Study to Determine the Effects of Nevirapine (VIRAMUNE®) on the Steady State Pharmacokinetics of Rifabutin (MYCOBUTIN®) in HIV+ Patients

An Open-label Study in HIV+ Patients to Determine the Effects of Nevirapine (VIRAMUNE®) on the Steady State Pharmacokinetics of Rifabutin (MYCOBUTIN®)

Study to determine the effects of nevirapine on the steady state pharmacokinetics of rifabutin and to assess the steady state pharmacokinetics of nevirapine when given in combination with rifabutin

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Nevirapine; Drug: Rifabutin

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

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 who are seropositive for HIV-1 antibody by an ELISA test and confirmed by an alternative method e.g. Western Blot
• Lymphocytes Expressing CD4+ Surface Marker (CD4+ cell count) >= 100 cells/mm³
• Patients must be taking at least 2 antiretroviral agents (with the exception of ritonavir, nelfinavir and non-nucleoside reverse transcriptase inhibitors taken continuously for at least 28 days prior to study entry (Day 0)
• Patients currently being treated with rifabutin during the screening period may be included provided that patients are receiving 300 mg once daily (or 150 mg once daily for patients concomitantly taking Zidovudine (ZDV), saquinavir or indinavir) and that there has been no change in dosing of > 25% within 28 days prior to Study Day 0

• Patients who meet the following laboratory parameter:

  • Granulocyte 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
• Female patients of childbearing potential must be willing to use a reliable form of contraception which must include a medically form of barrier contraception
• Patients able to provide written consent and comply with study requirements

Exclusion Criteria:

• Female patients who are pregnant or breast-feeding
• Seated systolic blood pressure below 100 mmHg or greater than 150 mmHg and/or heart rate less than 50 or greater than 90 beats/min.
• History of drug allergy or known drug hypersensitivity
• Patients receiving any investigational drug, antineoplastic agent or radiotherapy other than local skin radiotherapy treatment within 12 weeks before starting study medication
• Patients requiring systemic treatment with corticosteroids or drugs known to be hepatic enzyme inducers or inhibitors within 14 days of study entry (Study Day 0). Such substances in theses categories include: macrolide antibiotics (erythromycin, clarithromycin, azithromycin) azole antifungals (ketoconazole, fluconazole, itraconazole) rifampin and phenytoin
• Use of ritonavir, nelfinavir or non-nucleoside reverse transcriptase inhibitors within 28 days of Study Day 0 or during the trial
• Patients with clinical evidence of active tuberculosis (TB) or undergoing treatment or prophylaxis for TB
• Patients with a current history of intravenous drug abuse, alcohol or substance abuse (within the last year)
• History of any clinically important disease including hepatic, renal, cardiovascular or gastrointestinal
• Patients with malabsorption, severe chronic diarrhea or subject unable to maintain adequate oral intake
• Patients with no previous antiretroviral background therapy taken continuously for the 28 days prior to study entry (Day 0)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: single group; Nevirapine: Study days 15-28 dose given once a day (q.d.) Study days 29-42 dose given twice a day (b.i.d.) Rifabutin: Study Days 0 to 42	Drug: Nevirapine; Drug: Rifabutin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax,ss (maximum observed concentration at steady state)	predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose at day 14 and day 42
Cmin,ss (minimum observed concentration at steady state)	predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose at day 14 and day 42
Tmax,ss (Time of Cmax at steady state)	predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose at day 14 and day 42
Area under the plasma concentration time curve over the dosing interval	predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose at day 14 and day 42
CL/F (apparent total clearance)	predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose at day 14 and day 42

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patient with adverse events	up to day 43

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 1998
• Primary Completion (Actual): December 1, 1998

Study Registration Dates

• First Submitted: July 8, 2014
• First Submitted That Met QC Criteria: July 8, 2014
• First Posted (Estimate): July 9, 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; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Nevirapine; Rifabutin
• Other Study ID Numbers: 1100.1258