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Trial record 3 of 10 for:    elvitegravir 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

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Acquired Immunodeficiency Syndrome
HIV Infections
Intervention Drug: EVG/COBI/FTC/TDF
Enrollment 50
Recruitment Details Participants were enrolled at study sites in the United States, South Africa, and Thailand. The first participant was screened on 06 December 2012. The last study visit occurred on 29 January 2018.
Pre-assignment Details 56 participants were screened.
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) (150/150/200/300 mg) single-tablet regimen (STR) administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase.
Period Title: Overall Study
Started 50
Completed 43 [1]
Not Completed 7
Reason Not Completed
Lack of Efficacy             1
Non- Compliance with Study Drug             3
Withdrew Consent             1
Lost to Follow-up             2
[1]
34 participants transitioned to commercial Stribild or to an individual patient use (IPU) program
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Overall Number of Baseline Participants 50
Hide Baseline Analysis Population Description
Safety Analysis Set: all participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 50 participants
15  (1.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
Female
15
  30.0%
Male
35
  70.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
Asian
14
  28.0%
Black
34
  68.0%
White
1
   2.0%
Other
1
   2.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
Hispanic or Latino
2
   4.0%
Not Hispanic or Latino
47
  94.0%
Not Permitted
1
   2.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
United States
14
  28.0%
South Africa
22
  44.0%
Thailand
14
  28.0%
HIV-1 RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 copies/mL
Number Analyzed 50 participants
4.60  (0.551)
HIV-1 RNA Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
≤ 100,000 copies/mL
40
  80.0%
> 100,000 copies/mL
10
  20.0%
CD4 Cell Count  
Mean (Standard Deviation)
Unit of measure:  cells/µL
Number Analyzed 50 participants
399  (127.6)
CD4 Cell Count Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
≤ 199 cells/µL
2
   4.0%
200 ≥ and ≤ 349 cells/µL
16
  32.0%
350 ≥ and ≤ 499 cells/µL
22
  44.0%
≥ 500 cells/µL
10
  20.0%
1.Primary Outcome
Title For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG
Hide Description AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description:
EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ng•h/mL
31620.9  (13978.07)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EVG/COBI/FTC/TDF
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments A sample size of 14 participants was estimated to provide over 95% power to show pharmacokinetic equivalence between adult and adolescent participants. EVG population PK from historical adult data was used for comparison. The inter-subject standard deviation (natural log scale) of EVG AUCtau observed in the population PK data was 0.31 (historical data).
Method of Estimation Estimation Parameter Geometric least squares mean ratio
Estimated Value 1.3029
Confidence Interval (2-Sided) 90%
1.0479 to 1.6200
Estimation Comments [Not Specified]
2.Primary Outcome
Title Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)
Hide Description [Not Specified]
Time Frame Up to Week 48 plus 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all participants who received at least 1 dose of study drug.
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description:
EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Overall Number of Participants Analyzed 50
Measure Type: Count of Participants
Unit of Measure: Participants
SAEs
4
   8.0%
AEs
45
  90.0%
3.Secondary Outcome
Title For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI
Hide Description Ctau is defined as the observed drug concentration at the end of the dosing interval.
Time Frame Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description:
EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
EVG 579.3  (455.20)
FTC 102.6  (30.85)
TFV 86.6  (23.58)
COBI 39.7  (68.52)
4.Secondary Outcome
Title For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI
Hide Description Cmax is defined as the maximum concentration of drug.
Time Frame Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description:
EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
EVG 2624.3  (1239.64)
FTC 2217.4  (664.64)
TFV 438.5  (170.69)
COBI 1500.4  (975.29)
5.Secondary Outcome
Title For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI
Hide Description AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description:
EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ng•h/mL
FTC 15136.5  (4702.06)
TFV 4450.7  (1312.27)
COBI 11884.8  (11220.94)
6.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
Hide Description [Not Specified]
Time Frame Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug.
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description:
EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Overall Number of Participants Analyzed 50
Measure Type: Number
Unit of Measure: percentage of participants
Week 24 88.0
Week 48 88.0
7.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
Hide Description [Not Specified]
Time Frame Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug.
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description:
EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Overall Number of Participants Analyzed 50
Measure Type: Number
Unit of Measure: percentage of participants
Week 24 94.0
Week 48 92.0
8.Secondary Outcome
Title Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48
Hide Description [Not Specified]
Time Frame Baseline; Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug.
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description:
EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Overall Number of Participants Analyzed 50
Mean (Standard Deviation)
Unit of Measure: log10 copies/mL
Change at Week 24 -3.08  (0.922)
Change at Week 48 -3.16  (0.705)
9.Secondary Outcome
Title Change From Baseline in CD4+ Cell Count at Weeks 24 and 48
Hide Description [Not Specified]
Time Frame Baseline; Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description:
EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Overall Number of Participants Analyzed 49
Mean (Standard Deviation)
Unit of Measure: cells/µL
Change at Week 24 Number Analyzed 49 participants
178  (165.4)
Change at Week 48 Number Analyzed 48 participants
229  (245.3)
10.Secondary Outcome
Title Change From Baseline in CD4 Percentage at Weeks 24 and 48
Hide Description [Not Specified]
Time Frame Baseline; Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description:
EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Overall Number of Participants Analyzed 49
Mean (Standard Deviation)
Unit of Measure: percentage
Change at Week 24 Number Analyzed 49 participants
7.4  (4.70)
Change at Week 48 Number Analyzed 48 participants
8.1  (5.34)
Time Frame Baseline up to the last dose date plus 30 days (maximum exposure: 250.7 weeks)
Adverse Event Reporting Description Safety Analysis Set: all participants who received at least 1 dose of study drug.
 
Arm/Group Title EVG/COBI/FTC/TDF
Hide Arm/Group Description EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
All-Cause Mortality
EVG/COBI/FTC/TDF
Affected / at Risk (%)
Total   0/50 (0.00%) 
Hide Serious Adverse Events
EVG/COBI/FTC/TDF
Affected / at Risk (%)
Total   5/50 (10.00%) 
Blood and lymphatic system disorders   
Anaemia  1  1/50 (2.00%) 
Gastrointestinal disorders   
Food poisoning  1  1/50 (2.00%) 
Haemorrhoids  1  1/50 (2.00%) 
Immune system disorders   
Immune reconstitution inflammatory syndrome  1  1/50 (2.00%) 
Infections and infestations   
Disseminated tuberculosis  1  1/50 (2.00%) 
Gastroenteritis shigella  1  1/50 (2.00%) 
Oral candidiasis  1  1/50 (2.00%) 
Pneumonia  1  1/50 (2.00%) 
Metabolism and nutrition disorders   
Dehydration  1  1/50 (2.00%) 
Psychiatric disorders   
Suicidal behaviour  1  1/50 (2.00%) 
Renal and urinary disorders   
Acute kidney injury  1  1/50 (2.00%) 
Respiratory, thoracic and mediastinal disorders   
Asthma  1  1/50 (2.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
EVG/COBI/FTC/TDF
Affected / at Risk (%)
Total   46/50 (92.00%) 
Gastrointestinal disorders   
Diarrhoea  1  8/50 (16.00%) 
Haemorrhoids  1  4/50 (8.00%) 
Nausea  1  8/50 (16.00%) 
Toothache  1  3/50 (6.00%) 
Vomiting  1  10/50 (20.00%) 
General disorders   
Pyrexia  1  3/50 (6.00%) 
Infections and infestations   
Bronchitis  1  4/50 (8.00%) 
Influenza  1  3/50 (6.00%) 
Nasopharyngitis  1  4/50 (8.00%) 
Oral herpes  1  3/50 (6.00%) 
Oropharyngeal gonococcal infection  1  3/50 (6.00%) 
Pharyngitis  1  6/50 (12.00%) 
Proctitis gonococcal  1  3/50 (6.00%) 
Respiratory tract infection viral  1  3/50 (6.00%) 
Secondary syphilis  1  3/50 (6.00%) 
Tonsillitis  1  3/50 (6.00%) 
Upper respiratory tract infection  1  18/50 (36.00%) 
Urinary tract infection  1  3/50 (6.00%) 
Injury, poisoning and procedural complications   
Skin abrasion  1  3/50 (6.00%) 
Investigations   
Weight decreased  1  4/50 (8.00%) 
Metabolism and nutrition disorders   
Decreased appetite  1  3/50 (6.00%) 
Vitamin D deficiency  1  9/50 (18.00%) 
Musculoskeletal and connective tissue disorders   
Myalgia  1  3/50 (6.00%) 
Nervous system disorders   
Dizziness  1  4/50 (8.00%) 
Headache  1  12/50 (24.00%) 
Skin and subcutaneous tissue disorders   
Acne  1  8/50 (16.00%) 
Dermatitis  1  3/50 (6.00%) 
Dermatitis contact  1  3/50 (6.00%) 
Rash  1  4/50 (8.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gilead Clinical Study Information Center
Organization: Gilead Sciences
EMail: GileadClinicalTrials@gilead.com
Publications of Results:
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
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01721109    
Other Study ID Numbers: GS-US-236-0112
2015-000313-40 ( EudraCT Number )
First Submitted: November 1, 2012
First Posted: November 4, 2012
Results First Submitted: February 24, 2017
Results First Posted: April 10, 2017
Last Update Posted: August 17, 2018