Pharmacokinetics Study on Nevirapine Resistance in Tanzania - Full Text View

Sponsor:	Radboud University
Information provided by:	Radboud University
ClinicalTrials.gov Identifier:	NCT00294892

Purpose

Primary

pharmacokinetics of single dose nevirapine
the effect of single dose carbamazepine on the pk of single dose nevirapine
resistance against nevirapine before and after.
follow-up on HIV status newborns
relation between nevirapine levels in cord blood and plasma

Secondary

* safety of single dose nevirapine and nevirapine/carbamazepine

Hypothesis:

Single dose carbamazepine decreases development of resistance to nevirapine in HIV positive pregnant Tanzanian women by decreasing nevirapine half-life.

Condition	Intervention	Phase
HIV Infections	Drug: carbamazepine and nevirapine Drug: Nevirapine	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Pharmacokinetics Study
Official Title:	The Effect of Single Dose Carbamazepine on the Pharmacokinetics of Single Dose Nevirapine (Viramune, NVP) and Development of NVP Resistance, PMTCT Program of Moshi, Tanzania (VITA1)

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Nevirapine Carbamazepine

U.S. FDA Resources

Further study details as provided by Radboud University:

Primary Outcome Measures:

Cord blood will be taken less than 30 minutes after delivery [ Time Frame: 0 - 30 min after delivery ] [ Designated as safety issue: No ]
Blood samples from mother will be taken less than 30 minutes after delivery to measure viral load and CD4 count. [ Time Frame: 0 - 30 min after delivery ] [ Designated as safety issue: No ]
Blood samples will be drawn from mother and child at week 1 (day 6-8), week 2 (day 13-15) and week 3 (day 20-22) [ Time Frame: day 6 - 22 after delivery ] [ Designated as safety issue: No ]
From all samples plasma nevirapine and if applicable carbamazepine levels will be determined in women and newborns. [ Time Frame: 0 30 min after delivery - week 3 after delivery ] [ Designated as safety issue: No ]

Estimated Enrollment:	144
Study Start Date:	February 2006
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Carbamazepine: Active Comparator An oral dose of 400mg Carbamazepine is added to the 200mg oral dose Nevirapine intake prior delivery	Drug: carbamazepine and nevirapine Carbamazepine 400mg and Nevirapine 200mg are taken just before delivery during labor.
Nevirapine: Placebo Comparator Standard therapy of 200mg Nevirapine oral prior to delivery	Drug: Nevirapine Nevirapine 200mg is taken prior to delivery during labor.

Detailed Description:

Without the use of preventative measures, the risk of mother-to-child transmission (MTCT) of HIV-1 is estimated to vary between 25 and 48%. The regimen of single dose of nevirapine to the mother just before delivery and a single dose of nevirapine to the newborn within 24 - 72 hours after birth reduces the risk of MTCT by 50%, is affordable in many situations and is therefore standard of care in many African countries, like Tanzania. Recent studies, however, have shown that this single dose to the mother can induce the occurrence of nevirapine resistance in a large number of mothers. The mechanism of occurrence of nevirapine resistance already after a single dose is most likely related to the long elimination half-life of the drug. The subtherapeutic plasma levels present the perfect environment for the occurrence of resistance as the concentrations are subinhibitory for several days.

Eligibility

Ages Eligible for Study:	18 Years to 40 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV infected
antiretroviral naive
not intending to relocate out of area during study
willing to adhere to follow up scheme
ability and willing to give written consent
pregnant between 18 and 40 years
willing and able to regularly attend the Antenatal clinic

Exclusion Criteria:

serious illness that requires systemic treatment or hospitalization
any condition that would compromise subject's ability to participate
previously treated for HIV with antiretroviral agents, including single dose nevirapine used for MTCT
inability to understand the nature and extent of the trial and procedures

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00294892

Contacts

Contact: Eva P. Muro, PhamD	+255 748468553	muroeva123@yahoo.com
Contact: Rafaella F. l'homme, Drs.	+31 24 3616405	r.lhomme@akf.umcn.nl

Locations

Tanzania
Kilimanjaro Christian Medical College	Recruiting
Moshi, Tanzania
Sub-Investigator: W. Schimana, MD
Sub-Investigator: O. Oneko, MD

Sponsors and Collaborators

Radboud University

Investigators

Principal Investigator:

David M. Burger, Dr.

Radboud University (RUNMC)

More Information

No publications provided

Responsible Party:	Radboud Universstiry Medical Centre ( Dr. D.M. Burger, hospital pharmacist )
Study ID Numbers:	VITA1
Study First Received:	February 21, 2006
Last Updated:	July 21, 2009
ClinicalTrials.gov Identifier:	NCT00294892 History of Changes
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:

HIV
mother to child transmission; MTCT
nevirapine resistance
pharmacokinetics
Treatment Naive

Additional relevant MeSH terms:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Sensory System Agents
Therapeutic Uses
Analgesics
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections

Anti-HIV Agents
Tranquilizing Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Central Nervous System Depressants
Enzyme Inhibitors
Antimanic Agents
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
Nevirapine
Carbamazepine
HIV Infections
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on February 08, 2010