Clinical Trial Results:
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
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Summary
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EudraCT number |
2015-000313-40 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
29 Jan 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Aug 2018
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First version publication date |
05 Aug 2018
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GS-US-236-0112
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01721109 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Gilead Sciences
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Sponsor organisation address |
333 Lakeside Drive, Foster City, CA, United States, 94404
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Public contact |
Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
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Scientific contact |
Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000970-PIP01-10 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Jan 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Oct 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Jan 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objectives of this study were 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.
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Protection of trial subjects |
The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements.
This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Dec 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 14
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Country: Number of subjects enrolled |
South Africa: 22
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Country: Number of subjects enrolled |
Thailand: 14
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Worldwide total number of subjects |
50
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
50
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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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. | ||||||||||||||||||
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Pre-assignment
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Screening details |
56 participants were screened. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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EVG/COBI/FTC/TDF | ||||||||||||||||||
Arm description |
EVG/COBI/FTC/TDF STR for 48 weeks, followed by EVG/COBI/FTC/TDF during the optional extension phase. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
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Investigational medicinal product code |
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Other name |
EVG/COBI/FTC/TDF, Stribild®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
150/150/200/300 mg STR administered once daily with food
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| Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: These 34 participants were counted as "Completed" because they switched to commercial Stribild or to an individual patient use (IPU) program. |
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Baseline characteristics reporting groups
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Reporting group title |
EVG/COBI/FTC/TDF
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Reporting group description |
EVG/COBI/FTC/TDF STR for 48 weeks, followed by EVG/COBI/FTC/TDF during the optional extension phase. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
EVG/COBI/FTC/TDF
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Reporting group description |
EVG/COBI/FTC/TDF STR for 48 weeks, followed by EVG/COBI/FTC/TDF during the optional extension phase. | ||
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End point title |
For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG [1] | ||||||||
End point description |
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). PK Substudy Analysis Set included all enrolled and treated participants from Part A who evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at Day 10 intensive PK visit.
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End point type |
Primary
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End point timeframe |
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis of this primary endpoint is provided in the attachment. |
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Attachments |
Statistical Analysis |
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| No statistical analyses for this end point | |||||||||
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End point title |
Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs) [2] | ||||||||||||
End point description |
Safety Analysis Set included all participants who received at least 1 dose of study drug.
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End point type |
Primary
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End point timeframe |
Up to Week 48 plus 30 days
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical comparison was planned or performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI | ||||||||||||||||
End point description |
Ctau is defined as the observed drug concentration at the end of the dosing interval. Participants in the PK Substudy Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI | ||||||||||||||||
End point description |
Cmax is defined as the maximum concentration of drug. Participants in the PK Substudy Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI | ||||||||||||||
End point description |
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). Participants in the PK Substudy Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis | ||||||||||||
End point description |
The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 (or Week 48) was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Full Analysis Set included all participants who were enrolled in the study and received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Weeks 24 and 48
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis | ||||||||||||
End point description |
The percentage of participants achieving HIV-1 RNA < 400 copies/mL at Week 24 (or Week 48) was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Weeks 24 and 48
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48 | ||||||||||||
End point description |
Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline; Weeks 24 and 48
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 | ||||||||||||
End point description |
Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Change From Baseline in CD4+ Cell Count at Weeks 24 and 48
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in CD4 Percentage at Weeks 24 and 48 | ||||||||||||
End point description |
Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline; Weeks 24 and 48
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to the last dose date plus 30 days (maximum exposure: 250.7 weeks)
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Adverse event reporting additional description |
Safety Analysis Set included all participants who received at least 1 dose of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
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Reporting groups
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Reporting group title |
EVG/COBI/FTC/TDF
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Reporting group description |
EVG/COBI/FTC/TDF STR for 48 weeks, followed by EVG/COBI/FTC/TDF during the optional extension phase. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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08 Aug 2012 |
● Added cystatin C at baseline and Weeks 2, 4, 24, and 48 as an exploratory measure to assess renal function
● Added additional safety contact information by region
● Updated toxicity grading scale to avoid overlap with central laboratory normal ranges; sodium, calcium, magnesium, phosphorus, uric acid, urine red blood cells
● Updated Tanner stage to conform to standard clinical evaluations for determining Tanner stage classification
● Added language to the effect that increases in the concentration of norgestimate when norgestimate/ethinyl estradiol-containing oral contraceptives are coadministered with Stribild are not known |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
