Study ID Numbers: 113020
Study First Received: July 23, 2009
Last Updated: May 30, 2013
Health Authority: Argentina: Ministry of Health - A.N.M.A.T

Keywords provided by ViiV Healthcare:
IDX12899
adaptive
monotherapy
pharmacokinetics
Treatment-naive
HIV-1
GSK2248761
NNRTI
HIV Infections
treatment naive

Additional relevant MeSH terms:
Infection
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Lopinavir
Ritonavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 30, 2014