Clinical Trial Results:
First Line Pazopanib in Poor Risk Patients with Metastatic Renal Cell Carcinoma
Summary
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EudraCT number |
2011-001138-40 |
Trial protocol |
DE |
Global end of trial date |
31 Jul 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Mar 2018
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First version publication date |
31 Mar 2018
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Other versions |
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Summary report(s) |
FLIPPER Synopsis |
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 |
IOM-605
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01521715 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
iOMEDICO AG
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Sponsor organisation address |
Hanferstr. 28, Freiburg, Germany, 79108
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Public contact |
iOMEDICO AG, iOMEDICO AG, 0049 761152420, info@iomedico.com
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Scientific contact |
iOMEDICO AG, iOMEDICO AG, 0049 761152420, info@iomedico.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 |
23 Jan 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jul 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jul 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Primary analysis will focus on the rate of poor risk patients as defined by the MSKCC criteria who are free of disease progression at 6 months after start of first line treatment with pazopanib.
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Protection of trial subjects |
Informed consent of patient has been obtained in accordance with § 40 I 3 No. 3 Lit. b), II 1 AMG and § 40 I 3 No. 3 Lit. c). IIa 1&2 AMG by each investigator prior to inclusion of each patient to the study. The nature, objective and importance of the study, the possible benefits and disadvantages or risks, and the study procedures were explained to each patient orally and in writing. The patients were informed that their participation was voluntary, that they were free to withdraw from the study at any time, and that choosing not to participate would not impact on the patient’s care or future treatment.
The patients were also informed that, by signing the ICF, they explicitly permitted authorized representatives of the sponsor and the regulatory authorities access to study-related personal data to the extent permitted by the applicable law(s) and/or regulations without violating the confidentiality of the patient, to the extent permitted by the applicable law(s) and/or regulations. The patients were also informed that their consent to access their data might not be revoked.
Each patient was given sufficient time to read the ICF and to ask questions to the investigator prior to giving his/her written consent. Before entry to the study and prior to the conduct of any study-related procedure consent was recorded by means of the patient’s dated signature. The patient was given a copy of the information sheet and his/her signed consent form. The consent form was retained by the investigator as part of the study records. The investigator did not undertake any investigation specifically required only for the clinical study until valid consent has been obtained. The terms of the consent and the date when it was obtained were also documented in the electronic case report form (eCRF).
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Background therapy |
Not applicable. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
24 Jan 2012
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
7 Months | ||
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 |
Germany: 44
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Worldwide total number of subjects |
44
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EEA total number of subjects |
44
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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) |
18
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From 65 to 84 years |
24
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85 years and over |
2
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Recruitment
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Recruitment details |
The investigator enrolled patients based on previously defined inclusion (IC) and exclusion criteriea (EC). Patients who fulfilled all of the IC and non of the EC were eligible to FLIPPER trial. The recruitment of eligible patients was competitive among the centers participating in the trial. | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
In total n=60 patients were screened and according to the inclusion and exclusion criteria n=44 patients were enrolled into the study . One patient enrolled did not receive study treatment. Screening period was performed from day -30 to start of treatment. Tumor assessemnt was to be performed no later than 14 days prior to start of study treatment. | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Blinding implementation details |
Not applicable.
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Arms
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Arm title
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Pazopanib Treatment | ||||||||||||||||||||||||
Arm description |
As recommended in the SmPC, 800 mg (2x400 mg) pazopanib per day were to be taken orally without food at least one hour before or two hours after a meal at approximately the same time of day. Administration should have been continued until progression or occurrence of intolerable toxicity. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Pazopanib
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Investigational medicinal product code |
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Other name |
Votrient
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Administration of pazopanib: 2 tablets with a dose of 400 mg once daily (total daily dose 800 mg)
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Safety Analysis Set (SAF)
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The SAF set includes all patients who received at least one dose of pazopanib. This population is relevant for all safety parameters.
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Subject analysis set title |
mITT
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The mITT population includes all patients who received at least one dose of pazopanib and which fulfill one of the following points:
• have PD prior to 26 weeks +7 days after therapy start
• died because of tumor progression prior to 26 weeks +7 days after therapy start
• are assessable with regard to their disease status at 26 weeks ±7 days after therapy start (3rd tumor evaluation)
• experience SD, partial remission or complete remission after 26 weeks +7 days after therapy start
The mITT set is relevant for the analyses of the primary and secondary efficacy parameters.
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End points reporting groups
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Reporting group title |
Pazopanib Treatment
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Reporting group description |
As recommended in the SmPC, 800 mg (2x400 mg) pazopanib per day were to be taken orally without food at least one hour before or two hours after a meal at approximately the same time of day. Administration should have been continued until progression or occurrence of intolerable toxicity. | ||
Subject analysis set title |
Safety Analysis Set (SAF)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The SAF set includes all patients who received at least one dose of pazopanib. This population is relevant for all safety parameters.
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Subject analysis set title |
mITT
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
The mITT population includes all patients who received at least one dose of pazopanib and which fulfill one of the following points:
• have PD prior to 26 weeks +7 days after therapy start
• died because of tumor progression prior to 26 weeks +7 days after therapy start
• are assessable with regard to their disease status at 26 weeks ±7 days after therapy start (3rd tumor evaluation)
• experience SD, partial remission or complete remission after 26 weeks +7 days after therapy start
The mITT set is relevant for the analyses of the primary and secondary efficacy parameters.
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End point title |
6-month PFS rate [1] | ||||||
End point description |
Proportion of patients free of progression at 6 months (26 weeks ±7 days) after start of first-line therapy with pazopanib. The analysis includes all patients that received at least one dose of pazopanib and which are assessable with regard to their disease status at 26 weeks ±7 days (or before in case of progressive disease (PD) prior to 26 weeks ±7 days after therapy start).
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Final result: 6-months PFS rate [n (%, [95%-CI])]: 12 (35.29%, [19.7 - 53.5])
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End point type |
Primary
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End point timeframe |
Time from first application of pazopanib to progression or death of any cause.
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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: Planned patient number (n=80) could not be reached in a timely manner and patient number of the mITT population (n=34) was substantially lower than expected. Therefore, the statistical analysis for the primary endpoint is merely descriptive. |
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No statistical analyses for this end point |
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End point title |
Median Progression Free Survival (PFS) - Kaplan-Meier | ||||||||
End point description |
PFS is defined as time from first application of pazopanib to progression (PD according to RECIST 1.1) or death of any cause before start of new antineoplastic treatment. Patients without PD or death were censored at their last date of tumor evaluation.
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End point type |
Secondary
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End point timeframe |
Time from first application of pazopanib to progression or death of any cause.
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Attachments |
PFS (mITT) |
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No statistical analyses for this end point |
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End point title |
Overall survival (OS) | ||||||||
End point description |
OS defined as time from first application of pazopanib to death of any cause. Patients alive at the end of the study were censored with the date of the last contact to the patient
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End point type |
Secondary
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End point timeframe |
OS is defined as time from first application of pazopanib to death of any cause.
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Attachments |
OS Kaplan-Meier Plot (mITT) |
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No statistical analyses for this end point |
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End point title |
Objective Response Rate (ORR) | ||||||
End point description |
ORR was defined as rate of patients with complete response (CR) or partial response (PR).
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End point type |
Secondary
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End point timeframe |
Treatment period of pazopanib treatment [Time from first occurrence of a response (at least PR) to a documented PD or death due to PD (whichever came first)].
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No statistical analyses for this end point |
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End point title |
Duration of Response (DOR) | ||||||||
End point description |
DOR was calculated as the time from first occurrence of a response (at least PR) to a documented PD. If a patient did not experience PD prior to onset of a subsequent therapy the time was censored at last date of tumor evaluation or start of new antineoplastic treatment, whatever came first. The analysis was only conducted for patients with response (at least PR).
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End point type |
Secondary
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End point timeframe |
Time from first occurrence of a response (at least PR) to a documented PD or death due to PD (whichever came first).
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Notes [2] - The analysis was conducted only for patients with response (at least partial response) |
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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 |
TEAE were recorded from day of first dose of study medication to 30 days after last dose of study medication.
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Adverse event reporting additional description |
The analysis of safety data will be based on SAF population.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |
Pazopanib Treatment
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Reporting group description |
The analysis of safety data is based on SAF population. AE were recorded from day of first dose of study medication to 30 days after last dose of study medication (TEAE). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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26 Feb 2014 |
Amendment to study protocol (v2.0 dated 19-Nov-2013) and patient informed consent form. |
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09 May 2017 |
Amendment to study protocol (v4.0 dated 13-Apr-2017) and patient informed consent form (implementation of prematurely study end due to poor recruitment) |
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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 |