A Study of Invirase (Saquinavir)/Ritonavir in HIV-Infected Infants and Children.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00623597
First received: February 18, 2008
Last updated: February 4, 2016
Last verified: February 2016
Results First Received: December 10, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: ritonavir
Drug: saquinavir [Invirase]

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 18 participants were recruited from 8 centers in Argentina (3 centers), Spain (1 center) and Thailand (4 centers). This study was conducted between May 20, 2008 and March 11, 2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were human immunodeficiency virus (HIV) infected infants and young children who met the eligibility criteria were stratified into 2 groups - low age (>= 4 months to <2 years) and high age group (>= 2 years to <6 years). Participants commenced treatment with saquinavir and ritonavir along with background antiretroviral (ARV) regimen.

Reporting Groups
  Description
Group A Participants (infants >= 4 months to <2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to < 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight > 40 kg plus >= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Group B Participants (children >= 2 years to <6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to < 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight > 40 kg plus >= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.

Participant Flow:   Overall Study
    Group A     Group B  
STARTED     5     13  
COMPLETED     4     13  
NOT COMPLETED     1     0  
Failed to return                 1                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

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.
The Safety Analysis Population (SAP) comprised all participants who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses

Reporting Groups
  Description
Group A Participants (infants >= 4 months to <2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to < 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight > 40 kg plus >= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Group B Participants (children >= 2 years to <6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to < 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight > 40 kg plus >= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Total Total of all reporting groups

Baseline Measures
    Group A     Group B     Total  
Number of Participants  
[units: participants]
  5     13     18  
Age  
[units: years]
Mean (Standard Deviation)
  0.8  (0.45)     4.0  (1.08)     3.1  (1.75)  
Gender  
[units: participants]
     
Female     3     8     11  
Male     2     5     7  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Plasma Trough Concentrations (Ctrough) for Saquinavir   [ Time Frame: Pre-dose at Weeks 8, 12, 24. ]

2.  Primary:   Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours (AUC0-12h) for Saquinavir   [ Time Frame: Pre-dose and 3, 4, 8, 12 hours (post-dose) on Day 14 (± 2 days), or Day 28(+ 2 days) for patients switching from an Non-nucleoside reverse transcriptase inhibitor [NNRTI] containing regimen). ]

3.  Primary:   Incidence of Adverse Events (AE) and Serious Adverse Events (SAE)   [ Time Frame: From Baseline (Day 1) till Week 48 and Follow-up (Week 52) ]

4.  Primary:   Change In Hematocrit From Baseline   [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ]

5.  Primary:   Change In Hemoglobin, Total Protein And Total Albumin From Baseline   [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ]

6.  Primary:   Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline   [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ]

7.  Primary:   Change In Red Blood Cell (RBC) Counts From Baseline   [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ]

8.  Primary:   Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline   [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ]

9.  Primary:   Change In Total Bilirubin, Creatinine, Uric Acid From Baseline   [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ]

10.  Primary:   Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline   [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ]

11.  Primary:   Change In Hematuria, Glycosuria And Proteinuria From Baseline   [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ]

12.  Secondary:   Plasma Trough Concentrations (Ctrough) for Ritonavir   [ Time Frame: Pre-dose at Weeks 8, 12, 24 ]

13.  Secondary:   Maximum Observed Concentration (Cmax) for Saquinavir and Ritonavir   [ Time Frame: Pre-dose and 3, 4, 8, 12 hours (post-dose) on Day 14 (± 2 days), or Day 28(+ 2 days) for patients switching from an NNRTI containing regimen and at Week 24 ]

14.  Secondary:   Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours (AUC0-12h) for Ritonavir   [ Time Frame: Pre-dose and 3, 4, 8, 12 hours (post-dose) on Day 14 (± 2 days), or Day 28(+ 2 days) for patients switching from an NNRTI containing regimen). ]

15.  Secondary:   Change From Baseline in Mean Human Immunodeficiency Virus Viral Load   [ Time Frame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 (or upon premature discontinuation); a baseline collection was made if there was not already a value available taken within the previous 4 weeks. ]

16.  Secondary:   Number of Participants With Human Immunodeficiency Virus (HIV) –Ribonucleic Acid (RNA) <400 Copies/mL   [ Time Frame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 (or upon premature discontinuation); a baseline collection was made if there was not already a value available taken within the previous 4 weeks. ]

17.  Secondary:   Number of Participants With Human Immunodeficiency Virus (HIV) –Ribonucleic Acid (RNA) <50 Copies/mL   [ Time Frame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 (or upon premature discontinuation); a baseline collection was made if there was not already a value available taken within the previous 4 weeks. ]

18.  Secondary:   Number of Participants With >1 Log Decrease From Baseline in Human Immunodeficiency Virus (HIV) –Ribonucleic Acid (RNA )   [ Time Frame: From Week 8 till Week 48 ]

19.  Secondary:   Number of Participants With Virological Failure   [ Time Frame: From Week 12 till Week 48 ]

20.  Secondary:   Change From Baseline in Cluster Differentiation Antigen 4 (CD4) Lymphocyte Count   [ Time Frame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation ]

21.  Secondary:   Change From Baseline in Cluster Differentiation Antigen 8 (CD8) Lymphocyte Count   [ Time Frame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information
  Hide More Information

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: Roche Trial Information Hotline
Organization: F. Hoffmann-La Roche AG
phone: +41 61 6878333
e-mail: global.trial_information@roche.com



Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00623597     History of Changes
Other Study ID Numbers: NV20911
2007-004617-34
Study First Received: February 18, 2008
Results First Received: December 10, 2015
Last Updated: February 4, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration