Back to resultsA Phase 2 Study to Evaluate Pharmacokinetics, Safety and Efficacy of TMC114/Ritonavir (Rtv) in Human Immunodeficiency Virus (HIV)-1 Infected Children and Adolescents
Primary Purpose
HIV-1, HIV Infections
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TMC114
Ritonavir
Sponsored by
About this trial
This is an interventional treatment trial for HIV-1 focused on measuring HIV-1, Darunavir, Ritonavir, TMC114
Eligibility Criteria
Inclusion Criteria: Participants with documented human immunodeficiency virus (HIV)-1 infection failing their current antiretroviral therapy Body weight for Part 1: greater than or equal to 20 Kilogram (kg) but less than 50 kg and body weight for Part 2: greater than or equal to 50 kg and from greater than or equal to 20 but less than 50 kg after pediatric dose selection Able to swallow the TMC114 tablet formulations, the ritonavir capsule formulation, and to tolerate the ritonavir liquid formulation Stable cluster of differentiation 4 (CD4+) percentage; that is no more than 5 percent decrease in CD4+ percentage between the Screening visit and the last available CD4+ measurement Female participants who are sexually active and able to become pregnant must use a safe and effective birth control method Exclusion Criteria: For Part 1: Use of the non-nucleoside analogue reverse transcriptase inhibitor (NNRTI) efavirenz as part of the current regimen was not allowed and for Part 2: Use of efavirenz as part of the current regimen was allowed and use of any antiretroviral and non-antiretroviral investigational agents within 30 days prior to screening Presence of any currently active acquired immune deficiency syndrome (AIDS) defining illness (Category C conditions according to the Centers for Disease Control [CDC] Classification System for HIV Infection 1993 or according to the 1994 revised CDC Classification System for HIV infection in children less than 13 years of age) Pregnant or breastfeeding female participants Previous allergy or hypersensitivity to any excipients of the investigational medication (TMC114) or ritonavir Any Grade 3 or 4 toxicity as defined by the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading scale
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Group A with >= 20 kg to < 30 kg body weight
Group A with >= 30 kg to < 40 kg body weight
Group A with >= 40 kg to < 50 kg body weight
Group B with >= 20 kg to < 30 kg body weight
Group B with >= 30 kg to < 40 kg body weight
Group B with >= 40 kg to < 50 kg body weight
Participants with >= 50 kg body weight
Arm Description
300 milligram (mg) of TMC114 tablet with 50 mg (which is equivalent to 0.625 milliliter [mL]) of ritonavir liquid (80 milligram/milliliter [mg/ml]) will be administered orally twice daily.
300 mg of TMC114 tablet with 50 mg (which is equivalent to 0.625 milliliter [mL]) of ritonavir liquid (80 milligram/milliliter [mg/ml]) will be administered orally twice daily.
450 mg of TMC114 tablet with 100 mg of ritonavir capsule will be administered orally twice daily.
375 mg of TMC114 tablet with 50 mg (which is equivalent to 0.625 mL) of ritonavir liquid (80 mg/mL) will be administered orally twice daily.
450 mg of TMC114 tablet with 60 mg (which is equivalent to 0.75 mL) of ritonavir liquid (80 mg/mL) will be administered orally twice daily.
600 mg of TMC114 tablet with 100 mg of ritonavir capsule will be administered orally twice daily.
600 mg of TMC114 tablet with 100 mg of ritonavir capsule will be administered orally twice daily.
Outcomes
Primary Outcome Measures
Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 hours After Dosing (AUC 0-12h) - Part 1
The Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption.
Predose Plasma Concentration (C0) - Part 1
The C0 is the predose plasma concentration.
Maximum Observed Plasma Concentration (Cmax) - Part 1
The Cmax is the maximum observed plasma concentration.
Recommended Dose of TMC114 per Body Weight
The recommended dose of TMC114 will be determined in participants with a body weight: greater than and equal to 20 Kilogram (kg) to less than 30 kg; greater than and equal to 30 kg to less than 40 kg; and greater than 40 kg.
Change From Baseline in Plasma Viral Load at Week 2 - Part 1
Plasma viral load levels will be determined using Roche amplicor human immunodeficiency virus (HIV)-1 monitor test (Version 1.5).
Change From Baseline in Plasma Viral Load at Week 24- Part 2
Plasma viral load levels will be determined using Roche amplicor HIV-1 monitor test (Version 1.5).
Number of Participants With Adverse Events
Adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment.
Number of Participants With Adverse Events
Adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment.
Secondary Outcome Measures
Change From Baseline in Plasma Viral Load at Week 48 - Part 2
Plasma viral load levels will be determined using Roche amplicor HIV-1 monitor test (Version 1.5).
Change from Baseline in Cluster of Differentiation 4 (CD4+) cell count - Part 2
The immunologic change will be determined by changes in CD4+ cell count.
Number of Participants With Resistance - Part 2
Resistance will be determined by viral phenotype and genotype determinations, which will be performed by Virco BVBA, by means of the antivirogram and Virco type HIV-1 respectively. Resistance determinations will only be generated if the viral load is greater than 1000 HIV-1 RNA copies/milliliter.
Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 hours After Dosing (AUC 0-12h) - Part 2
The Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption.
Predose Plasma Concentration (C0) - Part 2
The C0 is the predose plasma concentration.
Oral Clearance (CL/F) - Part 2
The CL/F is the oral clearance; that is clearance based on oral bioavailability.
Full Information
NCT ID
NCT00355524
First Posted
July 21, 2006
Last Updated
July 5, 2013
Sponsor
Tibotec Pharmaceuticals, Ireland
1. Study Identification
Unique Protocol Identification Number
NCT00355524
Brief Title
A Phase 2 Study to Evaluate Pharmacokinetics, Safety and Efficacy of TMC114/Ritonavir (Rtv) in Human Immunodeficiency Virus (HIV)-1 Infected Children and Adolescents
Official Title
A Phase II, Open-label Trial, to Investigate Pharmacokinetics, Safety, Tolerability and Antiviral Activity of TMC114/Rtv b.i.d in Treatment-Experienced HIV-1 Infected Children and Adolescents
Study Type
Interventional
2. Study Status
Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
June 2006 (undefined)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
March 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tibotec Pharmaceuticals, Ireland
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time), safety, tolerability and antiviral activity to support dose recommendations of TMC114 with ritonavir and other antiretroviral agents in treatment-experienced, human immunodeficiency virus (HIV)-1 infected children and adolescents.
Detailed Description
This is an open-label (all people know the identity of the intervention) and randomized (study drug assigned by chance) study to evaluate pharmacokinetics, safety, tolerability, efficacy, antiviral activity, immunology and resistance characteristics of TMC114 with ritonavir in treatment-experienced, HIV-1 infected children and adolescent participants. The study consists of 3 periods: Screening period (maximum 4 weeks); Treatment period (maximum 48 weeks); and Follow-up period (4 weeks). The Treatment period consists of two parts: Part-1 for pediatric dose selection and Part-2 for the recommendation of pediatric or adult dose. Part-1 was further divided into two groups: Group A with adult equivalent dose of TMC114 with ritonavir twice daily and Group B with 20-33 percent higher dose of TMC114 with ritonavir twice daily. The recommended dose will be selected based on short-term safety, tolerability, antiviral activity and pharmacokinetics at Week 2. Once selected, all Part-1 participants who will not be on the selected dose will be switched to the selected dose at their next visit and will continue the study up to 48 weeks in Part-2. Participants with less than or equal to 18 years at Week 48 visit, and continued to benefit from treatment with TMC114 and will be living in a country where TMC114 pediatric use is not yet part of the label, will have the opportunity to roll-over to the extension phase where they will continue to receive TMC114/ritonavir until the participant became 18 years and TMC114 will be available through the local Health Care Systems or until TMC114 is indicated for use in pediatrics. Efficacy will primarily be evaluated by virologic response. Participants' safety will be monitored throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1, HIV Infections
Keywords
HIV-1, Darunavir, Ritonavir, TMC114
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A with >= 20 kg to < 30 kg body weight
Arm Type
Experimental
Arm Description
300 milligram (mg) of TMC114 tablet with 50 mg (which is equivalent to 0.625 milliliter [mL]) of ritonavir liquid (80 milligram/milliliter [mg/ml]) will be administered orally twice daily.
Arm Title
Group A with >= 30 kg to < 40 kg body weight
Arm Type
Experimental
Arm Description
300 mg of TMC114 tablet with 50 mg (which is equivalent to 0.625 milliliter [mL]) of ritonavir liquid (80 milligram/milliliter [mg/ml]) will be administered orally twice daily.
Arm Title
Group A with >= 40 kg to < 50 kg body weight
Arm Type
Experimental
Arm Description
450 mg of TMC114 tablet with 100 mg of ritonavir capsule will be administered orally twice daily.
Arm Title
Group B with >= 20 kg to < 30 kg body weight
Arm Type
Experimental
Arm Description
375 mg of TMC114 tablet with 50 mg (which is equivalent to 0.625 mL) of ritonavir liquid (80 mg/mL) will be administered orally twice daily.
Arm Title
Group B with >= 30 kg to < 40 kg body weight
Arm Type
Experimental
Arm Description
450 mg of TMC114 tablet with 60 mg (which is equivalent to 0.75 mL) of ritonavir liquid (80 mg/mL) will be administered orally twice daily.
Arm Title
Group B with >= 40 kg to < 50 kg body weight
Arm Type
Experimental
Arm Description
600 mg of TMC114 tablet with 100 mg of ritonavir capsule will be administered orally twice daily.
Arm Title
Participants with >= 50 kg body weight
Arm Type
Experimental
Arm Description
600 mg of TMC114 tablet with 100 mg of ritonavir capsule will be administered orally twice daily.
Intervention Type
Drug
Intervention Name(s)
TMC114
Other Intervention Name(s)
Darunavir
Intervention Description
TMC114 will be administered as oral tablets (75 milligram [mg] or 300 mg) twice daily at a dose ranging from 300-600 mg up to 48 weeks.
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Intervention Description
Ritonavir will be administered as oral capsules (100 mg) or liquid (80 mg/mL) twice daily at a dose ranging from 50 mg (0.625 mL)-100 mg up to 48 weeks.
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 hours After Dosing (AUC 0-12h) - Part 1
Description
The Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption.
Time Frame
Week 2
Title
Predose Plasma Concentration (C0) - Part 1
Description
The C0 is the predose plasma concentration.
Time Frame
Week 2
Title
Maximum Observed Plasma Concentration (Cmax) - Part 1
Description
The Cmax is the maximum observed plasma concentration.
Time Frame
Week 2
Title
Recommended Dose of TMC114 per Body Weight
Description
The recommended dose of TMC114 will be determined in participants with a body weight: greater than and equal to 20 Kilogram (kg) to less than 30 kg; greater than and equal to 30 kg to less than 40 kg; and greater than 40 kg.
Time Frame
Week 2
Title
Change From Baseline in Plasma Viral Load at Week 2 - Part 1
Description
Plasma viral load levels will be determined using Roche amplicor human immunodeficiency virus (HIV)-1 monitor test (Version 1.5).
Time Frame
Baseline and Week 2
Title
Change From Baseline in Plasma Viral Load at Week 24- Part 2
Description
Plasma viral load levels will be determined using Roche amplicor HIV-1 monitor test (Version 1.5).
Time Frame
Baseline and Week 24
Title
Number of Participants With Adverse Events
Description
Adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment.
Time Frame
Week 2
Title
Number of Participants With Adverse Events
Description
Adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in Plasma Viral Load at Week 48 - Part 2
Description
Plasma viral load levels will be determined using Roche amplicor HIV-1 monitor test (Version 1.5).
Time Frame
Baseline and Week 48
Title
Change from Baseline in Cluster of Differentiation 4 (CD4+) cell count - Part 2
Description
The immunologic change will be determined by changes in CD4+ cell count.
Time Frame
Baseline and Week 48
Title
Number of Participants With Resistance - Part 2
Description
Resistance will be determined by viral phenotype and genotype determinations, which will be performed by Virco BVBA, by means of the antivirogram and Virco type HIV-1 respectively. Resistance determinations will only be generated if the viral load is greater than 1000 HIV-1 RNA copies/milliliter.
Time Frame
Week 48
Title
Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 hours After Dosing (AUC 0-12h) - Part 2
Description
The Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption.
Time Frame
Week 48
Title
Predose Plasma Concentration (C0) - Part 2
Description
The C0 is the predose plasma concentration.
Time Frame
Week 48
Title
Oral Clearance (CL/F) - Part 2
Description
The CL/F is the oral clearance; that is clearance based on oral bioavailability.
Time Frame
Week 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants with documented human immunodeficiency virus (HIV)-1 infection failing their current antiretroviral therapy
Body weight for Part 1: greater than or equal to 20 Kilogram (kg) but less than 50 kg and body weight for Part 2: greater than or equal to 50 kg and from greater than or equal to 20 but less than 50 kg after pediatric dose selection
Able to swallow the TMC114 tablet formulations, the ritonavir capsule formulation, and to tolerate the ritonavir liquid formulation
Stable cluster of differentiation 4 (CD4+) percentage; that is no more than 5 percent decrease in CD4+ percentage between the Screening visit and the last available CD4+ measurement
Female participants who are sexually active and able to become pregnant must use a safe and effective birth control method
Exclusion Criteria:
For Part 1: Use of the non-nucleoside analogue reverse transcriptase inhibitor (NNRTI) efavirenz as part of the current regimen was not allowed and for Part 2: Use of efavirenz as part of the current regimen was allowed and use of any antiretroviral and non-antiretroviral investigational agents within 30 days prior to screening
Presence of any currently active acquired immune deficiency syndrome (AIDS) defining illness (Category C conditions according to the Centers for Disease Control [CDC] Classification System for HIV Infection 1993 or according to the 1994 revised CDC Classification System for HIV infection in children less than 13 years of age)
Pregnant or breastfeeding female participants
Previous allergy or hypersensitivity to any excipients of the investigational medication (TMC114) or ritonavir
Any Grade 3 or 4 toxicity as defined by the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading scale
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tibotec Pharmaceuticals Limited, Ireland Clinical Trial
Organizational Affiliation
Tibotec Pharmaceuticals, Ireland
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
Country
United States
City
Washington
State/Province
District of Columbia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Worcester
State/Province
Massachusetts
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Memphis
State/Province
Tennessee
Country
United States
City
Buenos Aires
Country
Argentina
City
Belo Horizonte
Country
Brazil
City
Nova Iguacu
Country
Brazil
City
Ribeirao Preto
Country
Brazil
City
Rio De Janeiro
Country
Brazil
City
Toronto
State/Province
Ontario
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada
City
Paris
Country
France
City
Bucuresti
Country
Romania
City
Constanta
Country
Romania
City
Cape Town Cape
Country
South Africa
City
Durban
Country
South Africa
City
Johannesburg Gauteng
Country
South Africa
City
Esplugues De Llobregat
Country
Spain
City
Madrid
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
19724191
Citation
Blanche S, Bologna R, Cahn P, Rugina S, Flynn P, Fortuny C, Vis P, Sekar V, van Baelen B, Dierynck I, Spinosa-Guzman S. Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents. AIDS. 2009 Sep 24;23(15):2005-13. doi: 10.1097/QAD.0b013e328330abaa.
Results Reference
result
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=987&filename=CR002797_CSR.pdf
Description
A Phase II, Open-label Trial, to Investigate Pharmacokinetics, Safety, Tolerability and Antiviral Activity of TMC114/rtv b.i.d in Treatment-Experienced HIV-1 Infected Children and Adolescents
Learn more about this trial
A Phase 2 Study to Evaluate Pharmacokinetics, Safety and Efficacy of TMC114/Ritonavir (Rtv) in Human Immunodeficiency Virus (HIV)-1 Infected Children and Adolescents
We'll reach out to this number within 24 hrs