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Anti-HIV Activity and Safety of 3 Different Doses of Mifepristone in HIV Infected People

Phase 1
Completed
Conditions
HIV Infections
Registration Number
NCT00099645
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

The purpose of this study is to determine the anti-HIV activity and safety of 3 different doses of mifepristone (also known as VGX-410 and RU486) in HIV infected people.

Hypothesis: Mifepristone will be generally safe (no serious adverse effects) and well tolerated.

Detailed Description

Mifepristone is a potent anti-glucocorticoid compound that effectively inhibits replication of both laboratory and clinical HIV isolates in vitro. This study will evaluate the anti-HIV activity and safety of 3 different doses of mifepristone in HIV infected people.

This study will last approximately 2 months. Participants will be randomly assigned to one of 4 study arms, and will receive either mifepristone or placebo daily for 28 days. Arm A participants will receive one of three doses of placebo; Arm B participants will receive 75 mg mifepristone; Arm C participants will receive 150 mg mifepristone; and Arm D participants will receive 225 mg mifepristone. A thorough neck and thyroid examination will be performed within 30 days prior to study entry. Blood collection and vital signs measurement will occur at study entry and Days 3, 7, 14, 21, 28, and 56. Urine collection and pill counts will also be done at some study visits.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
48
Inclusion Criteria
  • HIV-1 infected
  • CD4 count of 350 cells/mm3 or more within 90 days prior to study entry
  • HIV-1 viral load of 2000 copies/ml or more within 90 days prior to study entry
  • Willing to use acceptable forms of contraception during the study and for 30 days after stopping study medication
  • If currently taking precautionary concomitant medications, must be on stable doses for more than 8 weeks prior to study entry and have no plans to change medications or doses for the duration of the study
  • Body weight at least 40 kg (88 lbs) within 90 days prior to study entry
Exclusion Criteria
  • Antiretroviral treatment (ART) within 16 weeks prior to study entry, or intend to start ART within 60 days after entry
  • Adrenal disorders
  • History of autoimmune endocrine disease in self or family
  • History of active hepatitis B or C
  • Current treatment for hepatitis B or C
  • Moderate to severe liver disease
  • Blood disorders or current anticoagulant therapy
  • Prior pituitary tumor, surgery, radiation treatment, or pituitary failure
  • Moderate to large goiters or thyroid nodules
  • Diabetes mellitus
  • Unusual uterine bleeding within 12 months prior to study entry
  • Current hormonal contraception or intrauterine (IUD) use, including progesterone-containing vaginal rings
  • Pregnancy within 90 days prior to study entry
  • Breast-feeding
  • Drugs that act as inhibitors or inducers of metabolism by cytochrome P450 3A4
  • Systemic corticosteroids or hormonal agents within 90 days prior to study entry
  • Any immunomodulator, HIV vaccine, or investigational therapy within 90 days prior to study entry
  • Any vaccination within 30 days prior to study entry
  • Systemic cytotoxic chemotherapy within 90 days prior to study entry
  • History of allergy to mifepristone or the study formulations
  • Current drug or alcohol abuse that, in the opinion of the investigator, may interfere with the study
  • Any other conditions that may interfere with participant evaluation during the study
  • Serious illness requiring systemic treatment or hospitalization. Patients who complete therapy or are clinically stable on therapy for at least 14 days prior to study entry are not excluded.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Changes in HIV-1 viral load from baseline to Days 14 and 28
Secondary Outcome Measures
NameTimeMethod
Within 28 days on study, occurrence of toxicity, rash, and symptoms of adrenal insufficiency, including fatigue, nausea, anorexia, vomiting, and dizziness
changes from baseline viral load on Days 7, 14, 21, 28, and 56
pre-dose concentrations of mifepristone on Days 14 and 28 and serum level of alpha-1 acidic glycoprotein (AAG) at Day 0
percentage and counts of CD4 and CD8 cells at baseline and on Days 14, 28, and 56
Vpr amino acid sequences on Days 0, 14, 28, and 56
comparison of the magnitude and diversity of effector T cell response to HIV antigens at Days 0, 28, and 56
change in fasting concentrations of plasma insulin, free fatty acids, high-density lipoprotein (HDL) cholesterol and triglycerides, and in insulin sensitivity between Days 0 and 28

Trial Locations

Locations (10)

University of Minnesota, ACTU

🇺🇸

Minneapolis, Minnesota, United States

Georgetown University CRS (GU CRS)

🇺🇸

Washington, District of Columbia, United States

Washington U CRS

🇺🇸

Saint Louis, Missouri, United States

Harbor-UCLA Med. Ctr. CRS

🇺🇸

Torrance, California, United States

The Ohio State Univ. AIDS CRS

🇺🇸

Columbus, Ohio, United States

Hosp. of the Univ. of Pennsylvania CRS

🇺🇸

Philadelphia, Pennsylvania, United States

Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.

🇺🇸

Philadelphia, Pennsylvania, United States

Pitt CRS

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Washington AIDS CRS

🇺🇸

Seattle, Washington, United States

Unc Aids Crs

🇺🇸

Chapel Hill, North Carolina, United States

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