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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01721109
First received: November 1, 2012
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

This study is 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) in HIV-1 infected, antiretroviral (ARV) treatment-naive adolescents. Safety, tolerability, and efficacy will also be evaluated through Week 48.

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.

Condition Intervention Phase
Acquired Immunodeficiency Syndrome
HIV Infections
Drug: EVG/COBI/FTC/TDF
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • For Part A, plasma pharmacokinetics (PK) parameter of EVG as measured by AUCtau [ Time Frame: 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)

  • For Part B, incidence of treatment-emergent serious adverse events (SAEs) and all treatment-emergent adverse events (AEs) [ Time Frame: Baseline to Week 48 plus 30 days ] [ Designated as safety issue: No ]
    SAEs and AEs will be summarized.


Secondary Outcome Measures:
  • For Part A, PK parameter of EVG as measured by Ctau and Cmax and PK parameter of emtricitabine (FTC), tenofovir (TFV), and cobicistat (COBI) as measured by AUCtau, Cmax, and Ctau [ Time Frame: Day 10 ] [ 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 observed concentration of drug in plasma
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)

  • For Part B, percentage of participants with plasma HIV-1 RNA < 50 copies/mL [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • For Part B, percentage of participants with plasma HIV-1 RNA < 400 copies/mL [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • For Part B, change from baseline in plasma log10 HIV-1 RNA (copies/mL) [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • For Part B, change from baseline in CD4+ cell count (cells/μL) and percentage [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: December 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EVG/COBI/FTC/TDF Drug: EVG/COBI/FTC/TDF
Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (EVG/COBI/FTC/TDF) single-tablet regiment (STR) administered orally once daily with food
Other Name: Stribild®

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01721109

Contacts
Contact: Skanda Goudar 650-524-4274 skanda.goudar@gilead.com

Locations
United States, California
East Bay AIDS Center Medical Group Recruiting
Oakland, California, United States, 94609
Principal Investigator: Jeffrey Burack         
United States, Florida
University of Florida, Jacksonville Recruiting
Jacksonville, Florida, United States, 32209
University of South Florida - Department of Pediatrics Recruiting
Tampa, Florida, United States, 33606
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
New York University School of Medicine Recruiting
New York, New York, United States, 10016
SUNY Upstate Medical University Recruiting
Syracuse, New York, United States, 13210
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact    919-668-4851      
United States, Pennsylvania
St. Christopher's Hospital for Children Recruiting
Philadelphia, Pennsylvania, United States, 19134
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Mexico
Hospital Civil de Guadalajara Withdrawn
Guadalajara, Jalisco, Mexico, 44280
South Africa
Rahima Moosa Mother and Child Hospital (Wits) Recruiting
Johannesburg, Gauteng, South Africa, 2112
Dr Latiff Private Practice Recruiting
Durban, Kwazulu-Natal, South Africa, 4001
Desmond Tutu HIV Research Centre Recruiting
Cape Town, South Africa, 7925
Mpati Medical Center Recruiting
Dundee, South Africa, 3000
Perinatal HIV Research Unit Recruiting
Gauteng, South Africa, 2013
Clinical HIV Research Unit Recruiting
Johannesburg, South Africa, 2092
University of Stellenbosch Not yet recruiting
Stellenbosch, South Africa, 7602
Thailand
Siriraj Hospital, Mahidol University Recruiting
Bangkok, Thailand, 10700
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) Recruiting
Bangkok, Thailand, 10330
Queen Savang Vadhana Memorial Hospital Recruiting
Chonburi, Thailand, 20110
Srinakarind Hospital Recruiting
Khon Kaen, Thailand, 40002
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Sean Bennett, MD, PhD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01721109     History of Changes
Other Study ID Numbers: GS-US-236-0112
Study First Received: November 1, 2012
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Adolescents
HIV-1
HIV
Treatment Naive

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Tenofovir
Tenofovir disoproxil
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 28, 2014