A Phase 2 Study to Evaluate Pharmacokinetics, Safety and Efficacy of TMC114/Ritonavir (Rtv) in Human Immunodeficiency Virus (HIV)-1 Infected Children and Adolescents
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
2 other identifiers
interventional
80
8 countries
22
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jun 2006
Longer than P75 for phase_2
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2006
CompletedFirst Submitted
Initial submission to the registry
July 21, 2006
CompletedFirst Posted
Study publicly available on registry
July 24, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2007
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2011
CompletedJuly 8, 2013
July 1, 2013
1.2 years
July 21, 2006
July 5, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (8)
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.
Week 2
Predose Plasma Concentration (C0) - Part 1
The C0 is the predose plasma concentration.
Week 2
Maximum Observed Plasma Concentration (Cmax) - Part 1
The Cmax is the maximum observed plasma concentration.
Week 2
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.
Week 2
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).
Baseline and Week 2
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).
Baseline and Week 24
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.
Week 2
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.
Week 24
Secondary Outcomes (6)
Change From Baseline in Plasma Viral Load at Week 48 - Part 2
Baseline and Week 48
Change from Baseline in Cluster of Differentiation 4 (CD4+) cell count - Part 2
Baseline and Week 48
Number of Participants With Resistance - Part 2
Week 48
Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 hours After Dosing (AUC 0-12h) - Part 2
Week 48
Predose Plasma Concentration (C0) - Part 2
Week 48
- +1 more secondary outcomes
Study Arms (7)
Group A with >= 20 kg to < 30 kg body weight
EXPERIMENTAL300 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.
Group A with >= 30 kg to < 40 kg body weight
EXPERIMENTAL300 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.
Group A with >= 40 kg to < 50 kg body weight
EXPERIMENTAL450 mg of TMC114 tablet with 100 mg of ritonavir capsule will be administered orally twice daily.
Group B with >= 20 kg to < 30 kg body weight
EXPERIMENTAL375 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.
Group B with >= 30 kg to < 40 kg body weight
EXPERIMENTAL450 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.
Group B with >= 40 kg to < 50 kg body weight
EXPERIMENTAL600 mg of TMC114 tablet with 100 mg of ritonavir capsule will be administered orally twice daily.
Participants with >= 50 kg body weight
EXPERIMENTAL600 mg of TMC114 tablet with 100 mg of ritonavir capsule will be administered orally twice daily.
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (22)
Unknown Facility
Los Angeles, California, United States
Unknown Facility
Washington D.C., District of Columbia, United States
Unknown Facility
Chicago, Illinois, United States
Unknown Facility
Boston, Massachusetts, United States
Unknown Facility
Worcester, Massachusetts, United States
Unknown Facility
Philadelphia, Pennsylvania, United States
Unknown Facility
Memphis, Tennessee, United States
Unknown Facility
Buenos Aires, Argentina
Unknown Facility
Belo Horizonte, Brazil
Unknown Facility
Nova Iguaçu, Brazil
Unknown Facility
Ribeirão Preto, Brazil
Unknown Facility
Rio de Janeiro, Brazil
Unknown Facility
Toronto, Ontario, Canada
Unknown Facility
Montreal, Quebec, Canada
Unknown Facility
Paris, France
Unknown Facility
Bucharest, Romania
Unknown Facility
Constanța, Romania
Unknown Facility
Cape Town Cape, South Africa
Unknown Facility
Durban, South Africa
Unknown Facility
Johannesburg Gauteng, South Africa
Unknown Facility
Esplugues de Llobregat, Spain
Unknown Facility
Madrid, Spain
Related Publications (1)
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.
PMID: 19724191RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Tibotec Pharmaceuticals Limited, Ireland Clinical Trial
Tibotec Pharmaceuticals, Ireland
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 21, 2006
First Posted
July 24, 2006
Study Start
June 1, 2006
Primary Completion
August 1, 2007
Study Completion
March 1, 2011
Last Updated
July 8, 2013
Record last verified: 2013-07