Clinical Trials Register

Summary
EudraCT Number:	2011-001713-14
Sponsor's Protocol Code Number:	PROCEED
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:	2012-03-20
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

2011-001713-14

A.3

Full title of the trial

A PROSPECTIVE, RANDOMIZED, CROSS-OVER, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE ANTIPROTEINURIC EFFECT OF SELECTIVE VITAMIN D RECEPTOR ACTIVATION BY PARICALCITOL IN TYPE 2 DIABETES PATIENTS ON LOW OR HIGH SODIUM DIET AND STABLE RAS INHIBITOR THERAPY

Studio prospettico, randomizzato, in cross-over, in doppio cieco, controllato con placebo per valutare l'effetto antiproteinurico dell'attivazione selettiva di un recettore della vitamina D del paracalcitolo in pazienti affetti da diabete di tipo 2 in dieta ad alto o basso contenuto di sodio e in terapia stabile con un inibitore del sistema renina angiotensina

A.3.1

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

A prospective, randomized, cross-over,double blind study to evaluate if paricalcitol antiproteinuric effect in type 2 patients and stable RAS inhibitory therapy depens on dietary sodium intake

Studio prospettico, randomizzato, in cross-over e in doppio cieco per valutare se l’efficacia del paracalcitolo nel ridurre la proteinuria in pazienti con nefropatia diabetica e in terapia stabile con un antagonista del recettore dell’angiotensina (ARB) e' influenzata dal contenuto di sodio della dieta

A.3.2

Name or abbreviated title of the trial where available

Salt intake and antiproteinuric effect of Paricalcitol in type 2 diabetes

Apporto di sodio ed effetto antiproteinurico del p

A.4.1

Sponsor's protocol code number

PROCEED

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	IST. DI RICERCHE FARMACOLOG. M. NEGRI
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	Istituto di Ricerche Farmacologiche Mario negri
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Abbott
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	Istituto di Ricerche Farmacologiche Mario Negri
B.5.2	Functional name of contact point	Lab. att. regolatorie studi clinici
B.5.3	Address:
B.5.3.1	Street Address	via G. Camozzi, 3
B.5.3.2	Town/ city	Ranica
B.5.3.3	Post code	24020
B.5.3.4	Country	Italy
B.5.4	Telephone number	035 453531
B.5.5	Fax number	035 4535371
B.5.6	E-mail	paola.boccardo@marionegri.it

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	ZEMPLAR*28CPS 1MCG
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	Capsule, soft
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	PARICALCITOL
D.3.9.1	CAS number	131918-61-1
D.3.9.4	EV Substance Code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	Capsule, soft
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

Type 2 diabetes

Diabete di tipo 2

E.1.1.1

Medical condition in easily understood language

Type 2 diabetes

Diabete di tipo 2

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

MedDRA Classification

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	10045242
E.1.2	Term	Type II diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition 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

To compare changes in urinary albumin excretion rate achieved by one month paricalcitol therapy vs placebo in patients on stable RAS inhibitor therapy on high (>200 mEq/day) or low (<100 mEq/day) sodium intake.

Paragonare le variazioni dell’escrezione urinaria di albumina dopo un mese di terapia con paracalcitolo o con placebo in pazienti in terapia stabile con farmaci inibitori del sistema renina angiotensina con elevato, (>200 mEq/giorno), o basso, (<100 mEq/giorno), intake di sodio.

E.2.2

Secondary objectives of the trial

To compare the effects of paricalcitol therapy in subjects with high or low sodium intake on the following parameters: - Ambulatory and 24-hour blood pressure (BP) profile; - Pulse wave velocity and other markers of vascular stiffness; - Glomerular Filtration Rate (GFR) as measured by the iohexol plasma clearance technique and as estimated by 14 different prediction formula; - Albumin and IgG fractional clearance, urinary albumin/creatinine ratio; - Serum calcium, phosphorus, parathyroide hormone (PTH), bone specific alkalyne phosphatase, serum 25 hydroxyvitamin D3 levels, 24 hour urinary calcium and 25 hydroxyvitamin D3 excretion; - Serum total, LDL, HDL cholesterol, triglycerides, apolipoprotein A and B levels; - Serum C Reactive Protei

Paragonare gli effetti della terapia con paracalcitolo in soggetti con elevato o basso intake di sodio sui seguenti parametri: - Pressione in ambulatorio e profilo nelle 24 ore; - Frequenza del polso e altri marcatori di rigidità vascolare; - Velocità di filtrazione glomerulare (misurata come clearance plasmatica dello ioexolo) e stimata by 14 different prediction formula; - Clearance frazionata dell’albumina e delle IgG, rapporto albumina/creatinina urinarie; - Calcio sierico, fosforo, ormone paratiroideo (PTH), Serum calcium, phosphorus, parathyroide hormone (PTH), isoenzima osseo della fosfatasi alcalina, livelli serum 25 OH vitamina D, calcio urinario delle 24 ore e escrezione di 25 OH vitamina D; - Colesterolo totale, LDL, HDL, trigliceridi, livelli di apolipoproteina A e B; - Proteina C reattiva.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male and female patients; - Age > 18 years; - Type 2 diabetes patients on low or high sodium diet and stable RAS inhibitor therapy with the following conditions: - Urinary albumin excretion (UAE) rate >300mg/24 hours (200 mcg/min); - Serum creatinine <2 mg/dL, PTH ≥ 20 mEq/L and <110 mEq/L; - Calcium and phosphorus levels < 9.5 mg/dl and < 5mg/dl, respectively; - Controlled BP (systolic/diastolic <140/90 mmHg) while on stable RAS inhibitor therapy with losartan 100 mg/day since at least one month; - Written informed consent.

- Uomini e donne di età superiore ai 18 anni; - Pazienti diabetici di tipo 2, con dieta ad elevato o basso contenuto di sodio e terapia stabile con farmaci inibitori del sistema renina-angiotensina; - Escrezione urinaria di albumina >300mg/24 ore (200 mcg/min); - Creatinina sierica <2 mg/dL, PTH ≥ 20 mEq/L and <110 mEq/L; - Calcio e fosforo < 9.5 mg/dl and < 5mg/dl, rispettivamente; - Pressione arteriosa controllata (sistolica/diastolica <140/90 mmHg) con terapia stabile con losartan 100 mg/giorno da almeno un mese; - Capacità di comprendere gli obiettivi dello studio; - Consenso informato scritto (firmato e datato dal paziente).

E.4

Principal exclusion criteria

- Previous Vitamin D or Vitamin D analogs therapy (within 3 months prior to the study entry); - History of kidney stones; - Poorly controlled Diabetes: Hb1Ac > 12%; - Therapy with calcitonin, bisphosphonates, cinacalcet, glucocorticoids, immunosuppressive drugs or other drug that may affect calcium or bone metabolism; - Cancer and any severe systemic disease or clinical condition that may jeopardize data interpretation or completion of the study; - Any clinically relevant conditions that might affect study participation and/or study results; - Any contraindication to be exposed to Paricalcitol; - Pregnancy or lactating; - Women of childbearing potential without following a scientifically accepted form of contraception; - Legal incapacity.

- Terapia con vitamina D o analoghi nei tre mesi precedenti lo studio; - Anamnesi di calcoli renali; - Diabete scarsamente controllato: Hb1Ac > 12%; - Terapia con calcitonina, bifosfonati, cinacalcet, glucocorticoidi, farmaci immunosoppressivi o altri farmaci che possono agire sul calcio o sul metabolismo osseo; - Presenza di tumori o altre patologie sistemiche gravi o condizioni cliniche che possano mettere a rischio l’interpretazione dei dati o il completamento dello studio; - Qualsiasi condizione clinica rilevante che possa compromettere la partecipazione allo studio e/o i risultati dello studio stesso; - Qualsiasi controindicazione all’assunzione di Paracalcitolo; - Gravidanza o allattamento; - Donne potenzialmente fertili che non utilizzino metodi contraccettivi scientificamente approvati; - Incapacità legale.

E.5 End points

E.5.1

Primary end point(s)

Changes in urinary albumin excretion rate between patients on paricalcitol and placebo on high (>200 mEq/day) or low (<100 mEq/day) sodium intake.

Variazioni dell’escrezione urinaria di albumina dopo un mese di terapia con paracalcitolo o con placebo in pazienti con elevato, (>200 mEq/giorno), o basso, (<100 mEq/giorno), intake di sodio.

E.5.1.1

Timepoint(s) of evaluation of this end point

At basal and every month after randomization.

Al basale e, dopo la randomizzazione, ogni mese.

E.5.2

Secondary end point(s)

- Ambulatory and 24-hour blood pressure (BP) profile; - Pulse wave velocity and other markers of vascular stiffness; - Glomerular Filtration Rate (GFR) as measured by the iohexol plasma clearance technique and as estimated by 14 different prediction formula; - Albumin and IgG fractional clearance, urinary albumin/creatinine ratio; - Serum calcium, phosphorus, parathyroide hormone (PTH), bone specific alkalyne phosphatase, serum 25 hydroxyvitamin D3 levels, 24 hour urinary calcium and 25 hydroxyvitamin D3 excretion; - Serum total, LDL, HDL cholesterol, triglycerides, apolipoprotein A and B levels; - Serum C Reactive Protein

Confronto dei seguenti parametri tra i soggetti con elevato o basso intake di sodio (in subjects with high or low sodium intake treated with paricalcitol vs placebo): - Pressione in ambulatorio e profilo nelle 24 ore; - Frequenza del polso e altri marcatori di rigidità vascolare; - Velocità di filtrazione glomerulare (misurata come clearance plasmatica dello ioexolo) e stimata by 14 different prediction formula; - Clearance frazionata dell’albumina e delle IgG, rapporto albumina/creatinina urinarie; - Calcio sierico, fosforo, ormone paratiroideo (PTH), Serum calcium, phosphorus, parathyroide hormone (PTH), isoenzima osseo della fosfatasi alcalina, livelli serum 25 OH vitamina D, calcio urinario delle 24 ore e escrezione di 25 OH vitamina D; - Colesterolo totale, LDL, HDL, trigliceridi, livelli di apolipoproteina A e B; - Proteina C reattiva.

E.5.2.1

Timepoint(s) of evaluation of this end point

At basal and every month after randomization.

Al basale e, dopo la randomizzazione, ogni mese.

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

Yes

E.6.4

Safety

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.6

Cross over

Yes

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

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:

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

112

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)

At the end of the study, on the basis of results, the physician will consider the possibility to prescribe to the patient a therapy with vitamin D or its analogues.

Al termine dello studio, sulla base dei risultati ottenuti, il medico valuterà la possibilità di prescrivere al paziente una terapia con la vitamina D o suoi analoghi.

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

2011-05-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-04-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-05-29

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