A Study in Underrepresented Patient Population or Regimen Tolerability: SUPPoRT (SUPPoRT)

The hope of this study is to gather data and information about the tolerability and effectiveness of Lexiva versus Sustiva in patients who have have been generally underrepresented in clinical trials.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus Infections
• Intervention / Treatment: Drug: Boosted Lexiva; Drug: Efavirenz 600mg

Detailed Description

The objective of this study is to gain tolerability and efficacy data for Norvir-boosted Lexiva versus Sustiva, both used in combination with Epzicom, as components of a first-line, once daily regimen for the treatment of HIV-1 infection in a patient population that is underrepresented in US clinical research.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Screening plasma HIV-1 RNA viral load >5000 copies/mL Self-identification as having any non-White/Caucasian European geographic ancestry (i.e., an individual is eligible if she/he does not have any White/Caucasian European ancestry; OR an individual is eligible if she/he indicates a mix of White/Caucasian European ancestry AND one or more other geographic ancestries); Antiretroviral-naïve (no treatment with any antiretroviral drug in the 28 days prior to study entry and ≤14 days of treatment ever with any antiretroviral drug) Negative test for the HLA-B*5701 allele Ability and willingness to give written informed consent

Either gender is eligible, but enrollment of at least two female subjects to every one male subject is strongly encouraged. A female subject is eligible to participate in the study if she is of:

1. Non-childbearing potential or,
2. Childbearing potential with a negative pregnancy test at screen and agrees to use one of the following methods of contraception:

i. Agreement for complete abstinence from intercourse from 2 weeks prior to administration of investigational products, throughout the study, and for 2 weeks after discontinuation of all study medications; ii. Double barrier contraception (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide); iii. Any intrauterine device (IUD) with published data showing that the expected failure rate is less than 1% per year (not all IUDs meet this criterion); iv. Any other method with published data showing that the lowest expected failure rate for the method is less than 1% per year. v. Sterilization (female subject or male partner of female subject)

Exclusion Criteria:

Screening HIV-1 genotype indicating the presence of any of the following mutations in the reverse transcriptase (RT) region: K65R, L74V, K103N, Y115F, Y181C/I, Y188C/L/H or G190S/A, or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, associated with resistance to abacavir, lamivudine, or efavirenz; OR within the protease region, detection of any of the following mutations associated with resistance to fosamprenavir or ritonavir: I50V, I54L/M, I84V, or the combination of the two mutations V32I+I147V Positive for Hepatitis B surface antigen (HBsAg+)

Requirement for active treatment for hepatitis C virus infection, as indicated by both a positive Hepatitis C Virus serology AND either:

1. Decompensated liver disease, or
2. Aspartate aminotransferase (AST) >3X the upper limit of normal (ULN), or
3. Alanine aminotransferase (ALT) >3X the ULN Currently pregnant, intending to become pregnant during the study period, or breast-feeding Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), any vaccinations, systemic cytotoxic chemotherapy, or investigational therapy within 28 days prior to study entry. Chronic treatment with prednisone at a daily dose of 10 mg or less is permitted. Acute treatment (less than 21 days) with larger doses of corticosteroids for acute therapy is permitted.

Active or suspected drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements Judged by the investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results Active or acute Centers for Disease Control Clinical Category C event at screening. (Note: Treatment for the acute event must have been completed at least 28 days prior to screening.) Clinically relevant pancreatitis or clinically relevant hepatitis at screening Hgb<8g/dl, platelet count <50,000/mm3, calculated creatinine clearance <50ml/min via Cockroft-Gault equation, or AST or ALT > 5X the ULN Any Grade 4 laboratory abnormality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A : Boosted Lexiva plus Epzicom; Once daily (QD) regimen of Lexiva (fosamprenavir 1400 mg) + Norvir (ritonavir 100 mg) + Epzicom (abacavir 600 mg / lamivudine 300 mg).	Drug: Boosted Lexiva; Once daily (QD) regimen of Lexiva (fosamprenavir 1400 mg) + Norvir (ritonavir 100 mg) + Epzicom (abacavir 600 mg / lamivudine 300 mg) The intervention may be switched for the following reasons: To resolve a Grade 3 or 4 Adverse Event; The subject experienced a virologic failure (as defined in section 3.6.2); The investigator believes the subject is at a significant risk for failing to comply with the protocol AND the investigator believes a regimen substitution is likely to resolve the compliance issue; The investigator believes there is any other significant safety concern for the subject associated with remaining on the current regimen (e.g., hypersensitivity reaction, increased risk of suicide); Other Names: Fosamprenavir(Lexiva)
Experimental: Arm B: Efavirenz plus Epzicom; QD regimen of Sustiva (efavirenz 600 mg) + Epzicom (abacavir 600 mg / lamivudine 300 mg)	Drug: Efavirenz 600mg; QD regimen of Sustiva (efavirenz 600 mg) + Epzicom (abacavir 600 mg / lamivudine 300 mg) The intervention may be switched for the following reasons: To resolve a Grade 3 or 4 Adverse Event; The subject experienced a virologic failure (as defined in section 3.6.2); The investigator believes the subject is at a significant risk for failing to comply with the protocol AND the investigator believes a regimen substitution is likely to resolve the compliance issue; The investigator believes there is any other significant safety concern for the subject associated with remaining on the current regimen (e.g., hypersensitivity reaction, increased risk of suicide); Other Names: Efavirenz(Sustiva)600 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Needing to Switch Comparator Drugs (FPV/r or EFV)	Subjects were randomized and initiated treatment on one of the antiretroviral arms(FPV/r or EFV) at study Entry visit. Subjects would be switched for the follwing reasons: To resolve a Grade 3 or 4 Adverse Event; The subject experienced a virologic failure (as defined in section 3.6.2); The investigator believes the subject is at a significant risk for failing to comply with the protocol AND the investigator believes a regimen substitution is likely to resolve the compliance issue; The investigator believes there is any other significant safety concern for the subject associated with remaining on the current regimen (e.g., hypersensitivity reaction, increased risk of suicide)	96 weeks
Number of Subjects Developing Any Treatment-related Grade 3-4 Adverse Events		96 weeks

Collaborators and Investigators

• Sponsor: Georgetown University
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Princy Kumar, MD, Georgetown University

Publications and helpful links

General Publications

• Kumar P, DeJesus E, Huhn G, Sloan L, Small CB, Edelstein H, Felizarta F, Hao R, Ross L, Stancil B, Pappa K, Ha B; SUPPORT Study Team. Evaluation of cardiovascular biomarkers in a randomized trial of fosamprenavir/ritonavir vs. efavirenz with abacavir/lamivudine in underrepresented, antiretroviral-naive, HIV-infected patients (SUPPORT): 96-week results. BMC Infect Dis. 2013 Jun 7;13:269. doi: 10.1186/1471-2334-13-269.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: July 31, 2008
• First Submitted That Met QC Criteria: August 1, 2008
• First Posted (Estimate): August 4, 2008

Study Record Updates

• Last Update Posted (Estimate): July 2, 2013
• Last Update Submitted That Met QC Criteria: June 28, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Efavirenz; Fosamprenavir
• Other Study ID Numbers: COL 110408