Clinical Trial Results:
The TEAM Study (Thiopurine EnhAnced Maintenance therapy)
A Phase 1-2 Study of 6-Thioguanine in Combination with Methotrexate and 6-Mercaptopurine During Maintenance Therapy of Childhood, Adolescent, and Adult Lymphoblastic Non-Hodgkin’s Lymphoma and Acute Lymphoblastic Leukemia
Summary
|
|
EudraCT number |
2014-002248-42 |
Trial protocol |
DK FI |
Global end of trial date |
12 Mar 2020
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
21 Mar 2021
|
First version publication date |
21 Mar 2021
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
0JMC-2014-6TG/6MP
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02912676 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Bonkolab, Rigshospitalet
|
||
Sponsor organisation address |
Blegdamsvej 9, Copenhagen Ø, Denmark, DK-21000
|
||
Public contact |
Bonkolab, Rigshospitalet, Bonkolab, +45 35454652, Kjeld.Schmiegelow@regionh.dk
|
||
Scientific contact |
Bonkolab, Rigshospitalet, Bonkolab, +45 35454652, Kjeld.Schmiegelow@regionh.dk
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
31 Aug 2020
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
12 Mar 2020
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
12 Mar 2020
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To explore the feasibility of 6TG as a supplement to maintenance therapy of Acute Lymphoblastic Leukemia and Lymphoblastic Non-Hodgkin’s Lymphoma in order to improve the existing dose adjustment strategies. We hypothesize that MTX/6MP/6TG combination therapy will achieve a higher DNA-TGN level and enhance the effect of 6MP. We will describe toxicities, hematology and thiopurine metabolite levels during MTX/6MP/6TG combination therapy.
This study will be the first to assess the applicability of 6TG in combination with standard MTX/6MP maintenance therapy.
|
||
Protection of trial subjects |
During 6TG therapy the frequency of controls was increased from biweekly to every week in order to note any toxicities early. In case of myelo-/hepatotoxicity or infection the recommendations in the NOPHO therapy guidelines were followed with regards to the dosing of 6MP and MTX. In case of toxicity the administration of 6TG was either withheld or reduced depending on the toxicity.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 2016
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Denmark: 33
|
||
Country: Number of subjects enrolled |
Finland: 1
|
||
Worldwide total number of subjects |
34
|
||
EEA total number of subjects |
34
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
3
|
||
Children (2-11 years) |
22
|
||
Adolescents (12-17 years) |
4
|
||
Adults (18-64 years) |
5
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
|||||||||||||
Recruitment
|
|||||||||||||
Recruitment details |
Eligible patients were included, when they reached maintenance therapy phase II (maintenance-II). Patients were included during the entire course of maintenance-II but had to have at least 3 months of remaining therapy upon first visit. Inclusion was completed in December 2018, and the last TEAM patient finished therapy in March 2020. | ||||||||||||
Pre-assignment
|
|||||||||||||
Screening details |
Patients aged 1–45 years with non-high risk ALL (i.e. standard and intermediate risk) and treated according to the NOPHO ALL2008 protocol were eligible for the study. Eligible patients were included, when they reached maintenance therapy phase II. Patients had to have at least three months of remaining therapy upon first visit. | ||||||||||||
Period 1
|
|||||||||||||
Period 1 title |
Before TEAM
|
||||||||||||
Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||
Blinding used |
Not blinded | ||||||||||||
Arms
|
|||||||||||||
Arm title
|
Before TEAM | ||||||||||||
Arm description |
TEAM-patients before TEAM. Time period before TEAM was defined as two months prior to initiation of 6TG treatment. | ||||||||||||
Arm type |
Active comparator | ||||||||||||
Investigational medicinal product name |
6-mercaptopurine
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
Xaluprine, Puri-nethol
|
||||||||||||
Pharmaceutical forms |
Tablet, Oral suspension
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
Dosing of daily oral 6MP is targeted to a WBC level of 1.5–3.0 x109/L. Therapy was discontinued 2.5 years from diagnosis.
|
||||||||||||
Investigational medicinal product name |
Methotrexat
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
MTX
|
||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
Dosing of weekly oral MTX is targeted to a WBC level of 1.5–3.0 x109/L. Therapy was discontinued 2.5 years from diagnosis.
|
||||||||||||
|
|||||||||||||
Period 2
|
|||||||||||||
Period 2 title |
TEAM
|
||||||||||||
Is this the baseline period? |
No | ||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||
Blinding used |
Not blinded | ||||||||||||
Arms
|
|||||||||||||
Arm title
|
TEAM | ||||||||||||
Arm description |
TEAM patients. Time period before TEAM was defined as two months prior to initiation of 6TG treatment. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
6-Thioguanine
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
6TG
|
||||||||||||
Pharmaceutical forms |
Oral solution, Tablet
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
Incremental 6TG doses were added to standard MTX/6MP maintenance therapy at a dose of 2.5 mg/m2/day and increased by 2.5 mg/m2/day biweekly until reaching maximum 6TG dose of 12.5 mg/m2/day. DNA-TG target level was DNA-TG above 500 fmol/µg DNA (approximate mean DNA-TG at end of MTX/6MP based maintenance therapy). TEAM patients followed the same WBC target of 1.5–3.0 x109/L. If DNA-TG and/or WBC targets were not reached at maximum 6TG doses (i.e. 12.5 mg/m2/day) 6MP and/or MTX dosages were adjusted.
|
||||||||||||
Investigational medicinal product name |
6-mercaptopurine
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
Xaluprine, Puri-nethol
|
||||||||||||
Pharmaceutical forms |
Oral suspension, Tablet
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
Dosing of daily oral 6MP is targeted to a WBC level of 1.5–3.0 x109/L. Therapy was discontinued 2.5 years from diagnosis.
|
||||||||||||
Investigational medicinal product name |
Methotrexat
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
MTX
|
||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
Dosing of weekly oral MTX is targeted to a WBC level of 1.5–3.0 x109/L. Therapy was discontinued 2.5 years from diagnosis.
|
||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||
Reporting group title |
Before TEAM
|
||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Before TEAM
|
||
Reporting group description |
TEAM-patients before TEAM. Time period before TEAM was defined as two months prior to initiation of 6TG treatment. | ||
Reporting group title |
TEAM
|
||
Reporting group description |
TEAM patients. Time period before TEAM was defined as two months prior to initiation of 6TG treatment. |
|
|||||||||||||
End point title |
DNA-TG | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
DNA-TG was measured weekly or biweekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [1] | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
251
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
160 | ||||||||||||
upper limit |
341 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [1] - Paired t-test |
|
|||||||||||||
End point title |
Ery-TGN | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Ery-TGN was measured weekly or biweekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [2] | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
470
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
349 | ||||||||||||
upper limit |
590 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [2] - Paired t-test |
|
|||||||||||||
End point title |
6MP dose | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
6MP dose was adjusted weekly or biweekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [3] | ||||||||||||
P-value |
= 0.09 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-19 | ||||||||||||
upper limit |
1 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [3] - Paired t-test |
|
|||||||||||||
End point title |
MTX dose | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
measured weekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [4] | ||||||||||||
P-value |
= 0.99 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.02
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.8 | ||||||||||||
upper limit |
2.7 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [4] - Paired t-test |
|
|||||||||||||
End point title |
Ery-MeMP | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured weekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [5] | ||||||||||||
P-value |
= 0.06 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.948
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.011 | ||||||||||||
upper limit |
115 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [5] - Paired t-test |
|
|||||||||||||
End point title |
WBC | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured weekly or biweekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [6] | ||||||||||||
P-value |
= 0.78 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.05
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.31 | ||||||||||||
upper limit |
0.41 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [6] - Paired t-test |
|
|||||||||||||
End point title |
ANC | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured weekly or biweekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [7] | ||||||||||||
P-value |
= 0.4 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.13
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.19 | ||||||||||||
upper limit |
0.45 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [7] - Paired-t-test |
|
|||||||||||||
End point title |
TBC | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured weekly or biweekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [8] | ||||||||||||
P-value |
= 0.02 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
19
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
2.7 | ||||||||||||
upper limit |
35 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [8] - Paired-t-test |
|
|||||||||||||
End point title |
Hgb | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured weekly or biweekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [9] | ||||||||||||
P-value |
= 0.1 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.17
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.04 | ||||||||||||
upper limit |
0.4 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [9] - Paired t-test |
|
|||||||||||||
End point title |
ALAT | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured weekly or biweekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [10] | ||||||||||||
P-value |
= 0.23 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-13
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-35 | ||||||||||||
upper limit |
9 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [10] - Paired t-test |
|
|||||||||||||
End point title |
Coagulation factors II-VII-X | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured weekly or biweekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [11] | ||||||||||||
P-value |
= 0.42 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.02
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.04 | ||||||||||||
upper limit |
0.08 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [11] - Paired t-test |
|
|||||||||||||
End point title |
INR | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured weekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [12] | ||||||||||||
P-value |
= 0.06 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.08
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.15 | ||||||||||||
upper limit |
0.002 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [12] - Paired t-test |
|
|||||||||||||
End point title |
Bilirubin | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured weekly or biweekly during the time period from initiation of 6TG until discontinuation of all therapy
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Before TEAM v TEAM
|
||||||||||||
Number of subjects included in analysis |
64
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [13] | ||||||||||||
P-value |
= 0.95 | ||||||||||||
Method |
Welch´s t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.06
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.8 | ||||||||||||
upper limit |
1.9 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Notes [13] - Paired t-test |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From inclusion untill 24 hours after the last 6TG dose.
Follow-up for 5 years - off-study.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
All subjects
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |