Abacavir/Lamivudine Versus Emtricitabine/Tenofovir Both In Combination With Lopinavir/Ritonavir For The Treatment Of HIV (HEAT)

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00244712
First received: October 25, 2005
Last updated: June 3, 2010
Last verified: June 2010
  Purpose

This study was designed to test the safety and effectiveness of EPZICOM(abacavir/lamivudine) and TRUVADA (emtricitabine/tenofovir) for the treatment of HIV infection when both are used in combination with KALETRA (lopinavir/ritonavir) over 96 weeks


Condition Intervention Phase
HIV Infection
Drug: emtricitabine/tenofovir
Drug: abacavir/lamivudine
Phase 4

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 96-Week, Phase IV, Randomized, Double-Blind, Multicenter Study of the Safety and Efficacy of EPZICOM Versus TRUVADA Administered in Combination With KALETRA in Antiretroviral-Naive HIV-1 Infected Subjects

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 by Missing=Failure (M=F), Switched Included Analysis. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Week 48. The percentage of participants with HIV-1 RNA <50 copies/mL were tabulated by treatment arm with stratification by baseline HIV-1 RNA (<100,000 copies/mL and >=100,000 copies/mL).


Secondary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Week 48. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 were tabulated by treatment arm with stratification by baseline HIV-1 RNA levels (<100,000 copies/mL and >=100,000 copies/mL).

  • Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Week 96. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 were tabulated by treatment arm with stratification by baseline HIV-1 RNA levels (<100,000 copies/mL and >=100,000 copies/mL).

  • Percentage of Participants With HIV-1 RNA <50 Copies/mL at Weeks 48 and 96 in Participants With Baseline HIV-1 RNA <100,000 Copies/mL [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]
    A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Weeks 48 and 96. The percentage of participants with HIV-1 RNA <50 copies/mL at Weeks 48 and 96 were tabulated by treatment arm in participants with baseline HIV-1 RNA <100,000 copies/mL.

  • Percentage of Participants With HIV-1 RNA <50 Copies/mL at Weeks 48 and 96 in Participants With Baseline HIV-1 RNA >=100,000 Copies/mL [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]
    A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Week 48 and 96. The percentage of participants with HIV-1 RNA <50 copies/mL at Weeks 48 and 96 were tabulated by treatment arm in participants with baseline HIV-1 RNA >=100,000 copies/mL.

  • Percentage of Participants With HIV-1 RNA <400 Copies/mL at Weeks 48 and 96 [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]
    A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Week 48 and 96. The percentage of participants with HIV-1 RNA <400 copies/mL at Weeks 48 and 96 were tabulated by treatment arm with stratification by baseline HIV-1 RNA levels (<100,000 copies/mL and >=100,000 copies/mL).

  • Percentage of Participants With HIV-1 RNA <400 Copies/mL at Weeks 48 and 96 in Participants With Baseline HIV-1 RNA <100,000 Copies/mL [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]
    A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Weeks 48 and 96. The percentage of participants with HIV-1 RNA <400 copies/mL at Weeks 48 and 96 were tabulated by treatment arm in participants with baseline HIV-1 RNA <100,000 copies/mL.

  • Percentage of Participants With HIV-1 RNA <400 Copies/mL at Weeks 48 and 96 in Participants With Baseline HIV-1 RNA >=100,000 Copies/mL [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]
    A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Weeks 48 and 96. The percentage of participants with HIV-1 RNA <400 copies/mL at Weeks 48 and 96 were tabulated by treatment arm in participants with baseline HIV-1 RNA >=100,000 copies/mL.

  • Median Change From Baseline in HIV-1 RNA at Week 48 and 96 [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]
    A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Weeks 48 and 96. Change from baseline was defined as HIV-1 RNA level at Weeks 48 and 96 minus HIV-1 RNA level at baseline.

  • Median Change From Baseline in CD4+ Cells at Weeks 48 and 96 [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]
    A blood sample was drawn to determine the CD4+ cell count at Weeks 48 and 96. Change from baseline was defined as CD4+ cell count at week 96 minus CD4+ cell count at baseline.

  • Number of Participants Who Meet the Protocol-defined Virologic Failure (PDVF) Criteria at Week 96 [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: No ]
    The number of participants that failed to respond to therapy based on the protocol definition of virologic failure (PDVF) was tabulated. PDVF was defined as either no confirmed HIV-1 RNA <200 copies/mL or HIV-1 RNA rebound >= 200 copies/mL on two consecutive occasions.

  • Number of Confirmed Virologic Failure Participants Who Had Treatment-emergent Genotypic Resistance Through 96 Weeks [ Time Frame: Baseline and time of virologic failure (up to Week 96) ] [ Designated as safety issue: No ]
    A blood sample was drawn for participants failing to respond to therapy and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New mutations that developed at the time of failure was tabulated by drug class. NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

  • Number of Confirmed Virologic Failure Participants at Week 96 With Genotypic Resistance to Lamivudine (3TC) and Emtricitabine (FTC) and Had Phenotypic Reduced Susceptibility [ Time Frame: Baseline and time of virologic failure (up to Week 96) ] [ Designated as safety issue: No ]
    A blood sample was drawn for participants failing to respond to therapy and the mutations present in the virus were identified. New mutations that developed to the NRTI class at the time of failure that no longer responded to lamivudine or emtricitabine were tabulated by drug class.

  • Number of Participants Who Reported a Suspected Abacavir Hypersensitivity Reaction (ABC HSR) Reaction or Proximal Renal Tubule Dysfunction [ Time Frame: Baseline through 96 weeks ] [ Designated as safety issue: No ]
    The number of participants that experienced symptoms of a suspected abacavir hypersensitivity reaction was tabulated. The number of participants that developed laboratory signs of proximal renal tubule dysfunction was tabulated.


Enrollment: 688
Study Start Date: July 2005
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ABC/3TC
The intervention is a regimen containing abacavir/lamivudine + tenofovir/emtricitabine placebo +lopinavir/ritonavir.
Drug: abacavir/lamivudine
The experimental intervention is a regimen containing abacavir/lamivudine + tenofovir/emtricitabine placebo + lopinavir/ritonavir.
Other Name: abacavir/lamivudine
Active Comparator: TDF/FTC
The intervention is a regimen containing tenofovir/emtricitabine + abacavir/lamivudine placebo + lopinavir/ritonavir.
Drug: emtricitabine/tenofovir
The intervention is an active comparator regimen containing tenofovir/emtricitabine + abacavir/lamivudine placebo + lopinavir/ritonavir.
Other Name: emtricitabine/tenofovir

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Males as females at least 18 years old. (A female is eligible to enter and participate in this study if she is of: non child-bearing potential, child bearing potential with a negative pregnancy test and agrees to approved contraception methods, or agreement for complete abstinence.)
  • Subject is antiretroviral-naïve (defined as having ≤14 days of prior therapy with any NRTI and no prior therapy with either a PI or NNRTI).
  • Subject has plasma HIV-1 RNA ≥ 1,000 copies/mL at screening.
  • Subject is willing and able to understand and provide written informed consent prior to participation in this study.

Exclusion criteria:

  • Subject has an active or acute CDC Clinical Category C event (exclusive of cutaneous Kaposi's sarcoma) at screening. Treatment for the acute event must have been completed at least 30 days prior to screening.
  • Subject is enrolled in one or more investigational drug protocols, which may impact HIV-1 RNA suppression.
  • Subject is, in the opinion of the investigator, unable to complete the 96-week dosing period and protocol evaluations and assessments.
  • Subject is either pregnant or breastfeeding.
  • Subject has an ongoing clinically relevant pancreatitis or clinically relevant hepatitis at screening.
  • Subject suffers from a serious medical condition, such as cirrhosis, diabetes, congestive heart failure, cardiomyopathy or other cardiac dysfunction, which in the opinion of the investigator would compromise the safety of the subject.
  • Subject has a pre-existing mental, physical, or substance abuse disorder which, in the opinion of the investigator, may interfere with the subject's ability to comply with the dosing schedule and protocol evaluations and assessments.
  • Subject has a history of inflammatory bowel disease or malignancy, intestinal ischemia, malabsorption, or other gastrointestinal dysfunction which may interfere with drug absorption or render the subject unable to take oral medication.
  • Subject has any acute laboratory abnormality at screening, which, in the opinion of the investigator, precludes the subject's participation in the study of an investigational compound. Any grade 4 laboratory abnormality will exclude a subject from study participation.
  • Subject has estimated creatinine clearance <50 mL/min via Cockroft-Gault method.
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN).
  • Subject has required treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to screening, or has an anticipated need for these agents within the study period.
  • Subject requires treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, vaccines, or interferons) within 28 days prior to Screen, or subject has received an HIV-1 immunotherapeutic vaccine within 90 days prior to Screen. Asthmatic subjects using inhaled corticosteroids are eligible for enrollment.
  • Subject requires treatment with foscarnet, hydroxyurea or other agents with documented activity against HIV-1 in vitro within 28 days of study administration.
  • Subjects who require treatment with the prohibited medications within 28 days of commencement of investigational product, or an anticipated need during the study.
  • Subject has a history of allergy to any of the study drugs or any excipients therein
  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: NCT00244712

  Show 74 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00244712     History of Changes
Other Study ID Numbers: EPZ104057, EPZ104057
Study First Received: October 25, 2005
Results First Received: April 23, 2009
Last Updated: June 3, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
HEAT
Antiretroviral-naive
HIV
EPZICOM
TRUVADA
KALETRA
once-daily

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

ClinicalTrials.gov processed this record on July 22, 2014