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Safety and Pharmacokinetics (PK) of Raltegravir in HIV (Human Immunodeficiency Virus)-Infected Children and Adolescents

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00485264
First received: June 11, 2007
Last updated: December 18, 2014
Last verified: December 2014
Results First Received: February 28, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Raltegravir poloxamer film coated tablet
Drug: Raltegravir chewable tablet
Drug: Raltegravir oral granules for suspension (20 mg/mL)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Cohort I Participants between the ages of 12 and 18 years; receiving raltegravir poloxamer film coated tablet; final selected dose: 400-mg tablet taken orally twice daily.
Cohort IIA Participants between the ages of 6 and 11 years; receiving raltegravir poloxamer film coated tablet: final selected dose: 400-mg tablet taken orally twice daily for participants weighing at least 25 kg.
Cohort IIB Participants between the ages of 6 and 11 years; receiving raltegravir chewable tablet: final selected dose: Weight based dose of ~6 mg/kg to a maximum dose of 300 mg, taken orally twice daily.
Cohort III Participants between the ages of 2 and 5 years; receiving raltegravir chewable tablet: final selected dose: Weight based dose of ~6 mg/kg to a maximum dose of 300 mg, taken orally twice daily.
Cohort IV Participants between the ages of 6 and 23 months; receiving raltegravir oral granules for suspension (20 mg/mL): Stage I starting dose of 6 mg/kg orally twice daily according to dosing table in protocol or the dose determined by review of all available data. Not included in this interim analysis.
Cohort V Participants between the ages of 4 weeks and 5 months; receiving raltegravir oral granules for suspension (20 mg/mL): Stage I starting dose of 6 mg/kg orally twice daily according to dosing table in protocol or the dose determined by review of all available data. Not included in this interim analysis.

Participant Flow:   Overall Study
    Cohort I     Cohort IIA     Cohort IIB     Cohort III     Cohort IV     Cohort V  
STARTED     71     16     18     21     0 [1]   0 [1]
Completed Week 24     67     16     18     21     0     0  
COMPLETED     65 [2]   15 [2]   18 [2]   11 [2]   0 [1]   0 [1]
NOT COMPLETED     6     1     0     10     0     0  
Non-compliant                 6                 0                 0                 0                 0                 0  
Physician Decision                 0                 1                 0                 0                 0                 0  
Lack of Efficacy                 0                 0                 0                 1                 0                 0  
Data frozen before reaching week 48                 0                 0                 0                 9                 0                 0  
[1] Not included in this interim analysis
[2] Completed week 48



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Treated Population: All patients exposed to raltegravir (at any dose); Cohorts IV and V were not included in this interim analysis.

Reporting Groups
  Description
Cohort I Participants between the ages of 12 and 18 years; receiving raltegravir poloxamer film coated tablet; final selected dose: 400-mg tablet taken orally twice daily.
Cohort IIA Participants between the ages of 6 and 11 years; receiving raltegravir poloxamer film coated tablet: final selected dose: 400-mg tablet taken orally twice daily for participants weighing at least 25 kg.
Cohort IIB Participants between the ages of 6 and 11 years; receiving raltegravir chewable tablet: final selected dose: Weight based dose of ~6 mg/kg to a maximum dose of 300 mg, taken orally twice daily.
Cohort III Participants between the ages of 2 and 5 years; receiving raltegravir chewable tablet: final selected dose: Weight based dose of ~6 mg/kg to a maximum dose of 300 mg, taken orally twice daily.
Cohort IV Participants between the ages of 6 and 23 months; receiving raltegravir oral granules for suspension (20 mg/mL): Stage I starting dose of 6 mg/kg orally twice daily according to dosing table in protocol or the dose determined by review of all available data. Not included in this interim analysis.
Cohort V Participants between the ages of 4 weeks and 5 months; receiving raltegravir oral granules for suspension (20 mg/mL): Stage I starting dose of 6 mg/kg orally twice daily according to dosing table in protocol or the dose determined by review of all available data. Not included in this interim analysis.
Total Total of all reporting groups

Baseline Measures
    Cohort I     Cohort IIA     Cohort IIB     Cohort III     Cohort IV     Cohort V     Total  
Number of Participants  
[units: participants]
  71     16     18     21     0     0     126  
Age  
[units: years]
Mean ± Standard Deviation
  15  ± 2     9.1  ± 1.6     8.9  ± 1.6     3.2  ± 1.2             11.4  ± 4.8  
Gender  
[units: participants]
             
Female     34     7     7     13             61  
Male     37     9     11     8             65  
Ethnicity (NIH/OMB)  
[units: participants]
             
Hispanic or Latino     26     4     12     8             50  
Not Hispanic or Latino     42     11     6     10             69  
Unknown or Not Reported     3     1     0     3             7  
Race (NIH/OMB)  
[units: participants]
             
American Indian or Alaska Native     1     0     0     0             1  
Asian     0     0     0     0             0  
Native Hawaiian or Other Pacific Islander     0     0     0     0             0  
Black or African American     42     12     7     13             74  
White     25     3     10     5             43  
More than one race     0     0     0     1             1  
Unknown or Not Reported     3     1     1     2             7  
Plasma HIV RNA, log10 copies/mL  
[units: log10 copies/mL]
Mean ± Standard Deviation
  4.3  ± 0.6     4.3  ± 0.6     4.3  ± 0.5     4.4  ± 0.8             4.3  ± 0.6  
Plasma HIV RNA, copies/mL  
[units: participants]
             
0 to ≤4,000     10     2     2     2             16  
>4,000 to ≤50,000     40     12     11     11             74  
>50,000 to ≤100,000     14     1     4     4             23  
>100,000     7     1     1     4             13  
CD4 cell count, cells/µL  
[units: cells/µL]
Mean ± Standard Deviation
  411  ± 238.2     652.3  ± 360.4     545.4  ± 280.2     1122.9  ± 537.1             581.6  ± 415.3  
CD4 percentage  
[units: Percentage of total lymphocytes]
Mean ± Standard Deviation
  19.9  ± 9.6     25.4  ± 8.2     26.7  ± 10.6     27.9  ± 8.2             22.9  ± 9.9  
CDC HIV Clinical Classification [1]
[units: participants]
             
A     17     5     6     5             33  
B     28     4     5     1             38  
C     25     6     2     8             41  
N     1     1     5     7             14  
Number of antiretroviral (ARV) classes previously used  
[units: participants]
             
0     0     0     0     1             1  
1     2     0     0     2             4  
2     9     5     8     13             35  
≥3     60     11     10     5             86  
Duration of ARVs previously used  
[units: years]
Mean ± Standard Deviation
  12  ± 3.8     8.5  ± 2.3     7.1  ± 3     2.4  ± 1.4             9.3  ± 4.8  
Prior use of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)  
[units: participants]
             
Yes     60     14     15     10             99  
No     11     2     3     11             27  
Use of prior PIs  
[units: participants]
             
Yes     69     13     13     13             108  
No     2     3     5     8             18  
Phenotypic Sensitivity score [2]
[units: participants]
             
0     5     1     0     0             6  
1     15     4     7     2             28  
2     26     2     8     7             43  
≥3     20     7     2     7             36  
Missing     5     2     1     5             13  
Genotypic sensitivity score [3]
[units: participants]
             
0     9     1     0     0             10  
1     23     4     9     2             38  
2     21     6     7     10             44  
≥3     17     5     2     8             32  
Missing     1     0     0     1             2  
[1] The CDC Classification System for HIV Infection is the medical classification system used by the United States Centers for Disease Control and Prevention (CDC) to classify HIV disease and infection. http://www.cdc.gov/mmwr/preview/mmwrhtml/00032890.htm
[2] The Phenotypic Sensitivity score (PSS) was defined as the total number of ARVs in optimized background therapy (OBT) to which the subject's viral isolate showed phenotypic sensitivity, based on pre-study resistance tests. The PSS score range is from 0 (meaning there was no ARV the subject was sensitive to) to >=3 (the subject was sensitive to >=3 of the ARVs in his/her OBT). If no resistance results were available for a drug, it was scored as one active drug in the PSS if there was history of prior use, and was considered not active if no prior use. Scoring did not include Raltegravir.
[3] The Genotypic Sensitivity score (GSS) was defined as the total number of ARVs in OBT to which the subject's viral isolate showed genotypic sensitivity, based on pre-study resistance tests. The GSS score range is from 0 (meaning there was no ARV the subject was sensitive to) to >=3 (the subject was sensitive to >=3 of the ARVs in his/her OBT). If no resistance results were available for a drug, it was scored as one active drug in the GSS if there was history of prior use, and was considered not active if no prior use. Scoring did not include Raltegravir.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Grade 3 or 4 Adverse Events (AEs)   [ Time Frame: From study entry through Week 24 ]

2.  Primary:   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 ]

3.  Primary:   Number of Participants Who Died   [ Time Frame: From study entry through Week 24 ]

4.  Primary:   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. ]

5.  Primary:   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. ]

6.  Primary:   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. ]

7.  Primary:   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. ]

8.  Secondary:   Percentage of Participants With Grade 3 or 4 Adverse Events (AEs)   [ Time Frame: From study entry through Week 48 ]

9.  Secondary:   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 ]

10.  Secondary:   Number of Participants Who Died   [ Time Frame: From study entry through Week 48 ]

11.  Secondary:   Percentage of Participants With ≥1 log10 Drop From Baseline in HIV RNA or HIV RNA <400 Copies/mL   [ Time Frame: Baseline, Week 24, 48 ]

12.  Secondary:   Change of CD4 Count (Cells/µL) From Baseline   [ Time Frame: Baseline, Week 24, 48 ]

13.  Secondary:   Change of CD4 Percent From Baseline   [ Time Frame: Baseline, Week 24, 48 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Melissa Allen, Director, IMPAACT Operations Center
Organization: Family Health International (FHI 360)
phone: (919) 405-1429
e-mail: mallen@fhi360.org


Publications of Results:
Other Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00485264     History of Changes
Other Study ID Numbers: P1066, 10495, IMPAACT P1066, PACTG P1066
Study First Received: June 11, 2007
Results First Received: February 28, 2014
Last Updated: December 18, 2014
Health Authority: United States: Food and Drug Administration