Clinical Trials Register

Summary
EudraCT Number:	2014-004340-35
Sponsor's Protocol Code Number:	CAMG-14-I
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-12-16
Trial 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

2014-004340-35

A.3

Full title of the trial

Randomized controlled trial of two different combinations of Calcium-containing Phosphate binders (Ca-PiB) plus non-Calcium-non-Aluminum containing Phosphate binders (no-Ca-Al-PiB): a pharma-economic approach.

Studio controllato randomizzato di due diverse combinazioni di chelanti del Fosfato contenenti Calcio (Ca-PiB) in associazione a chelanti del Fosfato non contenenti Calcio né Alluminio (no-Ca-Al-PiB): un approccio farmaco-economico.

A.3.1

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

Pharma-economic comparison regarding the use of medicines to control the levels of Phosphate in the blood in patients suffering from Chronic Kidney Disease associated with mineral and bone disorder.

Comparazione farmaco-economica nell’utilizzo di farmaci per il controllo dei livelli di Fosfato nel sangue in pazienti che soffrono di Malattia Renale Cronica associata a disordine minerale e osseo.

A.3.2

Name or abbreviated title of the trial where available

OSvaren vs CAlcium carbonate Research - OSCAR

A.4.1

Sponsor's protocol code number

CAMG-14-I

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	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
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	Fresenius Medical Care Italia SpA
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Fondazione Onlus "D'Amico" per la ricerca sulle malattie renali
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	Sintesi Research Srl
B.5.2	Functional name of contact point	Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	Via Giuseppe Ripamonti 89
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20141
B.5.3.4	Country	Italy
B.5.4	Telephone number	003902873512
B.5.5	Fax number	00390297374301
B.5.6	E-mail	info@sintesiresearch.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	Osvaren 435 mg/235 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Fresenius Medical Care Nephrologica Deutschland GmbH
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	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	Calcium acetate
D.3.9.1	CAS number	62-54-4
D.3.9.3	Other descriptive name	CALCIUM ACETATE ANHYDROUS
D.3.9.4	EV Substance Code	SUB89444
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	435
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Magnesium carbonate
D.3.9.1	CAS number	39409-82-0
D.3.9.3	Other descriptive name	MAGNESIUM CARBONATE HYDROXIDE
D.3.9.4	EV Substance Code	SUB14419MIG
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	235
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	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.2.1.2	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.3.1	Product name	Calcium carbonate
D.3.4	Pharmaceutical form	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	Calcium carbonate
D.3.9.1	CAS number	471-34-1
D.3.9.3	Other descriptive name	CALCIUM CARBONATE
D.3.9.4	EV Substance Code	SUB13166MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	500 to 2500
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

Hyperphosphatemia associated with Chronic Kidney Disease (CKD) in patients undergoing hemodialysis.

Iperfosfatemia associata a Malattia Renale Cronica (CKD) in pazienti sottoposti ad emodialisi.

E.1.1.1

Medical condition in easily understood language

High levels of Phosphate in the blood of dialytic patients suffering from Chronic Kidney Disease.

Livelli elevati di Fosfato nel sangue di pazienti dializzati che soffrono di patologia renale cronica.

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10020712
E.1.2	Term	Hyperphosphatemia
E.1.2	System Organ Class	100000004861

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the efficacy of Osvaren in maintaining serum phosphate levels <5.5 mg / dl, reaching an optimal level of 4.5 mg / dl, in comparison with Calcium carbonate, with a potential sparing effect on the use of Calcium-free Phosphate binders through their delayed introduction in the therapy.

Valutare l'efficacia di Osvaren nel mantenere i livelli di fosfato sierico <5,5 mg / dl, raggiungendo un livello ottimale di 4,5 mg / dl, in confronto con il Carbonato di calcio, con un potenziale effetto di risparmio nell'utilizzo di chelanti del Fosfato non contenenti Calcio, attraverso una loro introduzione ritardata nella terapia.

E.2.2

Secondary objectives of the trial

To evaluate the progression of vascular calcifications and the occurrence of vertebral fractures in patients treated.

Valutare la progressione di calcificazioni vascolari e la comparsa di fratture vertebrali nei pazienti trattati.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Male and female patients with Chronic Kidney Disease (CKD5D) in HD treatment with scheduled three sessions/week since at least three months / Age >18 years old / Serum Phosphate >5.5 mg/dl without P binders prescription OR serum Phosphate >5,5 mg/dl at the end of first wash-out week, if P binders were prescribed OR serum Phosphate >5,5 mg/dl at the end of second wash-out week, in case serum P values are not >5,5 mg/dl at the end of first wash-out week, if P binders were prescribed OR patients previously selected for the enrollment if Serum Phosphate >5,5 mg/dl after the second wash-out week, at any time during the six months after the first patient being enrolled at the center / If the patient is a female of childbearing potential, she is using an acceptable method of contraception during the study period.

Pazienti ambosessi con malattia renale cronica in stadio 5D (CKD5D) in trattamento emodialitico da almeno tre mesi, con regime di tre sedute a settimana / Età >18 anni / Fosfato sierico >5.5 mg/dl senza prescrizione di chelanti del Fosfato, OPPURE fosfato sierico >5,5 mg/dl alla fine della prima settimana di wash-out, se vi era prescrizione di chelanti del Fosfato, OPPURE fosfato sierico >5,5 mg/dl alla fine della seconda settimana di wash-out nel caso in cui i valori di P sierico non fossero >5,5 mg/dl alla fine della prima settimana di wash-out, se vi era prescrizione di chelanti del Fosfato, OPPURE pazienti preselezionati per l’arruolamento in caso di Fosfato sierico >5,5 mg/dl dopo la seconda settimana di wash-out, in qualunque momento durante i sei mesi successivi all’arruolamento del primo paziente presso il centro sperimentale / in caso di partecipanti donne in età fertile, utilizzano un metodo accettabile di contraccezione per la durata del periodo di studio.

E.4

Principal exclusion criteria

Severe hyperphosphatemia despite the use of P binders (serum P >8 mg/dl) / Severe hyperparathyroidism (defined as PTH levels >9 times superior to normal level, by definition of KDIGO guidelines) according to Patient’s Medical History / PTH levels excessively suppressed (< 100 pg/mL) according to Patient’s Medical History / Patients treated with Aluminum-containing P binders / Persistent or recurrent hypercalcemia with total Calcium levels, corrected for albumin, >10 mg/dl, according to Patient’s Medical History / Poor compliance, upon Investigator’s opinion / Inadequate dialysis at screening (Kt/V< 1.2 or URR< 65%) / Oral anticoagulants intake / Malignancy with survival perspective <1 year / Active autoimmune diseases treated with steroids / Pregnancy at time of enrolment / Refusal of consent to participate / Contraindications or hypersensitivity to the Investigational Product (elevated sMg levels of more than 2 mmol/l (4,85 mg/dl), and/or symptoms of hypermagnesaemia / AV-block III° / Myasthenia gravis).

Iperfosfatemia severa nonostante l’uso di chelanti del Fosfato (P sierico >8 mg/dl) / Iperparatiroidismo severo (definito come livelli di PTH >9 volte il livello normale, secondo definizione delle linee guida KDIGO) in accordo con la storia clinica del paziente / Livelli di PTH eccessivamente soppressi (<100 pg/mL) in accordo con la storia clinica del paziente / Pazienti trattati con chelanti del Fosfato a base di Alluminio / Ipercalcemia ricorrente o persistente con livelli di Calcio totale, corretti per l’albumina, >10 mg/dl, in accordo con la storia clinica del paziente / Scarsa compliance del paziente, in base all’opinione dello sperimentatore / Dialisi inadeguata al momento dello screening (Kt/V< 1.2 o URR< 65%) / Assunzione di anticoagulanti orali / Neoplasia maligna con prognosi <1 anno / Patologia autoimmune attiva in trattamento con steroidi / Stato di gravidanza al momento dell’arruolamento / Rifiuto del consenso alla partecipazione allo studio / Controindicazioni od ipersensibilità al prodotto in sperimentazione (elevati livelli di Mg sierico > 2 mmol/l (4.85 mg/dl) e/o sintomi di ipermagnesiemia / blocco AV di III grado / Miastenia grave).

E.5 End points

E.5.1

Primary end point(s)

Time lag (days) from the start of the study (week 0) to the day of possible introduction of a Calcium/Aluminum-free Phosphate binder (Sevelamer / Lanthanum carbonate). This will be translated into a pharma-economic difference in the cost of treatment, taking into account the drug and dose used in the individual patient.

Tempo (giorni) tra l’inizio dello studio (settimana 0) ed il momento in cui il paziente inizierà ad assumere un chelante non contenente Calcio od Alluminio (Sevelamer / Lantanio Carbonato), tradotto in un’analisi farmaco-economica che terrà conto del farmaco e del suo dosaggio, per tutti i tipi di chelante usati nel singolo paziente.

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluations during the whole study period.

Valutazioni durante l'intero periodo di studio.

E.5.2

Secondary end point(s)

1) Progression of abdominal aorta vascular calcifications, through Kauppila scoring system / 2) Characterization of vertebral fractures, through quantitative vertebral morphometry / 3) Measurement of optimal serum Magnesium concentration (safety outcome).

1) Progressione di calcificazioni vascolari a livello dell’aorta addominale, in base ad Indice di Kauppila / 2) Caratterizzazione di fratture vertebrali attraverso analisi morfometrica vertebrale quantitativa / 3) Misurazione della concentrazione ottimale sierica di Magnesio (outcome di sicurezza).

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Baseline vs Half vs End of treatment period / 2) Baseline vs Half vs End of treatment period / 3) Evaluations during the whole study period.

1) Valutazioni all’inizio, a metà ed alla fine del periodo di trattamento / 2)Valutazioni all’inizio, a metà ed alla fine del periodo di trattamento / 3) Valutazioni durante l'intero periodo di studio.

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

Yes

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

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 (Last Visit Last Subject).

LVLS (Ultima Visita dell'Ultimo Paziente).

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.1.1.1

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:

160

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

230

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)

After the end of study period patients will continue their routine hemodialysis treatment according to standard clinical practice. The Investigational Product treatment received during the study period may continue to be administered to patients according to the judgement of their physicians, as the study drugs (Osvaren / Ca carbonate) are commonly available on the market.

Dopo la fine del periodo di studio i pazienti proseguiranno il loro routinario trattamento emodialitico, secondo pratica clinica standard. Il trattamento farmacologico in studio verrà proseguito secondo giudizio del medico curante, essendo i farmaci in studio (Osvaren / Ca Carbonato) disponibili sul mercato.

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

2015-03-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-01-13

P. End of Trial
P.	End of Trial Status	Ongoing

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