HIV InfectionsPhase 1/2NCT00485264
Safety and Pharmacokinetics (PK) of Raltegravir in HIV (Human Immunodeficiency Virus)-Infected Children and Adolescents
A Phase 1/2 study testing Raltegravir poloxamer film coated tablet, Raltegravir chewable tablet and Raltegravir oral granules for suspension (20 mg/mL) in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 42 sites in 6 countries.
Trial summary
Integrase is 1 of 3 HIV (Human Immunodeficiency Virus)-1 enzymes required for viral replication. Raltegravir is a drug that prevents integrase from working properly. This drug has been tested for safety and efficacy in adults, but this is the first study to examine raltegravir in children and adolescents. Read more about this study
- Who is it for?
- Ages 30 days to 18 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Raltegravir poloxamer film coated tablet, Raltegravir chewable tablet and Raltegravir oral granules for suspension (20 mg/mL)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 153 participants
- Where
- 42 sitesin 6 countries
- Study dates
- 17 Sep 2007to 18 May 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 30 days to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Documentation of HIV-1 infection, defined as positive results from two samples collected at different time points. More information on this criterion can be found in the protocol.
- For participants in Cohorts I, IIA, IIB, and III: On unchanged therapeutic regimen for at least 12 weeks, or treatment experienced (not including therapy to interrupt maternal-to-child-transmission (MTCT)) but on no treatment for 4 or more weeks prior to study entry. More information on this criterion can be found in the protocol.
- Participants in Cohorts IV must have received therapy to either interrupt MTCT and/or to treat HIV infection and participants in Cohort V must have received therapy to interrupt MTCT but have not received other anti-HIV therapies.
- HIV RNA (ribonucleic acid) of 1,000 copies/mL or greater at screening
- Demonstrated ability or willingness to take assigned raltegravir preparation
- Parent or legal guardian or participant able and willing to provide signed informed consent when applicable
- Female participants who are sexually active and potentially able to become pregnant must use two methods of birth control while on study and for 3 months after stopping study drug. More information on this criterion can be found in the protocol. Male participants must not participate in sperm donation programs. Male participants engaging in sexual activity that could lead to pregnancy must use a condom.
- Willing to be re-registered within same cohort if a dose change is recommended
Who cannot join
- Known Grade 3 or higher of any of the following laboratory tests within 30 days prior to study entry: neutrophil count, hemoglobin, platelets, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lipase, serum creatinine
- Clinical evidence of pancreatitis
- Treatment for active tuberculosis (TB) infection or disease.
- History of lactic acidosis in 3 months prior to study entry. More information on this criterion can be found in the protocol.
- Diagnosis of new Centers for Disease Control Stage C criteria or opportunistic or bacterial infection diagnosed within 30 days prior to study screening and not considered clinically stable
- Prior treatment with another experimental HIV integrase inhibitor
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- Immunosuppressive therapy within 30 days prior to beginning raltegravir study treatment. Participants taking short courses of corticosteroids are not excluded.
- Current or anticipated use of any disallowed medications, listed in the protocol.
- Any history of malignancy
- Participants who are unlikely to adhere to the study procedures or keep appointments
- Participants who are planning to relocate during study
- Any clinically significant diseases (other than HIV) or findings during the screening medical history or physical examination that, in the opinion of the investigator, would compromise the outcome of the study
- Current or past participation in an investigational study with a compound or device that is not commercially available within 30 days of signing informed consent
- Participants who are pregnant or breastfeeding. Infants who are receiving breastmilk are allowed to enroll.
- For participants in Cohorts IV and V, participant's caregiver is unable to access clean water supply (as defined by local standards) to re-suspend raltegravir oral granules
- Stage I mini cohort (initial 4 participants) only: current or anticipated use of antiretroviral regimen that includes atazanavir, tenofovir, or tipranavir during Stage I. Any other commercially available antiretroviral drugs are acceptable.
- Stage I participants enrolling after initial 4 participants: use of atazanavir, tenofovir, or tipranavir prior to the intensive PK testing. More information on this criterion can be found in the protocol.
- Exclusion Criteria for Stage II Participants Taking Atazanavir as Part of Their Background Regimen:
- Total bilirubin of Grade 4 or higher within 30 days of study entry
- Total bilirubin value lower than Grade 4 but direct bilirubin or concurrent transaminase greater than 1.5 times the upper limit of normal and participant is symptomatic, within 30 days prior to study entry
Trial locations and contacts
42 sites in 6 countries.
42 sites in 6 countries
United States29 sites
Usc La Nichd Crs
Alhambra, California, 91803
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, 80045
Johns Hopkins Univ. Baltimore NICHD CRS
Baltimore, Maryland, 21287
Children's Hosp. of Boston NICHD CRS
Boston, Massachusetts, 02115
Boston Medical Center Ped. HIV Program NICHD CRS
Boston, Massachusetts, 02118
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, 60612
Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, 60614-3393
DUMC Ped. CRS
Durham, North Carolina, 27710
South Florida CDTC Ft Lauderdale NICHD CRS
Fort Lauderdale, Florida, 33316
Texas Children's Hospital CRS
Houston, Texas, 77030-2399
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, 32209
University of California, UC San Diego CRS
La Jolla, California, 92093-0672
Children's Hospital of Los Angeles NICHD CRS
Los Angeles, California, 90027-6062
David Geffen School of Medicine at UCLA NICHD CRS
Los Angeles, California, 90095-1752
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, 38105-3678
Tulane Univ. New Orleans NICHD CRS
New Orleans, Louisiana, 70112
Nyu Ny Nichd Crs
New York, New York, 10016
Metropolitan Hosp. NICHD CRS
New York, New York, 10029
Columbia IMPAACT CRS
New York, New York, 10032
Philadelphia IMPAACT Unit CRS
Philadelphia, Pennsylvania, 19104
Univ. of California San Francisco NICHD CRS
San Francisco, California, 94143
Seattle Children's Research Institute CRS
Seattle, Washington, 98105
SUNY Stony Brook NICHD CRS
Stony Brook, New York, 11794-8111
USF - Tampa NICHD CRS
Tampa, Florida, 33606
Bronx-Lebanon Hospital Center NICHD CRS
The Bronx, New York, 10457
Jacobi Med. Ctr. Bronx NICHD CRS
The Bronx, New York, 10461
Children's National Med. Ctr. Washington DC NICHD CRS
Washington D.C., District of Columbia, 20010
Howard Univ. Washington DC NICHD CRS
Washington D.C., District of Columbia, 20060
WNE Maternal Pediatric Adolescent AIDS CRS
Worcester, Massachusetts, 01605
Brazil6 sites
SOM Federal University Minas Gerais Brazil NICHD CRS
Belo Horizonte, Minas Gerais, 30.130-100
Hospital Nossa Senhora da Conceicao NICHD CRS
Porto Alegre, Rio Grande do Sul, 91350-200
Hospital Federal dos Servidores do Estado NICHD CRS
Rio de Janeiro, 20221-903
Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS
Rio de Janeiro, 21941-612
Inst de Infectologia Emilio Ribas Sao Paulo Brazil NICHD CRS
São Paulo, 01246-900
Univ. of Sao Paulo Brazil NICHD CRS
São Paulo, 14049-900
South Africa4 sites
Durban Paediatric HIV CRS
Durban, KwaZulu-Natal, 4001
Soweto IMPAACT CRS
Johannesburg, Gauteng, 1862
Shandukani Research CRS
Johannesburg, Gauteng, 2001
Family Clinical Research Unit (FAM-CRU) CRS
Tygerberg, Western Cape, 7505
Argentina1 site
Hosp. General de Agudos Buenos Aires Argentina NICHD CRS
Ciudad de Buenos Aires, Buenos Aires, C1221ADC
About this study
Official title: A Phase I/II, Multicenter, Open-Label, Noncomparative Study of the International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Group to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Raltegravir (Isentress, MK-0518) in HIV-1 Infected Children and Adolescents
Integrase is 1 of 3 HIV (Human Immunodeficiency Virus)-1 enzymes required for viral replication. Raltegravir is a drug that prevents integrase from working properly. This drug has been tested for safety and efficacy in adults, but this is the first study to examine raltegravir in children and adolescents. The purpose of this study was to determine the appropriate dose for raltegravir across the pediatric age range from 4 weeks to 18 years of age, by acquiring short and long term safety data, intensive and population pharmacokinetic (PK) data, and efficacy experience with raltegravir in HIV-infected children and adolescents.
Read the detailed description
Integrase is one of three enzymes necessary for HIV replication. Integrase allows for the integration of HIV DNA (deoxyribonucleic acid) into the human genome. Raltegravir is a strong and selective inhibitor of HIV integrase. In adults, raltegravir has shown significant antiretroviral activity in clinical trials and is well tolerated. The purpose of this study was to determine the appropriate dose for raltegravir across the pediatric age range from 4 weeks (30 days) to 18 years of age, by acquiring short and long term safety data, intensive and population PK data, and efficacy experience with raltegravir in treatment-experienced, HIV-infected children and adolescents.
The study consisted of two sequential Stages: I and II. The dose finding period of Stage I was intended to examine the pharmacokinetics and short term tolerability and safety of raltegravir in a limited number of participants to permit dose selection for further study in Stage II. The dose finding algorithm required a preliminary assessment of data from the first 4 patients of each cohort (termed a "mini-cohort"). Failure to meet PK targets required dose adjustments, contingent upon the mini-cohort's dose having met safety criteria, followed by reassessment of safety and PK data from the new mini-cohort dose. When a mini-cohort dose had passed both safety and PK criteria, further accrual to and an assessment of results from the full cohort could occur. Again, failure to meet PK targets required dose adjustments contingent upon the full cohort's dose having met safety criteria with subsequent PK and safety evaluation of data from a new cohort taking the new dose.
Chronic dosing, which includes Stage I extension (the period after Stage I dose finding) and Stage II (additional participants enrolled), was intended to provide longer term safety and antiviral activity data in a larger sample of participants. Participants accrued into Stage I and treated only at the dose ultimately selected for their cohorts were combined with those accrued into Stage II, where all patients received only the final selected doses for their respective cohorts. This group is denoted as the Final Dose Population, and results from this group are considered primary, since they reflect only the age-specific doses proposed for commercial use. The group with all participants exposed to raltegravir (at any dose) is denoted as the All Treated Population.
Stage I lasted for a minimum of 48 weeks, Stage II was for 48 weeks, and a long-term follow-up period lasted for 5 years from initial exposure (i.e., 48 weeks of treatment plus 4 years of follow-up). Participants were stratified by age and assigned to one of six cohorts. Participants in Cohort I were between the ages of 12 and 18 years and received poloxamer film coated raltegravir tablets. Participants in Cohort IIA were between the ages of 6 and 11 years, weighed at least 25 kg, and received poloxamer film coated raltegravir tablets. Participants in Cohort IIB were between the ages of 6 and 11 years and received chewable raltegravir tablets. Participants in Cohort III were between the ages of 2 and 5 years and received chewable raltegravir tablets. Participants in Cohort IV were between the ages of 6 months (defined as 180 days) and 23 months and received oral granules for suspension. Participants in Cohort V were between the ages of 4 weeks (defined as 30 days) and 5 months and received oral granules for suspension.
Enrollment for Stage I of this study began with Cohort I and progressed to the other cohorts once preliminary dosage had been determined and safety data were reviewed. When this information had been determined for Cohort I, Cohorts IIA and IIB began enrollment. Once safety and dose data for these cohorts were reviewed, enrollment into Cohort III began. Once safety and dose data for Cohort III were reviewed, enrollment into Cohort IV began and once safety and dose data for Cohort IV were reviewed, enrollment into Cohort V began.
During Stage II of this study, participants took raltegravir at the dosage determined as safe and reaching PK targets based on the the Stage I data. The purpose of Stage II was to determine long-term safety of raltegravir once a safe dose meeting PK targets has been determined.
Participants whose Stage I dose was different from the dose determined for Stage II and who had not had individual dose adjustments because of extreme PK values had their raltegravir dose changed to the selected Stage II dose once it was determined. If individualizing the dose for participants in this manner resulted in a dose increase, these participants had an additional safety visit 4 weeks after the dose modification, and then continued on study visits with no further changes in the visit schedule.
There were at least 9 study visits for participants in this study, occurring during the 48-week raltegravir treatment period. For participants who completed 48 weeks of study and appeared to have benefited from receiving study drug, raltegravir was provided until five years after initial raltegravir exposure. For participants who opted to continue on study-provided raltegravir, extended provision of drug was implemented as part of a protocol extension involving visits every 4 months for five years after initial raltegravir exposure. Participants who did not continue on study-provided raltegravir were followed with annual visits for five years after initial raltegravir exposure (i.e. 48 weeks of raltegravir treatment plus 4 years follow-up). At each visit, a physical exam, blood collection, and determination of treatment adherence occurred. At some visits, urine collection and Tanner staging occurred. Selected cohorts underwent a taste evaluation at 1 of 2 visits. Participants aged 2 to less than 6 years of age were asked to participate in an additional PK substudy in which blood was collected two times over a 12-hour visit (or, if more convenient, this assessment may have been completed in 2 separate visits) in order to collect additional Cmin PK data. Participants were re-registered into the same cohort if a dose change was recommended.
Current pediatric Food and Drug Administration approval and dosing recommendations are based upon evaluations in 122 Final Dose participants aged ≥4 weeks to 18 years enrolled in this study.
The results present safety and efficacy results of the complete 5 year follow up data (primary and key secondary endpoints) of the participants from IMPAACT P1066, the Final Dose Population. By the date on which most of the data were frozen, 24 July 2017, all participants enrolled had Week 24 data (i.e., had either completed the Week 24 visit, or, for those who discontinued before Week 24, had the potential to have experienced the Week 24 visit), had also completed (or had the potential to have experienced) the Week 48 visit, and had either completed 240 weeks of study and were subsequently taken off study, or had prematurely discontinued study and were no longer in follow up.
- Conditions
- HIV Infections
- Being tested
- Raltegravir poloxamer film coated tablet, Raltegravir chewable tablet, Raltegravir oral granules for suspension (20 mg/mL)
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Raltegravir poloxamer film coated tabletDrug
Also called Isentress
Final Selected Dose: 400-mg tablet taken orally twice daily.
Raltegravir chewable tabletDrug
Also called Isentress
Final Selected Dose: Weight based dose of ~6 mg/kg according to the dosing table, to a maximum dose of 300 mg, taken orally twice daily.
Raltegravir oral granules for suspension (20 mg/mL)Drug
Also called Isentress
Weight based dose of ~6 mg/kg orally every 12 hours according to dosing table in protocol or the dose determined by review of all available data.
Raltegravir poloxamer film coated tabletDrug
Also called Isentress
Final Selected Dose: 400-mg tablet taken orally twice daily for participants weighing at least 25 kg. Participants < 25 kg were switched to a weight-based dose of the chewable tablet.
| Study group | Role | What they receive |
|---|---|---|
| Cohort I | Experimental | Participants between the ages of 12 and 18 years; receiving raltegravir poloxamer film coated tablet:
Stage I starting dose: Weight based dose of ~6 mg/kg based on protocol dosing table, taken orally twice daily.
Final Selected Dose: 400-mg tablet taken orally twice daily. Receives: Drug: Raltegravir poloxamer film coated tablet |
| Cohort IIA | Experimental | Participants between the ages of 6 and 11 years, receiving raltegravir poloxamer film coated tablet:
Stage I starting dose: Weight based dose of ~8 mg/kg based on protocol dosing table, taken orally twice daily.
Final Selected Dose: 400-mg tablet taken orally twice daily for participants weighing at least 25 kg. Participants < 25 kg were switched to a weight-based dose of the chewable tablet. Receives: Drug: Raltegravir poloxamer film coated tablet |
| Cohort IIB | Experimental | Participants between the ages of 6 and 11 years; receiving raltegravir chewable tablet:
Stage I starting dose: Weight based dose of ~8 mg/kg based on protocol dosing table, taken orally twice daily.
Final Selected Dose: Weight based dose of ~6 mg/kg according to the dosing table, to a maximum dose of 300 mg, taken orally twice daily. Receives: Drug: Raltegravir chewable tablet |
| Cohort III | Experimental | Participants between the ages of 2 and 5 years; receiving raltegravir chewable tablet:
Stage I starting dose: Weight based dose of ~6 mg/kg based on protocol dosing table, taken orally twice daily.
Final Selected Dose: Weight based dose of ~6 mg/kg according to the dosing table, to a maximum dose of 300 mg, taken orally twice daily. Receives: Drug: Raltegravir chewable tablet |
| Cohort IV | Experimental | Participants between the ages of 6 and 23 months; receiving raltegravir oral granules for suspension (20 mg/mL):
Stage I starting dose: Weight based dose of ~6 mg/kg orally every 12 hours according to dosing table in protocol or the dose determined by review of all available data. Receives: Drug: Raltegravir oral granules for suspension (20 mg/mL) |
| Cohort V | Experimental | Participants between the ages of 4 weeks and 5 months; receiving raltegravir oral granules for suspension (20 mg/mL):
Stage I starting dose: Weight based dose of ~6 mg/kg orally every 12 hours according to dosing table in protocol or the dose determined by review of all available data. Receives: Drug: Raltegravir oral granules for suspension (20 mg/mL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Grade 3 or 4 Adverse Events (AEs)
Adverse events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0. All grade 3 and higher signs, symptoms, and laboratory toxicities were included.
Measured: From study entry through Week 24
Number of Participants Terminated From Treatment Due to Suspected Adverse Drug Reaction (SADR) Attributable to the Study Medication
The attribution of relationship of serious adverse events to study drug for the purposes of employing the start, stop and pause rules was by consensus among the site investigator, study team (which includes representatives from Merck) and the Division of AIDS medical officer; if unanimous agreement between them cannot be established, the attribution made by the majority of these 3 persons or entities will be used. Gradation of relationship will use the following terminology: Not related, Probably not related, Possibly related, Probably related or Definitely related.
Measured: From study entry through Week 24
Number of Participants Who Died
Number of participants who died were summarized.
Measured: From study entry through Week 24
Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC12h)
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods (WinNonlin version 4.01, Pharsight Corp., Mountain View, CA). AUC12h (area-under-the-curve from 0 to 12 hours) were determined using the linear-log trapezoidal rule.
Measured: Measured between days 5 and 12 of raltegravir initiation; Blood samples were drawn pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post dosing.
PK Parameter: Maximum Plasma Concentration (Cmax)
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods (WinNonlin version 4.01, Pharsight Corp., Mountain View, CA). Maximum plasma concentration (Cmax) was taken directly from the observed concentration-time data.
Measured: Measured between days 5 and 12 of raltegravir initiation; Blood samples were drawn pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post dosing.
PK Parameter: Time to Half of Maximum Plasma Concentration Cmax (T1/2)
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods (WinNonlin version 4.01, Pharsight Corp., Mountain View, CA). Time to half of maximum plasma concentration Cmax (T1/2) was taken directly from the observed concentration-time data.
Measured: Measured between days 5 and 12 of raltegravir initiation; Blood samples were drawn pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post dosing.
PK Parameter: Concentration at 12 Hours Postdose (C12h)
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods (WinNonlin version 4.01, Pharsight Corp., Mountain View, CA). Plasma concentration at 12 hours postdose (C12h) was taken directly from the observed concentration-time data.
Measured: Measured between days 5 and 12 of raltegravir initiation; Blood samples were drawn pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post dosing.
Secondary outcomes (6)
Percentage of Participants With Grade 3 or 4 Adverse Events (AEs)
Adverse events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0. All grade 3 and higher signs, symptoms, and laboratory toxicities were included.
Measured: From study entry through Week 48
Number of Participants Terminated From Treatment Due to Suspected Adverse Drug Reaction (SADR) Attributable to the Study Medication
The attribution of relationship of serious adverse events to study drug for the purposes of employing the start, stop and pause rules was by consensus among the site investigator, study team (which includes representatives from Merck) and the Division of AIDS medical officer; if unanimous agreement between them cannot be established, the attribution made by the majority of these 3 persons or entities will be used. Gradation of relationship will use the following terminology: Not related, Probably not related, Possibly related, Probably related or Definitely related.
Measured: From study entry through Week 48
Number of Participants Who Died
Number of participants who died were summarized.
Measured: From study entry through Week 48
Percentage of Participants With ≥1 log10 Drop From Baseline in HIV RNA or HIV RNA <400 Copies/mL
Plasma HIV RNA concentrations were determined at entry and at regular intervals using the HIV-1 MONITOR Test, version 1.5 (Roche Molecular Diagnostics) or RealTime HIV-1 (Abbott Molecular), and analyses used the Observed Failure Approach.
Measured: Baseline, Week 24, 48
Change of CD4 Count From Baseline
Change in CD4 cell count from baseline was calculated as the value at later visit minus the value at baseline.
Measured: Baseline, Week 24, 48
Change of CD4 Percent From Baseline
Change in CD4 percent from baseline was calculated as the value of the later visit minus the value at baseline.
Measured: Baseline, Week 24, 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2007 (estimated)
- Study start17 Sep 2007
- Primary completion3 Jun 2013
- Study completion18 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Sharon A. Nachman, MD, Study chair, State University of New York at Stony Brook, Health Science CenterAndrew Wiznia, MD, Study chair, Jacobi Medical Center, Albert Einstein College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00485264
- Sponsor's protocol ID
- P1066
- Other IDs
- 10495, IMPAACT P1066
- Status last verified
- Oct 2021
- First submitted
- 11 Jun 2007
- Last updated
- 2 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Cooper D, Gatell J, Rockstroh J, Katlama C, Yeni P, Lazzarin A, Chen J, Isaacs R, Teppler H, Nguyen B, and for the BENCHMRK-1 Study Group. Results of BENCHMRK-1, a Phase III Study Evaluating the Efficacy and Safety of MK-0518, a Novel HIV-1 Integrase Inhibitor, in Patients with Triple-class Resistant Virus. 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA, Abstract 105aLB, 2007.
Dayam R, Al-Mawsawi LQ, Neamati N. HIV-1 integrase inhibitors: an emerging clinical reality. Drugs R D. 2007;8(3):155-68. doi: 10.2165/00126839-200708030-00003.
PubMed 17472411Markowitz M, Morales-Ramirez JO, Nguyen BY, Kovacs CM, Steigbigel RT, Cooper DA, Liporace R, Schwartz R, Isaacs R, Gilde LR, Wenning L, Zhao J, Teppler H. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):509-15. doi: 10.1097/QAI.0b013e31802b4956.
PubMed 17133211Nair V, Chi G. HIV integrase inhibitors as therapeutic agents in AIDS. Rev Med Virol. 2007 Jul-Aug;17(4):277-95. doi: 10.1002/rmv.539.
PubMed 17503547Sharon Nachman, Edward Acosta, Nan Zheng, Hedy Tepler, Brenda Homony, Terence Fenton, Edward Handelsman, Carol Worrell, Bobbie Graham, Andrew Wiznia , and the P1066 Group. Interim Results for IMPAACT P1066 Raltegravir (RAL) Oral Chewable Tablet (CT) Formulation on Children 2-5 Years. CROI 2011, Boston, MA, Feb27-March2, 2011.
S. Nachman, E. Acosta, N. Zheng, H. Teppler, B. Homony, X. Xu, C. Alvero, E. Handelsman, C. Worrell, B. Graham, M. Toye, A. Wiznia, and the P1066 Group. IMPAACT P1066: Raltegravir (RAL) safety and efficacy in treatment experienced HIV infected (+) youth 2 to 18 years of age through week 48. XIX International AIDS Conference, July 22-27, 2012, Washington, DC.
Julie Nelson, A Loftis, K Below, D Cole, S Nachman, L Frenkel, C Alvero, N Zheng, J Eron, and S Fiscus. Absence of Integrase Inhibitor Resistance Mutations in Children Not Treated with Integrase Inhibitor. CROI 2012, Seattle, WA. March 2012.
Nachman S, Zheng N, Acosta EP, Teppler H, Homony B, Graham B, Fenton T, Xu X, Wenning L, Spector SA, Frenkel LM, Alvero C, Worrell C, Handelsman E, Wiznia A; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1066 Study Team. Pharmacokinetics, safety, and 48-week efficacy of oral raltegravir in HIV-1-infected children aged 2 through 18 years. Clin Infect Dis. 2014 Feb;58(3):413-22. doi: 10.1093/cid/cit696. Epub 2013 Oct 21.
PubMed 24145879Nachman S, Alvero C, Teppler H, Homony B, Rodgers AJ, Graham BL, Fenton T, Frenkel LM, Browning RS, Hazra R, Wiznia AA; IMPAACT 1066 study team. Safety and efficacy at 240 weeks of different raltegravir formulations in children with HIV-1: a phase 1/2 open label, non-randomised, multicentre trial. Lancet HIV. 2018 Dec;5(12):e715-e722. doi: 10.1016/S2352-3018(18)30257-1.
PubMed 30527329
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Multicenter, Open-Label, Noncomparative Study of the International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Group to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Raltegravir (Isentress, MK-0518) in HIV-1 Infected Children and Adolescents
- ClinicalTrials.gov ID
- NCT00485264
- Acronym / sponsor ID
- P1066
- Conditions
- HIV Infections
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 153 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 17 Sep 2007 (actual)
- Primary completion
- 3 Jun 2013 (actual)
- Study completion
- 18 May 2017 (actual)
- First posted
- 12 Jun 2007 (estimated)
- Results
- Posted 22 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Integrase is 1 of 3 HIV (Human Immunodeficiency Virus)-1 enzymes required for viral replication. Raltegravir is a drug that prevents integrase from working properly. This drug has been tested for safety and efficacy in adults, but this is the first study to examine raltegravir in children and adolescents. The purpose of this study was to determine the appropriate dose for raltegravir across the pediatric age range from 4 weeks to 18 years of age, by acquiring short and long term safety data, intensive and population pharmacokinetic (PK) data, and efficacy experience with raltegravir in HIV-infected children and adolescents.
Detailed description
Integrase is one of three enzymes necessary for HIV replication. Integrase allows for the integration of HIV DNA (deoxyribonucleic acid) into the human genome. Raltegravir is a strong and selective inhibitor of HIV integrase. In adults, raltegravir has shown significant antiretroviral activity in clinical trials and is well tolerated. The purpose of this study was to determine the appropriate dose for raltegravir across the pediatric age range from 4 weeks (30 days) to 18 years of age, by acquiring short and long term safety data, intensive and population PK data, and efficacy experience with raltegravir in treatment-experienced, HIV-infected children and adolescents.
The study consisted of two sequential Stages: I and II. The dose finding period of Stage I was intended to examine the pharmacokinetics and short term tolerability and safety of raltegravir in a limited number of participants to permit dose selection for further study in Stage II. The dose finding algorithm required a preliminary assessment of data from the first 4 patients of each cohort (termed a "mini-cohort"). Failure to meet PK targets required dose adjustments, contingent upon the mini-cohort's dose having met safety criteria, followed by reassessment of safety and PK data from the new mini-cohort dose. When a mini-cohort dose had passed both safety and PK criteria, further accrual to and an assessment of results from the full cohort could occur. Again, failure to meet PK targets required dose adjustments contingent upon the full cohort's dose having met safety criteria with subsequent PK and safety evaluation of data from a new cohort taking the new dose.
Chronic dosing, which includes Stage I extension (the period after Stage I dose finding) and Stage II (additional participants enrolled), was intended to provide longer term safety and antiviral activity data in a larger sample of participants. Participants accrued into Stage I and treated only at the dose ultimately selected for their cohorts were combined with those accrued into Stage II, where all patients received only the final selected doses for their respective cohorts. This group is denoted as the Final Dose Population, and results from this group are considered primary, since they reflect only the age-specific doses proposed for commercial use. The group with all participants exposed to raltegravir (at any dose) is denoted as the All Treated Population.
Stage I lasted for a minimum of 48 weeks, Stage II was for 48 weeks, and a long-term follow-up period lasted for 5 years from initial exposure (i.e., 48 weeks of treatment plus 4 years of follow-up). Participants were stratified by age and assigned to one of six cohorts. Participants in Cohort I were between the ages of 12 and 18 years and received poloxamer film coated raltegravir tablets. Participants in Cohort IIA were between the ages of 6 and 11 years, weighed at least 25 kg, and received poloxamer film coated raltegravir tablets. Participants in Cohort IIB were between the ages of 6 and 11 years and received chewable raltegravir tablets. Participants in Cohort III were between the ages of 2 and 5 years and received chewable raltegravir tablets. Participants in Cohort IV were between the ages of 6 months (defined as 180 days) and 23 months and received oral granules for suspension. Participants in Cohort V were between the ages of 4 weeks (defined as 30 days) and 5 months and received oral granules for suspension.
Enrollment for Stage I of this study began with Cohort I and progressed to the other cohorts once preliminary dosage had been determined and safety data were reviewed. When this information had been determined for Cohort I, Cohorts IIA and IIB began enrollment. Once safety and dose data for these cohorts were reviewed, enrollment into Cohort III began. Once safety and dose data for Cohort III were reviewed, enrollment into Cohort IV began and once safety and dose data for Cohort IV were reviewed, enrollment into Cohort V began.
During Stage II of this study, participants took raltegravir at the dosage determined as safe and reaching PK targets based on the the Stage I data. The purpose of Stage II was to determine long-term safety of raltegravir once a safe dose meeting PK targets has been determined.
Participants whose Stage I dose was different from the dose determined for Stage II and who had not had individual dose adjustments because of extreme PK values had their raltegravir dose changed to the selected Stage II dose once it was determined. If individualizing the dose for participants in this manner resulted in a dose increase, these participants had an additional safety visit 4 weeks after the dose modification, and then continued on study visits with no further changes in the visit schedule.
There were at least 9 study visits for participants in this study, occurring during the 48-week raltegravir treatment period. For participants who completed 48 weeks of study and appeared to have benefited from receiving study drug, raltegravir was provided until five years after initial raltegravir exposure. For participants who opted to continue on study-provided raltegravir, extended provision of drug was implemented as part of a protocol extension involving visits every 4 months for five years after initial raltegravir exposure. Participants who did not continue on study-provided raltegravir were followed with annual visits for five years after initial raltegravir exposure (i.e. 48 weeks of raltegravir treatment plus 4 years follow-up). At each visit, a physical exam, blood collection, and determination of treatment adherence occurred. At some visits, urine collection and Tanner staging occurred. Selected cohorts underwent a taste evaluation at 1 of 2 visits. Participants aged 2 to less than 6 years of age were asked to participate in an additional PK substudy in which blood was collected two times over a 12-hour visit (or, if more convenient, this assessment may have been completed in 2 separate visits) in order to collect additional Cmin PK data. Participants were re-registered into the same cohort if a dose change was recommended.
Current pediatric Food and Drug Administration approval and dosing recommendations are based upon evaluations in 122 Final Dose participants aged ≥4 weeks to 18 years enrolled in this study.
The results present safety and efficacy results of the complete 5 year follow up data (primary and key secondary endpoints) of the participants from IMPAACT P1066, the Final Dose Population. By the date on which most of the data were frozen, 24 July 2017, all participants enrolled had Week 24 data (i.e., had either completed the Week 24 visit, or, for those who discontinued before Week 24, had the potential to have experienced the Week 24 visit), had also completed (or had the potential to have experienced) the Week 48 visit, and had either completed 240 weeks of study and were subsequently taken off study, or had prematurely discontinued study and were no longer in follow up.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort I | Experimental | Drug: Raltegravir poloxamer film coated tabletParticipants between the ages of 12 and 18 years; receiving raltegravir poloxamer film coated tablet: Stage I starting dose: Weight based dose of ~6 mg/kg based on protocol dosing table, taken orally twice daily. Final Selected Dose: 400-mg tablet taken orally twice daily. |
| Cohort IIA | Experimental | Drug: Raltegravir poloxamer film coated tabletParticipants between the ages of 6 and 11 years, receiving raltegravir poloxamer film coated tablet: Stage I starting dose: Weight based dose of ~8 mg/kg based on protocol dosing table, taken orally twice daily. Final Selected Dose: 400-mg tablet taken orally twice daily for participants weighing at least 25 kg. Participants < 25 kg were switched to a weight-based dose of the chewable tablet. |
| Cohort IIB | Experimental | Drug: Raltegravir chewable tabletParticipants between the ages of 6 and 11 years; receiving raltegravir chewable tablet: Stage I starting dose: Weight based dose of ~8 mg/kg based on protocol dosing table, taken orally twice daily. Final Selected Dose: Weight based dose of ~6 mg/kg according to the dosing table, to a maximum dose of 300 mg, taken orally twice daily. |
| Cohort III | Experimental | Drug: Raltegravir chewable tabletParticipants between the ages of 2 and 5 years; receiving raltegravir chewable tablet: Stage I starting dose: Weight based dose of ~6 mg/kg based on protocol dosing table, taken orally twice daily. Final Selected Dose: Weight based dose of ~6 mg/kg according to the dosing table, to a maximum dose of 300 mg, taken orally twice daily. |
| Cohort IV | Experimental | Drug: Raltegravir oral granules for suspension (20 mg/mL)Participants between the ages of 6 and 23 months; receiving raltegravir oral granules for suspension (20 mg/mL): Stage I starting dose: Weight based dose of ~6 mg/kg orally every 12 hours according to dosing table in protocol or the dose determined by review of all available data. |
| Cohort V | Experimental | Drug: Raltegravir oral granules for suspension (20 mg/mL)Participants between the ages of 4 weeks and 5 months; receiving raltegravir oral granules for suspension (20 mg/mL): Stage I starting dose: Weight based dose of ~6 mg/kg orally every 12 hours according to dosing table in protocol or the dose determined by review of all available data. |
Who may qualify
- Ages
- 30 days to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Documentation of HIV-1 infection, defined as positive results from two samples collected at different time points. More information on this criterion can be found in the protocol.
- For participants in Cohorts I, IIA, IIB, and III: On unchanged therapeutic regimen for at least 12 weeks, or treatment experienced (not including therapy to interrupt maternal-to-child-transmission (MTCT)) but on no treatment for 4 or more weeks prior to study entry. More information on this criterion can be found in the protocol.
- Participants in Cohorts IV must have received therapy to either interrupt MTCT and/or to treat HIV infection and participants in Cohort V must have received therapy to interrupt MTCT but have not received other anti-HIV therapies.
- HIV RNA (ribonucleic acid) of 1,000 copies/mL or greater at screening
- Demonstrated ability or willingness to take assigned raltegravir preparation
Key exclusion criteria (20 listed)
- Known Grade 3 or higher of any of the following laboratory tests within 30 days prior to study entry: neutrophil count, hemoglobin, platelets, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lipase, serum creatinine
- Clinical evidence of pancreatitis
- Treatment for active tuberculosis (TB) infection or disease.
- History of lactic acidosis in 3 months prior to study entry. More information on this criterion can be found in the protocol.
- Diagnosis of new Centers for Disease Control Stage C criteria or opportunistic or bacterial infection diagnosed within 30 days prior to study screening and not considered clinically stable
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 |
|---|---|---|
| Raltegravir poloxamer film coated tabletAlso: IsentressFinal Selected Dose: 400-mg tablet taken orally twice daily. | Drug | Cohort I |
| Raltegravir chewable tabletAlso: IsentressFinal Selected Dose: Weight based dose of ~6 mg/kg according to the dosing table, to a maximum dose of 300 mg, taken orally twice daily. | Drug | Cohort IIB, Cohort III |
| Raltegravir oral granules for suspension (20 mg/mL)Also: IsentressWeight based dose of ~6 mg/kg orally every 12 hours according to dosing table in protocol or the dose determined by review of all available data. | Drug | Cohort IV, Cohort V |
| Raltegravir poloxamer film coated tabletAlso: IsentressFinal Selected Dose: 400-mg tablet taken orally twice daily for participants weighing at least 25 kg. Participants < 25 kg were switched to a weight-based dose of the chewable tablet. | Drug | Cohort IIA |
Primary outcome
Percentage of Participants With Grade 3 or 4 Adverse Events (AEs)
Time frame: From study entry through Week 24
Adverse events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0. All grade 3 and higher signs, symptoms, and laboratory toxicities were included.
Number of Participants Terminated From Treatment Due to Suspected Adverse Drug Reaction (SADR) Attributable to the Study Medication
Time frame: From study entry through Week 24
The attribution of relationship of serious adverse events to study drug for the purposes of employing the start, stop and pause rules was by consensus among the site investigator, study team (which includes representatives from Merck) and the Division of AIDS medical officer; if unanimous agreement between them cannot be established, the attribution made by the majority of these 3 persons or entities will be used. Gradation of relationship will use the following terminology: Not related, Probably not related, Possibly related, Probably related or Definitely related.
Number of Participants Who Died
Time frame: From study entry through Week 24
Number of participants who died were summarized.
Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC12h)
Time frame: Measured between days 5 and 12 of raltegravir initiation; Blood samples were drawn pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post dosing.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods (WinNonlin version 4.01, Pharsight Corp., Mountain View, CA). AUC12h (area-under-the-curve from 0 to 12 hours) were determined using the linear-log trapezoidal rule.
PK Parameter: Maximum Plasma Concentration (Cmax)
Time frame: Measured between days 5 and 12 of raltegravir initiation; Blood samples were drawn pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post dosing.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods (WinNonlin version 4.01, Pharsight Corp., Mountain View, CA). Maximum plasma concentration (Cmax) was taken directly from the observed concentration-time data.
PK Parameter: Time to Half of Maximum Plasma Concentration Cmax (T1/2)
Time frame: Measured between days 5 and 12 of raltegravir initiation; Blood samples were drawn pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post dosing.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods (WinNonlin version 4.01, Pharsight Corp., Mountain View, CA). Time to half of maximum plasma concentration Cmax (T1/2) was taken directly from the observed concentration-time data.
PK Parameter: Concentration at 12 Hours Postdose (C12h)
Time frame: Measured between days 5 and 12 of raltegravir initiation; Blood samples were drawn pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post dosing.
Pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods (WinNonlin version 4.01, Pharsight Corp., Mountain View, CA). Plasma concentration at 12 hours postdose (C12h) was taken directly from the observed concentration-time data.
6 secondary outcomes
Percentage of Participants With Grade 3 or 4 Adverse Events (AEs)
Time frame: From study entry through Week 48
Number of Participants Terminated From Treatment Due to Suspected Adverse Drug Reaction (SADR) Attributable to the Study Medication
Time frame: From study entry through Week 48
Number of Participants Who Died
Time frame: From study entry through Week 48
Percentage of Participants With ≥1 log10 Drop From Baseline in HIV RNA or HIV RNA <400 Copies/mL
Time frame: Baseline, Week 24, 48
Change of CD4 Count From Baseline
Time frame: Baseline, Week 24, 48
Change of CD4 Percent From Baseline
Time frame: Baseline, Week 24, 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundCooper D, Gatell J, Rockstroh J, Katlama C, Yeni P, Lazzarin A, Chen J, Isaacs R, Teppler H, Nguyen B, and for the BENCHMRK-1 Study Group. Results of BENCHMRK-1, a Phase III Study Evaluating the Efficacy and Safety of MK-0518, a Novel HIV-1 Integrase Inhibitor, in Patients with Triple-class Resistant Virus. 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA, Abstract 105aLB, 2007.
- Background: PubMed 17472411Dayam R, Al-Mawsawi LQ, Neamati N. HIV-1 integrase inhibitors: an emerging clinical reality. Drugs R D. 2007;8(3):155-68. doi: 10.2165/00126839-200708030-00003.
- Background: PubMed 17133211Markowitz M, Morales-Ramirez JO, Nguyen BY, Kovacs CM, Steigbigel RT, Cooper DA, Liporace R, Schwartz R, Isaacs R, Gilde LR, Wenning L, Zhao J, Teppler H. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):509-15. doi: 10.1097/QAI.0b013e31802b4956.
- Background: PubMed 17503547Nair V, Chi G. HIV integrase inhibitors as therapeutic agents in AIDS. Rev Med Virol. 2007 Jul-Aug;17(4):277-95. doi: 10.1002/rmv.539.
- Results publicationSharon Nachman, Edward Acosta, Nan Zheng, Hedy Tepler, Brenda Homony, Terence Fenton, Edward Handelsman, Carol Worrell, Bobbie Graham, Andrew Wiznia , and the P1066 Group. Interim Results for IMPAACT P1066 Raltegravir (RAL) Oral Chewable Tablet (CT) Formulation on Children 2-5 Years. CROI 2011, Boston, MA, Feb27-March2, 2011.
- Results publicationS. Nachman, E. Acosta, N. Zheng, H. Teppler, B. Homony, X. Xu, C. Alvero, E. Handelsman, C. Worrell, B. Graham, M. Toye, A. Wiznia, and the P1066 Group. IMPAACT P1066: Raltegravir (RAL) safety and efficacy in treatment experienced HIV infected (+) youth 2 to 18 years of age through week 48. XIX International AIDS Conference, July 22-27, 2012, Washington, DC.
- Results publicationJulie Nelson, A Loftis, K Below, D Cole, S Nachman, L Frenkel, C Alvero, N Zheng, J Eron, and S Fiscus. Absence of Integrase Inhibitor Resistance Mutations in Children Not Treated with Integrase Inhibitor. CROI 2012, Seattle, WA. March 2012.
- Results publication: PubMed 24145879Nachman S, Zheng N, Acosta EP, Teppler H, Homony B, Graham B, Fenton T, Xu X, Wenning L, Spector SA, Frenkel LM, Alvero C, Worrell C, Handelsman E, Wiznia A; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1066 Study Team. Pharmacokinetics, safety, and 48-week efficacy of oral raltegravir in HIV-1-infected children aged 2 through 18 years. Clin Infect Dis. 2014 Feb;58(3):413-22. doi: 10.1093/cid/cit696. Epub 2013 Oct 21.
- Derived from this study: PubMed 30527329Nachman S, Alvero C, Teppler H, Homony B, Rodgers AJ, Graham BL, Fenton T, Frenkel LM, Browning RS, Hazra R, Wiznia AA; IMPAACT 1066 study team. Safety and efficacy at 240 weeks of different raltegravir formulations in children with HIV-1: a phase 1/2 open label, non-randomised, multicentre trial. Lancet HIV. 2018 Dec;5(12):e715-e722. doi: 10.1016/S2352-3018(18)30257-1.
- DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004; Clarification, August 2009Link provided by the sponsor.
- Description: Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010Link provided by the sponsor.
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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.
Sharon A. Nachman, MD study chair
State University of New York at Stony Brook, Health Science Center
Andrew Wiznia, MD study chair
Jacobi Medical Center, Albert Einstein College of Medicine
42 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Raltegravir poloxamer film coated tablet, Raltegravir chewable tablet and Raltegravir oral granules for suspension (20 mg/mL) in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 42 sites in 6 countries.
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 8 inclusion and 20 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 2 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 42 sites in United States, Brazil, South Africa, Argentina, Botswana and 1 more country. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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.
What does the primary outcome measure?
Percentage of Participants With Grade 3 or 4 Adverse Events (AEs) (time frame: From study entry through Week 24). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00485264, which also lists 9 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 2 Nov 2021.