Switching From Efavirenz to Atazanavir/ Ritonavir in HIV-infected Subjects With Good Virologic Suppression

NCT01194856 | Terminated Phase 4 Results DMC

• 3 other identifiers: 10-4185K23AI070078BMS100MT
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purposes of this study are to evaluate if switching an antiretroviral medication from efavirenz (EFV) to atazanavir/ ritonavir (ARV/r) will, in a 96-week period, change:

1. 1.the amount of fat in HIV patients with lipoatrophy,
2. 2.metabolic lab values such as your lipid (fat) profile, glucose (blood sugar), and insulin (a hormone that regulates glucose) in HIV patients with lipoatrophy.

Conditions

HIV Infection; Mitochondrial Dysfunction

Keywords

HIV; Lipoatrophy; mitochondrial dysfunction

Outcome Measures

Primary Outcomes (1)

• Change in DEXA-measured Limb Fat Between the EFV and ATV/r Arms

  To examine the effect of switching from EFV- to ATV/r on limb fat in HIV-1 infected patients with established lipoatrophy, the primary objective of this trial will be to compare changes over 48 weeks in DEXA-measured limb fat between the EFV arm and ATV/r.

  48 weeks

Secondary Outcomes (7)

• Compare Changes for DEXA-measured Limb Fat Between EFV and ATV/r Arms

  96 weeks

• Compare Changes in CD4, HIV-1 RNA Levels and Adverse Events in Two Arms

  96 weeks

• Compare Changes in Fat mtDNA, mtRNA and Fat Apoptosis Between the Two Arms

  96 weeks

• Comparing Fasting Lipid Levels Between the Two Arms

  96 weeks

• Comparing Glucose Metabolism (Fasting Insulin, QUIKI and HOMA-IR) Between the Two Arms

  96 weeks

Study Arms (2)

Efavirenz 600 mg

ACTIVE COMPARATOR

Serving as the Control Arm - patients will maintain EFV-containing antiretroviral regimen

Drug: Efavirenz

Arm B - Atazanavir/Ritonavir

EXPERIMENTAL

Atazanavir 300 mg orally with Ritonavir 100 mg orally once daily for 96 wks

Drug: Atazanavir/ritonavir

Interventions

Atazanavir/ritonavir DRUG

300 mg orally once daily with Ritonavir 100mg orally once daily for 96 weeks

Also known as: Reyataz®: 100 mg, 150 mg, 200 mg, 300 mg, Norvir®: 100 mg

Arm B - Atazanavir/Ritonavir

Efavirenz DRUG

Maintain dosage - 600 mg orally QHS for 96 weeks

Also known as: Sustiva®: 50 mg, 200 mg

Efavirenz 600 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV infection
• Age \> or = 18 years old.
• Signed informed consent.
• Clinical lipoatrophy of at least moderate severity and in at least two different areas of the following: face, arms, legs, or buttocks (as self reported by the patient and confirmed by the physician).
• Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized.
• All subjects must not participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female subject/ male partner must use condoms (male or female) in addition to one of the following forms of contraception while on study: either a spermicidal agent, diaphragm, cervical cap, IUD, or hormonal-based contraception.
• Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.
• Receiving EFV-containing antiretroviral regimen for at least the last 48 weeks prior to study entry. Backbone NRTI regimens can include tenofovir, abacavir, emtricitabine, and/ or lamivudine. Backbone NRTI regimens cannot include zidovudine, stavudine, or didanosine. Breaks in therapy for a maximum of 5 consecutive days will be allowed during these 48 weeks, including the period immediately preceding study entry.
• Patient willing and able to stop aspirin/ NSAIDS for 7 days before study entry and the scheduled skin biopsy procedures.
• HIV-1 RNA \< 400 copies/mL for at least 90 days prior to study entry.
• Laboratory values obtained within 60 days prior to study entry:
• Absolute neutrophil count (ANC) ≥ 500 / mm3
• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 75,000/ mm3
• Creatinine clearance \> 50 mL / min

You may not qualify if:

• Receipt of AZT, d4T, ddI, or ddC at study entry or within 24 weeks of entry
• Life expectancy \< 12 months
• Women who are pregnant or breastfeeding
• WOCBP unwilling to use contraception WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period
• Women with a positive pregnancy test.
• Sexually active fertile men not using effective birth control if their partners are WOCBP.
• Prisoners or subjects who are involuntarily incarcerated.
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
• Clinically important illness within 14 days prior to study entry
• Inability to communicate effectively with the study personnel.
• Bleeding diathesis
• Supplementation with recombinant growth hormone, growth hormone releasing factor, anabolic steroids, estrogen or testosterone, unless it is for replacement purposes.
• Have no plans to alter any vitamin supplementation that subjects are receiving at study entry. This includes all vitamin supplementation, coenzyme Q, N acetyl cysteine, L-acetyl carnitine, and uridine.

Sponsors & Collaborators

• The Cleveland Clinic: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Case Western Reserve University: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

HIV Infections; Mitochondrial Diseases; Lipodystrophy

Interventions

atazanavir, ritonavir drug combination; Atazanavir Sulfate; Ritonavir; efavirenz

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Limitations and Caveats

Data not collected for analysis due to low enrollment and participant discontinuation.

Results Point of Contact

• Title: Marisa Tungsiripat
• Organization: Cleveland Clinic

tungsim@ccf.org

2164442037

Study Officials

• Marisa Tungsiripat, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

Study Record Dates

• First Submitted: September 2, 2010
• First Posted: September 3, 2010
• Study Start: October 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: August 11, 2017
• Results First Posted: August 11, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)