Clinical Trials Register

Summary
EudraCT Number:	2011-003826-28
Sponsor's Protocol Code Number:	Z7190L01
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-09-12
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-003826-28

A.3

Full title of the trial

Evaluation of efficacy and safety of Ibuprofen Arginine 600 mg tid vs. Ibuprofen 600 mg tid in the treatment of pain and inflammation in Osteoarthritis (OA) patients with hypertension pharmacologically stabilized.

Valutazione dell efficacia e della sicurezza di Ibuprofene Arginina 600 mg tid rispetto a Ibuprofene 600 mg tid nel trattamento di dolore e infiammazione nei pazienti affetti da osteoartrite (OA) con ipertensione stabilizzata farmacologicamente.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study comparing ibuprofen and ibuprofen arginine in the control of spontaneous pain in patients with osteoarthritis and stabilized hypertension.

Studio di confronto tra ibuprofene arginina e ibuprofene nel controllo del dolore spontaneo in pazienti affetti da osteoartrite e ipertensione stabilizzata.

A.4.1

Sponsor's protocol code number

Z7190L01

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ZAMBON S.p.A.
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Zambon S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Zambon S.p.A.
B.5.2	Functional name of contact point	Sponsor Contact Point
B.5.3	Address:
B.5.3.1	Street Address	Via Lillo del Duca, 10
B.5.3.2	Town/ city	Bresso (Milano)
B.5.3.3	Post code	20091
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390266524513
B.5.5	Fax number	+390266524841
B.5.6	E-mail	massimo.bagolan@zambongroup.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	SPIDIFEN*OS GRAT 30BUST 600MG
D.2.1.1.2	Name of the Marketing Authorisation holder	ZAMBON ITALIA Srl
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Granules
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	15687-27-1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	600
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	BRUFEN*OS GRAT 30BUST 600MG
D.2.1.1.2	Name of the Marketing Authorisation holder	ABBOTT Srl
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Effervescent granules
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	15687-27-1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	600
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Osteoarthritis of the knee or hip that requires taking NSAIDs for at least 14 days and hypertension stabilized with drugs.

Osteoartrite del ginocchio o dell’anca che richiede assunzione di FANS per almeno 14 giorni e ipertensione stabilizzata con farmaci.

E.1.1.1

Medical condition in easily understood language

Cronic pain and inflammation in patients with osteoarthritis with high blood pressure stabilized through the use of drugs.

Dolore continuo e infiammazione in pazienti affetti da osteoartrite con pressione elevata stabilizzata tramite l'utilizzo di farmaci.

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	LLT
E.1.2	Classification code	10023476
E.1.2	Term	Knee osteoarthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	LLT
E.1.2	Classification code	10029875
E.1.2	Term	OA hip
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objective of the study is to compare IBA vs. IBU in the change from baseline of daily spontaneous pain in patients suffering from OA and stabilized hypertension.

Confrontare IBA e IBU in termini di variazione rispetto al basale del dolore quotidiano spontaneo in pazienti affetti da osteoartrite e ipertensione stabilizzata.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1)Male or female patients aged ≥ 50 and ≤ 80 years; 2)Patients suffering from knee or hip OA symptoms exacerbation requiring intake of NSAIDs for at least 14 days; 3)Hypertensive stabilized patients (sitting office systolic blood pressure [SBP] <160 mmHg and sitting office diastolic blood pressure [DBP] <100 mmHg) since six months under pharmacological treatment in monotherapy or with no more than three antihypertensive drugs association among the following: AT1 antagonists or ACE inhibitors or Calcium-channel-blockers or diuretics (except the monotherapy with Calcium-channel-blockers or diuretics and their association); 4)Patients having moderate to severe pain (pain intensity ≥ 50 on a 0-100 VAS) at the randomization visit; 5)Signed informed consent; 6)Willing and able to comply with study procedures.

1)Pazienti di sesso maschile o femminile di età compresa tra ≥ 50 e ≤ 80 anni; 2)Pazienti colpiti da aggravamento dei sintomi di OA del ginocchio o dell’anca che richieda l’assunzione di FANS per almeno 14 giorni; 3)Pazienti con ipertensione stabilizzata (pressione arteriosa sistolica [PAS] clinica in posizione seduta < 160 mmHg e pressione arteriosa diastolica [PAD] clinica in posizione seduta < 100 mmHg), da sei mesi in trattamento farmacologico in monoterapia, o con non più di tre associazioni farmacologiche antipertensive tra le seguenti: farmaci AT1-antagonisti, ACE-inibitori, bloccanti dei canali del calcio o diuretici (fatta eccezione per la monoterapia a base di bloccanti dei canali del calcio o diuretici e relativa associazione); 4)Pazienti affetti da dolore da moderato a intenso (intensità del dolore ≥ 50 su una scala VAS 0-100) alla visita di randomizzazione; 5)Modulo di consenso informato firmato; 6)Pazienti in grado di, e disponibili ad attenersi alle procedure dello studio.

E.4

Principal exclusion criteria

1)Ascertained or presumptive hypersensitivity to the active compound and/or any of the formulation excipients; 2)History of anaphylaxis to drugs or allergic reactions; in particular, history of hypersensitivity reactions (e.g. bronchospasm, rhinitis, urticaria, angioedema) to non-steroidal anti-inflammatory drugs (NSAIDs); 3)Obstructive respiratory syndromes (asthma or COPD), nasal polyposis or any other chronic respiratory disease; 4)History of psychosis (e.g. schizophrenia or psychotic depression) or major depression (requiring treatment); 5)Severe neurological diseases, including dementia, anxiety, mental retardation, multiple sclerosis, Parkinson’s disease, uncontrolled epilepsy; 6)Transient ischemic attack or cerebrovascular accident within the last three months before the screening visit; 7)Myocardial infarction, unstable angina, arrhythmias, cardiac failure (NYHA class II-IV) or other chronic cardiac diseases; 8)Significant kidney (Creatinine Clearance <80 ml/minute) or liver disease (serum transaminases ≥ 3 x upper limit of normal); 9)History of gastrointestinal diseases, active peptic ulcer, gastrointestinal intolerance or gastrointestinal bleeding in the preceding 6 months before the screening visit.

1)Ipersensibilità accertata o presunta al composto attivo e/o a uno qualsiasi degli eccipienti della formulazione; 2)Anamnesi di anafilassi da farmaci o di reazioni allergiche; in particolare, anamnesi di reazioni di ipersensibilità (ad es. broncospasmo, rinite, orticaria, angioedema) ai farmaci antinfiammatori non steroidei (FANS); 3)Sindrome respiratoria ostruttiva (asma o BPCO), poliposi nasale o qualsiasi altra malattia respiratoria cronica; 4)Anamnesi di psicosi (ad es. schizofrenia o depressione psicotica) o depressione maggiore (che richieda il trattamento); 5)Gravi malattie neurologiche, comprese demenza, ansia, ritardo mentale, sclerosi multipla, malattia di Parkinson, epilessia non controllata; 6)Attacco ischemico transitorio o incidente cerebrovascolare nei tre mesi che precedono la visita di screening; 7)Infarto miocardico, angina instabile, aritmie, insufficienza cardiaca (di classe NYHA II-IV) o altre malattie cardiache croniche; 8)Grave malattia renale (clearance della creatinina < 80 ml/minuto) o epatica (transaminasi sieriche ≥ 3 volte il limite superiore dell’intervallo normale); 9)Anamnesi di malattie gastrointestinali, ulcera peptica in fase attiva, intolleranza gastrointestinale o emorragia gastrointestinale nei 6 mesi che precedono la visita di screening.

E.5 End points

E.5.1

Primary end point(s)

Change versus baseline of daily spontaneous pain, assessed by Visual-Analogical Scale (VAS), in both treatment arms, reported by Patients on daily diaries from Day 0 to Day 14.

Variazione rispetto al basale del dolore quotidiano spontaneo, valutata tramite scala analogica visiva (Visual-Analogical Scale, VAS) in entrambi i bracci di trattamento, riportata dai pazienti in diari quotidiani redatti dal Giorno 0 al Giorno 14.

E.5.1.1

Timepoint(s) of evaluation of this end point

from Day 0 to Day 14

Dal giorno 0 al giorno 14

E.5.2

Secondary end point(s)

•Change versus baseline (Day 0) in Office sitting SBP and DBP at Day 7 and 15 measured and recorded with Microlife Watch BP Office Target by the Investigator in the office visit; •Change versus baseline in Seven Day Average SBP and DBP measured by Home BP Monitoring (HBPM) calculated after 7 (interval day 1 to 7) and after 14 days (interval day 8 to 14) , with Microlife Watch BP 03 (Home mode); •Change versus baseline in 24-hour average SBP and DBP measured by ABPM (at Day -1 to 0 and at Day 14 to 15) by Microlife Watch BP 03 (Ambulatory mode); •Change versus baseline (Day -1 to 0) in day-time pulse pressure (SBP-DBP) measured at Day 14 to 15 with Microlife Watch BP 03 (Ambulatory mode); •Change versus baseline in ADMA test (Asimmetric DiMetilArginine) measured at Day 0 and Day 15, after 14 days treatment; •Change versus baseline (Day 0) in daily morning stiffness by VAS values, assessed daily at morning, at wake up time, by patient from Day 0 to Day 14 - after 14 days of treatment; •Change versus baseline of Fatigue based on FSS questionnaire at Day 0 and Day 15, - after 14 days of treatment, administered by Investigator.

•Variazione rispetto al basale (Giorno 0) di PAS e PAD clinica in posizione seduta nei Giorni 7 e 15, misurata e registrata tramite Microlife Watch BP Office Target da parte dello sperimentatore in occasione della visita presso la clinica; •Variazione rispetto al basale di PAS e PAD in una media di sette giorni misurata da Home BP Monitoring (HBPM), calcolata dopo 7 giorni (intervallo dal Giorno 1 al Giorno 7) e dopo 14 giorni (intervallo dal Giorno 8 al Giorno 14), con Microlife Watch BP 03 (modalità home); •Variazione rispetto al basale di PAS e PAD in una media di 24 ore misurata da ABPM (dal Giorno -1 al Giorno 0 e dal Giorno 14 al Giorno 15) tramite Microlife Watch BP 03 (modalità ambulatoriale); •Variazione rispetto al basale (dal Giorno -1 al Giorno 0) della pressione al polso (PAS - PAD) nell’arco di un giorno, misurata dal Giorno 14 al Giorno 15 con Microlife Watch BP 03 (modalità ambulatoriale); •Variazione rispetto al basale dell’esame ADMA (dimetilarginina asimmetrica) misurata il Giorno 0 e il Giorno 15, dopo 14 giorni di trattamento; •Variazione rispetto al basale (Giorno 0) della rigidità mattutina quotidiana sulla base dei valori VAS, valutata quotidianamente di mattina, al risveglio, da parte del/della paziente dal Giorno 0 al Giorno 14, dopo 14 giorni di trattamento; •Variazione rispetto al basale dell’affaticamento sulla base del questionario FSS, somministrato dallo sperimentatore il Giorno 0 e il Giorno 15, dopo 14 giorni di trattamento.

E.5.2.1

Timepoint(s) of evaluation of this end point

See what reported above.

Si veda quanto riportato sopra.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

130

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

160

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patient will be treated according to the normal clinical practice.

Il paziente verrà trattato secondo la normale prassi clinica.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-10-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-09-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2013-12-02

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