Know Cancer

forgot password

A Phase I Study of Capravirine (AG 1549), a Novel Non-Nucleoside Reverse Transcriptase Inhibitor in Children With HIV Infection

Phase 1
Not Enrolling
HIV Infection

Thank you

Trial Information

A Phase I Study of Capravirine (AG 1549), a Novel Non-Nucleoside Reverse Transcriptase Inhibitor in Children With HIV Infection

This is a pediatric phase I dose escalation study to determine a biologically active dose
and to obtain information concerning the safety, tolerability, and pharmacokinetics of
capravirine (AG
1549)(5-[(3,5-dichlorophenyl)thio]-4-(1-methylethyl)-1-(4-pyridinylmethyl)-1H-imidazol-2-methanol carbamate), a potent non-nucleoside HIV-1 reverse transcriptase (RT) inhibitor, that induces a novel pattern of resistance mutations. In addition to obtaining needed biological activity, pediatric safety, tolerability, and pharmacokinetic data, the study will utilize capravirine's potent antiretroviral activity and novel resistance mutation pattern, together with serial measurements of plasma HIV viral load, flow cytometry, and genotypic and phenotypic viral resistance analysis to conduct pilot studies in pediatric HIV pathogenesis, the response to antiretroviral therapy, and to develop strategies to optimize the management of pediatric antiretroviral therapy. We will also use initial viral decay dynamics and other patient characteristics to model predictions for the long-term response to antiretroviral therapy. We will enroll children who have become refractory to or have experienced toxicity on prior therapy. The study will include resistance testing on the failing regimen, a one week period off antiretrovirals (washout period), an initial 6 days of capravirine monotherapy followed by capravirine in combination with the optimal antiretroviral therapy as determined by their baseline viral resistance mutation pattern and history. The patients will be followed for at least 48 weeks to assess long-term tolerability and toxicity, and to assess the clinical, virological, and immunological response to capravirine.

Inclusion Criteria


Age: Two age groups will be enrolled and studied separately.

Group 1: 4 months to less than 2 years.

Group 2: 2 years to less than 21 years.

Gender and Ethnicity: There will be no restriction as to genderor ethnicity. A resonable
effort will be made to include chldren of both genders and all ethnic backgrounds.

HIV-infected children between the ages of 4 months and 21 years.

An indication for treatment with antiretrovirals.

One of the following: Children failing current treatment after at least 12 weeks of
therapy as defined by the most recent Guidelines for the Use of Antiretroviral Agents in n
Pediatric HIV Infection or accepted practice OR Intolerant to or are showing evidence of
toxicity from other antiretroviral treatments.

HIV RNA greater than or equal to 5,000 copies per/mL within the past 3 months (may be from
outside institution).

Women of childbearing age must agree to avoid becoming pregnant while on study and for 4
months afterwards.

Hematologic Function:

Total WBC greater than 1,500/mm(3),

Absolute neutrophil count greater than 750/mm(3),

Hemoglobin greater than 8.0 gm/dL, and

Platelet count greater than 75,000/mm(3) at study entry.

Hepatic Function:

Liver transaminases must be less than or equal to 3.0 times the upper limit of normal;

Serum amylase less than 1.5 times the upper limit of normal and if abnormal, fractionated
pancreatic amylase less than 45 U/L;

Lipase less than 1.5 times the upper limit of normal;

Creatinine phosphokinase (CPK) less than 2.5 times the upper limit of normal.

Renal Function:

Patients must have an age-adjusted normal serum creatinine OR a creatinine clearance
greater than or equal to 70 mL/min/1.73:


Therapeutic regimens including:

Immunomodulating agents (within 30 days of entry), other than GCSF, erythropoeitin,
corticosteroids, IVIG, or anti-D;

Treatment with chemotherapeutic agents (including hydroxyurea) or radiation therapy within
the past 6 weeks;

Current chronic use of medications known to inhibit or induce cytochrome P450, including
but not limited to: isoniazid, rifampin, rifabutin, astemizole, terfenadine, cisapride,
triazolam, midazolam, nifedipine, diltiazem, verapamil, cimetidine, dexamethasone,
carbamazepine, phenytoin, phenobarbital, propoxyphene, quinidine, amiodarone, or ergot
alkaloids, azole antifungals (ketoconazole, fluconazole, itraconazole), or macrolide
antibiotics (erythromycin, clarithromycin);

Current use of highly plasma protein bound drugs including but not limited to, warfarin
and phenytoin;

Current use, or use within the last 28 days, of any investigational agent.

Clinically significant, unrelated systemic illness (serious infections or significant
cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgement of the
Principal Investigator or Chairperson would compromise the patient's ability to tolerate
this therapy or is likely to interfere with the study procedures or results will be

Weighting less than 10 kg.

Pregnant or breast feeding females will be excluded.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

November 2000

Completion Date:

October 2004

Related Keywords:

  • HIV Infection
  • Pharmacokinetic
  • Pediatric AIDS
  • Resistance Testing
  • Combination Therapy
  • Viral Drug Dynamics
  • Treatment Experienced
  • HIV Infections
  • Acquired Immunodeficiency Syndrome



National Cancer Institute (NCI) Bethesda, Maryland  20892