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    Clinical Trial Results:
    A phase I/II study of Invirase® boosted with Ritonavir in HIV infected infants and children 4 months to less than 6 years old

    Summary
    EudraCT number
    2007-004617-34
    Trial protocol
    GB  
    Global end of trial date
    11 Mar 2010

    Results information
    Results version number
    v1(current)
    This version publication date
    04 Mar 2016
    First version publication date
    04 Mar 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    NV20911
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00623597
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche Ltd
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    16 Apr 2010
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Mar 2010
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Mar 2010
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    • To evaluate the pharmacokinetics of saquinavir that, when boosted with ritonavir, provides a systemic exposure in human immunodeficiency virus (HIV)-1 infected infants and children 4 months to < 6 years similar to that which has been shown to be safe and effective in older children and adults. • To determine the safety and tolerability of saquinavir when boosted with ritonavir in HIV-1 infected infants and children 4 months to < 6 years of age.
    Protection of trial subjects
    The investigators ensured that this study was conducted in full conformance with the principles of the “Declaration of Helsinki” (as amended in Tokyo, Venice, Hong Kong and South Africa) or with the laws and regulations of the country in which the research was conducted, whichever afforded greater protection to the individual. The study adhered fully to the principles outlined in “Guideline for Good Clinical Practice” ICH Tripartite Guideline (January 1997) or with local law if it afforded greater protection to the participant. In countries where a “Guideline for Good Clinical Practice” existed, Roche and the investigators were to strictly ensure adherence to the stated provisions.
    Background therapy
    The participants in the study were allowed to take >= 2 background antiretroviral (ARV) regimen. Background ARVs included nucleosides (nucleoside reverse transcriptase inhibitor) and could also include ritonavir boosted lopinavir (LPV/r), as deemed appropriate by the investigator, considering the participant’s prior history as well as the participant’s viral resistance assessed at screening. If LPV/r was used, the total dose of ritonavir (including ritonavir that was co-formulated with lopinavir) was specified. The background ARVs was revised when initiating saquinavir and ritonavir, or remained unchanged from prestudy, as per the judgment of the investigator. Background ARVs were changed during the course of the study as needed for toxicity management or if the participant’s virological or immunological response was insufficient.
    Evidence for comparator
    Nil
    Actual start date of recruitment
    20 May 2008
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    Argentina: 7
    Country: Number of subjects enrolled
    Thailand: 10
    Worldwide total number of subjects
    18
    EEA total number of subjects
    1
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    5
    Children (2-11 years)
    13
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    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
    Screening details
    Participants were HIV infected infants and young children who met the eligibility criteria were stratified into 2 groups - low age group (>= 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.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Group A
    Arm description
    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.
    Arm type
    Experimental

    Investigational medicinal product name
    Saquinavir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard, Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received saquinavir mesylate (Invirase ®200 mg hard capsules [HC] and/or 500 mg film coated tablet [FCT]) up to 48 weeks. For participants who could not swallow Invirase capsules, the 200 mg capsule(s) were opened and the contents of the capsule administered in a vehicle [sugar syrup (sorbitol syrup for children with diabetes mellitus or glucose intolerance), jam or baby formula] along with ritonavir oral solution. At home saquinavir and ritonavir was to be taken concomitantly with food. On days of sampling blood for pharmacokinetic study, dosing was approximately 30 minutes after the start of breakfast. For participants who could swallow capsules and or tablets no vehicle was required. The saquinavir mesylate 500 mg FCT was not to be crushed prior to administration.

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral drops, solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ritonavir (Norvir® 80 mg/mL oral solution) 3 mg/kg BID for body weight from 5 to <15 kg for up to 48 weeks. If a participant was prescribed Kaletra® (lopinavir/ritonavir) as part of the background ARV regimen, the ritonavir dose specified in the protocol for a child of a given weight was the total dose of ritonavir, including the ritonavir that was co-formulated in Kaletra. Thus, for participants taking Invirase plus Kaletra, the ritonavir included in the Kaletra was sufficient for boosting of both the Invirase and the lopinavir, and no additional ritonavir was to be given. At home ritonavir was to be taken concomitantly with food. On days of sampling blood for pharmacokinetic study, dosing was approximately 30 minutes after the start of breakfast.

    Arm title
    Group B
    Arm description
    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.
    Arm type
    Experimental

    Investigational medicinal product name
    Saquinavir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard, Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received saquinavir mesylate (Invirase ®200 mg HC and/or 500 mg FCT) up to 48 weeks. For participants who could not swallow Invirase capsules, the 200 mg capsule(s) were opened and the contents of the capsule administered in a vehicle [sugar syrup (sorbitol syrup for children with diabetes mellitus or glucose intolerance), jam or baby formula] and ritonavir oral solution. At home saquinavir and ritonavir was to be taken concomitantly with food. On days of sampling blood for pharmacokinetic study, dosing was approximately 30 minutes after the start of breakfast. For participants who could swallow capsules and or tablets no vehicle was required. The saquinavir mesylate 500 mg FCT was not to be crushed prior to administration.

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral drops, solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ritonavir (Norvir® 80 mg/mL oral solution) 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 for up to 48 weeks. If a participant was prescribed Kaletra® (lopinavir/ritonavir) as part of the background ARV regimen, the ritonavir dose specified in the protocol for a child of a given weight was the total dose of ritonavir, including the ritonavir that was co-formulated in Kaletra. Thus, for participants taking Invirase plus Kaletra, the ritonavir included in the Kaletra was sufficient for boosting of both the Invirase and the lopinavir, and no additional ritonavir was to be given. At home ritonavir was to be taken concomitantly with food. On days of sampling blood for pharmacokinetic study, dosing was approximately 30 minutes after the start of breakfast.

    Number of subjects in period 1
    Group A Group B
    Started
    5
    13
    Completed
    4
    13
    Not completed
    1
    0
         Failed to return
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group A
    Reporting group description
    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.

    Reporting group title
    Group B
    Reporting group description
    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.

    Reporting group values
    Group A Group B Total
    Number of subjects
    5 13 18
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    5 0 5
        Children (2-11 years)
    0 13 13
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    0 0 0
        From 65-84 years
    0 0 0
        85 years and over
    0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    0.8 ± 0.45 4 ± 1.08 -
    Gender categorical
    Units: Subjects
        Female
    3 8 11
        Male
    2 5 7

    End points

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    End points reporting groups
    Reporting group title
    Group A
    Reporting group description
    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.

    Reporting group title
    Group B
    Reporting group description
    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.

    Subject analysis set title
    All Patient Population
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The All Patient Population (APP) comprised all participants who were enrolled in the study, regardless of whether they received any study drug.

    Subject analysis set title
    PK Analysis Population
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    The pharmacokinetics Analysis Population (PKP) comprised all the participants from whom blood samples for pharmacokinetic analysis were collected. Participants could be excluded from the PKP if no reliable PK parameters could be determined. Moreover, participants could be excluded from the PK analysis population if justified by circumstances (e.g. vomiting after drug administration) and in agreement with the sponsor.

    Subject analysis set title
    Safety Analysis Population
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    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.

    Primary: Plasma Trough Concentrations for Saquinavir

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    End point title
    Plasma Trough Concentrations for Saquinavir [1]
    End point description
    Plasma trough concentration (Ctrough) is the average steady state concentration prior to morning and evening dose. Ctrough of Saquinavir was normalized to a dose of 50 mg/kg. The PKP was used for this endpoint analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose at Weeks 8, 12, and 24
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were done for this end point.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: nanogram per mililitre (ng/mL)
        arithmetic mean (standard deviation)
    645 ± 536
    1860 ± 1060
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours for Saquinavir

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    End point title
    Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours for Saquinavir [2]
    End point description
    The area under the plasma concentration-time curve from time zero to twelve hours (AUC0-12h) is area under the plasma concentration-time curve from time zero through actual tlast. The area under the plasma concentration-time curve from time zero to twelve hours of saquinavir was normalized to a dose of 50 mg/kg. The PKP was used for this endpoint analysis.
    End point type
    Primary
    End point timeframe
    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).
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were done for this end point.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: hour* microgram per mililitre (h*ug/mL)
        arithmetic mean (standard deviation)
    18.7 ± 20
    38 ± 18.1
    No statistical analyses for this end point

    Primary: Change In Hemoglobin, Total Protein And Total Albumin From Baseline at Week 24 and Week 48

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    End point title
    Change In Hemoglobin, Total Protein And Total Albumin From Baseline at Week 24 and Week 48 [3]
    End point description
    Change in Hemoglobin, Total Protein and Total Albumin from baseline (BL) was calculated as the post-baseline value minus the baseline value. Week=Wk. The SAP was used for analysis of this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1), Week 24 and 48
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were done for this end point.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: gram per litre (g/L)
    arithmetic mean (standard deviation)
        Hemoglobin-Change from BL at Wk 24 (n=4, 13)
    0 ± 3.3
    1 ± 12.1
        Hemoglobin-Change from BL at Wk 48 (n=4, 13)
    6 ± 11.8
    0 ± 14.4
        Total Protein-Change from BL at Wk 24 (n=4, 13)
    -4 ± 6
    2 ± 12.6
        Total Protein-Change from BL at Wk 48 (n=4, 13)
    -5 ± 5.7
    0 ± 14.3
        Total Albumin-Change from BL at Wk 24 (n=4, 13)
    0.5 ± 5.41
    5 ± 7.68
        Total Albumin-Change from BL at Wk 48 (n=4, 13)
    1.3 ± 2.29
    4 ± 8.7
    No statistical analyses for this end point

    Primary: Change In Hematocrit From Baseline at Week 24 and Week 48

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    End point title
    Change In Hematocrit From Baseline at Week 24 and Week 48 [4]
    End point description
    Change from baseline was calculated as the post-baseline value minus the baseline value. The SAP was used for analysis of this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1), Week 24 and 48
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were done for this end point.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: fraction
    arithmetic mean (standard deviation)
        Change from Baseline at Week 24 (n= 4, 13)
    0.01 ± 0.011
    0 ± 0.03
        Change from Baseline at Week 48 (n= 4, 13)
    0.03 ± 0.037
    -0.01 ± 0.044
    No statistical analyses for this end point

    Primary: Change In White Blood Cell, Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline at Week 24 and Week 48

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    End point title
    Change In White Blood Cell, Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline at Week 24 and Week 48 [5]
    End point description
    Change from Baseline in White Blood Cell, Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil and Eosinophil Cell Counts was calculated as the post-baseline value minus the baseline value. The SAP was used for analysis of this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 48
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were done for this end point.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: 10*9/L
    arithmetic mean (standard deviation)
        White Blood Cell-Change from BL at Wk 24 (n=4,13)
    -3 ± 2.31
    -1 ± 4.35
        White Blood Cell-Change from BL at Wk 48 (n=4,13)
    -2.1 ± 1.72
    -0.9 ± 4.38
        Platelet-Change from BL at Wk 24 (n=4,13)
    -119 ± 93.4
    24 ± 148.9
        Platelet-Change from BL at Wk 48 (n=4,13)
    -50 ± 130.4
    -2 ± 118.9
        Basophil-Change from BL at Wk 24 (n=4,13)
    -0.02 ± 0.028
    0 ± 0.031
        Basophil-Change from BL at Wk 48 (n=4,13)
    0 ± 0.03
    -0.01 ± 0.029
        Lymphocyte-Change from BL at Wk 24 (n=2,2)
    -0.9 ± 0.3
    -1.1 ± 1.2
        Lymphocyte-Change from BL at Wk 48 (n=2,2)
    -1.5 ± 0.29
    -0.7 ± 1.05
        Monocyte-Change from BL at Wk 24 (n=4,13)
    -0.41 ± 0.295
    -0.01 ± 0.361
        Monocyte-Change from BL at Wk 48 (n=4,13)
    -0.21 ± 0.179
    -0.05 ± 0.384
        Neutrophil-Change from BL at Wk 24 (n=2,2)
    -1.4 ± 0.33
    -2.8 ± 1.87
        Neutrophil-Change from BL at Wk 48 (n=2,2)
    -1.7 ± 1.15
    -1.6 ± 2.55
        Eosinophil-Change from BL at Wk 24 (n=2,2)
    0 ± 0.2
    0 ± 0.1
        Eosinophil-Change from BL at Wk 48 (n=2,2)
    0 ± 0.2
    0 ± 1.1
    No statistical analyses for this end point

    Primary: Change In Red Blood Cell Counts From Baseline at Week 24 and Week 48

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    End point title
    Change In Red Blood Cell Counts From Baseline at Week 24 and Week 48 [6]
    End point description
    Change from baseline in Red Blood Cell (RBC) counts was calculated as the post-baseline value minus the baseline value. The SAP was used for analysis of this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 48
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were done for this end point.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: 10*12/L
    arithmetic mean (standard deviation)
        RBC Count-Change from BL at Wk24 (n=4,13)
    -0.18 ± 0.227
    -0.07 ± 0.673
        RBC Count-Change from BL at Wk48 (n=4,13)
    0.02 ± 0.125
    -0.16 ± 0.74
    No statistical analyses for this end point

    Primary: Change In Creatine Kinase, Serum Glutamic Oxaloacetic Transaminase, Alkaline Phosphatase, Serum Glutamic-Pyruvic Transaminase, Gamma-Glutamyl Transferase Counts From Baseline at Week 24 and Week 48

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    End point title
    Change In Creatine Kinase, Serum Glutamic Oxaloacetic Transaminase, Alkaline Phosphatase, Serum Glutamic-Pyruvic Transaminase, Gamma-Glutamyl Transferase Counts From Baseline at Week 24 and Week 48 [7]
    End point description
    Change from baseline in Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT), Alkaline Phosphatase (AP) was calculated as the post-baseline value minus the baseline value. The SAP was used for this endpoint analysis.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 48
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were done for this end point.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: units per litre (U/L)
    arithmetic mean (standard deviation)
        CK, Change from Baseline at Week 24 (n= 3, 3)
    112 ± 112
    -12 ± 115.9
        CK, Change from Baseline at Week 48 (n= 3, 3)
    257 ± 244.8
    -7 ± 84
        SGOT, Change from Baseline at Week 24 (n= 4,13)
    0 ± 1.5
    0 ± 8.2
        SGOT, Change from Baseline at Week 48 (n= 4,13)
    -1 ± 7.8
    0 ± 6.9
        ALP, Change from Baseline at Week 24 (n=4, 12)
    10 ± 29.8
    26 ± 23.2
        ALP, Change from Baseline at Week 48 (n=4, 12)
    47 ± 87.6
    36 ± 26.5
        SGPT, Change from Baseline at Week 24 (n=4,13)
    -9 ± 15.3
    -2 ± 13.6
        SGPT, Change from Baseline at Week 48 n=4,13)
    -2 ± 13.4
    -3 ± 12.1
        GGT, Change from Baseline at Week 24 (n=4, 13)
    5 ± 4.7
    -7 ± 18.7
        GGT, Change from Baseline at Week 48 (n=4, 13)
    5 ± 2.1
    -5 ± 18.5
    No statistical analyses for this end point

    Primary: Change In Total Bilirubin, Creatinine, Uric Acid From Baseline at Week 24 and Week 48

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    End point title
    Change In Total Bilirubin, Creatinine, Uric Acid From Baseline at Week 24 and Week 48 [8]
    End point description
    Change from baseline in Total Bilirubin, Creatinine, Uric Acid was calculated as the post-baseline value minus the baseline value. The SAP was used for this endpoint analysis.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 48
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were done for this end point.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: micromolar per litre (umol/L)
    arithmetic mean (standard deviation)
        Total Bilirubin-Change from BL at Wk 24(n=4,12)
    2 ± 2.8
    2 ± 5.5
        Total Bilirubin-Change from BL at Wk 48(n=4,12)
    1 ± 1.1
    2 ± 6.9
        Cretainine- Change from BL at Wk 24 (n=4, 13)
    -2 ± 6.7
    3 ± 10
        Cretainine- Change from BL at Wk 48 (n=4, 13)
    3 ± 10.7
    5 ± 9.2
        Uric acid- Change from BL at Wk 24 (n=4, 13)
    -27 ± 54.3
    68 ± 55.1
        Uric acid- Change from BL at Wk 48 (n=3,13)
    -42 ± 108.4
    61 ± 63.5
    No statistical analyses for this end point

    Primary: Change In Blood Urea Nitrogen, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol, Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline at Week 24 and Week 48

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    End point title
    Change In Blood Urea Nitrogen, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol, Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline at Week 24 and Week 48 [9]
    End point description
    Change from baseline in Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose was calculated as the post-baseline value minus the baseline value. The SAP was used for this endpoint analysis.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 48
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were done for this end point.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: millimole per litre (mmol/L)
    arithmetic mean (standard deviation)
        BUN,Change from Baseline at Week 24 (n= 3, 13)
    -1.5 ± 2.78
    1 ± 2.2
        BUN,Change from Baseline at Week 48 (n= 3, 13)
    0.4 ± 0.66
    1.1 ± 2
        LDL,Change from Baseline at Week 24 (n= 3, 13)
    0.21 ± 0.237
    0.21 ± 1.389
        LDL,Change from Baseline at Week 48 (n= 3, 13)
    0.23 ± 0.596
    -0.11 ± 1.038
        HDL,Change from Baseline at Week 24 (n= 3, 13)
    0.21 ± 0.202
    0.13 ± 0.369
        HDL,Change from Baseline at Week 48 (n= 3, 13)
    0.41 ± 0.233
    0.17 ± 0.387
        Triglyceride,Change from BL at Wk 24 (n=4,13)
    -0.28 ± 0.597
    -0.19 ± 1.376
        Triglyceride,Change from BL at Wk 48 (n=4,13)
    -0.19 ± 0.496
    -0.15 ± 1.558
        Calcium,Change from BL at Wk 24 (n=2, 12)
    -0.15 ± 0.04
    0.15 ± 0.17
        Calcium,Change from BL at Wk 48 (n=2, 12)
    -0.16 ± 0.09
    0.09 ± 0.17
        Potassium,Change from BL at Wk 24 (n=4,13)
    -0.1 ± 0.16
    -0.3 ± 0.63
        Potassium,Change from BL at Wk 48 (n=4,13)
    0.2 ± 0.59
    -0.2 ± 0.54
        Sodium,Change from BL at Wk 24 (n=4,13)
    2 ± 1.3
    -1 ± 2.3
        Sodium,Change from BL at Wk 48 (n=4,13)
    1 ± 2.2
    -1 ± 3.8
        Chloride,Change from BL at Wk 24 (n=4,13)
    -1 ± 2.8
    -2 ± 4.2
        Chloride,Change from BL at Wk 48 (n=4,13)
    1 ± 1.3
    -2 ± 3.6
        Phosphate,Change from BL at Wk 24 (n=2, 12)
    -0.02 ± 0.114
    0.17 ± 0.188
        Phosphate,Change from BL at Wk 48 (n=2, 13)
    -0.26 ± 0
    0.12 ± 0.212
        Fasting Glucose,Change from BL at Wk 24(n=4,13)
    -0.26 ± 0.963
    0.02 ± 1.253
        Fasting Glucose,Change from BL at Wk 48(n=4,13)
    -0.07 ± 0.857
    0.14 ± 1.537
    No statistical analyses for this end point

    Primary: Change In Hematuria, Glycosuria And Proteinuria From Baseline at Week 24 and Week 48

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    End point title
    Change In Hematuria, Glycosuria And Proteinuria From Baseline at Week 24 and Week 48 [10]
    End point description
    Change from baseline in Hematuria, Glycosuria And Proteinuria was calculated as the post-baseline value minus the baseline value. ThThe SAP was used for analysis of this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 48
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were done for this end point.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: [0 to 4+]
    arithmetic mean (standard deviation)
        Hematuria-Change from BL at Wk 24 (n= 1, 2)
    0 ± 0
    0 ± 0
        Hematuria-Change from BL at Wk 48 (n= 1, 2)
    0 ± 0
    0 ± 0
        Glycosuria-Change from BL at Wk 24 (n= 1, 2)
    0 ± 0
    0 ± 0
        Glycosuria-Change from BL at Wk 48 (n= 1, 2)
    0 ± 0
    0 ± 0
        Proteinuria-Change from BL at Wk 24 (n= 1, 2)
    0 ± 0
    0 ± 0
        Proteinuria-Change from BL at Wk 48 (n= 1, 2)
    0 ± 0
    0 ± 0
    No statistical analyses for this end point

    Primary: Incidence of Adverse Events and Serious Adverse Events

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    End point title
    Incidence of Adverse Events and Serious Adverse Events [11]
    End point description
    An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes. The SAP was used for this endpoint analysis.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were done for this end point.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: Number
        Subjects with serious adverse events
    1
    2
        Subjects with non-serious adverse events
    5
    9
    No statistical analyses for this end point

    Secondary: Plasma Trough Concentrations for Ritonavir

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    End point title
    Plasma Trough Concentrations for Ritonavir
    End point description
    Plasma trough concentration is the average steady state concentration prior to morning and evening dose. Ctrough of Ritonavir was normalized to a dose of 100 mg/kg. The PKP was used for analysis of this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose at Weeks 8, 12, 24
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: ng/mL
        arithmetic mean (standard deviation)
    577 ± 366
    995 ± 548
    No statistical analyses for this end point

    Secondary: Maximum Observed Concentration for Saquinavir and Ritonavir

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    End point title
    Maximum Observed Concentration for Saquinavir and Ritonavir
    End point description
    The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Cmax was normalized to a dose of 50 mg/kg for Saquinavir and 100 mg/kg for Ritonavir. The PKP was used for analysis of this endpoint.
    End point type
    Secondary
    End point timeframe
    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.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: ng/mL
    arithmetic mean (standard deviation)
        Saquinavir
    2910 ± 3110
    5570 ± 2780
        Ritonavir
    2050 ± 1270
    3370 ± 2020
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours for Ritonavir

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    End point title
    Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours for Ritonavir
    End point description
    The area under the plasma concentration-time curve from time zero to twelve hours (AUC0-12h) is area under the plasma concentration-time curve from time zero through actual tlast. The area under the plasma concentration-time curve from time zero to twelve hours of ritonavir was normalized to a dose of 100 mg/kg. The PKP was used for analysis of this endpoint.
    End point type
    Secondary
    End point timeframe
    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
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: h*ug/ml
        arithmetic mean (standard deviation)
    13.6 ± 8.18
    21.8 ± 11.6
    No statistical analyses for this end point

    Secondary: Change From Baseline in Mean Human Immunodeficiency Virus Viral Load

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    End point title
    Change From Baseline in Mean Human Immunodeficiency Virus Viral Load
    End point description
    Change from baseline in plasma HIV-1 RNA was derived as Change from baseline = Log10 (HIV-1 RNA at week x) – Log10 (HIV-1 RNA at baseline). A baseline collection was made if there was not already a value available taken within the previous 4 weeks. The SAP was used for analysis of this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation.
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: log10 copies/mL
    arithmetic mean (standard deviation)
        Change from Baseline at Week 24 (n= 3, 13)
    -0.75 ± 1.48
    -1.81 ± 1.57
        Change from Baseline at Week 48 (n= 3, 13)
    -1.27 ± 1.01
    -1.39 ± 1.53
    No statistical analyses for this end point

    Secondary: Number of Participants with Human Immunodeficiency Virus –Ribonucleic acid <400 copies/mL

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    End point title
    Number of Participants with Human Immunodeficiency Virus –Ribonucleic acid <400 copies/mL
    End point description
    The number of participants with HIV-1 RNA results <400 copies/mL were reported. A baseline collection was made if there was not already a value available taken within the previous 4 weeks. The SAP was used for analysis of this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: Number
        Baseline (n= 5, 13)
    1
    5
        Week 24 (n= 3, 13)
    2
    13
        Week 48 (n= 3, 13)
    2
    11
    No statistical analyses for this end point

    Secondary: Number of Participants with Human Immunodeficiency Virus –Ribonucleic acid <50 copies/mL

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    End point title
    Number of Participants with Human Immunodeficiency Virus –Ribonucleic acid <50 copies/mL
    End point description
    The number of participants with Human Immunodeficiency Virus (HIV)-1 Ribonucleic acid (RNA) results <50 copies/mL were reported. A baseline collection was made if there was not already a value available taken within the previous 4 weeks. The SAP was used for analysis of this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: Number
        Baseline (n= 5, 13, 18)
    0
    4
        Week 24 (n= 3, 13, 16)
    2
    11
        Week 48 (n= 3, 13, 16)
    2
    9
    No statistical analyses for this end point

    Secondary: Number of Participants with >1 log Decrease from Baseline in Human Immunodeficiency Virus–Ribonucleic acid

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    End point title
    Number of Participants with >1 log Decrease from Baseline in Human Immunodeficiency Virus–Ribonucleic acid
    End point description
    The number of participants experiencing a greater than 1 log drop from baseline (day 1) (log 10 transformed) were reported. The SAP was used for analysis of this endpoint.
    End point type
    Secondary
    End point timeframe
    From Week 8, 24 and 48
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: Number
        Week 8 (n= 4, 12)
    1
    7
        Week 24 (n= 3, 13)
    1
    8
        Week 48 (n= 3, 13)
    1
    7
    No statistical analyses for this end point

    Secondary: Number of participants with Virological Failure

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    End point title
    Number of participants with Virological Failure
    End point description
    Virological failure was defined as: viral load >= 400 copies/mL on two consecutive occasions (missing visits was assumed to be above 400 copies/mL). The number of participants classified as virological failure by age group and viral load (<= 10,000 copies, >10,000 copies) were presented. Week=Wk, Virological failure =VF, Baseline= BL, copies per microlitre=c/mL. The SAP was used for analysis of this endpoint.
    End point type
    Secondary
    End point timeframe
    From Week 12 till Week 48
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: Number
        VF at Week 12 (n= 5, 13)
    2
    1
        VF at Week 24 (n= 5, 13)
    2
    0
        VF at Week 48 (n= 5, 13)
    3
    1
        HIV-RNA <= 10,000 copies/mL at Wk 12 (n= 3, 6)
    1
    0
        HIV-RNA <= 10,000 copies/mL at Wk 24 (n= 3, 6)
    1
    0
        HIV-RNA <= 10,000 copies/mL at Wk 48 (n= 3, 6)
    2
    0
        HIV-RNA >10,000 copies/mL at Week 12 (n= 2, 7)
    1
    1
        HIV-RNA >10,000 copies/mL at Week 24 (n= 2, 7)
    1
    0
        HIV-RNA >10,000 copies/mL at Week 48 (n= 2, 7)
    1
    1
    No statistical analyses for this end point

    Secondary: Change From Baseline in Cluster Differentiation Antigen 4 Lymphocyte Count

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    End point title
    Change From Baseline in Cluster Differentiation Antigen 4 Lymphocyte Count
    End point description
    Change from Baseline in Cluster Differentiation Antigen 4 (CD4+) lymphocyte count at 24 weeks and 48 weeks were presented by age group. Change from baseline in CD4+ lymphocyte count was derived as follows: Change from baseline = (CD4+ count at week 24/48) – (CD4+ count at baseline). A baseline collection was made if there was not already a value available taken within the previous 4 weeks. Baseline was on Day 1. The SAP was used for analysis of this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: counts per microlitre (c/µL)
    arithmetic mean (standard deviation)
        Change from Baseline at Week 24 (n= 3, 12)
    94.9 ± 643.28
    -34.53 ± 821.31
        Change from Baseline at Week 48 (n= 3, 12)
    -50.07 ± 1013.23
    126.11 ± 528.49
    No statistical analyses for this end point

    Secondary: Change From Baseline in Cluster Differentiation Antigen 8 Lymphocyte Count

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    End point title
    Change From Baseline in Cluster Differentiation Antigen 8 Lymphocyte Count
    End point description
    Change from baseline in Cluster Differentiation Antigen 8 (CD8+) lymphocyte count at 24 weeks and 48 weeks were presented by age group. Change from baseline in CD8+ lymphocyte count was derived as follows: Change from baseline = (CD8+ count at week 24/48) – (CD8+ count at baseline). A baseline collection was made if there was not already a value available taken within the previous 4 weeks. Baseline was on Day 1. The SAP was used for analysis of this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation
    End point values
    Group A Group B
    Number of subjects analysed
    5
    13
    Units: counts per microlitre (c/µl)
    arithmetic mean (standard deviation)
        Change from Baseline at Week 24 (n= 3, 12)
    -200.49 ± 161.05
    -3.5 ± 790.86
        Change from Baseline at Week 48 (n= 3, 12)
    -92.07 ± 455.23
    40.52 ± 641.27
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 56 weeks
    Adverse event reporting additional description
    Serious adverse events and non-serious adverse events are reported in Safety Population Set. 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.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    12.1
    Reporting groups
    Reporting group title
    Group A
    Reporting group description
    -

    Reporting group title
    Group B
    Reporting group description
    -

    Reporting group title
    Total
    Reporting group description
    Participants 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.

    Serious adverse events
    Group A Group B Total
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 5 (20.00%)
    2 / 13 (15.38%)
    3 / 18 (16.67%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 13 (7.69%)
    2 / 18 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Group A Group B Total
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 5 (100.00%)
    9 / 13 (69.23%)
    14 / 18 (77.78%)
    Investigations
    Weight Decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Epistaxis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    General disorders and administration site conditions
    Gait Disturbance
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 13 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    1
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    1 / 5 (20.00%)
    2 / 13 (15.38%)
    3 / 18 (16.67%)
         occurrences all number
    1
    13
    14
    Diarrhoea
         subjects affected / exposed
    0 / 5 (0.00%)
    3 / 13 (23.08%)
    3 / 18 (16.67%)
         occurrences all number
    0
    4
    4
    Dental Caries
         subjects affected / exposed
    1 / 5 (20.00%)
    2 / 13 (15.38%)
    3 / 18 (16.67%)
         occurrences all number
    1
    2
    3
    Constipation
         subjects affected / exposed
    2 / 5 (40.00%)
    0 / 13 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    2
    0
    2
    Abdominal Pain
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 13 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    1
    Abdominal Pain Lower
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Gingivitis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Renal and urinary disorders
    Enuresis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Intertrigo
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Musculoskeletal and connective tissue disorders
    Synovitis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Infections and infestations
    Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 13 (7.69%)
    2 / 18 (11.11%)
         occurrences all number
    1
    2
    3
    Bronchitis
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 13 (15.38%)
    2 / 18 (11.11%)
         occurrences all number
    0
    2
    2
    Impetigo
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    2
    2
    Otitis Media
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    2
    2
    Cellulitis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Cystitis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Gastroenteritis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Giardiasis
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 13 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    1
    Herpangina
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 13 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    1
    Otitis Media Acute
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Pharyngitis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Pneumonia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Pyoderma
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Rhinitis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Toxocariasis
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 13 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    1
    Urinary Tract Infection
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 13 (7.69%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Mar 2008
    The protocol was amended to clarify -units for AUC, inclusion and exclusion criteria, information added on funding of ARV medication, criteria for premature withdrawal, genotypic resistance testing in screening examination and HIV-RNA viral load assessment, instruction for ritonavir dosing, footnotes and correction of units and typographical errors.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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