A Phase 2 Study to Evaluate Pharmacokinetics, Safety and Efficacy of TMC114/Ritonavir (Rtv) in Human Immunodeficiency Virus (HIV)-1 Infected Children and Adolescents
Information source: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV-1; HIV Infections
Intervention: TMC114 (Drug); Ritonavir (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Tibotec Pharmaceuticals, Ireland Official(s) and/or principal investigator(s): Tibotec Pharmaceuticals Limited, Ireland Clinical Trial, Study Director, Affiliation: Tibotec Pharmaceuticals, Ireland
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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 hours After Dosing (AUC 0-12h) - Part 1Predose Plasma Concentration (C0) - Part 1 Maximum Observed Plasma Concentration (Cmax) - Part 1 Recommended Dose of TMC114 per Body Weight Change From Baseline in Plasma Viral Load at Week 2 - Part 1 Change From Baseline in Plasma Viral Load at Week 24- Part 2 Number of Participants With Adverse Events Number of Participants With Adverse Events
Secondary outcome: Change From Baseline in Plasma Viral Load at Week 48 - Part 2Change from Baseline in Cluster of Differentiation 4 (CD4+) cell count - Part 2 Number of Participants With Resistance - Part 2 Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 hours After Dosing (AUC 0-12h) - Part 2 Predose Plasma Concentration (C0) - Part 2 Oral Clearance (CL/F) - Part 2
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.
Eligibility
Minimum age: 6 Years.
Maximum age: 17 Years.
Gender(s): Both.
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
Locations and Contacts
Buenos Aires, Argentina
Belo Horizonte, Brazil
Nova Iguacu, Brazil
Ribeirao Preto, Brazil
Rio De Janeiro, Brazil
Paris, France
Bucuresti, Romania
Constanta, Romania
Cape Town Cape, South Africa
Durban, South Africa
Johannesburg Gauteng, South Africa
Esplugues De Llobregat, Spain
Madrid, Spain
Los Angeles, California, United States
Washington, District of Columbia, United States
Chicago, Illinois, United States
Boston, Massachusetts, United States
Worcester, Massachusetts, United States
Toronto, Ontario, Canada
Philadelphia, Pennsylvania, United States
Montreal, Quebec, Canada
Memphis, Tennessee, United States
Additional Information
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
Starting date: June 2006
Last updated: July 5, 2013
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