Clinical Trials Register

Summary
EudraCT Number:	2006-001363-31
Sponsor's Protocol Code Number:	M05-741
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:	2007-07-23
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

2006-001363-31

A.3

Full title of the trial

VITAL Study - Selective VITamin D Receptor Activator (Paricalcitol) for Albuminuria Lowering Study: A Phase 2, Prospective, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Safety and Efficacy of Paricalcitol Capsules on Reducing Albuminuria in Type 2 Diabetic Nephropathy Subjects who are Currently Being Treated with Renin-angiotensin System Inhibitors

Studio multicentrico di fase II, prospettico, randomizzato, in doppio cieco verso placebo; per valutare la sicurezza e l`efficacia del Paracalcitolo capsule nel ridurre l`Albuminuria in soggetti nefropatici affetti da diabete di tipo 2 in trattamento con inibitori del sistema Renina-angiotensina

A.3.2

Name or abbreviated title of the trial where available

Vital

A.4.1

Sponsor's protocol code number

M05-741

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	Abbott GmbH & Co KG
B.1.3.4	Country	Germany
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
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	No
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	Paracalcitol
D.3.2	Product code	NA
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	131918611
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.3	Concentration number	2
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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile

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 diabetic nephropathy

Soggetti nefropatici affetti da 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	PT
E.1.2	Classification code	10038444
E.1.2	Term	Renal failure chronic
E.1.2	System Organ Class	10038359 - Renal and urinary 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 study objective is to evaluate the safety and efficacy of paricalcitol capsules on albuminuria reduction in Chronic Kidney Disease (CKD) subjects with Type 2 diabetic nephropathy receiving optimal ACEi and/or ARB therapy.

L'obiettivo principale consiste nel valutare la sicurezza e l'efficacia del Paracalcitolo capsule nel ridurre l'Albuminuria in soggetti nefropatici affetti da diabete di tipo 2

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A subject will be selected for study participation if he/she meets the following criteria:
1.Subject has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject has had the opportunity to ask questions. The informed consent must be signed before any study-specific procedures are performed.
2.Male or female subjects ³ 20 years old.
3.Subject has Type 2 Diabetes Mellitus and has been treated with at least one anti-hyperglycemic medication within the 12 months prior to the Screening Phase.
4.Subject has been receiving stable dose (i.e., same type and regimen) of ACEi and/or ARB for at least three months prior to the Screening Phase. However, subject may have switched to different brands but at equivalent doses during the three months prior to the Screening Phase.
5.Subject is not expected to begin dialysis for at least 6 months.
6.If female, subject is not breast feeding or is not pregnant (verified by negative urine pregnancy test prior to the Treatment Phase); or is not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy); or is of childbearing potential and practicing one of the following methods of birth control:·Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD)·Contraceptives (oral or parenteral) for three months prior to study drug administration·Maintains a monogamous relationship with a vasectomized partner·Total abstinence from sexual intercourse
7.For entry in the Treatment Phase the subject must satisfy the following criteria based on the Screening laboratory values:·Estimated GFR between 25-75 mL/min/1.73m2 by simplified MDRD formula·UACR between 200 and 1800 mg/g as determined by the mean of the three first morning void urine specimens obtained within one week·Corrected serum calcium level £ 9.5 mg/dL·iPTH value between 50-500 pg/mL·HbA1c £ 1 Serum albumin > 3.0 g/dL·Negative urine pregnancy test for female subjects

I pazienti potranno prendere parte allo studio se avranno soddisfatto i seguenti criteri:
1.Il soggetto ha volontariamente firmato e datato il modulo di consenso informato, approvato dal Comitato etico indipendente, dopo aver ricevuto adeguate informazioni sulla natura della sperimentazione e dopo aver avuto l'opportunita' di porre domande. Il consenso informato va firmato prima di intraprendere una qualsiasi procedura specifica della sperimentazione.
2.Individui di sesso maschile o femminile di eta' ≥20.
3.Il soggetto e' affetto da diabete mellito di tipo 2 ed e' stato trattato con almeno un farmaco anti-ipererglicemico nei 12 mesi precedenti la fase di screening.
4.Il soggetto sta assumendo una dose stabile (vale a dire medesimo tipo e regime) di ACEi e/o ARB almeno da tre mesi precedenti la fase di screening; tuttavia, durante i tre mesi precedenti tale fase, il paziente, pur mantenendo dosi equivalenti, puo' essere passato a marchi differenti dello stesso principio attivo.
5.Si prevede che il soggetto non debba essere sottoposto a dialisi per almeno 6 mesi.
6.Se di sesso femminile, la paziente non dovra' allattare al seno o essere in stato di gravidanza (verificato attraverso la negativita' a un test di gravidanza sulle urine effettuato prima della fase di trattamento); oppure non dovra' essere potenzialmente fertile, cioe' dovra' essere in post-menopausa da almeno 1 anno od essere stata sottoposta a intervento chirurgico per indurre sterilita' (legatura bilaterale delle tube, ooforectomia bilaterale o isterectomia); oppure se potenzialmente fertile, dovra' praticare uno dei seguenti metodi di controllo delle nascite:
·Preservativi, spugne, schiume, gelatine, diaframmi o dispositivi intrauterini (IUD)
·Contraccettivi (orali o parenterali) per i tre mesi precedenti la somministrazione del medicinale sperimentale
·Mantenimento di una relazione monogama con un partner sottoposto a vasectomia
·Astinenza totale dai rapporti sessuali
7.Per poter essere inserito nella fase di trattamento, il soggetto deve aver soddisfatto i seguenti criteri sulla base dei valori di laboratorio allo screening:
·GFR stimata tra 25 e 75 ml/min/1,73 m2 per mezzo della formula MDRD semplificata
·UACR tra 200 e 1800 mg/g, come stabilito dalla media di tre campioni di urine del mattino ottenuti nell'arco di una settimana
·Livello corretto del calcio sierico ≤9,5 mg/dl
·Valore di iPTH compreso fra 50 e 500 pg/ml· HbA1c ≤12%
·Albumina sierica > 3,0 g/dl
·Negativita' al test di gravidanza delle urine

E.4

Principal exclusion criteria

Subjects meeting the following criteria will be excluded from the study:
1.Subject has been on prescription-based vitamin D therapy within the 6 months prior to the Screening Phase. 2.Subject has a history of an allergic reaction or significant sensitivity to paricalcitol or to drugs similar to the study drug.
3.Subject has primary glomerulonephritis or secondary nephritis in addition to diabetic nephropathy.
4.Subject has had acute renal failure within 12 weeks of the Screening Phase defined by an acute rise in serum creatinine (of at least 0.5 mg/dL or 44 mmol/L) to more than 4 mg/dL (350 mmol/L).
5.Subject has chronic gastrointestinal disease, which in the Investigator's opinion may cause significant GI malabsorption.
6.Subject has secondary hypertension (i.e., renal artery stenosis, primary aldosteronism or pheochromocytoma). 7.Subject has poorly controlled hypertension (systolic blood pressure ³ 160 mmHg and or diastolic blood pressure ³ 100 mmHg).
8.Subject has a history of kidney stones.
9.Subject has a history of drug or alcohol abuse within 6 months prior to the Screening Phase.
10.Subject has evidence of poor compliance with diet or medication that may interfere, in the Investigator's opinion, with adherence to the protocol.
11.Subject has received any investigational drug within 30 days prior to study drug administration. 12.Subject is taking calcitonin, bisphosphonates, cinacalcet, glucocorticoids (except topical glucocorticoids), or other drugs that may affect calcium or bone metabolism, other than calcium containing phosphate binder or female subjects on stable (same dose and product for 3 months) estrogen and/or progestin therapy.
13.For any reason, subject is considered by the Investigator to be an unsuitable candidate to receive paricalcitol capsules or is put at risk by study procedures.
14.Subject is known to be HIV positive.

1.Al soggetto e' stata prescritta una terapia a base di vitamina D durante i 6 mesi precedenti la fase di screening.
2.Il soggetto presenta una storia di reazioni allergiche o di sensibilita' significativa nei confronti del Paracalcitolo o di altri farmaci analoghi al medicinale sperimentale.
3.Oltre alla nefropatia diabetica, il soggetto e' affetto da glomerulonefrite primaria o da nefrite secondaria.
4.Il soggetto e' stato colpito da insufficienza renale acuta nelle 12 settimane precedenti la fase di screening, definita per mezzo di un innalzamento acuto della creatinina sierica (pari almeno a 0,5 mg/dl, o 44 mmoli/l) sino a piu' di 4 mg/dl (350 mmoli/l).
5.Il soggetto e' affetto da malattia gastrointestinale cronica che, a parere dello sperimentatore, puo' determinare un malassorbimento significativo a livello GI.
6.Il soggetto evidenzia ipertensione secondaria (vale a dire stenosi arteriosa renale, aldosteronismo primario o feocromocitoma
7.Il soggetto ha un'ipertensione scarsamente controllata (pressione sanguigna sistolica ≥160 mm Hg e/o pressione sanguigna diastolica ≥100 mm Hg).).
8.Il soggetto ha una storia di calcoli renali.
9.Il soggetto ha una storia di abuso di droghe o di alcool nei 6 mesi precedenti la fase di screening
10.Il soggetto presenta evidenze di scarsa compliance con la dieta o con medicinali che, a parere dello sperimentatore, possono interferire con l'adesione al protocollo.
11.Al soggetto e' stato somministrato un qualsiasi medicinale sperimentale entro i 30 giorni precedenti la somministrazione del medicinale sperimentale.
12.Il soggetto sta assumendo calcitonina, bisfosfonati, cinacalcet, glucocorticoidi (eccezion fatta per i glucocorticoidi ad uso topico), oppure altri farmaci che possono incidere sul metabolismo del calcio o delle ossa diversi da un chelante del fosforo contenente calcio, oppure si tratta di donne in terapia stabile (stessa dose e prodotto per 3 mesi) con estrogeni e/o progestinici.
13.Lo sperimentatore ritiene che, per un qualunque motivo, il soggetto rappresenti un candidato non adatto all'assunzione di capsule di Paracalcitolo, oppure le procedure dello studio lo mettono in pericolo.
14.E' nota una positivita' del soggetto all'HIV

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint will be the percent change from baseline to the last on-treatment UACR measurement using UACR levels determined from the first morning void urine collections

consiste nel cambiamento in percentuale rispetto al basale dell'ultimo UACR in fase di trattamento utilizzando livelli di UACR determinati attraverso la raccolta delle prime urine della mattina dopo le 5.00

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)

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

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

Yes

E.8.2.3.1

Comparator description

- Stesso farmaco ad altro dosaggio

- same IMP used at different dosage

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

Information not present in EudraCT

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

Last patient, last visit

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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.1.3

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

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

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

donne in eta' fertile che assumono adeguati metodi contraccettivi

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

162

F.4.2.2

In the whole clinical trial

258

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)

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

2007-08-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-06-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-05-26

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