NCT00000962

Brief Summary

To assess the safety and tolerance of multiple oral doses of Nevirapine (BI-RG-587). To generate data on the pharmacokinetics and dose proportionality of Nevirapine with multiple dosing. To characterize the pattern of virological activity in vivo. Improvement in virological end points will be examined for association with dose and absorption. To determine whether development of resistance is reflected in return of virological activity and, if so, when markers reflect this resistance. To determine if improvements of immunological endpoints are detectable in the number of patients studied. A compound free of the toxic effects of nucleoside chain terminators such as zidovudine (AZT) may have an advantage over currently available treatments for HIV infection. Such a compound has further advantages if it is active against AZT-resistant isolates. Nevirapine (BI-RG-587) has shown in vitro inhibitory activity against HIV-1 reverse transcriptase (RT). The molecular mechanism of the RT inhibitory effect is hypothesized to be non-competitive inhibition due to its binding to an RT site distinct from those for the RNA template primer, the deoxynucleotide triphosphate or the RNase H catalytic site.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1 hiv-infections

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 2, 1999

Completed
1.8 years until next milestone

First Posted

Study publicly available on registry

August 31, 2001

Completed
Last Updated

August 4, 2008

Status Verified

December 1, 1994

First QC Date

November 2, 1999

Last Update Submit

August 1, 2008

Conditions

HIV Infections

Keywords

Drug EvaluationAcquired Immunodeficiency SyndromeAIDS-Related ComplexNevirapine

Interventions

NevirapineDRUG

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Concurrent Medication:
  • Allowed:
  • Pentamidine or dapsone prophylaxis for Pneumocystis carinii pneumonia (PCP) in patients with a CD4+ cell count = or \< 200 cells/mm3.
  • Antifungal prophylaxis with oral fluconazole or ketoconazole.
  • Antiviral prophylaxis with a maximum of 1 gram of oral acyclovir per day.
  • Acute therapy for intercurrent infections so long as that therapy is not an excluded medication of an excluded opportunistic infection.
  • Patients must have:
  • Positive HIV antibody test results by ELISA.
  • Average of CD4+ cell count at 60 and at 21 days prior to study beginning = or \< 400 cells/mm3.
  • Seven of 10 patients in each treatment arm must have p24 antigen levels = or \> 70 pg/ml (\> 50 pg/ml at U. of Mass. site only) or be plasma viremic.
  • Preserved hematologic, hepatic, and renal function as defined by required lab values.
  • Ambulatory performance score of = or \> 70 Karnofsky.
  • Ability to voluntarily provide written informed consent prior to treatment.
  • Willingness and ability to follow protocol requirements.

You may not qualify if:

  • Co-existing Condition:
  • Patients with the following symptoms or conditions are excluded:
  • Active cytomegalovirus disease.
  • Toxoplasmic encephalitis requiring suppressive therapy.
  • Mycobacteriosis requiring maintenance chemotherapy.
  • Visceral Kaposi's sarcoma requiring chemotherapy and/or irradiation.
  • Malignancy other than Kaposi's sarcoma or limited cutaneous basal cell carcinoma.
  • More than mild diarrhea (defined as more than transient or \> 4 loose stools per day).
  • Concurrent Medication:
  • The following medications / substances may NOT be ingested up to one hour before or 4 hours after a Nevirapine dose:
  • Antacids (particularly those containing calcium carbonate).
  • Cimetidine.
  • Carafate.
  • Cholestyramine resin.
  • Alcohol and alcohol-containing substances.
  • +33 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Univ of California / San Diego Treatment Ctr

San Diego, California, 921036325, United States

Location

Univ of Massachusetts Med Ctr

Worcester, Massachusetts, 01655, United States

Location

Univ of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (10)

  • Greenough TC. Quantitative virology: the experience during the nevirapine phase I/II trials. ACTG 164/168 Study Team. Int Conf AIDS. 1992 Jul 19-24;8(2):B192 (abstract no PoB 3610)

    BACKGROUND

  • Havlir D, Cheeseman SH, McLaughlin M, Murphy R, Erice A, Spector SA, Greenough TC, Sullivan JL, Hall D, Myers M, et al. High-dose nevirapine: safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection. J Infect Dis. 1995 Mar;171(3):537-45. doi: 10.1093/infdis/171.3.537.

    PMID: 7533197BACKGROUND

  • Havlir D. Antiviral activity of nevirapine at 400 mg in p24 antigen positive adults. ACTG 164 and 168 Study Teams. Int Conf AIDS. 1993 Jun 6-11;9(1):69 (abstract no WS-B26-1)

    BACKGROUND

  • Richman DD. Loss of nevirapine activity associated with the emergence of resistance in clinical trials. The ACTG 164/168 Study Team. Int Conf AIDS. 1992 Jul 19-24;8(2):B183 (abstract no PoB 3576)

    BACKGROUND

  • Hattox S. Pharmacokinetics of nevirapine alone and in combination with zidovudine. The ACTG 164/168 Study Team. Int Conf AIDS. 1992 Jul 19-24;8(2):B185 (abstract no PoB 3591)

    BACKGROUND

  • Cheeseman SH, Murphy RL, Saag MS, Havlir D. Safety of high dose nevirapine (NVP) after 200 mg/d lead-in. ACTG 164/168 Study Team. Int Conf AIDS. 1993 Jun 6-11;9(1):487 (abstract no PO-B26-2109)

    BACKGROUND

  • Cheeseman SH. Nevirapine (NVP) alone and in combination with zidovudine (ZDV): safety and activity. The ACTG 164/168 Study Team. Int Conf AIDS. 1992 Jul 19-24;8(1):Mo15 (abstract no MoB 0053)

    BACKGROUND

  • Zhang H, Dornadula G, Wu Y, Havlir D, Richman DD, Pomerantz RJ. Kinetic analysis of intravirion reverse transcription in the blood plasma of human immunodeficiency virus type 1-infected individuals: direct assessment of resistance to reverse transcriptase inhibitors in vivo. J Virol. 1996 Jan;70(1):628-34. doi: 10.1128/JVI.70.1.628-634.1996.

    PMID: 8523584BACKGROUND

  • Murphy RL, Montaner J. Nevirapine: A review of its development, pharmacological profile and potential for clinical use. Exp Opin Invest Drugs. 1996;5(9): 1183-1199

    BACKGROUND

  • Cheeseman SH, Havlir D, McLaughlin MM, Greenough TC, Sullivan JL, Hall D, Hattox SE, Spector SA, Stein DS, Myers M, et al. Phase I/II evaluation of nevirapine alone and in combination with zidovudine for infection with human immunodeficiency virus. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Feb 1;8(2):141-51.

    PMID: 7530585BACKGROUND

MeSH Terms

Conditions

HIV InfectionsAcquired Immunodeficiency SyndromeAIDS-Related Complex

Interventions

Nevirapine

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesSlow Virus Diseases

Intervention Hierarchy (Ancestors)

PyridinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Design

Study Type
interventional
Phase
phase 1
Purpose
TREATMENT
Sponsor Type
NIH

Study Record Dates

First Submitted

November 2, 1999

First Posted

August 31, 2001

Last Updated

August 4, 2008

Record last verified: 1994-12

Locations

US(3)