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Trial record 4 of 10 for:    cobicistat children

Pharmacokinetics, Safety, and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in Adolescents

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01721109
Recruitment Status : Completed
First Posted : November 4, 2012
Results First Posted : April 10, 2017
Last Update Posted : August 17, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE November 1, 2012
First Posted Date  ICMJE November 4, 2012
Results First Submitted Date  ICMJE February 24, 2017
Results First Posted Date  ICMJE April 10, 2017
Last Update Posted Date August 17, 2018
Actual Study Start Date  ICMJE December 6, 2012
Actual Primary Completion Date October 22, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2018)
  • For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG [ Time Frame: Predose, 2, 4, 4.5, 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).
  • Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs) [ Time Frame: Up to Week 48 plus 30 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 1, 2012)
Intensive Pharmacokinetics (PK) Evaluation [ Time Frame: Day 10 ]
The primary endpoint is PK parameter of AUCtau for EVG.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2018)
  • For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI [ Time Frame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10 ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.
  • For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI [ Time Frame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10 ]
    Cmax is defined as the maximum concentration of drug.
  • For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI [ Time Frame: Predose, 2, 4, 4.5, 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).
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis [ Time Frame: Weeks 24 and 48 ]
  • Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis [ Time Frame: Weeks 24 and 48 ]
  • Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48 [ Time Frame: Baseline; Weeks 24 and 48 ]
  • Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 [ Time Frame: Baseline; Weeks 24 and 48 ]
  • Change From Baseline in CD4 Percentage at Weeks 24 and 48 [ Time Frame: Baseline; Weeks 24 and 48 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 1, 2012)
  • The percentage of subjects with plasma HIV-RNA <50 copies/mL [ Time Frame: Weeks 24 and 48 ]
    The secondary efficacy endpoint is the percentage of subjects with plasma HIV-1 RNA <50 copies/mL at Weeks 24 and 48
  • The percentage of subjects with plasma HIV-1 RNA < 400 copies/mL [ Time Frame: Weeks 24 and 48 ]
    The secondary endpoint is the percentage of subjects with plasma HIV-1 RNA <400 copies/mL at Weeks 24 and 48
  • The change from baseline in plasma log10 HIV-1 RNA (copies m/L) and in CD4+ cell count (cells/μL) and percentage at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
    The secondary endpoints are the change from baseline in plasma log 10 HIV-1 RNA (copies/mL) and in CD4+ cell count (cells/μL)and percentage at Weeks 24 and 48
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics, Safety, and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in Adolescents
Official Title  ICMJE A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/ Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents
Brief Summary

The primary objectives of this study are to evaluate the steady-state pharmacokinetics (PK) and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) single-tablet regimen (STR) (Part A) and to evaluate the safety and tolerability of EVG/COBI/FTC/TDF STR through Week 48 (Part B) in HIV-1 infected, antiretroviral (ARV) treatment-naive adolescents.

A total of 50 adolescent participants (12 to < 18 years of age) will be enrolled to receive EVG/COBI/FTC/TDF as follows:

  • Part A: Twelve to 16 eligible participants will be enrolled to evaluate steady-state PK, and confirm the dose, with the intent to enroll at least 4 participants 12 to < 15 and at least 4 participants 15 to < 18 years of age.
  • Part B: Following confirmation of EVG exposure in at least 12 participants from Part A, 34 to 38 participants in addition to those enrolled in Part A will be enrolled to evaluate the safety, tolerability, and antiviral activity of EVG/COBI/FTC/TDF STR.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acquired Immunodeficiency Syndrome
  • HIV Infections
Intervention  ICMJE Drug: EVG/COBI/FTC/TDF
150/150/200/300 mg STR administered orally once daily with food
Other Name: Stribild®
Study Arms  ICMJE Experimental: EVG/COBI/FTC/TDF
Participants will receive treatment for 48 weeks and then had the option to enter an Extension Phase to receive EVG/COBI/FTC/TDF until 1) the age of 18, 2) EVG/COBI/FTC/TDF becomes commercially available in the country the participant is enrolled, or 3) Gilead elects to terminate the development of EVG/COBI/FTC/TDF in that country.
Intervention: Drug: EVG/COBI/FTC/TDF
Publications *
  • Gaur A, Fourie J, Chokephaibulkit K, Bekker L-G, Yin X, Custodio J, Bennett S, Cheng A, Quirk E. Pharmacokinetics, Efficacy and Safety of an Integrase Inhibitor-Based Single-Tablet Regimen in HIV-Infected Treatment-Naïve Adolescents. 21st Conference on Retroviruses and Opportunistic Infections (CROI). March 2014. Boston, MA, USA
  • Chokephaibulkit K, Gaur A, Fourie J, Bekker L-G, Shao Y, Custodio J, Bennett S, Cheng A, Quirk E. Safety and Efficacy of the Integrase Inhibitor-Based Stribild Single-Tablet Regimen in HIV-Infected Adolescents Through 24 Weeks of Treatment. 20th International AIDS Conference. July 2014. Melbourne, Australia
  • Porter DP, Bennett S, Quirk E, Miller MD, White KL. Lack of Emergent Resistance in HIV-1-Infected Adolescents on Elvitegravir-Based STRs. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). February 2015. Seattle, WA, USA
  • Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Chokephaibulkit K, Fourie J, Bekker LG, Shao Y, Bennett S, Quirk E. Changes in renal laboratory markers and bone mineral density in treatment-naïve HIV-1-infected adolescents initiating INSTI-based single-tablet regimens containing tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF). 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention. July 2015. Vancouver, Canada

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 1, 2012)
50
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 29, 2018
Actual Primary Completion Date October 22, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • 12 years to < 18 years of age at baseline
  • Able to give written assent prior to any screening evaluations
  • Parent or guardian able to give written informed consent prior to any screening evaluations and willing to comply with study requirements
  • Plasma HIV-1 RNA levels of ≥ 1,000 copies/mL
  • CD4+ cell count > 100 cells/µL
  • Weight ≥ 35 kg (77 lbs)
  • Screening genotype report must show sensitivity to FTC and TDF
  • Able to swallow oral tablets
  • Adequate renal function
  • Clinically normal ECG
  • Documented screening for active pulmonary tuberculosis per local standard of care within 6 months of a screening visit
  • Hepatic transaminases ≤ 5 x upper limit of normal
  • Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
  • Individuals with a positive Hepatitis B surface antigen screening test can participate in the study, providing that alternate therapy (other than TDF) for chronic Hepatitis B infection is available as a part of local standard of care
  • Adequate hematologic function
  • Negative serum pregnancy test for all females
  • 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
  • Males must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product
  • Must be willing and able to comply with all study requirements
  • Life expectancy ≥ 1 year

Key Exclusion Criteria:

  • A new AIDS-defining condition diagnosed within the 30 days prior to screening
  • Prior treatment with any approved or investigational or experimental anti HIV-1 drug for any length of time (other than that given for prevention of mother-to-child transmission)
  • Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit
  • Anticipated to require rifamycin treatment for mycobacterial infection while participating in the study. Note: prophylactic Isoniazid (INH) therapy for latent tuberculosis (TB) treatment is allowed.
  • Individuals experiencing decompensated cirrhosis
  • Pregnant or lactating females
  • Have any serious or active medical or psychiatric illness which would interfere with treatment, assessment, or compliance with the protocol. This would include uncontrolled renal, cardiac, hematological, hepatic, pulmonary, endocrine, central nervous, gastrointestinal, vascular, metabolic, immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment within 30 days prior to the study dosing.
  • Current alcohol or substance abuse that will potentially interfere with compliance
  • Have history of significant drug sensitivity or drug allergy
  • Known hypersensitivity to the study drugs, the metabolites or formulation excipients
  • Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening or expected to receive these agents during the study
  • A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
  • 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
  • Receiving ongoing therapy with any disallowed medications, including drugs not to be used with EVG, COBI, FTC, TDF or individuals with any known allergies to the excipients of EVG/COBI/FTC/TDF STR tablets

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE South Africa,   Thailand,   United States
Removed Location Countries Mexico
 
Administrative Information
NCT Number  ICMJE NCT01721109
Other Study ID Numbers  ICMJE GS-US-236-0112
2015-000313-40 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date July 2018

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