Trial Outcomes & Findings for A Safety Study to Evaluate the Antiviral Activity of Darunavir in Combination With Ritonavir in HIV 1 Infected Children (NCT NCT00919854)
NCT ID: NCT00919854
Last Updated: 2014-04-23
Results Overview
The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
COMPLETED
PHASE2
27 participants
Week 24
2014-04-23
Participant Flow
This study was conducted in 5 countries: Argentina, Brazil, India, Kenya, and South Africa.
27 participants were recruited and treated in this study; as Good Clinical Practice (GCP) requirements were not consistently adhered to at one site (involving 6 participants), analyses were performed excluding the participants from this site, resulting in 21 participants used for analyses.
Participant milestones
| Measure |
DRV/Rtv
Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and \<20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg
|
|---|---|
|
Overall Study
STARTED
|
21
|
|
Overall Study
COMPLETED
|
20
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
DRV/Rtv
Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and \<20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
A Safety Study to Evaluate the Antiviral Activity of Darunavir in Combination With Ritonavir in HIV 1 Infected Children
Baseline characteristics by cohort
| Measure |
DRV/Rtv
n=21 Participants
Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and \<20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg
|
|---|---|
|
Age, Continuous
|
4.6 years
FULL_RANGE 0.89 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
Argentina
|
4 participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
6 participants
n=5 Participants
|
|
Region of Enrollment
India
|
1 participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
10 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
15.1 kg/m^2
STANDARD_DEVIATION 1.51 • n=5 Participants
|
PRIMARY outcome
Timeframe: Week 24Population: 27 participants were recruited and received at least 1 dose of study medication; as Good Clinical Practice (GCP) requirements were not consistently adhered to at one site (involving 6 participant), analyses were performed excluding the participants from this site, resulting in 21 participants used for analyses.
The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Outcome measures
| Measure |
DRV/Rtv
n=21 Participants
Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and \<20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg
|
|---|---|
|
Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 24 - Time to Loss of Virologic Response (TLOVR)
|
13 Participants
|
SECONDARY outcome
Timeframe: Week 48Population: 27 participants were recruited and received at least 1 dose of study medication; as Good Clinical Practice (GCP) requirements were not consistently adhered to at one site (involving 6 participant), analyses were performed excluding the participants from this site, resulting in 21 participants used for analyses.
Outcome measures
| Measure |
DRV/Rtv
n=21 Participants
Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and \<20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg
|
|---|---|
|
Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 48
|
17 Participants
|
SECONDARY outcome
Timeframe: Week 24 and Week 48Population: 27 participants were recruited and received at least 1 dose of study medication; as Good Clinical Practice (GCP) requirements were not consistently adhered to at one site (involving 6 participant), analyses were performed excluding the participants from this site, resulting in 21 participants used for analyses.
Outcome measures
| Measure |
DRV/Rtv
n=21 Participants
Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and \<20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg
|
|---|---|
|
Number of Participants With Virological Response (Viral Load Less Than 400 Copies/mL) at Week 24 and Week 48
Week 48
|
18 Participants
|
|
Number of Participants With Virological Response (Viral Load Less Than 400 Copies/mL) at Week 24 and Week 48
Week 24
|
17 Participants
|
SECONDARY outcome
Timeframe: Week 24 and Week 48Population: 27 participants were recruited and received at least 1 dose of study medication; as Good Clinical Practice (GCP) requirements were not consistently adhered to at one site (involving 6 participant), analyses were performed excluding the participants from this site, resulting in 21 participants used for analyses.
Outcome measures
| Measure |
DRV/Rtv
n=21 Participants
Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and \<20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg
|
|---|---|
|
Number of Participants With Less Than or Equal to 1 log10 Decrease in Plasma Viral Load at Week 24 and Week 48
Week 24
|
17 Participants
|
|
Number of Participants With Less Than or Equal to 1 log10 Decrease in Plasma Viral Load at Week 24 and Week 48
Week 48
|
19 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24 and Week 48Population: 27 participants were recruited and received at least 1 dose of study medication; as Good Clinical Practice (GCP) requirements were not consistently adhered to at one site (involving 6 participant), analyses were performed excluding the participants from this site, resulting in 21 participants used for analyses.
Outcome measures
| Measure |
DRV/Rtv
n=21 Participants
Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and \<20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg
|
|---|---|
|
Mean Change From Baseline to Week 24 and Week 48 in Plasma log10 Viral Load
Week 24
|
-2.04 log10 copies/mL
Standard Error 0.244
|
|
Mean Change From Baseline to Week 24 and Week 48 in Plasma log10 Viral Load
Week 48
|
-2.14 log10 copies/mL
Standard Error 0.257
|
SECONDARY outcome
Timeframe: Baseline, Week 24 and Week 48Population: 27 participants were recruited and received at least 1 dose of study medication; as Good Clinical Practice (GCP) requirements were not consistently adhered to at one site (involving 6 participant), analyses were performed excluding the participants from this site, resulting in 21 participants used for analyses.
Outcome measures
| Measure |
DRV/Rtv
n=21 Participants
Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and \<20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg
|
|---|---|
|
Mean Change From Baseline to Week 24 and Week 48 in CD4+ Percentage
Week 24
|
4 Percentage of lymphocytes
Standard Error 0.9
|
|
Mean Change From Baseline to Week 24 and Week 48 in CD4+ Percentage
Week 48
|
4 Percentage of lymphocytes
Standard Error 1.3
|
Adverse Events
DRV/Rtv
Serious adverse events
| Measure |
DRV/Rtv
n=21 participants at risk
Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and \<20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Asthmatic crisis
|
4.8%
1/21 • 48 weeks
|
|
Musculoskeletal and connective tissue disorders
Trigger finger
|
4.8%
1/21 • 48 weeks
|
Other adverse events
| Measure |
DRV/Rtv
n=21 participants at risk
Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and \<20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg
|
|---|---|
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Blood and lymphatic system disorders
Neutropenia
|
9.5%
2/21 • 48 weeks
|
|
Infections and infestations
Otitis media acute
|
9.5%
2/21 • 48 weeks
|
|
Infections and infestations
Pharyngitis
|
9.5%
2/21 • 48 weeks
|
|
General disorders
Pyrexia
|
14.3%
3/21 • 48 weeks
|
|
Cardiac disorders
Tachycardia
|
9.5%
2/21 • 48 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
28.6%
6/21 • 48 weeks
|
|
Infections and infestations
Tinea capitis
|
23.8%
5/21 • 48 weeks
|
|
Infections and infestations
Nasopharyngitis
|
19.0%
4/21 • 48 weeks
|
|
Infections and infestations
Impetigo
|
14.3%
3/21 • 48 weeks
|
|
Infections and infestations
Rhinitis
|
14.3%
3/21 • 48 weeks
|
|
Infections and infestations
Lower respiratory tract infection
|
9.5%
2/21 • 48 weeks
|
|
Infections and infestations
Otitis media chronic
|
9.5%
2/21 • 48 weeks
|
|
Infections and infestations
Tinea faciei
|
9.5%
2/21 • 48 weeks
|
|
Infections and infestations
Tonsillitis
|
9.5%
2/21 • 48 weeks
|
|
Infections and infestations
Varicella
|
9.5%
2/21 • 48 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
23.8%
5/21 • 48 weeks
|
|
Gastrointestinal disorders
Vomiting
|
19.0%
4/21 • 48 weeks
|
|
Gastrointestinal disorders
Dental caries
|
9.5%
2/21 • 48 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
23.8%
5/21 • 48 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
14.3%
3/21 • 48 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
14.3%
3/21 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.3%
3/21 • 48 weeks
|
|
Ear and labyrinth disorders
Ear pain
|
9.5%
2/21 • 48 weeks
|
Additional Information
Senior Director R&D
Janssen R&D US
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60