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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
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

NV20911

ISRCTN number

US NCT number

NCT00623597

WHO universal trial number (UTN)

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

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

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?

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

Independent data monitoring committee (IDMC) involvement?

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

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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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.

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 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

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.

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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Reporting group title

Group A

Reporting group description

Reporting group title

Group B

Reporting group description

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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Reporting group title

Group A

Reporting group description

Reporting group title

Group B

Reporting group description

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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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 name

MedDRA

Dictionary version

12.1

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
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
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
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
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
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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Were there any global substantial amendments to the protocol? Yes

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.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Plasma Trough Concentrations for Saquinavir

Primary: Plasma Trough Concentrations for Saquinavir

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Primary: Incidence of Adverse Events and Serious Adverse Events

Primary: Incidence of Adverse Events and Serious Adverse Events

Secondary: Plasma Trough Concentrations for Ritonavir

Secondary: Plasma Trough Concentrations for Ritonavir

Secondary: Maximum Observed Concentration for Saquinavir and Ritonavir

Secondary: Maximum Observed Concentration for Saquinavir and Ritonavir

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

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

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

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

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

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

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

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

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

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

Secondary: Number of participants with Virological Failure

Secondary: Number of participants with Virological Failure

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

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

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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