Clinical Trial Results:
A Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults with Chronic Hepatitis C Virus (HCV) Genotypes 1-6 Infection and Human Immunodeficiency Virus-1 (HIV-1) Co-infection (EXPEDITION-2)
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Summary
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EudraCT number |
2015-005577-20 |
Trial protocol |
GB DE PL |
Global end of trial date |
07 Jun 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Apr 2018
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First version publication date |
12 Apr 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 |
M14-730
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02738138 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AbbVie Deutschland GmbH & Co. KG
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Sponsor organisation address |
AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB
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Public contact |
EU Clinical Trials Helpdesk, AbbVie, 001 800-633-9110,
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Scientific contact |
Roger Trinh, AbbVie, roger.trinh@abbvie.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
27 Sep 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Jun 2017
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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 purpose of this study is to assess the efficacy and safety of ABT-493/ABT-530 in adults with chronic hepatitis C virus genotype 1-6 infection and human immunodeficiency virus-1 co-infection.
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Protection of trial subjects |
Subject read and understood the information provided about the study and gave written permission.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 May 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Poland: 15
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Country: Number of subjects enrolled |
United Kingdom: 15
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Country: Number of subjects enrolled |
France: 14
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Country: Number of subjects enrolled |
Germany: 21
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Country: Number of subjects enrolled |
Australia: 6
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Country: Number of subjects enrolled |
Belarus: 4
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Country: Number of subjects enrolled |
Puerto Rico: 14
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Country: Number of subjects enrolled |
Russian Federation: 20
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Country: Number of subjects enrolled |
United States: 44
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Worldwide total number of subjects |
153
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EEA total number of subjects |
65
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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) |
0
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Adults (18-64 years) |
151
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||
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Pre-assignment
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Screening details |
The study included a 35-day screening period. | |||||||||||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Arm A: ABT-493/ABT-530 for 8 weeks | |||||||||||||||||||||
Arm description |
HCV Genotype (GT)1-6/HIV-1 co-infected non-cirrhotic subjects treated with ABT-493/ABT-530 300 mg/120 mg coformulated tablet administered orally once a day (QD) for 8 weeks | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
ABT-493/ABT-530
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Investigational medicinal product code |
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Other name |
ABT-493 also known as glecaprevir, ABT-530 also known as pibrentasvir, MAVIRET
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Tablet; ABT-493 coformulated with ABT-530 administered orally
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Arm title
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Arm B: ABT-493/ABT-530 for 12 Weeks | |||||||||||||||||||||
Arm description |
HCV GT1-6/HIV-1 coinfected subjects with compensated cirrhosis treated with ABT-493/ABT-530 300 mg/120 mg coformulated tablet administered orally once a day (QD) for 12 weeks | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
ABT-493/ABT-530
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Investigational medicinal product code |
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Other name |
ABT-493 also known as glecaprevir, ABT-530 also known as pibrentasvir, MAVIRET
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Tablet; ABT-493 coformulated with ABT-530 administered orally
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Baseline characteristics reporting groups
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Reporting group title |
Arm A: ABT-493/ABT-530 for 8 weeks
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Reporting group description |
HCV Genotype (GT)1-6/HIV-1 co-infected non-cirrhotic subjects treated with ABT-493/ABT-530 300 mg/120 mg coformulated tablet administered orally once a day (QD) for 8 weeks | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B: ABT-493/ABT-530 for 12 Weeks
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Reporting group description |
HCV GT1-6/HIV-1 coinfected subjects with compensated cirrhosis treated with ABT-493/ABT-530 300 mg/120 mg coformulated tablet administered orally once a day (QD) for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Arm A: ABT-493/ABT-530 for 8 weeks
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Reporting group description |
HCV Genotype (GT)1-6/HIV-1 co-infected non-cirrhotic subjects treated with ABT-493/ABT-530 300 mg/120 mg coformulated tablet administered orally once a day (QD) for 8 weeks | ||
Reporting group title |
Arm B: ABT-493/ABT-530 for 12 Weeks
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Reporting group description |
HCV GT1-6/HIV-1 coinfected subjects with compensated cirrhosis treated with ABT-493/ABT-530 300 mg/120 mg coformulated tablet administered orally once a day (QD) for 12 weeks | ||
Subject analysis set title |
Intention-to-treat (ITT) Population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Per protocol, all efficacy analyses were performed using the intention-to-treat (ITT) population (all enrolled participants who received at least 1 dose of study drug); in addition, efficacy analyses were performed overall, combining Treatment Arms A and B.
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End point title |
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [1] | ||||||||
End point description |
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of active study drug.
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End point type |
Primary
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End point timeframe |
12 weeks after last dose of study drug
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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: Descriptive data are summarized for this end point per protocol. |
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End point title |
Percentage of Participants With On-treatment Virologic Failure | ||||||||
End point description |
On-treatment virologic failure was defined as confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < LLOQ during treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment.
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End point type |
Secondary
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End point timeframe |
Up to 12 weeks
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End point title |
Percentage of Participants With Post-treatment Relapse | ||||||||
End point description |
Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment.
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End point type |
Secondary
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End point timeframe |
From the end of treatment through 12 weeks after the last dose of study drug
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| Notes [2] - Per protocol, ITT population including only those with post-treatment data, excluding reinfection. |
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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 |
Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 16 weeks).
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Adverse event reporting additional description |
TEAEs and SAEs are defined as any AE or SAE from the first dose of study drug to 30 days after the last dose of study drug (up to 16 weeks).
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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 |
20.0
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Reporting groups
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Reporting group title |
Arm A: ABT-493/ABT-530 for 8 weeks
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Reporting group description |
HCV Genotype (GT)1-6/HIV-1 co-infected non-cirrhotic subjects treated with ABT-493/ABT-530 300 mg/120 mg coformulated tablet administered orally once a day (QD) for 8 weeks | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B: ABT-493/ABT-530 for 12 Weeks
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Reporting group description |
HCV GT1-6/HIV-1 coinfected subjects with compensated cirrhosis treated with ABT-493/ABT-530 300 mg/120 mg coformulated tablet administered orally once a day (QD) for 12 weeks | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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01 Mar 2016 |
The purpose of this amendment was to update text throughout the protocol to remove all instances of glecaprevir/ pibrentasvir (GLE/PIB) dose of 200 mg/80 mg once daily dosing as well as the related treatment Arms B and D and to reflect that the 300 mg/120 mg dose of GLE/PIB was the only dose investigated in this study. In addition, this amendment included an update to text that revised permissive HIV-1 antiretrovirals based on completed drug interaction studies, and those HIV-1 antiretrovirals where no significant interaction was predicted based on metabolic and transporter pathways. An inclusion criterion was updated to clarify the qualifying HIV-1 antiretrovial treatment (ART) regimen. Finally, text was edited to clarify prohibited hormonal contraceptives/replacement therapy containing ethinyl estradiol. |
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21 Mar 2016 |
The purpose of this amendment was to revise the primary and secondary objectives to incorporate a comparison of the overall sustained virologic response 12 weeks post dosing (SVR12) rate with a historical threshold and to modify the population for the primary objective to the intent-to-treat (ITT) population. Edited text also included a description of how the historical threshold for the primary efficacy analysis was calculated, provided the rationale for selection of a 6% noninferiority margin, and updated sample size to describe the power to demonstrate noninferiority to the historical control SVR12 rate. Finally, this amendment included edits throughout to include Efficacy Treatment Adjustment Criteria Rationale to ensure optimal efficacy in the noncirrhotic population by incorporating the ability to extend treatment from 8 weeks to 12 weeks for Arm A based on a pre-specified evaluation of the number of subjects experiencing post-treatment HCV relapse. |
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12 Jul 2016 |
The purpose of this amendment was to update text throughout the protocol for the following reasons: to revise permissive Human Immunodeficiency Virus (HIV)-1 antiretrovirals based on either completed drug interaction studies, and/or those HIV-1 antiretrovirals for which no significant interaction was predicted based on metabolic and transporter pathways; to increase the overall sample size to allow for enrollment of additional HCV GT1 subjects; to edit inclusion criteria to clarify the qualifying HIV-1 ART regimen; and to clarify cirrhotic subjects who were receiving DRV and LPV were not eligible for the study. |
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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. | |||
