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| ID | Type | Description | Link |
|---|---|---|---|
| TMC114-C212 |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A with >= 20 kg to < 30 kg body weight | Experimental | 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. |
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| Group A with >= 30 kg to < 40 kg body weight | Experimental | 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. |
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| Group A with >= 40 kg to < 50 kg body weight | Experimental | 450 mg of TMC114 tablet with 100 mg of ritonavir capsule will be administered orally twice daily. |
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| Group B with >= 20 kg to < 30 kg body weight | Experimental | 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. |
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| Group B with >= 30 kg to < 40 kg body weight | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TMC114 | Drug | 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Baseline and Week 48 |
| Change from Baseline in Cluster of Differentiation 4 (CD4+) cell count - Part 2 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tibotec Pharmaceuticals Limited, Ireland Clinical Trial | Tibotec Pharmaceuticals, Ireland | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Los Angeles | California | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19724191 | Result | 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. |
| Label | URL |
|---|---|
| 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 | View source |
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| Group B with >= 40 kg to < 50 kg body weight | Experimental | 600 mg of TMC114 tablet with 100 mg of ritonavir capsule will be administered orally twice daily. |
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| Participants with >= 50 kg body weight | Experimental | 600 mg of TMC114 tablet with 100 mg of ritonavir capsule will be administered orally twice daily. |
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| Ritonavir | Drug | 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. |
|
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 |
The immunologic change will be determined by changes in CD4+ cell count. |
| Baseline and Week 48 |
| 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. | Week 48 |
| 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. | Week 48 |
| Predose Plasma Concentration (C0) - Part 2 | The C0 is the predose plasma concentration. | Week 48 |
| Oral Clearance (CL/F) - Part 2 | The CL/F is the oral clearance; that is clearance based on oral bioavailability. | Week 48 |
| Washington D.C. |
| District of Columbia |
| United States |
| Chicago | Illinois | United States |
| Boston | Massachusetts | United States |
| Worcester | Massachusetts | United States |
| Philadelphia | Pennsylvania | United States |
| Memphis | Tennessee | United States |
| Buenos Aires | Argentina |
| Belo Horizonte | Brazil |
| Nova Iguaçu | Brazil |
| Ribeirão Preto | Brazil |
| Rio de Janeiro | Brazil |
| Toronto | Ontario | Canada |
| Montreal | Quebec | Canada |
| Paris | France |
| Bucharest | Romania |
| Constanța | Romania |
| Cape Town Cape | South Africa |
| Durban | South Africa |
| Johannesburg Gauteng | South Africa |
| Esplugues de Llobregat | Spain |
| Madrid | Spain |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000069454 | Darunavir |
| D019438 | Ritonavir |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D005663 | Furans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013844 | Thiazoles |
| D001393 | Azoles |
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