Pharmacokinetic Evaluation of Changes in Nevirapine AUC Due to Differences in Weight (NAWS)

This study has been completed.
Sponsor:
Collaborator:
Jeffrey Goodman Clinic, LA Gay & Lesbian Center
Information provided by:
Western University of Health Sciences
ClinicalTrials.gov Identifier:
NCT01335360
First received: December 7, 2010
Last updated: April 12, 2011
Last verified: April 2011
  Purpose

This study would be a prospective cohort study, stratified by weight. Patients who are stable on nevirapine for at least 3 months prior to study entry, but no more than 1year will be recruited. For 1 week, subjects will take their morning dose of nevirapine in the clinic (and be observed taking it), and given their evening dose to take at home. Subjects will need to record the date and time they take their evening dose. At the end of the week, the subjects will be sequestered at the clinic for blood draws for a 12hr pharmacokinetic sampling. They will not be brought back in at 24hrs as they will need to be redosed after 12hrs. They will have Liver Function Tests (LFT's) and other labs drawn at study entry, and one month after the end of study. Pharmacokinetic levels will be analyzed using standard mathematical models, and Area Under the Curve (AUC), Maximum concentration (Cmax), and Minimum Concentration (Cmin) will be compared between groups.


Condition Intervention
HIV Infection
Drug: Nevirapine

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Pharmacokinetic Evaluation of Changes in Nevirapine AUC Due to Differences in Weight

Resource links provided by NLM:


Further study details as provided by Western University of Health Sciences:

Primary Outcome Measures:
  • Differences in AUC based on weight/BMI [ Time Frame: 12 hours ] [ Designated as safety issue: No ]
    This study was a "snapshot" of the PK levels following ingestion, and then compared AUC to weight and BMI.


Biospecimen Retention:   None Retained

Levels were drawn prior to dosing, and at the following time intervals: 0.5hr, 1hr, 1.5hr, 2hr, 4hr, 6hr, 8hr, 12hr. ~10cc of blood were drawn with each sample, centrifuged, and plasma separated into 2 cryovials. Samples were then frozen at -20oC. All samples (216) weresent to Consolidated Laboratory Services for level determination by appropriate means. All samples have now been destroyed.


Enrollment: 21
Study Start Date: May 2003
Study Completion Date: June 2003
Primary Completion Date: May 2003 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Subjects >80kg
As above
Drug: Nevirapine
200mg twice daily of nevirapine
Subjects <70kg
As above
Drug: Nevirapine
200mg twice daily of nevirapine
Subjects 70-80kg
As above
Drug: Nevirapine
200mg twice daily of nevirapine

  Hide Detailed Description

Detailed Description:

This will be a non-randomized, cohort study. 8 patients in each of 3 weight ranges (< 160lb, 161-200lb, > 200lb) will be recruited to participate in the study. Subjects will be HIV + patients currently on stable therapy with nevirapine (on medication for at least 3 months with minimal self-reported adherence) as part of a combination regimen for their Human Immunodeficiency Virus (HIV) infection (as prescribed by their primary care provider). Subjects are to be in good health with liver function tests will be < 2 times normal limits, measured within 1 month prior to the study period. All subjects will be male. The reasoning for this gender bias is as follows: if both genders are to be used, there should be an equal number of male and female subjects to remove any bias from the data. Since there are not enough females taking nevirapine to be able to appropriately recruit, females will be excluded.

Subjects will be asked to take their medications the night before the study period between 8:00pm and 8:30pm, and asked to abstain from alcohol for the 7 days prior to the study. On the study day, they will report to the Jeffrey Goodman Special Care Clinic at 7:30, prior to breakfast.

Subjects will randomly be divided into 4 groups during the study period. Four healthcare professionals (one physician, one family nurse practitioner, one registered nurse and one licensed vocational nurse, will be present throughout the study for catheter insertions and blood draws. IV catheters will be inserted upon arrival, with four patients (one from each group) having a time zero and receiving their study medication at each time point of 8:00, 8:05, 8:10, 8:15, 8:20, 8:25 (this is to allow for appropriate work-flow during the blood draw portion of the study. Serial blood samples will be drawn after dosing at the following times: 0.5hr, 1hr, 1.5hr, 2hr, 4hr, 6hr, 8hr, 12hr. Subjects will be allowed to eat breakfast (supplied by the study personnel) After the 1hr blood sample. Lunch and dinner will also be available for study subjects. 12hr sample, the catheters will be removed and the subjects allowed to leave (subjects will not be allowed to leave the premises with the catheter in place). Subjects will be paid $250 for their participation after the conclusion of the study.

Consolidated Laboratory Services will analyze all blood samples for nevirapine levels. AUC's and AUC comparisons will be calculated with appropriate statistical software (Systat).

Pharmacokinetic (PK) Levels:

Levels will be drawn prior to dosing, and at the following time intervals: 0.5hr, 1hr, 1.5hr, 2hr, 4hr, 6hr, 8hr, 12hr. ~10cc of blood will be drawn with each sample, centrifuged, and plasma separated into 2 cryovials. Samples will then be frozen at -20oC. All samples (216) will be sent to Consolidated Laboratory Services for level determination by appropriate means.

Safety monitoring:

A licensed physician and a licensed family nurse practitioner will be on site for the entire study. All study personnel are certified in Basic Life Support (and some in Advanced Cardiac Life Support). The clinic facilities are equipped for minor emergencies and 911 will be utilized for major emergencies.

Statistics:

AUC's will be calculated using non-linear mathematical modeling with statistical software. AUC's will be compared using appropriate statistical tests.

Evaluation of Adverse Events:

All adverse events will be recorded and treated (if necessary) on site. Adverse events not able to be treated on site will be referred to an emergency room or to their primary provider the following day (if it is not urgent).

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

HIV positive patients stable on a nevirapine containing regimen for at least 3 months

Criteria

Inclusion criteria:

  1. Documented HIV infection
  2. 18-50yrs of age
  3. Male
  4. Currently on nevirapine therapy for at least 3 months
  5. LFT's < 2 times normal limits within one month prior to study date
  6. In good health as judged by their primary care provider or a study provider within one month of the study date
  7. Willing to abstain for 1 week prior to study date
  8. No active opportunistic infections within one month prior to the study date
  9. Willingness to sign informed consent

Exclusion criteria:

  1. Active substance abuse
  2. Poor self reported adherence to nevirapine therapy
  3. Chronic liver disease or active hepatitis
  4. Concurrent administration of medications with a known or suspected pharmacokinetic drug interaction with nevirapine (such as …)
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01335360

Locations
United States, California
Jeffrey Goodman Clinic
Los Angeles, California, United States, 90028
Sponsors and Collaborators
Western University of Health Sciences
Jeffrey Goodman Clinic, LA Gay & Lesbian Center
Investigators
Principal Investigator: James D Scott, PharmD Western University of Health Sciences
  More Information

No publications provided

Responsible Party: James D. Scott, PharmD, Associate Professor, Western University
ClinicalTrials.gov Identifier: NCT01335360     History of Changes
Other Study ID Numbers: WesternU
Study First Received: December 7, 2010
Last Updated: April 12, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Western University of Health Sciences:
nevirapine
pharmacokinetics

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

ClinicalTrials.gov processed this record on September 16, 2014