HIV InfectionPhase 1NCT00006519
Capravirine to Treat Children With HIV Infection
A Phase 1 study testing Capravirine in people with HIV Infection, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This study will test the safety, side effects and anti-HIV activity of different doses of capravirine in children and adolescents with HIV infection. Capravirine belongs to a class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), which prevent the virus from replicating (making more copies of… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HIV Infection
- What is being tested?
- Capravirine
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2000to Oct 2004
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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:
Who cannot join
- 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.
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- 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 excluded.
- Weighting less than 10 kg.
- Pregnant or breast feeding females will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Study of Capravirine (AG 1549), a Novel Non-Nucleoside Reverse Transcriptase Inhibitor in Children With HIV Infection
This study will test the safety, side effects and anti-HIV activity of different doses of capravirine in children and adolescents with HIV infection. Capravirine belongs to a class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), which prevent the virus from replicating (making more copies of itself). Other NNRTIs are nevirapine, delavirdine and efavirenz.
HIV-infected children between the ages of 4 months and 21 years may be eligible for this study if they: 1) have received less than 6 weeks of treatment with antiretroviral drugs; 2) have not benefited from antiretroviral therapy after 12 weeks of treatment; 3) cannot continue antiretroviral treatment because of harmful side effects.
Read more
For the first week of the study, participants will have a 1-week "washout period" in which they will receive no anti-HIV therapy. During this time, they will have physical, eye and neuropsychologic examinations, blood and urine tests, echocardiogram, electrocardiogram (EKG), chest X-ray, head CT scan and skin tests. These physical exams and tests will be repeated throughout the study to determine changes in health.
After the washout period, patients will take capravirine once a day in the morning for 6 days. After each dose, a small amount of blood will be drawn at 8 different times over 12 hours to measure the activity of the drug and HIV blood levels. A heparin lock will be placed in the vein to avoid multiple needlesticks. After the 6 days of capravirine there will be another washout period, this time for 21 days. During this time, doctors will determine the optimum combination therapy for the individual patient.
After the second washout, patients will begin combination therapy with capravirine plus at least two other anti-HIV medicines. (These may include a reverse transcriptase inhibitor such as zidovudine, didanosine, lamuvidine, zalcitabine, or stavudine, and maybe one or more protease inhibitors such as ritonavir, nelfinavir, saquinavir, indinavir or amprenavir.) For the first week, patients will have a daily blood test to determine HIV blood levels. Afterwards, treatment will continue on an outpatient basis with clinic visits every 4 to 8 weeks for physical exams, lab tests and other procedures as required. The study will last approximately 48 weeks. Patients who benefit from capravirine therapy may be able to continue to receive the drug from the drug company sponsor or as part of another study, or the protocol for this study may be amended to lengthen the treatment period.
Read the detailed description
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.
- Conditions
- HIV Infection
- Being tested
- Capravirine
- Keywords
- Pharmacokinetic, Pediatric AIDS, Resistance Testing, Combination Therapy, Viral Drug Dynamics, Treatment Experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapravirineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2000 (estimated)
- Study startNov 2000
- Study completionOct 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 96 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006519
- Sponsor's protocol ID
- 010025
- Other IDs
- 01-C-0025
- Status last verified
- Oct 2004
- First submitted
- 23 Nov 2000
- Last updated
- 11 Jul 2006
- Results posted
- No
Publications
Carpenter CC, Cooper DA, Fischl MA, Gatell JM, Gazzard BG, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Saag MS, Schechter M, Schooley RT, Thompson MA, Vella S, Yeni PG, Volberding PA. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA. 2000 Jan 19;283(3):381-90. doi: 10.1001/jama.283.3.381.
PubMed 10647802Cavert W, Notermans DW, Staskus K, Wietgrefe SW, Zupancic M, Gebhard K, Henry K, Zhang ZQ, Mills R, McDade H, Schuwirth CM, Goudsmit J, Danner SA, Haase AT. Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection. Science. 1997 May 9;276(5314):960-4. doi: 10.1126/science.276.5314.960.
PubMed 9139661Condra JH. Resistance to HIV protease inhibitors. Haemophilia. 1998 Jul;4(4):610-5. doi: 10.1046/j.1365-2516.1998.440610.x.
PubMed 9873802
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Capravirine (AG 1549), a Novel Non-Nucleoside Reverse Transcriptase Inhibitor in Children With HIV Infection
- ClinicalTrials.gov ID
- NCT00006519
- Acronym / sponsor ID
- 010025
- Conditions
- HIV Infection
- Keywords
- Pharmacokinetic, Pediatric AIDS, Resistance Testing, Combination Therapy, Viral Drug Dynamics, Treatment Experienced
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Nov 2000
- Study completion
- Oct 2004
- First posted
- 24 Nov 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test the safety, side effects and anti-HIV activity of different doses of capravirine in children and adolescents with HIV infection. Capravirine belongs to a class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), which prevent the virus from replicating (making more copies of itself). Other NNRTIs are nevirapine, delavirdine and efavirenz.
HIV-infected children between the ages of 4 months and 21 years may be eligible for this study if they: 1) have received less than 6 weeks of treatment with antiretroviral drugs; 2) have not benefited from antiretroviral therapy after 12 weeks of treatment; 3) cannot continue antiretroviral treatment because of harmful side effects.
For the first week of the study, participants will have a 1-week "washout period" in which they will receive no anti-HIV therapy. During this time, they will have physical, eye and neuropsychologic examinations, blood and urine tests, echocardiogram, electrocardiogram (EKG), chest X-ray, head CT scan and skin tests. These physical exams and tests will be repeated throughout the study to determine changes in health.
After the washout period, patients will take capravirine once a day in the morning for 6 days. After each dose, a small amount of blood will be drawn at 8 different times over 12 hours to measure the activity of the drug and HIV blood levels. A heparin lock will be placed in the vein to avoid multiple needlesticks. After the 6 days of capravirine there will be another washout period, this time for 21 days. During this time, doctors will determine the optimum combination therapy for the individual patient.
After the second washout, patients will begin combination therapy with capravirine plus at least two other anti-HIV medicines. (These may include a reverse transcriptase inhibitor such as zidovudine, didanosine, lamuvidine, zalcitabine, or stavudine, and maybe one or more protease inhibitors such as ritonavir, nelfinavir, saquinavir, indinavir or amprenavir.) For the first week, patients will have a daily blood test to determine HIV blood levels. Afterwards, treatment will continue on an outpatient basis with clinic visits every 4 to 8 weeks for physical exams, lab tests and other procedures as required. The study will last approximately 48 weeks. Patients who benefit from capravirine therapy may be able to continue to receive the drug from the drug company sponsor or as part of another study, or the protocol for this study may be amended to lengthen the treatment period.
Detailed description
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Capravirine | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2006.
- Background: PubMed 10647802Carpenter CC, Cooper DA, Fischl MA, Gatell JM, Gazzard BG, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Saag MS, Schechter M, Schooley RT, Thompson MA, Vella S, Yeni PG, Volberding PA. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA. 2000 Jan 19;283(3):381-90. doi: 10.1001/jama.283.3.381.
- Background: PubMed 9139661Cavert W, Notermans DW, Staskus K, Wietgrefe SW, Zupancic M, Gebhard K, Henry K, Zhang ZQ, Mills R, McDade H, Schuwirth CM, Goudsmit J, Danner SA, Haase AT. Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection. Science. 1997 May 9;276(5314):960-4. doi: 10.1126/science.276.5314.960.
- Background: PubMed 9873802Condra JH. Resistance to HIV protease inhibitors. Haemophilia. 1998 Jul;4(4):610-5. doi: 10.1046/j.1365-2516.1998.440610.x.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Capravirine in people with HIV Infection, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00006519, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2006.