Clinical Trial Results:
A Multicenter, Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Velaglucerase Alfa in Chinese Subjects With Type 1 Gaucher Disease
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Summary
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EudraCT number |
2022-002323-35 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
05 Aug 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Feb 2025
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First version publication date |
20 Feb 2025
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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 |
TAK-669-3001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05529992 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Takeda
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Sponsor organisation address |
95 Hayden Ave, Lexington, Massachusetts, United States, 02421
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Public contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Scientific contact |
Study Director, Takeda, TrialDisclosures@takeda.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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
05 Aug 2024
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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 |
05 Aug 2024
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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 main aim of this study was to evaluate the safety of VPRIV in participants with type 1 Gaucher disease.
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Protection of trial subjects |
Each participant or their parents/guardians/legally authorized representatives signed an informed consent form (ICF) before participating in the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Jan 2023
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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 |
China: 20
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Worldwide total number of subjects |
20
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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) |
10
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Adolescents (12-17 years) |
5
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Adults (18-64 years) |
5
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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 took part in the study at various investigative sites in China from 3 January 2023 to 5 August 2024. | ||||||||||
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Pre-assignment
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Screening details |
Participants with a diagnosis of type 1 Gaucher disease were enrolled in this study to receive velaglucerase alfa (VPRIV) as intravenous (IV) infusion. | ||||||||||
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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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VPRIV | ||||||||||
Arm description |
Participants received VPRIV IV infusion at 60 U/kg body weight once EOW for 60 (+10) minutes up to Week 51. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Velaglucerase Alfa (VPRIV)
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Investigational medicinal product code |
TAK-669
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Other name |
VPRIV
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Pharmaceutical forms |
Powder and solvent for solution for infusion
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Routes of administration |
Intravenous use, Infusion
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Dosage and administration details |
VPRIV IV infusion at 60 U/kg body weight once every other week (EOW) for 60 (+10) minutes for up to 51 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
VPRIV
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Reporting group description |
Participants received VPRIV IV infusion at 60 U/kg body weight once EOW for 60 (+10) minutes up to Week 51. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
VPRIV
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Reporting group description |
Participants received VPRIV IV infusion at 60 U/kg body weight once EOW for 60 (+10) minutes up to Week 51. | ||
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End point title |
Percentage of Participants With at Least One Serious Treatment-Emergent Adverse Event (TEAE) [1] | ||||||||
End point description |
Adverse event(AE)=any untoward medical occurrence in clinical investigation participant administered drug;it does not necessarily have to have causal relationship with this treatment. AE can therefore be any unfavorable&unintended sign (example,clinically significant abnormal laboratory value),symptom/disease temporally associated with use of drug whether/not it is considered related to drug. TEAE=any event emerging/manifesting at or after initiation of investigational product or any existing event that worsens in either intensity or frequency following exposure to investigational product. SAE=any untoward clinical manifestation of signs, symptoms/outcomes(whether considered related to investigational product or not)&at any dose: results in death,is life-threatening,requires in-patient hospitalization/prolongation of hospitalization,results in persistent/significant disability/incapacity,results in congenital abnormality/birth defect,or is an important medical event.
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End point type |
Primary
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End point timeframe |
Up to 56.2 weeks
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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: Only descriptive analysis was planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With TEAEs | ||||||||
End point description |
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory value), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. A TEAE is defined as any event emerging or manifesting at or after the initiation of the investigational product or any existing event that worsens in either intensity or frequency following exposure to the investigational product. The Safety Set (SAF) included all participants in the ITT Set who received at least 1 dose of VPRIV.
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End point type |
Secondary
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End point timeframe |
Up to 56.2 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Infusion-related Reactions Reported as an Adverse Event | ||||||||
End point description |
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory value), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. An infusion-related AE was defined as an AE that 1) began either during or within 12 hours after the start of the infusion and 2) was judged as possibly or probably related to the study treatment. The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV.
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End point type |
Secondary
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End point timeframe |
Up to 56.2 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Development of Anti-VPRIV Antibodies and Neutralizing Antibodies at Week 53 | ||||||||||||
End point description |
Percentages were rounded off to the nearest single decimal place. The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Week 53
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants With Clinically Significant Changes in Laboratory Assessments at Week 53 | ||||||||||||||||||||||||||||||||||
End point description |
Clinical laboratory assessments included hematology and serum chemistry. Any clinically significant changes in the clinical laboratory assessment values based on the investigator’s interpretation were reported. Only categories with at least one participant with event are presented. MCH stands for mean corpuscular hemoglobin. The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Subjects analysed is the number of participants with data available for analyses. 'n' indicates the number of participants with data available for analysis for the specified category.
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End point type |
Secondary
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End point timeframe |
Week 53
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants With Abnormal Changes in Laboratory Assessments at Week 53: Urinalysis | ||||||||||||||||||||
End point description |
Any abnormal changes in the urinalysis assessment values based on the investigator’s interpretation were reported. Urinalysis comprised of the following parameters: bilirubin, ketones, glucose, nitrite, occult blood, protein, and urobilinogen. The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Subjects analysed is the number of participants with data available for analyses. 'n' indicates the number of participants with data available for analysis for the specified category.
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End point type |
Secondary
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End point timeframe |
Week 53
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Number of Participants With at Least One Abnormal Change in an Infusion Vital Sign Parameter at Week 53 | ||||||||||||||||||||||
End point description |
Participants with atleast 1 abnormal change (above or below normal) in an infusion vital sign parameter of pulse, temperature, respiratory rate,& blood pressure were reported. Normal ranges for each vital sign parameter were, pulse (beats per minutes [bpm]): 40-100(≥12 years old), 55-95(≥6 but <12 years old), 65-110(≥2 but <6 years old); body temperature(degree Celsius[˚C]): 36.5 to 37.2(all age groups),respiration rate(breaths/minutes):12-24(≥12 years old),12-22 (≥6 but <12 years old),20-30(≥2 but <6 years old);systolic blood pressure(BP) [millimeters of mercury{mm Hg}]: high: ≥140 (≥18 years old), ≥20+ 80+ 2*age(<18 years old), low: <90 (≥18 years old), < -20+ 80+ 2*age(<18 years old); diastolic BP(mm Hg):high:≥90 (≥18 years old), ≥20+ (80+2*age)*(2/3) (<18 years old) low: <50 (≥18 years old), < -20+ (80+2*age)*(2/3) (<18 years old). As per planned analysis,data was collected in a combined manner for all participants irrespective of age. Only non-zero categories are presented.
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End point type |
Secondary
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End point timeframe |
Week 53
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements at Week 53 | ||||||
End point description |
Participants with clinically significant changes in any ECG measurement, such as PR, QRS, QT, corrected QT intervals, and heart rate based on the investigator’s interpretation were reported. The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Week 53
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| No statistical analyses for this end point | |||||||
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End point title |
Change From Baseline to Week 53 in Hemoglobin Concentration | ||||||||
End point description |
The ITT Set included all participants who signed the ICF (and assent form, if applicable) and were eligible for the study based on the defined inclusion/exclusion criteria. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 53
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline to Week 53 in Platelet Count | ||||||||
End point description |
The ITT Set included all participants who signed the ICF (and assent form, if applicable) and were eligible for the study based on the defined inclusion/exclusion criteria. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 53
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline to Week 53 in Normalized Liver Volume | ||||||||
End point description |
Normalized liver volume was measured by abdominal magnetic resonance imaging (MRI) or computed tomography (CT) scan. Liver volume was normalized for percent body weight. The ITT Set included all participants who signed the ICF (and assent form, if applicable) and were eligible for the study based on the defined inclusion/exclusion criteria. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 53
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline to Week 53 in Normalized Spleen Volume | ||||||||
End point description |
Spleen volume was normalized for percent body weight. The ITT Set included all participants who signed the ICF (and assent form, if applicable) and were eligible for the study based on the defined inclusion/exclusion criteria. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 53
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline to Week 53 in 36-item Short Form General Health Survey (SF-36) Scores | ||||||||||||
End point description |
SF-36 Version 2 is a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100 for each component summary (i.e., PCS and MCS), where higher scores are associated with less disability and better quality of life. The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 53
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline to Week 53 in Childhood Health Questionnaire-Parent Form 50 (CHQ-PF50) Scores | ||||||||||||
End point description |
The CHQ-PF-50 is a 50-item questionnaire to be completed by the parents or guardians of children between 5 and 18 years of age. The 50 questions measure 14 domains (global health, physical functioning, role/social limitations (emotional/behavioral and physical), bodily pain/discomfort, behavior, global behavior, mental health, self-esteem, general health perceptions, change in health, parental impact (emotional and time), family activities, and family cohesion) which were summarized as the physical and psychological summary scores. Each summary score was transformed and could range from 0 to 100, with higher score indicating better physical and psychosocial health. A positive change from Baseline indicates improved well-being. The SAF included all participants in the ITT Set who received at least 1 dose of VPRIV. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 53
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Cmax: Maximum Observed Serum Concentration for VPRIV at Week 1 | ||||||||
End point description |
The Pharmacokinetic (PK) Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data.
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End point type |
Secondary
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End point timeframe |
Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
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| No statistical analyses for this end point | |||||||||
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End point title |
Serum Concentration for VPRIV at Week 37 | ||||||||
End point description |
The PK Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Within 3 minutes prior to the end of the 60-minute infusion at Week 37
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| No statistical analyses for this end point | |||||||||
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End point title |
Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for VPRIV | ||||||||
End point description |
The PK Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data.
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End point type |
Secondary
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End point timeframe |
Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
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| No statistical analyses for this end point | |||||||||
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End point title |
AUCinf: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for VPRIV | ||||||||
End point description |
ng*min/mL denotes nanograms*minutes per milliliter. The PK Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data.
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End point type |
Secondary
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End point timeframe |
Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
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| No statistical analyses for this end point | |||||||||
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End point title |
Terminal Phase Elimination Half-life (T1/2) for VPRIV | ||||||||
End point description |
The PK Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data.
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End point type |
Secondary
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End point timeframe |
Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
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| No statistical analyses for this end point | |||||||||
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End point title |
Oral Clearance (CL) for VPRIV | ||||||||
End point description |
mL/min/kg denotes milliliters per minutes per kilogram. The PK Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data.
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End point type |
Secondary
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End point timeframe |
Pre-dose and at multiple timepoints up to 120 minutes post-dose on Day 1 of Week 1
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| No statistical analyses for this end point | |||||||||
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End point title |
Apparent Steady-state Volume of Distribution (Vss) for VPRIV | ||||||||
End point description |
The PK Set included all naïve participants in the ITT set who received at least 1 dose of VPRIV and provided evaluable PK concentration data.
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End point type |
Secondary
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End point timeframe |
Pre-dose and at multiple timepoints(up to 120 minutes post-dose on Day 1 of Week 1
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent Change from Baseline to Week 53 in Biomarker: Plasma Chemokine [C-C motif] Ligand 18 | ||||||||
End point description |
The ITT Set included all participants who signed the ICF (and assent form, if applicable) and were eligible for the study based on the defined inclusion/exclusion criteria. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 53
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent Change from Baseline to Week 53 in Biomarker: Glucopsychosine | ||||||||
End point description |
The ITT Set included all participants who signed the ICF (and assent form, if applicable) and were eligible for the study based on the defined inclusion/exclusion criteria. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 53
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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 |
Up to 56.2 weeks
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Adverse event reporting additional description |
The SAF Set included all participants in the ITT Set who received at least 1 dose of VPRIV.
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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 |
27.0
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Reporting groups
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Reporting group title |
Velaglucerase Alfa
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Reporting group description |
Participants received VPRIV IV infusion at 60 U/kg body weight once EOW for 60 (+10) minutes up to Week 51. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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02 Aug 2022 |
The following changes were made as per Amendment 01: 1. Increased the frequency of the body weight test as body weight changes requires to recalculate the dose of investigational product. 2. Increased the number of clinical sites from ‘5 to 6’ to ‘at least 8’ to increase the recruitment capability. 3. Updated the previous inclusion criteria. |
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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 | |||
