Clinical Trials Register

Summary
EudraCT Number:	2007-001689-34
Sponsor's Protocol Code Number:	M10-030
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:	2008-04-16
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

2007-001689-34

A.3

Full title of the trial

Paricalcitol capsules benefits in Renal failure Induced cardiac MOrbidity in subjects with Chronic Kidney Disease Stage 3B/4.

A.3.2

Name or abbreviated title of the trial where available

PRIMO I

A.4.1

Sponsor's protocol code number

M10-030

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

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	Yes
D.2.1.1.1	Trade name	Zemplar
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbott Laboratories Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Information not present in EudraCT
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.3.10	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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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

Stage 3B/4 chronic kidney disease (CKD) in subjects who have left ventricular hypertrophy (LVH).

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10064848
E.1.2	Term	Chronic kidney disease

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10049773
E.1.2	Term	Left ventricular hypertrophy

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 investigate the effects of paricalcitol capsules on progression or regression of Left Ventricular Hypertrophy (LVH) in subjects with Stage 3B/4 Chronic Kidney Disease (CKD) compared to placebo as assessed by comparing changes in LV Mass Index (LVMI) over 48 weeks measured by sequential cardiac magnetic resonance imaging (MRI)

E.2.2

Secondary objectives of the trial

1.Echocardiographic assessment of diastolic function, will be assessed by evaluating changes in diastolic mitral annular relaxation velocity (E') and changes in additional measures of diastolic function (IVRT, E/E', DT). 2. Changes in biological and inflammatory markers that have been linked to CVD in CKD subjects. Specifically, the markers to be evaluated will include plasma T3, IL-6, troponin-T, BNP and hsCRP.

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

FARMACOGENETICA: Titolo:Blood samples for DNA/RNA and Additional Biomarkers Analysis

E.3

Principal inclusion criteria

To be eligible for participation, subjects must meet all of 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 between 18 and 75 years. 3. For entry into the Treatment Period the subject must satisfy the following criteria based on the Screening laboratory values:· Estimated GFR between 15-50 ml/min/1.73m2 by simplified 4-variable Modification of Diet Renal Disease (MDRD) formula (this includes a 10% variation in the upper limit of eGFR that will be allowed for the enrollment of subjects, this is to account for variability in the creatinine assay).· Serum iPTH value between 50-300 pg/ml.· Corrected serum calcium level 8.0-10.0 mg/dL (2.0-2.5 mmol/L).· Phosphorous level £ 5.2 mg/dL (1.68 mmol/L).· Serum albumin ³ 3.0 g/dL (30 g/L).· Negative serum pregnancy test for female subjects of childbearing potential. 4. For entry into the Treatment Period the subject must satisfy the following criteria based on the Screening echocardiogram:· For females, LV ejection fraction ³ 50% and septal wall thickness between 12-15 mm; and,· For males, LV ejection fraction ³ 50% and septal wall thickness between 13-16 mm. 5. In the opinion of the investigator, the subject must be receiving optimal medical management of left ventricular hypertrophy and CKD including appropriate use of RAAS inhibitors (ACEi, ARB, or aldosterone inhibitor) if indicated by the subject's medical condition. 6. If the subject is receiving RAAS inhibitors the dose must have been stable for at least three months prior to the Screening Period. However, subject may have switched to different brands but at equivalent doses as determined by the study physician during the three months prior to the Screening Period. 7. Subject must have a technically adequate baseline cardiac MRI. 8. If female, subject is not breast feeding or is not pregnant (verified by negative pregnancy test prior to the Treatment Period); or is not of childbearing potential, defined as postmenopausal for at least one 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:· Double-barrier method (condoms, contraceptive sponge, diaphragm, vaginal ring with spermicidal jellies or creams, or intrauterine device [IUD])· Hormonal contraceptives (oral, parenteral, or transdermal) for at least three months prior to and during study drug administration· Maintains a monogamous relationship with a vasectomized partner· Total abstinence from sexual intercourse during the study (minimum one complete menstrual cycle prior to study start)

E.4

Principal exclusion criteria

1.Il soggetto in precedenza e' stato trattato con una terapia prescritta di Vitamina D nei tre mesi precedenti il Periodo di Screening.2.Il soggetto ha una storia di reazioni allergiche oppure sensibilita' significativa al paracalcitolo oppure a farmaci simili a quello in sperimentazione (cioe' Vitamina D oppure composti correlati alla vitamina D).3.Gravidanza (confermata dal test di gravidanza su siero eseguito allo screening) oppure donne che allattano.4.Si prevede che il soggetto inizi una terapia renale sostitutiva entro un anno (trapianto, emodialisi o emodialisi peritoneale, ndt).5.Si prevede che il soggetto inizi una terapia con /o aumenti il dosaggio di inibitori RAAS (ACE inibitori e/o inibitori dei recettori dell’angiotensina (ARB) e/o terapia con Antagonisti dell’Aldosterone) durante il corso della sperimentazione.6.Il soggetto e' affetto da coronaropatia (CAD) clinicamente significativa nei tre mesi precedenti il Periodo di Screening, come descritto nel protocollo dello studio.7.Il soggetto presenta una anomalia significativa delle valvole cardiache correlata all’ipertrofia ventricolare sinistra e/o disfunzione diastolica, come descritto nel protocollo dello studio.8.Il soggetto presenta una ipertrofia settale asimmetrica, definita quale rapporto spessore della parete settale/spessore della parete posteriore > 1,5 in base all’ecocardiogramma dello screening.9.Il soggetto ha presentato un evento cerebrovascolare grave (CVA) (per esempio di tipo emorragico) negli ultimi tre mesi precedenti lo screening.10.Remissione completa da neoplasie per meno di un anno oppure anamnesi di metastasi ossee.11.Il soggetto presenta co-morbilita' (per esempio, neoplasia in fase avanzata, epatopatia in fase avanzata) con aspettativa di vita inferiore ad un anno.12.Il soggetto ha assunto qualsiasi farmaco sperimentale nei 30 giorni precedenti la somministrazione del medicinale sperimentale oppure e' al momento arruolato in un’altra sperimentazione clinico.13.Il soggetto ha una anamnesi di calcoli renali.14.Il soggetto soffre di ipertensione scarsamente controllata (pressione sistolica > 180 mmHg e/o pressione diastolica > 110 mmHg alla Visita di Screening (confermata da misurazione ripetuta).15.Il soggetto soffre di ipertensione secondaria (cioe' secondaria a stenosi dell’arteria renale, ad aldosteronismo primario oppure feocromocitoma).16.Il soggetto assume calcitonina, bisfosfonati, cinacalcet, glucocorticoidi (con l’eccezione di glucocorticoidi topici), oppure altri farmaci in grado di influenzare il metabolismo del calcio oppure quello osseo, diversi dai leganti di fosfato contenenti calcio oppure, se di sesso femminile, in trattamento stabile (stessa dose e stesso prodotto per tre mesi) con estrogeni oppure progestinici.17.Il soggetto e' attualmente in terapia immunosoppressiva e/o assume dosi elevate (non una terapia di mantenimento) di steroidi (≥ 5 mg/die di prednisone oppure farmaco equivalente).18.Il soggetto ha manifestato insufficienza renale acuta nelle 12 settimane precedenti la Fase di Screening, definita quale aumento acuto dei livelli di creatinina sierica (di almeno 0,5 mg/dL oppure 44 mmol/L) a oltre 4 g/dL (350 mmol/L).19. Il soggetto e' noto essere HIV positivo.20.Uso di noti inibitori (ad es. ketoconazolo) oppure induttori (ad es. carbamazepina) del citocroma P450 3A (CYP3A) nelle due settimane precedenti la somministrazione del medicinale sperimentale.21.Il soggetto presenta controindicazioni alla risonanza magnetica (per esempio, portatore di pacemaker).22.Per qualsiasi ragione, lo Sperimentatore ritiene che il soggetto non sia un candidato idoneo a ricevere paracalcitolo capsule oppure ritiene che le procedure della sperimentazione rappresentino un rischio per il soggetto.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variable is change from baseline in LVMI over 48 weeks measured by cardiac MRI. Left Ventricular Mass will be normalized to the subject's height by the following equation to obtain LVMI: LVM (g) divided by height(m)2,7

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.8.3

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

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

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
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	15
F.4.2	For a multinational trial
F.4.2.1	In the EEA	110
F.4.2.2	In the whole clinical trial	220

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

2008-08-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-03-27

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

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IMP with orphan designation in the indication
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