Clinical Trial Results:
Evaluation of the effect of the oral administration of perindopril orodispersible at a dose of 0.150 mg/kg/day onthe muscular and myocardial function in early stage Duchenne muscular dystrophy. Double blind two years study, randomised versus placebo.

Trial information Top of page
Trial identification
Sponsor protocol code	CL3-90652-004
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Institut de Recherches Internationales Servier
Sponsor organisation address	50 rue Carnot, Suresnes Cedex, France, 92284
Public contact	Clinical studies department, Institut de Recherches Internationales Servier 50 rue Carnot 92284 Suresnes Cedex, +33 155724366, clinicaltrials@servier.com
Scientific contact	Clinical studies department, Institut de Recherches Internationales Servier 50 rue Carnot 92284 Suresnes Cedex, +33 155724366, clinicaltrials@servier.com
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?	Yes
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	19 Oct 2011
Is this the analysis of the primary completion data?	Yes
Primary completion date	19 Oct 2011
Global end of trial reached?	Yes
Global end of trial date	19 Oct 2011
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	The main objective of the study was to assess the benefit versus placebo of the administration of perindopril on peripheral muscular function
Protection of trial subjects	the patient will be remove of the study if : the parents or the child choose to, the ACE tolerance is too low, the start of an other treatment is needed or the cardiac functions decrease (LVEF <55%).
Background therapy	No background therapy
Evidence for comparator	No reference treatment was identified
Actual start date of recruitment	11 Mar 2009
Long term follow-up planned	Yes
Long term follow-up rationale	Efficacy
Long term follow-up duration	2 Years
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	France: 40
Worldwide total number of subjects	40
EEA total number of subjects	40
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)	40
Adolescents (12-17 years)	0
Adults (18-64 years)	0
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	In all, 16 centres located in France, were opened and 14 centres included at least one patient.Children under 7 years.Confirmed DMD diagnosis: Either by the absence of dystrophin in the muscle biopsy. Or by the genetic study of the dystrophin gene in confirmed familial cases .
Pre-assignment
Screening details	No screening
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	Subject, Investigator, Monitor, Data analyst
Arms
Are arms mutually exclusive	Yes
Arm title	Perindopril
Arm description	-
Arm type	Experimental
Investigational medicinal product name	Perindopril
Investigational medicinal product code
Other name
Pharmaceutical forms	Orodispersible tablet
Routes of administration	Oral use
Dosage and administration details	0.150 mg/kg/day per os - once a day
Arm title	Placebo
Arm description	-
Arm type	Placebo
Investigational medicinal product name	Placebo
Investigational medicinal product code
Other name
Pharmaceutical forms	Orodispersible tablet
Routes of administration	Oral use
Dosage and administration details	1 tablet per day
Number of subjects in period 1 Perindopril Placebo Started 20 20 Completed 15 18 Not completed 5 2      Non Medical Reason 2 -      Protocol deviation 3 2

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Perindopril
Reporting group description	-
Reporting group title	Placebo
Reporting group description	-
Reporting group values Perindopril Placebo Total Number of subjects 20 20 40 Age categorical Units: Subjects     In utero 0 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0 0     Newborns (0-27 days) 0 0 0     Infants and toddlers (28 days-23 months) 0 0 0     Children (2-11 years) 20 20 40     Adolescents (12-17 years) 0 0 0     Adults (18-64 years) 0 0 0     From 65-84 years 0 0 0     85 years and over 0 0 0 Age continuous Units: years     arithmetic mean (standard deviation) 5.33 ( 1.23 ) 5.3 ( 1.17 ) - Gender categorical Units: Subjects     Female 0 0 0     Male 20 20 40 Disease Duration Units: Months     arithmetic mean (standard deviation) 24.8 ( 19.1 ) 18.5 ( 12.4 ) - Weight Units: Kg     arithmetic mean (standard deviation) 19.1 ( 3.96 ) 18.69 ( 2.43 ) -

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Perindopril
Reporting group description	-
Reporting group title	Placebo
Reporting group description	-

End points Top of page

Primary: 6 minute walking distance Top of page
End point title	6 minute walking distance
End point description	Change Last value under treatment minus Baseline value
End point type	Primary
End point timeframe	On the period M000-M024.
End point values Perindopril Placebo Number of subjects analysed 19 [1] 20 [2] Units: meters     arithmetic mean (standard deviation) -44.9 ( 132.7 ) -84.1 ( 134.3 )
Notes [1] - FAS [2] - FAS
Statistical analysis title	Between group comparison using an ANCOVA
Comparison groups	Perindopril v Placebo
Number of subjects included in analysis	39
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.05
Method	ANCOVA
Parameter type	Mean difference (final values)
Point estimate	60.39
Confidence interval
level	95%
sides	2-sided
lower limit	-30.96
upper limit	151.74
Variability estimate	Standard error of the mean
Dispersion value	44.95

Primary: 6 minute walking distance Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	Over the course of the study (M0-M24)
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	14.0
Reporting groups
Reporting group title	Perindopril
Reporting group description	-
Reporting group title	Placebo
Reporting group description	-
Serious adverse events Perindopril Placebo Total subjects affected by serious adverse events      subjects affected / exposed 6 / 19 (31.58%) 3 / 20 (15.00%)      number of deaths (all causes) 0 0      number of deaths resulting from adverse events Injury, poisoning and procedural complications accidental drug intake by child      subjects affected / exposed 0 / 19 (0.00%) 1 / 20 (5.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Face injury      subjects affected / exposed 1 / 19 (5.26%) 0 / 20 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Fall      subjects affected / exposed 1 / 19 (5.26%) 0 / 20 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Nervous system disorders Hypotonia      subjects affected / exposed 1 / 19 (5.26%) 0 / 20 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 General disorders and administration site conditions Malaise      subjects affected / exposed 1 / 19 (5.26%) 0 / 20 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Blood and lymphatic system disorders Lymphadenitis      subjects affected / exposed 0 / 19 (0.00%) 1 / 20 (5.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Respiratory, thoracic and mediastinal disorders Dyspnoea      subjects affected / exposed 1 / 19 (5.26%) 0 / 20 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Musculoskeletal and connective tissue disorders Myopathy      subjects affected / exposed 1 / 19 (5.26%) 1 / 20 (5.00%)      occurrences causally related to treatment / all 0 / 2 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Osteoporosis      subjects affected / exposed 1 / 19 (5.26%) 0 / 20 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Infections and infestations Ear infection      subjects affected / exposed 3 / 19 (15.79%) 0 / 20 (0.00%)      occurrences causally related to treatment / all 0 / 4 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 H1N1 influenza      subjects affected / exposed 1 / 19 (5.26%) 0 / 20 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Lobar pneumonia      subjects affected / exposed 1 / 19 (5.26%) 0 / 20 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Tonsillitis      subjects affected / exposed 1 / 19 (5.26%) 0 / 20 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events Perindopril Placebo Total subjects affected by non serious adverse events      subjects affected / exposed 17 / 19 (89.47%) 17 / 20 (85.00%) Injury, poisoning and procedural complications Fall      subjects affected / exposed 5 / 19 (26.32%) 0 / 20 (0.00%)      occurrences all number 6 0 joint sprain      subjects affected / exposed 2 / 19 (10.53%) 0 / 20 (0.00%)      occurrences all number 2 0 Nervous system disorders Headache      subjects affected / exposed 1 / 19 (5.26%) 1 / 20 (5.00%)      occurrences all number 1 1 General disorders and administration site conditions Asthenia      subjects affected / exposed 2 / 19 (10.53%) 0 / 20 (0.00%)      occurrences all number 2 0 Fatigue      subjects affected / exposed 2 / 19 (10.53%) 0 / 20 (0.00%)      occurrences all number 2 0 Pyrexia      subjects affected / exposed 1 / 19 (5.26%) 1 / 20 (5.00%)      occurrences all number 1 1 Gastrointestinal disorders Gastroenteritis      subjects affected / exposed 5 / 19 (26.32%) 2 / 20 (10.00%)      occurrences all number 7 2 Constipation      subjects affected / exposed 3 / 19 (15.79%) 1 / 20 (5.00%)      occurrences all number 3 1 Vomiting      subjects affected / exposed 2 / 19 (10.53%) 1 / 20 (5.00%)      occurrences all number 2 1 Respiratory, thoracic and mediastinal disorders Bronchitis      subjects affected / exposed 3 / 19 (15.79%) 5 / 20 (25.00%)      occurrences all number 4 8 Rhinitis      subjects affected / exposed 1 / 19 (5.26%) 6 / 20 (30.00%)      occurrences all number 1 6 Nasopharyngitis      subjects affected / exposed 2 / 19 (10.53%) 3 / 20 (15.00%)      occurrences all number 6 3 Oropharyngeal pain      subjects affected / exposed 3 / 19 (15.79%) 2 / 20 (10.00%)      occurrences all number 6 3 Cough      subjects affected / exposed 2 / 19 (10.53%) 1 / 20 (5.00%)      occurrences all number 6 1 Tracheitis      subjects affected / exposed 1 / 19 (5.26%) 2 / 20 (10.00%)      occurrences all number 1 7 Renal and urinary disorders Enuresis      subjects affected / exposed 2 / 19 (10.53%) 0 / 20 (0.00%)      occurrences all number 2 0 Musculoskeletal and connective tissue disorders Myopathy      subjects affected / exposed 1 / 19 (5.26%) 1 / 20 (5.00%)      occurrences all number 2 1 Pain in extremity      subjects affected / exposed 2 / 19 (10.53%) 0 / 20 (0.00%)      occurrences all number 2 0 Infections and infestations Ear infection      subjects affected / exposed 6 / 19 (31.58%) 3 / 20 (15.00%)      occurrences all number 8 3 Pharyngitis      subjects affected / exposed 1 / 19 (5.26%) 6 / 20 (30.00%)      occurrences all number 1 6 Tonsillitis      subjects affected / exposed 1 / 19 (5.26%) 3 / 20 (15.00%)      occurrences all number 2 5 H1N1 influenza      subjects affected / exposed 1 / 19 (5.26%) 1 / 20 (5.00%)      occurrences all number 1 1 Influenza      subjects affected / exposed 0 / 19 (0.00%) 2 / 20 (10.00%)      occurrences all number 0 2 Metabolism and nutrition disorders Hyperlipidaemia      subjects affected / exposed 0 / 19 (0.00%) 2 / 20 (10.00%)      occurrences all number 0 2

Adverse events Top of page

More information Top of page
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.
The section NSAE is filled with all emergent NSAEs on treatment. This decision has been taken by the sponsor to be in accordance with the existing ICH E3 Clinical Study Report.

More information Top of page