Clinical trial NCT00000808: A Phase I Study of Safety and Pharmacokinetics of Nevirapine in HIV-1 Infected Pregnant Women and Neonates Born to HIV-1 Infected Mothers
Official title: A Phase I Study of Safety and Pharmacokinetics of Nevirapine in HIV-1 Infected Pregnant Women and Neonates Born to HIV-1 Infected Mothers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Pregnancy
Keywords: Pregnancy
Pregnancy Complications, Infectious
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Nevirapine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 49
Sex: FEMALE
Minimum age (years): 13
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To determine the bioavailability, pharmacokinetics, and short-term safety and tolerance of nevirapine in HIV-1 infected pregnant women and their newborns when nevirapine is given to the mother during active labor, and when their neonates are dosed during the first week of life. To determine the short-term safety profile of mothers receiving zidovudine (AZT) who received nevirapine during active labor, and their neonates who received no dose, a single dose, or multiple doses of nevirapine and who are receiving AZT during the first 6 weeks of life.

Treatment of HIV-1 infected pregnant women during active labor may result in therapeutic levels of nevirapine in the neonate at the time of exposure to HIV-1 during parturition, decreasing the neonate's risk of infection.

Detailed description: Treatment of HIV-1 infected pregnant women during active labor may result in therapeutic levels of nevirapine in the neonate at the time of exposure to HIV-1 during parturition, decreasing the neonate's risk of infection.

Pregnant women in active labor receive single doses of oral nevirapine. The neonates of the first 4-6 (PER AMENDMENT 8/27/96, was 4) mothers receive no drug, while the neonates of the second 4-6 (PER AMENDMENT 8/27/96, was 4) patient cohort receive a single dose of nevirapine. If neonatal antiviral levels of nevirapine are not sustained for 7 days after the single dose, a third cohort of 4-6 (PER AMENDMENT 8/27/96, was 4) pregnant women will receive a single dose of nevirapine and their neonates will receive multiple doses of nevirapine to maintain an antiviral effect for 7 days.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* AZT (mothers and neonates).
* Oral asthma inhalers (mothers).

Concurrent Treatment:

Allowed:

* Phototherapy (neonates).

MOTHERS must have:

* HIV infection.
* Estimated gestational age \>= 34 weeks.
* No active opportunistic infection at study entry.

PER AMENDMENT 8/27/96:

* A pre-enrollment plasma HIV-1 RNA level greater than 10,000 copies/ml.

Exclusion Criteria

Co-existing Condition:

MOTHERS with the following symptoms or conditions are excluded:

* Intrauterine growth retardation.
* Fetal anomaly incompatible with life as determined by pre-entry ultrasound.
* Participation during current pregnancy in any other therapeutic or vaccine perinatal trial.
* Known hypersensitivity to any benzodiazepine.
* Serious bacterial infection.

Concurrent Medication:

Excluded:

* Any antiretroviral other than AZT.
* Corticosteroids (other than oral asthma inhalers).
* Anticoagulants.
* Any clavulanic acid-containing formulation (e.g., Augmentin, Timentin).
* Benzodiazepines other than study drug.
* Phenobarbital.
* Barbiturates.
* Antacids.
* Magnesium sulfate.

Prior Medication:

Excluded:

* Prior nevirapine.

Current use of illicit substances and/or active chronic alcohol use.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Med Ctr / Pediatrics / Clinical Sciences
state: California
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: Los Angeles
country: United States
facility: UCLA Med Ctr / Pediatric
state: California
city: Los Angeles
country: United States
facility: Harbor - UCLA Med Ctr / UCLA School of Medicine
state: California
city: San Francisco
country: United States
facility: San Francisco Gen Hosp
state: California
city: San Francisco
country: United States
facility: UCSF / Moffitt Hosp - Pediatric
state: California
city: Farmington
country: United States
facility: Univ of Connecticut / Farmington
state: Connecticut
city: Hartford
country: United States
facility: Connecticut Children's Med Ctr - Pediatric
state: Connecticut
city: Chicago
country: United States
facility: Chicago Children's Memorial Hosp
state: Illinois
city: Chicago
country: United States
facility: Univ of Chicago Children's Hosp
state: Illinois
city: Boston
country: United States
facility: Children's Hosp of Boston
state: Massachusetts
city: Boston
country: United States
facility: Boston City Hosp / Pediatrics
state: Massachusetts
city: Worcester
country: United States
facility: Univ of Massachusetts Med School
state: Massachusetts
city: Newark
country: United States
facility: Univ of Medicine & Dentistry of New Jersey / Univ Hosp
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Med Ctr / Pediatrics
state: New York
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp
Study officials:
name: Sullivan JL
role: STUDY_CHAIR
name: Sperling R
role: STUDY_CHAIR
References:
citation: Vazquez E. Two bucks a baby. Posit Aware. 1997 Mar-Apr;8(2):15.
citation: Benson M, Shannon M. Nevirapine: ethical dilemmas and care for HIV-infected mothers. Focus. 1995 Jun;10(7):5-6.
citation: McKinney RE Jr. Ongoing and future trials of antiretroviral therapy in the pediatric AIDS clinical trials group (PACTG). Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:173
citation: Mirochnick M, Sullivan J, Cort S, Mcnamara J, Fenton T, Sperling R. Safety and pharmacokinetics (pk) of nevirapine (NVP) in HIV-I infected pregnant women and their newborns. ACTG Protocol 250 Team. American Pediatric Association and Society for Pediatric Research annual meeting; 1996 May 6-10; Washington, D.C. Pediatr AIDS HIV Infect. 1996 Aug;7(4):280 (unnumbered abstract)
citation: Mirochnick M, Fenton T, Gagnier P, Pav J, Gwynne M, Siminski S, Sperling RS, Beckerman K, Jimenez E, Yogev R, Spector SA, Sullivan JL. Pharmacokinetics of nevirapine in human immunodeficiency virus type 1-infected pregnant women and their neonates. Pediatric AIDS Clinical Trials Group Protocol 250 Team. J Infect Dis. 1998 Aug;178(2):368-74. doi: 10.1086/515641.