Investigation of the Potential Pharmacokinetic Interaction Between Nevirapine, Abacavir and Amprenavir in HIV-1 Infected Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Naive Adults

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT02182765
First received: July 3, 2014
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

Study to determine the effects of 28 days of nevirapine treatment on the steady-state pharmacokinetics of amprenavir and of abacavir and to further evaluate the pharmacokinetics of nevirapine in combination with amprenavir and abacavir compared to historical controls treated with nevirapine but without amprenavir or abacavir. In addition safety/tolerance of nevirapine, amprenavir and abacavir was to be assessed based on adverse events and clinical laboratory data.


Condition Intervention Phase
HIV Infections
Drug: Nevirapine
Drug: Amprenavir
Drug: Abacavir
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Investigation of the Potential Pharmacokinetic Interaction Between Nevirapine (VIRAMUNE®), Abacavir and Amprenavir in HIV-1 Infected NNRTI Naive Adults

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • AUC (area under plasma concentration time curve) of amprenavir in the absence and presence of nevirapine [ Time Frame: Day 14, day 43 ] [ Designated as safety issue: No ]
  • Cmax (maximum observed concentration of the analyte in plasma) of amprenavir in the absence and presence of nevirapine [ Time Frame: Day 14, day 43 ] [ Designated as safety issue: No ]
  • AUC (area under plasma concentration time curve) of abacavir in the absence and presence of nevirapine [ Time Frame: Day 14, day 43 ]
  • Cmax (maximum observed concentration of the analyte in plasma) of abacavir in the absence and presence of nevirapine [ Time Frame: Day 14, day 43 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in HIV-1 Ribonucleic Acid (RNA) [ Time Frame: Baseline, day 14, 21, 28, 35, 43 (Part I), up to 168 days (Part II) ] [ Designated as safety issue: No ]
  • Change from baseline in Lymphocytes Expressing CD4+ cell count [ Time Frame: Baseline, day 14, 21, 28, 35, 43 (Part I), up to 168 days (Part II) ] [ Designated as safety issue: No ]
  • Proportion of patients who achieved RNA levels below limit of quantification (BLoQ) (responders) [ Time Frame: up to 43 days (Part I), up to 168 days (Part II) ] [ Designated as safety issue: No ]
  • Number of patients with adverse events [ Time Frame: up to 240 days ] [ Designated as safety issue: No ]
  • Number of patients with abnormal changes in laboratory parameters [ Time Frame: Baseline, day 14, 28, 43 (Part I), up to 168 days (Part II) ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: April 1999
Primary Completion Date: July 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nevirapine

Part I: Study days 15-43

Part II: Study day 44 to end of trial

Drug: Nevirapine
Active Comparator: Amprenavir

Part I: Study days 0 to 43

Part II: Study day 44 to end of trial

Drug: Amprenavir
Active Comparator: Abacavir

Part I: Study days 0 to 43

Part II Study day 44 to end of trial

Drug: Abacavir

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients between the ages of 18 and 65 years, inclusive;
  • Plasma HIV-1 RNA >= 5000 copies/mL, documenting HIV-1 infection
  • CD4+ cell count >= 100 cells/mm³
  • Patients who met the following laboratory parameter:

    • Lymphocyte count >= 1000 cells/mm³
    • Hemoglobin >= 9.0 g/dl (men and women)
    • Platelet count >= 75000 cells/mm3
    • Alkaline Phosphatase <= 3.0 times the upper limit of normal
    • Serum Glutamic-Oxaloacetic Transaminase (SGOT) and Serum Glutamic-Pyruvic Transaminase (SGPT) <= 3.0 times the upper limit of normal
    • Total bilirubin <= 1.5 times the upper limit of normal
    • Creatinine <= 2mg/dL
  • Female patients of reproductive potential had to be willing to use a reliable method of double-barrier contraception (such as diaphragm with spermicidal cream or jelly, or condoms with spermicidal foam)
  • Patients who were informed of and willing and able to comply with the investigational nature of the study and had signed a written consent in accordance with institutional and federal guidelines

Exclusion Criteria:

  • Female patients who were pregnant or breast-feeding
  • Female patients who intended to change their double-barrier contraception method within 28 days prior to Study Day 0 and throughout the trial
  • Patients who in the opinion of the investigator required treatment with a prohibited medication during the study including the potentially toxic substrates such as terfenadine, bepridil, astemizole, cisapride, triazolam, midazolam and ergotamine/dihydroergotamine containing regimes
  • Patients taking known inhibitors or inducers of Cytochrome P450 metabolic enzymes including macrolide antibiotics (erythromycin, clarithromycin, azithromycin) azole antifungals (fluconazole, itraconazole) and phenytoin within 28 days prior or Study day 0 and throughout the trial
  • Patients receiving immunomodulatory agents
  • Ketoconazole, rifabutin and rifampin were excluded during screening and throughout the trial
  • Patients with previous exposure to anti-retroviral, such as delavirdine, loviride, efavirenz, nevirapine, abacavir, saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, zidovudine, Lamivudine (3TC), Stavudine (d4T), Didanosine (ddI) and Zalcitabine (ddC)
  • Patients receiving any investigational drug or systemic corticosteroids within 30 days of the first dose of study medication and system corticosteroids initially as well as throughout the study and any antineoplastic agent of radiotherapy other than local skin radiotherapy treatment within 12 weeks before starting study medication
  • Patients with malabsorption, severe chronic diarrhea or patients unable to maintain adequate oral intake
  • Patients currently abusing alcohol or substance abusing; patients on methadone substitution programs might be considered for inclusion in the trial
  • Patients undergoing treatment for an active infection
  • Patients with hepatic insufficiency due to cirrhosis
  • Patients with renal insufficiency
  • Patients who were heavy smokers (e.g. > 20 cigarettes per day)
  • Patients whose reliability was deemed to put them at risk for non-compliance with the study
  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.

No Contacts or Locations Provided
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02182765     History of Changes
Other Study ID Numbers: 1100.1244
Study First Received: July 3, 2014
Last Updated: July 11, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 23, 2014