ABT-378/Ritonavir in Combination With Reverse Transcriptase Inhibitors in Antiretroviral Naïve HIV-Infected Subjects

Phase I/II Study of ABT-378/Ritonavir in Combination With Reverse Transcriptase Inhibitors in Antiretroviral Naive HIV-Infected Patients

To assess the safety, tolerability and antiviral activity of lopinavir/ritonavir when administered orally in antiretroviral-HIV-1 infected subjects.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Lopinavir/Ritonavir; Drug: Lamivudine; Drug: Stavudine

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Pacific Oaks Research
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Health Sciences Center
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • AIDS Research Consortium of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush-Presbyterian-St. Luke's Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern University Medical School
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • New York
    • New York, New York, United States, 10011
      • Cornell Clinical Trials Unit - Chelsea Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27516
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

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

• HIV-1 positive
• antiretroviral-adult males
• non-pregnant
• non-lactating females at least 18-years old with plasma HIV-1 RNA > 5000 copies/mL, who were not acutely ill

Exclusion Criteria

• History of:

  • prior antiretroviral therapy
  • significant drug hypersensitivity
  • psychiatric illness that precludes compliance
  • an active substance abuser
  • positive test results for drug abuse
  • abnormal lab test results (hemoglobin, absolute neutrophil count, platelet count, SGPT/AST or SGPT/ALT, creatinine, fasting triglycerides, significant abnormal ECG results
  • pregnancy or lactating female
  • received another investigational drug within 28 days of study initiation
  • unlikely to comply or unsuitable candidate in the opinion of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; Group 1, n=32 initiated with ABT-378 & ritonavir; after 3 wks stavudine and lamivudine was added.	Drug: Lopinavir/Ritonavir; Lopinavir, range from 200 mg to 400 mg, every 12 hrs and Ritonavir, range from 100 mg to 200 mg, every 12 hrs; Other Names: Kaletra; ABT-387; Drug: Lamivudine; 150 mg, every 12 hours; Drug: Stavudine; 40 mg every 12 hours
ACTIVE_COMPARATOR: 2; Group II patients (n=68) to be randomized after all Group I patients are enrolled and safety analysis is completed.	Drug: Lopinavir/Ritonavir; Lopinavir, range from 200 mg to 400 mg, every 12 hrs and Ritonavir, range from 100 mg to 200 mg, every 12 hrs; Other Names: Kaletra; ABT-387; Drug: Lamivudine; 150 mg, every 12 hours; Drug: Stavudine; 40 mg every 12 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with viral load below the limit of quantitation	24 weeks
Time to loss of virologic response	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with viral load below the limit of quantitation at each visit	At each visit

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: George Hanna, MD, Abbott

Publications and helpful links

General Publications

• Murphy R, King M, Brun S, Orth K, Hicks C, Eron J, Thommes J, Gulick R, Thompson M, White C, Benson C, Hammer S, Kessler H, Bertz R, Hsu A, Kempf D, Sun E, Japour A. ABT-378/ritonavir therapy in antiretroviral-naive HIV-I infected patients for 24 weeks. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:69 (abstract no 15)
• Murphy RL, Brun S, Hicks C, Eron JJ, Gulick R, King M, White AC Jr, Benson C, Thompson M, Kessler HA, Hammer S, Bertz R, Hsu A, Japour A, Sun E. ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection: 48-week results. AIDS. 2001 Jan 5;15(1):F1-9. doi: 10.1097/00002030-200101050-00002.

Study record dates

Study Major Dates

• Study Start: November 1, 1997
• Primary Completion (ACTUAL): April 1, 2005
• Study Completion (ACTUAL): April 1, 2005

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (ESTIMATE): August 31, 2001

Study Record Updates

• Last Update Posted (ESTIMATE): April 3, 2008
• Last Update Submitted That Met QC Criteria: April 2, 2008
• Last Verified: April 1, 2008

More Information

Terms related to this study

• Keywords: Reverse Transcriptase Inhibitors; Stavudine; Lamivudine; HIV Protease Inhibitors; Ritonavir
• 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; HIV Infections; 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; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lopinavir; Lamivudine; Stavudine
• Other Study ID Numbers: 285A; M97-720