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

An Investigation of the Potential Pharmacokinetic Interaction Between Nevirapine (VIRAMUNE®), Abacavir and Amprenavir in HIV-1 Infected NNRTI Naive Adults

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.

Study Overview

• Status: Terminated
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Nevirapine; Drug: Amprenavir; Drug: Abacavir

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC (area under plasma concentration time curve) of amprenavir in the absence and presence of nevirapine	Day 14, day 43
Cmax (maximum observed concentration of the analyte in plasma) of amprenavir in the absence and presence of nevirapine	Day 14, day 43
AUC (area under plasma concentration time curve) of abacavir in the absence and presence of nevirapine	Day 14, day 43
Cmax (maximum observed concentration of the analyte in plasma) of abacavir in the absence and presence of nevirapine	Day 14, day 43

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in HIV-1 Ribonucleic Acid (RNA)	Baseline, day 14, 21, 28, 35, 43 (Part I), up to 168 days (Part II)
Change from baseline in Lymphocytes Expressing CD4+ cell count	Baseline, day 14, 21, 28, 35, 43 (Part I), up to 168 days (Part II)
Proportion of patients who achieved RNA levels below limit of quantification (BLoQ) (responders)	up to 43 days (Part I), up to 168 days (Part II)
Number of patients with adverse events	up to 240 days
Number of patients with abnormal changes in laboratory parameters	Baseline, day 14, 28, 43 (Part I), up to 168 days (Part II)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 1999
• Primary Completion (ACTUAL): July 1, 2001

Study Registration Dates

• First Submitted: July 3, 2014
• First Submitted That Met QC Criteria: July 3, 2014
• First Posted (ESTIMATE): July 8, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): July 14, 2014
• Last Update Submitted That Met QC Criteria: July 11, 2014
• Last Verified: July 1, 2014

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; 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; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Nevirapine; Abacavir; Amprenavir
• Other Study ID Numbers: 1100.1244