Clinical Trial Results:
Randomised, double-blind, placebo-controlled, parallel-groups, multi-centre clinical trial Phase III with Diclofenac Sodium 140 mg medicated plaster in patients with fresh impact injuries of the limbs.
|
Summary
|
|
EudraCT number |
2010-020489-82 |
Trial protocol |
DE |
Global end of trial date |
14 Apr 2011
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
16 Jul 2021
|
First version publication date |
16 Jul 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 |
Q16-10-01
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Fidia Farmaceutici S.p.A.
|
||
Sponsor organisation address |
Via Ponte della Frabbrica 3/A, Abano Terme, Italy, 35031
|
||
Public contact |
General Services, Fidia Farmaceutici S.p.A., 0039 0498232222, servizioportineria@fidiapharma.it
|
||
Scientific contact |
Nicola Giordan, Head of Clinical Research, Fidia Farmaceutici S.p.A., 0039 0498232512, ngiordan@fidiapharma.it
|
||
|
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 |
25 Jul 2011
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
14 Apr 2011
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
14 Apr 2011
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The primary objective of the trial is to show superior efficacy of Diclofenac Sodium 140 mg medicated plaster over Placebo plaster as assessed by absolute change of pain on movement from baseline Visit 1 (Day 1) to Visit 3 (Day 3) in the indication fresh impact injuries of the limbs.
|
||
Protection of trial subjects |
Female patients who are not postmenopausal for at least 2 years or surgically sterilized and who are at risk of becoming pregnant must use a highly effective method of birth control. The contraceptive methods must be clearly stated in the patient documentation, and each of these women must have a negative pregnancy test before inclusion into the trial. The pregnancy tests has been provided by Fidia Farmaceutici S.p.A.
The investigator may withdraw the patient from the study at any time. Reasons for removing a patient from the trial include, but are not limited to:
- Adverse events
- Local intolerance of the plaster
- Unauthorised concomitant medication
- Major protocol violation that results in a significant risk to the patient's safety
- Unsatisfactory efficacy (defined as a worsening of pain on movement consisting in a difference on VAS scale of at least 19 mm from baseline Visit 135 to any other visit).
- Other reasons (e. g. randomisation code broken, pregnancy, etc.).
The patient should not take any concomitant treatment without the investigator's knowledge. All concomitant treatments/ therapies have to be recorded by the patient in the diary and then documented in the CRF by the investigator, giving INN, strength, galenic form, route of administration, dosage, date of start and end of treatment, and reason for therapy.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Sep 2010
|
||
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 |
Germany: 168
|
||
Worldwide total number of subjects |
168
|
||
EEA total number of subjects |
168
|
||
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) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
168
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
Studied period: September 2010 to April 2011 (7 months) Date of first enrolment: FPI: 14 September 2010 Date of last completed: LPO: 14 April 2011 Study centres: Four active centres in Germany | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
- | |||||||||
|
Pre-assignment period milestones
|
||||||||||
Number of subjects started |
168 | |||||||||
Number of subjects completed |
168 | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
Overall trial (overall period)
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
|
|||||||||
Blinding used |
Double blind | |||||||||
Roles blinded |
Investigator, Monitor, Subject, Data analyst | |||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
Diclofenac Sodium 140 mg medicated plaster | |||||||||
Arm description |
Diclofenac Sodium 140 mg medicated plaster, topical application in the morning and in the evening. Topical treatment is started after enrolment into the trial (following baseline measurement). The plaster is applied two times a day, approximately every 12 hours, in the morning and in the evening, continued for in total 7 days. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Diclofenac Sodium 140 mg medicated plaster
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Transdermal patch
|
|||||||||
Routes of administration |
Topical use
|
|||||||||
Dosage and administration details |
140 mg Diclofenac Sodium medicated plaster, topical application, applied two times a day, approximately every 12 hours, in the morning and in the evening, continued for in total 7 days.
|
|||||||||
|
Arm title
|
Placebo plaster | |||||||||
Arm description |
Placebo plaster, topical application according to the dosage instruction for Diclofenac Sodium 140 mg medicated plaster. | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo plaster
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Transdermal patch
|
|||||||||
Routes of administration |
Topical use
|
|||||||||
Dosage and administration details |
Placebo plaster, topical treatment is started after enrolment into the trial (following baseline measurement). The plaster is applied two times a day, approximately every 12 hours, in the morning and in the evening, continued for in total 7 days.
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall trial
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Full analysis set
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The full analysis set (FAS) will be defined as those patients who were randomised to one of the trial treatments (all randomised patients). In this trial population also patients with major protocol violations will be included.
The Full Analysis Set will be the primary population for the efficacy analyses in this superiority trial.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Safety Set SAF
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The safety set comprises all patients of the full analysis set who received at least one dose of the investigational medical product.
This patient population will be used to analyse the safety data (e.g. AEs).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Per-protocol set (PP)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The per-protocol set comprises all patients of the Full Analysis Set, who were treated with trial medication and who did not have any major protocol violations. Patients who terminated the trial prematurely due to inefficacy of the trial treatment and who did not have major protocol violations prior to trial termination will be included in the PP set.
The per-protocol set will be the secondary population for the efficacy analyses.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Diclofenac Sodium 140 mg medicated plaster
|
||
Reporting group description |
Diclofenac Sodium 140 mg medicated plaster, topical application in the morning and in the evening. Topical treatment is started after enrolment into the trial (following baseline measurement). The plaster is applied two times a day, approximately every 12 hours, in the morning and in the evening, continued for in total 7 days. | ||
Reporting group title |
Placebo plaster
|
||
Reporting group description |
Placebo plaster, topical application according to the dosage instruction for Diclofenac Sodium 140 mg medicated plaster. | ||
Subject analysis set title |
Full analysis set
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The full analysis set (FAS) will be defined as those patients who were randomised to one of the trial treatments (all randomised patients). In this trial population also patients with major protocol violations will be included.
The Full Analysis Set will be the primary population for the efficacy analyses in this superiority trial.
|
||
Subject analysis set title |
Safety Set SAF
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety set comprises all patients of the full analysis set who received at least one dose of the investigational medical product.
This patient population will be used to analyse the safety data (e.g. AEs).
|
||
Subject analysis set title |
Per-protocol set (PP)
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The per-protocol set comprises all patients of the Full Analysis Set, who were treated with trial medication and who did not have any major protocol violations. Patients who terminated the trial prematurely due to inefficacy of the trial treatment and who did not have major protocol violations prior to trial termination will be included in the PP set.
The per-protocol set will be the secondary population for the efficacy analyses.
|
||
|
|||||||||||||||||||||
End point title |
Absolute change from baseline (Visit 1 (Day 1)) to Visit 3 (Day 3) regarding pain-on-movement VAS values | ||||||||||||||||||||
End point description |
The primary efficacy variable was the absolute change from baseline (Visit 1 (Day 1)) to Visit 3 (Day 3) regarding pain-on-movement (POM) VAS values.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
from baseline (Visit 1 (Day 1)) to Visit 3 (Day 3)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
ANOVA | ||||||||||||||||||||
Statistical analysis description |
The absolute changes from baseline to Visit 3, Visit 4, and Visit 5 were compared by means of analysis-of-variance (ANOVA)
|
||||||||||||||||||||
Comparison groups |
Diclofenac Sodium 140 mg medicated plaster v Placebo plaster v Full analysis set v Per-protocol set (PP)
|
||||||||||||||||||||
Number of subjects included in analysis |
496
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.05 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
- | ||||||||||||||||||||
upper limit |
- | ||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Absolute change from baseline Visit 1 to Visit 4 in pain on movement assessed by patients using VAS. | ||||||||||||||||||||
End point description |
|||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
from baseline Visit 1 to Visit 4 .
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Absolute change from baseline Visit 1 to Visit 5 in pain on movement assessed by patients using VAS. | ||||||||||||||||||||
End point description |
|||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
from baseline Visit 1 to Visit 5
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Absolute change from baseline Visit 1 to Visit 3 in pain at rest assessed by patients using VAS. | ||||||||||||||||||||
End point description |
|||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
from baseline Visit 1 to Visit 3
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Absolute change from baseline Visit 1 to Visit 4 in pain at rest assessed by patients using VAS. | ||||||||||||||||||||
End point description |
|||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
from baseline Visit 1 to Visit 4
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Absolute change from baseline Visit 1 to Visit 5 in pain at rest assessed by patients using VAS. | ||||||||||||||||||||
End point description |
|||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
from baseline Visit 1 to Visit 5
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||
End point title |
Time to onset of efficacy. | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Time to onset of efficacy assessed by patient on Visit 2, possibly on Visit 3, 4 and 5, too. If the patient feels that the medication is not yet working at Visit 2, the investigator will ask the patient again at subsequent visits.
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Global assessment of treatment efficacy by patient and investigator. | ||||||||||||||||||
End point description |
Global assessment of treatment efficacy will be performed by patient and investigator at Visit 2, 3 and 4 (Day 2, 3 and 4) and the final visit (Visit 5) and is classified according the 5 point Likert scale
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
at Visit 2, 3 and 4 (Day 2, 3 and 4) and the final visit (Visit 5)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
||||||||||||||||
End point title |
Consumption of analgesic medication (paracetamol tablets). | |||||||||||||||
End point description |
The consumption of rescue medication paracetamol (maximum dose per day (24 h) 2000 mg Paracetamol, single dose maximal 500-1000 mg equivalent to 10-15 mg/kg body weight) will be recorded in the diary by the patient and will then be documented in the CRF by the investigator.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
From baseline to visit 5 (Day 8).
|
|||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
|||||||||||||||||||||
End point title |
Change from Baseline to V3 regarding the tenderness of injured site VAS values | ||||||||||||||||||||
End point description |
|||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Day 1) to V3 (Day 3)
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Change from Baseline to V4 regarding the tenderness of injured site VAS values | ||||||||||||||||||||
End point description |
|||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Day 1) to V4 (Day 5)
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
The AE assessment occurred at each visit at sites from V1 to V5. All AE occurred during the trial must be reported in the CRF. Any SAE occurring in a patient after providing informed consent and until 4 weeks after completion of the trial must be reported
|
||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
13.1
|
||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Safety Population SAF
|
||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All 168 patients enrolled who received at least one dose of the study medication were included in the safety population (SAF). Adverse events (AEs) with multiple descriptions were splitted into single AEs for analysis purposes. Recurring AEs were counted only once. If there were differences in the corresponding AE assessments, the worst assessment was used. | ||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0.1% | |||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||
|
|||
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 | |||
