Clinical trial NCT00000634: A Pilot Pharmacokinetic Phase I Evaluation of BI-RG-587 in HIV-Infected Children
Official title: A Pilot Pharmacokinetic Phase I Evaluation of BI-RG-587 in HIV-Infected Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Benzodiazepines
Drug Evaluation
Drugs, Investigational
Acquired Immunodeficiency Syndrome
Antiviral Agents
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Boehringer Ingelheim
First posted: 2001-08-31
Enrollment: 6
Sex: ALL
Minimum age (years): 2
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To generate initial information on the pharmacokinetics (blood levels) and dose proportionality of nevirapine (BI-RG-587) plasma levels in HIV-infected children; to assess the safety and tolerance of single rising oral doses of nevirapine in HIV-infected children; and to confirm that the single doses that achieve certain plasma levels in adults achieve similar levels in HIV-infected children.

Test tube studies have shown that nevirapine (BI-RG-587) inhibits replication (reproduction) of HIV. Nevirapine works with zidovudine (AZT) and is active against strains of the virus that are resistant to AZT. Studies of the drug in HIV-infected adults showed no serious adverse effects.

Detailed description: Test tube studies have shown that nevirapine (BI-RG-587) inhibits replication (reproduction) of HIV. Nevirapine works with zidovudine (AZT) and is active against strains of the virus that are resistant to AZT. Studies of the drug in HIV-infected adults showed no serious adverse effects.

Two doses, given by mouth, are evaluated: Three patients receive the lower dose, and 7 days after the third patient receives the lower dose, three additional patients receive the higher dose. After dosing, blood is drawn at 1, 2, 4, 8, 24, 48, 96, 168 hours to measure blood levels of the drug.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Intravenous gammaglobulin. Pneumocystis prophylaxis according to published guidelines.

Patients must have the following:

* HIV infection.
* Parent or guardian must be available to give written informed consent.

Exclusion Criteria

Concurrent Medication:

Excluded:

* Zidovudine (AZT).
* Steroid dependency.

Excluded within 1 hour before and 4 hours after study drug administration:

* Drugs that might interfere with the absorption of study drug (H2 blockers, antacids, carafate, cholestyramine).
* Benzodiazepines.
* Alcohol-containing substances.

Concurrent Treatment:

Excluded:

* Requiring supplemental oxygen.

Patients with the following are excluded:

* Active opportunistic or serious bacterial infection.
* Lymphoid interstitial pneumonitis (LIP) and steroid dependent or requiring supplemental oxygen or have a pretreatment pa02 \< 70 mm Hg.
* Pre-existing malignancies.

Prior Medication:

Excluded:

* Zidovudine (AZT) within 7 days prior to administration of study drug.

Excluded for at least 4 weeks prior to drug administration:

* Other approved or investigational antiretroviral agents. All other investigational agents. Biologic response modifiers (e.g., interferon) or immunomodulators. Immunosuppressive agents (including glucocorticoids). Coumadin and other anticoagulant medications.

Prior Treatment:

Excluded:

* Red blood cell transfusion within 4 weeks of study entry.

Patients may not have the following:

* Opportunistic or serious bacterial infection.

Zidovudine (AZT) \> 7 days prior to administration of study drug.

Active alcohol or drug abuse.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Worcester
country: United States
facility: Univ of Massachusetts Med Ctr / Biotech II
state: Massachusetts
Study officials:
References:
citation: Luzuriaga K, Bryson Y, McSherry G, Robinson J, Stechenberg B, Scott G, Lamson M, Cort S, Sullivan JL. Pharmacokinetics, safety, and activity of nevirapine in human immunodeficiency virus type 1-infected children. J Infect Dis. 1996 Oct;174(4):713-21. doi: 10.1093/infdis/174.4.713.