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Study Evaluating Pharmacokinetics (PK), Safety, and Efficacy of Cobicistat-boosted Atazanavir (ATV/co) or Cobicistat-boosted Darunavir (DRV/co) and Emtricitabine/Tenofovir Alafenamide (F/TAF) in HIV-1 Infected, Virologically Suppressed Pediatric Participants

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ClinicalTrials.gov Identifier: NCT02016924
Recruitment Status : Active, not recruiting
First Posted : December 20, 2013
Last Update Posted : May 21, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:

Cohort 1:

The primary objectives are:

  • To evaluate the steady-state pharmacokinetics (PK) of Atazanavir (ATV) and Darunavir (DRV) and confirm the dose of Cobicistat-boosted Atazanavir (ATV/co) or Cobicistat-boosted Darunavir (DRV/co) in HIV-1 infected, virologically suppressed adolescent participants weighing ≥ 25 kg (12 to < 18 years of age)
  • To evaluate the safety and tolerability of ATV/co or DRV/co through 24 weeks in HIV-1 infected, virologically suppressed adolescent participants weighing ≥ 25 kg (12 to < 18 years of age)

Cohort 2:

The primary objectives are:

  • To evaluate the steady-state PK of ATV and DRV and confirm the dose of ATV/co or DRV/co in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 25 to < 35 kg (6 to < 12 years of age)
  • To evaluate the steady-state PK of tenofovir alafenamide (TAF) and confirm the dose of emtricitabine/tenofovir alafenamide (F/TAF) in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 25 to < 35 kg (6 to < 12 years of age)
  • To evaluate the safety and tolerability of ATV/co, DRV/co, and F/TAF through 24 weeks in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 25 to < 35 kg (6 to < 12 years of age)

Cohort 3:

The primary objectives are:

  • To evaluate the steady-state PK of ATV and DRV and confirm the dose of ATV/co or DRV/co in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 14 to < 25 kg (≥ 3 years of age)
  • To evaluate the steady-state PK of TAF and confirm the dose of F/TAF in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 14 to < 25 kg (≥ 3 years of age)
  • To evaluate the safety and tolerability of ATV/co, DRV/co, and F/TAF through 24 weeks in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 14 to < 25 kg (≥ 3 years of age)

Condition or disease Intervention/treatment Phase
Acquired Immune Deficiency Syndrome (AIDS) HIV Infections Drug: ATV Drug: DRV Drug: Cobicistat Drug: BR Phase 2 Phase 3

Detailed Description:
13April2020: The study recruitment is currently on pause due to the coronavirus disease (COVID-19) pandemic. The overall status will be updated when the study begins recruiting again

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2/3, Multicenter, Open-label, Multicohort Study Evaluating Pharmacokinetics (PK), Safety, and Efficacy of Cobicistat-boosted Atazanavir (ATV/co) or Cobicistat-boosted Darunavir (DRV/co) and Emtricitabine/Tenofovir Alafenamide (F/TAF) in HIV-1 Infected, Virologically Suppressed Pediatric Participants
Actual Study Start Date : January 16, 2014
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : April 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Part A, Cohort 1
Participants ages 12 to <18 years old will receive cobicistat 150 mg with either ATV or DRV plus BR. The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.
Drug: ATV
Capsules administered once daily according to dosing recommendations per product monograph
Other Name: Reyataz®

Drug: DRV
Tablets administered once daily according to dosing recommendations per product monograph
Other Name: Prezista®

Drug: Cobicistat
Tablets administered orally once daily with food
Other Names:
  • GS-9350
  • Tybost®

Drug: BR
Prior to implementation protocol amendment 7, Background Regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). After implementation of protocol amendment 7, BR must include 2 NRTIs and a third agent per local prescribing guidelines.

Experimental: Cohort 2
Participants ages 6 to <12 years old will receive cobicistat 150 mg and emtricitabine/tenofovir alafenamide 200/25 mg with either ATV or DRV.
Drug: ATV
Capsules administered once daily according to dosing recommendations per product monograph
Other Name: Reyataz®

Drug: DRV
Tablets administered once daily according to dosing recommendations per product monograph
Other Name: Prezista®

Drug: Cobicistat
Tablets administered orally once daily with food
Other Names:
  • GS-9350
  • Tybost®

Experimental: Cohort 3
Participants ages ≥ 3 will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.
Drug: ATV
Capsules administered once daily according to dosing recommendations per product monograph
Other Name: Reyataz®

Drug: DRV
Tablets administered once daily according to dosing recommendations per product monograph
Other Name: Prezista®

Drug: Cobicistat
Tablets administered orally once daily with food
Other Names:
  • GS-9350
  • Tybost®

Experimental: Part B, Cohort 1
Participants ages 12 to <18 years old will receive cobicistat 150 mg with either ATV or DRV plus BR. The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.
Drug: ATV
Capsules administered once daily according to dosing recommendations per product monograph
Other Name: Reyataz®

Drug: DRV
Tablets administered once daily according to dosing recommendations per product monograph
Other Name: Prezista®

Drug: Cobicistat
Tablets administered orally once daily with food
Other Names:
  • GS-9350
  • Tybost®

Drug: BR
Prior to implementation protocol amendment 7, Background Regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). After implementation of protocol amendment 7, BR must include 2 NRTIs and a third agent per local prescribing guidelines.




Primary Outcome Measures :
  1. Pharmacokinetic (PK) Parameter: AUCtau of ATV and DRV [ Time Frame: Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  2. Pharmacokinetic (PK) Parameter: AUCtau of ATV, DRV, and TAF for Cohorts 2 and 3 [ Time Frame: Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  3. Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) and Treatment Emergent Laboratory Abnormalities Through Week 24 [ Time Frame: First dose date and up to 24 weeks plus 30 days ]

Secondary Outcome Measures :
  1. PK Parameter: Ctau of ATV, DRV, and COBI for Cohort 1 [ Time Frame: Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B). ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.

  2. PK Parameter: Cmax of ATV, DRV, and COBI for Cohort 1 [ Time Frame: Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B). ]
    Cmax is defined as the maximum observed concentration of drug.

  3. PK Parameter: CL/F of ATV, DRV, and COBI for Cohort 1 [ Time Frame: Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B). ]
    CL/F is defined as the apparent oral clearance following administration of the drug.

  4. PK Parameter: Vz/F of COBI for Cohort 1 [ Time Frame: Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B). ]
    Vz/F is defined as the apparent volume of distribution of the drug.

  5. PK Parameter: Ctau of ATV, DRV, COBI, FTC, and TFV for Cohorts 2 and 3 [ Time Frame: Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48 ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.

  6. PK Parameter: Cmax of ATV, DRV, COBI, TAF, FTC and TFV for Cohorts 2 and 3 [ Time Frame: Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48 ]
    Cmax is defined as the maximum observed concentration of drug.

  7. PK Parameter: CL/F of ATV, DRV, and TAF for Cohorts 2 and 3 [ Time Frame: Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48 ]
    CL/F is defined as the apparent oral clearance following administration of the drug.

  8. PK Parameter: Vz/F of COBI and TAF for Cohorts 2 and 3 [ Time Frame: Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48 ]
    Vz/F is defined as the apparent volume of distribution of the drug.

  9. The incidence of treatment-emergent AEs and treatment-emergent laboratory abnormalities through Week 48 [ Time Frame: Up to 48 weeks plus 30 days ]
  10. The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 and as defined by the US FDA-defined snapshot algorithm [ Time Frame: Week 24 ]
  11. The change from baseline in CD4+ cell counts [ Time Frame: Week 24 ]
  12. The change from baseline in CD4+ cell counts [ Time Frame: Week 48 ]
  13. The change from baseline in CD4+ percentages [ Time Frame: Week 24 ]
  14. The change from baseline in CD4+ percentages [ Time Frame: Week 48 ]
  15. Acceptability of COBI and F/TAF as Measured by Palatability [ Time Frame: Day 1, and at Weeks 4 (Day 10 for Cohort 1 Part A), 24 and 48. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   3 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • HIV-1 infected treatment-experienced, virologically suppressed males and females aged 3 years to < 18 years at the Day 1 visit (according to requirements of enrolling Cohort)
  • Body weight at screening ≥ 25 kg (Cohorts 1), 14 kg to < 25 kg (Cohort 3)
  • Stable antiretroviral regimen including 2 nucleoside reverse transcriptase inhibitors and either ritonavir-boosted atazanavir or ritonavir-boosted darunavir once or twice daily as per product label for a minimum of 3 months prior to the screening visit. Treatment-experienced pediatric individuals taking DRV/r must have no history of DRV resistance associated mutations.
  • Documented negative screening for active pulmonary tuberculosis (TB) per local standard of care within 6 months of a screening visit

Note: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02016924


Locations
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Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02016924    
Other Study ID Numbers: GS-US-216-0128
2013-001402-28 ( EudraCT Number )
First Posted: December 20, 2013    Key Record Dates
Last Update Posted: May 21, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gilead Sciences:
Pediatrics
Adolescents
HIV
HIV-1
Treatment experienced
Additional relevant MeSH terms:
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HIV Infections
Acquired Immunodeficiency Syndrome
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immune System Diseases
Slow Virus Diseases
Cobicistat
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors