Pharmacokinetics, Safety, and Efficacy of Cobicistat-boosted Atazanavir or Cobicistat-boosted Darunavir in HIV-1 Infected, Treatment-Experienced, Virologically Suppressed Pediatric Subjects

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02016924
First received: December 16, 2013
Last updated: September 9, 2014
Last verified: September 2014

December 16, 2013
September 9, 2014
January 2014
August 2017   (final data collection date for primary outcome measure)
  • Plasma pharmacokinetics (PK) parameters of ATV and DRV (as measured by AUCtau) at Day 10 [ Time Frame: Baseline to Day 10 ] [ Designated as safety issue: No ]
    AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
  • Incidence of treatment-emergent adverse events and laboratory abnormalities [ Time Frame: Baseline to Year 5 plus 30 days ] [ Designated as safety issue: No ]
    Incidence of adverse events and graded laboratory abnormalities will be summarized across the participant population. Graded laboratory abnormalities are those with at least one grade shift from baseline using the Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities.
  • Plasma pharmacokinetics (PK) parameters of ATV and DRV (as measured by AUCtau) [ Time Frame: Baseline to Day 10 ] [ Designated as safety issue: No ]
    AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
  • Incidence of treatment-emergent adverse events and laboratory abnormalities [ Time Frame: Baseline to Year 5 plus 30 days ] [ Designated as safety issue: No ]
    Incidence of adverse events and graded laboratory abnormalities will be summarized across the participant population. Graded laboratory abnormalities are those with at least one grade shift from baseline using the Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities.
Complete list of historical versions of study NCT02016924 on ClinicalTrials.gov Archive Site
  • PK parameters of ATV and DRV (as measured by Ctau, Cmax, CL/F) and cobicistat (as measured by AUCtau, Cmax, Ctau, CL/F, and Vz/F) [ Time Frame: Baseline to Year 5 ] [ Designated as safety issue: No ]
    • Ctau is defined as the observed drug concentration at the end of the dosing interval
    • Cmax is defined as the maximum concentration of drug
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
    • CL/F is the apparent oral clearance following administration of the drug
    • Vz/F is the apparent volume of distribution of the drug
  • Percentage of participants with plasma HIV-1 RNA < 50 copies/mL [ Time Frame: Weeks 12, 24, and 48, and every 12 weeks after Week 48 for up to 5 years ] [ Designated as safety issue: No ]
  • The time to pure virologic failure [ Time Frame: Baseline to Year 5 ] [ Designated as safety issue: No ]
    Pure Virologic failure includes participants who do not achieve confirmed suppression (ie, HIV-1 RNA < 50 copies/mL on 2 consecutive visit) or have confirmed rebound (ie, HIV-1 RNA ≥ 50 copies/mL on 2 consecutive visits or the last available HIV-1 RNA ≥ 50 copies/mL during study followed by premature discontinuation of study) after achieving confirmed suppression.
  • Change from baseline in log10 HIV-1 RNA (copies/mL) [ Time Frame: Baseline to Weeks 24 and 48, and every 12 weeks after Week 48 for up to 5 years ] [ Designated as safety issue: No ]
  • Change from baseline in CD4+ cell count (cells/µL) [ Time Frame: Baseline to Weeks 24 and 48, and every 12 weeks after Week 48 for up to 5 years ] [ Designated as safety issue: No ]
  • Acceptability (assessed by adherence) and palatability of cobicistat [ Time Frame: Baseline to Year 5 ] [ Designated as safety issue: No ]
    Acceptability (assessed by adherence) and palatability of cobicistat tablets and/or dispersible tablets in each cohort will be summarized.
  • Change from baseline in CD4 percentage [ Time Frame: Baseline to Weeks 24 and 48, and every 12 weeks after Week 48 for up to 5 years ] [ Designated as safety issue: No ]
  • Change from baseline in CD4 percentage in participants < 5 years old [ Time Frame: Baseline to Weeks 24 and 48, and every 12 weeks after Week 48 for up to 5 years ] [ Designated as safety issue: No ]
  • PK parameters of ATV and DRV (as measured by Ctau, Cmax, CL/F. and Vz/F) and Cobicistat (as measured by AUCtau, Cmax, Ctau, CL/F, and Vz/F) [ Time Frame: Baseline to Year 5 ] [ Designated as safety issue: No ]
    • Ctau is defined as the observed drug concentration at the end of the dosing interval
    • Cmax is defined as the maximum concentration of drug
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
    • CL/F is the apparent oral clearance following administration of the drug
    • Vz/F is the apparent volume of distribution of the drug
  • Percentage of participants with plasma HIV-1 RNA < 50 copies/mL [ Time Frame: Weeks 12, 24, and 48 ] [ Designated as safety issue: No ]
  • The time to pure virologic failure [ Time Frame: Baseline to Year 5 ] [ Designated as safety issue: No ]
    Pure Virologic failure includes participants who do not achieve confirmed suppression (ie, HIV-1 RNA < 50 copies/mL on 2 consecutive visit) or have confirmed rebound (ie, HIV-1 RNA ≥ 50 copies/mL on 2 consecutive visits or the last available HIV-1 RNA ≥ 50 copies/mL during study followed by premature discontinuation of study) after achieving confirmed suppression.
  • Change in CD4+ cell count and CD4 percentage [ Time Frame: Baseline to Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Assessment of physical development using Tanner Stages [ Time Frame: Day 1, Weeks 24 and 48, and age of first menses ] [ Designated as safety issue: No ]
    Tanner Stage assessments will be performed for participants ≥ 6 years of age at the time of the visit, at Day 1, Week 24, and Week 48. Once a participant is determined to be Tanner Stage 5, Tanner Stage assessments will no longer be performed. Date of first menses will be documented.
  • Acceptability (assessed by adherence) and palatability of cobicistat [ Time Frame: Baseline to Year 5 ] [ Designated as safety issue: No ]
    Acceptability (assessed by adherence) and palatability of COBI tablets and/or dispersible tablets in each cohort will be summarized.
Not Provided
Not Provided
 
Pharmacokinetics, Safety, and Efficacy of Cobicistat-boosted Atazanavir or Cobicistat-boosted Darunavir in HIV-1 Infected, Treatment-Experienced, Virologically Suppressed Pediatric Subjects
A Phase 2/3, Multicenter, Open-label, Multicohort, Two-Part Study Evaluating Pharmacokinetics (PK), Safety, and Efficacy of Cobicistat-boosted Atazanavir (ATV/co) or Cobicistat-boosted Darunavir (DRV/co), Administered With Background Regimen (BR) in HIV-1 Infected, Treatment-Experienced, Virologically Suppressed Pediatric Subjects

This study will evaluate the steady-state pharmacokinetics (PK) and confirm the dose of cobicistat-boosted atazanavir (ATV/co) or cobicistat-boosted darunavir (DRV/co) in HIV-1 infected antiretroviral treatment-experienced pediatric participants between the ages of 3 months to < 18 years of age.

It will also evaluate the safety, tolerability, and efficacy of ATV/co or DRV/co each co-administered with a background regimen (BR) through 48 weeks and during long-term treatment (total of 5 years).

There will be 2 parts to the study.

  • Part A: A minimum of 80 participants will be enrolled sequentially by age cohort to evaluate the steady state PK and confirm dose of ATV/co and DRV/co. Following screening, enrolled participants will continue their suppressive regimen of either ATV/r or DRV/r once-daily plus their BR from Day -10 through Day -1. All participants enrolled in Part A will participate in an intensive PK evaluation of ATV or DRV on Day -1 and COBI and ATV or DRV on Day 10. On Day 1, participants will discontinue ritonavir and initiate once daily cobicistat (COBI) to be taken with their ATV or DRV plus their BR. Following completion of the intensive PK visit, participants will continue to receive COBI coadministered with DRV or ATV each with a BR and return for scheduled study visits through 5 years or as specified in Part B.
  • Part B: A minimum of 20 participants will be enrolled to evaluate the safety, tolerability, and efficacy of the ATV/co or DRV/co regimen. For all cohorts in Part B, additional participants will be screened and initiated sequentially by each age cohort following confirmation of appropriate COBI exposure and PI exposures from the corresponding age cohort in Part A.

Overall, at least 100 participants in Parts A and B combined are planned to complete 5 years of the COBI containing treatment regimens.

Not Provided
Interventional
Phase 2
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acquired Immune Deficiency Syndrome (AIDS)
  • HIV Infections
  • Drug: ATV
    Atazanavir (ATV) will be administered once daily (at a dose of 150, 200, or 300 mg depending on weight) according to manufacturer's instructions.
    Other Name: Reyataz®
  • Drug: DRV
    Darunavir (DRV) will be administered once daily (at a dose of 600, 675, and 800 mg depending on weight) according to manufacturer's instructions.
    Other Name: Prezista®
  • Drug: Cobicistat
    Cobicistat 150 mg will be administered as two 75 mg tablets (cohorts 1 and 2), or 20 mg dispersible tablets as an oral suspension (cohorts 3 and 4).
    Other Names:
    • COBI
    • GS-9350
  • Drug: BR
    Background regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). 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.
  • Experimental: Part A, Cohort 1
    Participants ages 12 to 17 years old will receive cobicistat with either ATV or DRV plus BR.
    Interventions:
    • Drug: ATV
    • Drug: DRV
    • Drug: Cobicistat
    • Drug: BR
  • Experimental: Part A, Cohort 2
    Participants ages 6 to 11 years old will receive cobicistat with either ATV or DRV plus BR.
    Interventions:
    • Drug: ATV
    • Drug: DRV
    • Drug: Cobicistat
    • Drug: BR
  • Experimental: Part A, Cohort 3
    Participants ages 3 to 5 years old will receive cobicistat with either ATV or DRV plus BR.
    Interventions:
    • Drug: ATV
    • Drug: DRV
    • Drug: Cobicistat
    • Drug: BR
  • Experimental: Part A, Cohort 4
    Participants ages 3 months to 2 years old will receive cobicistat with ATV plus BR.
    Interventions:
    • Drug: ATV
    • Drug: Cobicistat
    • Drug: BR
  • Experimental: Part B, Cohort 1
    Participants ages 12 to 17 years old will receive cobicistat with either ATV or DRV plus BR.
    Interventions:
    • Drug: ATV
    • Drug: DRV
    • Drug: Cobicistat
    • Drug: BR
  • Experimental: Part B, Cohort 2
    Participants ages 6 to 11 years old will receive cobicistat with either ATV or DRV plus BR.
    Interventions:
    • Drug: ATV
    • Drug: DRV
    • Drug: Cobicistat
    • Drug: BR
  • Experimental: Part B, Cohort 3
    Participants ages 3 to 5 years old will receive cobicistat with either ATV or DRV plus BR.
    Interventions:
    • Drug: ATV
    • Drug: DRV
    • Drug: Cobicistat
    • Drug: BR
  • Experimental: Part B, Cohort 4
    Participants ages 3 months to 2 years old will receive cobicistat with ATV plus BR.
    Interventions:
    • Drug: ATV
    • Drug: Cobicistat
    • Drug: BR
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
August 2033
August 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV-1 infected treatment-experienced males and females aged 3 months to < 18 years at the Day -10 visit (according to requirements of enrolling Cohort)
  • Are able to provide written assent if they have the ability to read and write
  • Parent or legal guardian able to provide written informed consent prior to any screening evaluations and willing to comply with study requirements
  • Body weight at screening greater than 6.25 kg, 10.25 kg, or 15 kg dependent upon age cohort
  • Adequate renal function
  • Adequate hematologic function
  • Hepatic transaminases (AST and ALT) less than or equal to 5 x upper limit of normal (ULN)
  • For individuals on DRV/r, total bilirubin less than or equal to 1.5 mg/dL and normal direct bilirubin. For individuals on ATV/r, total bilirubin less than or equal to 3 mg/dL and normal direct bilirubin.
  • Negative serum pregnancy test
  • Individuals with evidence of suppressed viremia (< 50 copies/mL) at study entry
  • 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.
  • Males and females of childbearing potential must agree to utilize highly effective contraception methods while on study treatment or agree to abstain from heterosexual intercourse throughout the study period and for 30 days following the last dose of study drug
  • Documented negative screening for active pulmonary tuberculosis (TB) per local standard of care within 6 months of a screening visit
  • Must be willing and able to comply with all study requirements
  • No opportunistic infection within 30 days of study entry (at Day -10)

Exclusion Criteria:

  • Individuals with CD4+ cell counts at screening of less than 200 cells/mm^3
  • An AIDS defining condition with onset within 30 days prior to screening
  • Life expectancy of less than 1 year
  • An ongoing serious infection requiring systemic antibiotic therapy at the time of screening.
  • Evidence of active pulmonary or extra-pulmonary tuberculosis disease:

    • Within 3 months of the screening visit for all individuals 6 months of age or older
    • At anytime for individuals younger than 6 months
  • Anticipated requirement for rifamycin treatment while participating in the study. Note: prophylactic isoniazid therapy for latent TB is allowed.
  • Active hepatitis C virus (HCV) infection. Note: individuals with positive HCV antibody and without detectable HCV RNA are permitted to enroll.
  • Positive Hepatitis B surface antigen or other evidence of active hepatitis B virus (HBV) infection. Note: individuals with positive HBV surface antibody and no evidence of active HBV infection are permitted to enroll.
  • Individuals with clinically significant abnormal ECGs
  • Have any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with treatment, assessment, or compliance with the protocol.
  • Individuals experiencing decompensated cirrhosis
  • A history of or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma.
  • Pregnant or lactating females.
  • Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance.
  • Have history of significant drug sensitivity or drug allergy.
  • Known hypersensitivity to the study drug, the metabolites, or formulation excipients.
  • Have previously participated in an investigational trial involving administration of any investigational agent within 30 days prior to the study dosing.
  • Participation in any other clinical trial without prior approval from sponsor is prohibited while participating in this trial.
  • Individuals receiving ongoing therapy with any medication that is not to be taken with COBI or a component of the BR
Both
3 Months to 17 Years
No
Contact: Gilead Study Team GSUS2160128@gilead.com
United States,   Thailand
 
NCT02016924
GS-US-216-0128, 2013-001402-28
Yes
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Martin Rhee, MD Gilead Sciences
Gilead Sciences
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP