Clinical Trials Register

Summary
EudraCT Number:	2010-020917-97
Sponsor's Protocol Code Number:	ARC209
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-12-28
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

2010-020917-97

A.3

Full title of the trial

SPHERIC-1 (Sildenafil in the Chronic Obstructive Pulmonary Disease associated to Chronic Pulmonary Hypertension. Sixteen weeks long, multicentre, randomized, double blind study, in comparison with placebo, for the evaluation of sildenafil in the treatment of patients affected by pulmonary hypertension associated to COPD.

SPHERIC-1 (Sildenafil nelle Pneumopatie ostruttive cHE pResentano Ipertensione Polmonare Cronica) - Studio multicentrico, randomizzato, a doppio cieco, verso placebo, della durata di 16 settimane che valuta l’effetto del sildenafil nel trattamento di pazienti con ipertensione polmonare associata a BPCO

A.3.2

Name or abbreviated title of the trial where available

SPHERIC-1

A.4.1

Sponsor's protocol code number

ARC209

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	ASSOCIAZIONE ITALIANA PNEUMOLOGI OSPEDALIERI
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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.2.1.1.2	Name of the Marketing Authorisation holder	PFIZER 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	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/178
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
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.3.8	INN - Proposed INN	Sildenafil
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	20
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderate to severe pulmonary hypertension associated to moderate to mild COPD.

Ipertensione polmonare moderata-severa associata a BPCO lieve-moderata.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10064911
E.1.2	Term	Pulmonary arterial hypertension
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10010952
E.1.2	Term	COPD
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Demonstrate the superiority of sildenafil (20 mg tid) compared to placebo in the reduction of the pulmonary vascular resistance after 16 weeks of treatment.

Dimostrare la superiorita' del sildenafil (20 mg tid) rispetto al placebo nella riduzione delle resistenze vascolari polmonari di pazienti con ipertensione polmonare associata a BPCO dopo 16 settimane di trattamento.

E.2.2

Secondary objectives of the trial

Evaluation of sildenafil safety profile in comparison to placebo. Evaluation of sildenafil effect on the exercise capacity, symptoms and quality of life in comparison to placebo.

Valutare il profilo di sicurezza del sildenafil paragonato al placebo. Valutare l’effetto del sildenafil sulla tolleranza allo sforzo, sintomi e qualita' di vita rispetto al placebo.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

LIFE QUALITY:
Vers:1.0
Date:2010/05/21
Title:
Objectives:

QUALITA DELLA VITA:
Vers:1.0
Data:2010/05/21
Titolo:Questionario di Qualita' della Vita SF-36 nell'ambito del protocollo: SPHERIC-1 (Sildenafil nelle Pneumopatie ostruttive cHE pResentano Ipertensione Polmonare Cronica) - Studio multicentrico, randomizzato, a doppio cieco, verso placebo, della durata di 16 settimane che valuta l’effetto del sildenafil nel trattamento di pazienti con ipertensione polmonare associata a BPCO
Obiettivi:Valutazione della qualita' della vita correlata alla salute.

E.3

Principal inclusion criteria

Patient affected by stable COPD under optimal treatment, chronic oxygen therapy in patients with hypoxia, with PaO2 at rest ≥ 60 mmHg and PaCO2≤ 55 mmHg, aged between 18 and 80 years old: • Group 1: BPCO GOLD I‐III (post bronchodilator FEV1 ≥ 30%, FEV1/FVC ≤ 0,7 , TLC ≥ 70%) + PAPm ≥ 30 mmHg and PCP <15 mmHg • Group 2: BPCO GOLD IV (post bronchodilator FEV1 <30%, FEV1/FVC ≤ 0,7 , TLC ≥ 70%) + PAPm ≥ 35 mmHg and PCP <15 mmHg.

Pazienti con BPCO stabile in ottimale trattamento farmacologico e in O2 terapia a lungo termine se ipossici, con PaO2 a riposo in aria o corretta ≥ 60 mmHg e PaCO2≤ 55 mmHg, di eta' compresa fra i 18 e gli 80 anni: • Gruppo 1: BPCO GOLD I‐III (post broncodilatatore FEV1 ≥ 30%, FEV1/FVC ≤ 0,7 , TLC ≥ 70%) + PAPm ≥ 30 mmHg e PCP <15 mmHg • Gruppo 2: BPCO GOLD IV (post broncodilatatore FEV1 <30%, FEV1/FVC ≤ 0,7 , TLC ≥ 70%) + PAPm ≥ 35 mmHg e PCP <15 mmHg.

E.4

Principal exclusion criteria

• Different types of pulmonary hypertension (chronic, thromboembolic pulmonary hypertension, pulmonary arterial hypertension etc.) • Significant left cardiac disease (LVEF <45%, cardiomyopathy, valvulopathy, unstable coronaropathy) • Treatment with nitrates in the last 10 days, or in need of other nitrate therapy for different diseases • Treatment with other specific drugs for arterial pulmonary hypertension (less than 4 weeks) • Significant systemic disease other than COPD • Recent reacutization of chronic bronchitis (< 4 weeks) • Pregnancy or breastfeeding, or women without an adequate contraceptive method for the whole study duration • History of anaphylaxys or allergic reactions to 5-phosphodiesterase inhibitors • Cancers within the last 5 years with the exception of localized cancers of the skin or of the cervix • Hepatic insufficiency or chronic renal failure or hemoglobinemia < 10 g/dL during the screening phase • Contraindications to subministration as per SPC • Mental disorder, alcohol abuse, chronic alcoholism, drug abuse • Subjects unable to sign the informed consent form • Subjects unable to walk

• Altre forme di ipertensione polmonare (ipertensione polmonare cronica trombo embolica, ipertensione arteriosa polmonare, ecc.) • Significativa malattia cardiaca sinistra (LVEF <45%, cardiomiopatie, valvulopatie, coronaropatia instabile) • Trattamento con i nitrati negli ultimi 10 giorni, o necessita' di una terapia di nitrato per altre malattie • Trattamento con altri farmaci specifici per l'ipertensione arteriosa polmonare (da meno di 4 settimane) • Significativa malattia sistemica diversa da BPCO • Recente riacutizzazione bronchitica (< 4 settimane) • Donne in gravidanza o in allattamento, oppure donne in eta' fertile che non facciano uso di adeguati metodi anticoncezionali per tutta la durata dello studio • Storia di anafilassi o reazioni allergiche ai derivati degli inibitori della fosfodiesterasi‐5 • Presenza di malattia tumorale entro 5 anni ad eccezione di carcinomi localizzati della cute o della cervice • Insufficienza epatica o insufficienza renale cronica o emoglobinemia < 10 g/dL allo screening • Controindicazioni alla somministrazione del farmaco secondo quanto riportato in scheda tecnica • Instabilita' mentale, abuso di alcool o alcolismo cronico, uso di droghe • Soggetti non in grado di firmare un consenso informato • Soggetti non in grado di deambulare

E.5 End points

E.5.1

Primary end point(s)

Significant reduction of basal pulmonary vascular resistance at rest, after 16 weeks of treatment with sildenafil compared with placebo.

Riduzione significativa delle resistenze vascolari polmonari (RVP) basali a riposo dopo 16 settimane di trattamento con sildenafil rispetto al trattamento con placebo.

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

Yes

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

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

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	No
F.1.1	Number of subjects for this age range:	0
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	42

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

2010-06-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-06-23

P. End of Trial
P.	End of Trial Status	Completed

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