Clinical Trials Register

Summary
EudraCT Number:	2014-001501-41
Sponsor's Protocol Code Number:	156-13-208
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-01-15
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

France - ANSM

A.2

EudraCT number

2014-001501-41

A.3

Full title of the trial

A Multinational Trial to Collect Blood Samples to Explore Potential Genetic/Biomarkers Related to Increased Risk of Liver Injury in Adult Subjects from Prior Tolvaptan Clinical Trials for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Étude multinationale dans le but de recueillir des échantillons de sang pour l’exploration de paramètres génétiques et de biomarqueurs potentiels liés à une augmentation du risque de lésion hépatique chez les patients adultes ayant précédemment participé aux essais cliniques du tolvaptan dans le traitement de la polykystose rénale autosomique dominante (PKRAD)

A.3.1

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

A.4.1

Sponsor's protocol code number

156-13-208

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	Otsuka Pharmaceutical Development & Commercialization, Inc.
B.1.3.4	Country	United States
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	Otsuka Pharmaceutical Development & Commercialization, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Otsuka Pharmaceutical Development & Commercialization, Inc.
B.5.2	Functional name of contact point	Laurie Debuque
B.5.3	Address:
B.5.3.1	Street Address	2440, Research Boulevard
B.5.3.2	Town/ city	Rockville, MD
B.5.3.3	Post code	20850
B.5.3.4	Country	United States
B.5.4	Telephone number	+16095246894
B.5.5	Fax number	+12405143994
B.5.6	E-mail	Laurie.Debuque@otsuka-us.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	Jinarc
D.2.1.1.2	Name of the Marketing Authorisation holder	Otsuka Pharmaceutical Europe Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	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	Tolvaptan
D.3.9.1	CAS number	150683-30-0
D.3.9.2	Current sponsor code	Tolvaptan
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	15
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

Autosomal Dominant Polycystic Kidney Disease (ADPKD), Patients with Increased Risk of Liver Injury

Polykystose rénale autosomique dominante (PKRAD), patients avec une augmentation du risque de lésion hépatique

E.1.1.1

Medical condition in easily understood language

Autosomal Dominant Polycystic Kidney Disease (ADPKD), Patients with Increased Risk of Liver Injury

Polykystose rénale autosomique dominante (PKRAD), patients avec une augmentation du risque de lésion hépatique

E.1.1.2

Therapeutic area

Not possible to specify

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Obtain blood samples from subjects in prior tolvaptan ADPKD clinical trials who experienced qualifying elevated liver enzymes for subsequent identification of potential genetic markers and biomarkers (collectively genetic/biomarkers) for increased risk of liver injury.

Recueillir des échantillons sanguins de patients atteints de PKRAD ayant présenté une élévation des enzymes hépatiques au cours d’essais cliniques évaluant le tolvaptan, afin d’identifier ultérieurement les marqueurs génétiques et biologiques potentiels (collectivement qualifiés de marqueurs génétiques/biomarqueurs) liés à l'augmentation du risque de lésion hépatique.

E.2.2

Secondary objectives of the trial

not applicable

sans objet

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Participated in tolvaptan clinical Trial 156-04-251, 156-09-290, or another tolvaptan ADPKD clinical trial.
2. Blood and/or DNA sample is not available.
3. In one of the above studies experienced either:
• A serious or non-serious hepatic or liver function test abnormality AE that led to discontinuation of trial drug and was reported by the investigator;
or
• Liver enzyme elevations as listed below, even if they did not occur simultaneously and no AE was reported:
- To qualify for blood collection for DNA extraction, either:
 • ALT or AST of at least 2 × ULN or
 • BT of at least 2 × ULN
- And/or to qualify for blood collection for PBMC isolation, either:
• Met Hy’s Law criteria (> 3 × ULN for ALT and > 2 × ULN for total
bilirubin) or
 • Maximum ALT > 7 × ULN.

1. Participation aux essais cliniques 156-04-251, 156-09-290 ou autre, évaluant le tolvaptan dans la PKRAD
2. Absence d’échantillons sanguins ou d’ADN
3. Présence des éléments suivants au cours d’un des essais cliniques précités :
• Anomalie hépatique ou des explorations fonctionnelles hépatiques constituant un EI grave ou non grave rapporté par l’investigateur et ayant conduit à l’arrêt du médicament à l’étude,
ou
• Élévations citées précédemment des enzymes hépatiques, même si elles ne se sont pas produites simultanément et qu’aucun EI n’a été rapporté :
- Pour des prélèvements sanguins destinés à l’extraction d’ADN, les élévations qualifiantes doivent répondre aux critères suivants :
 • ALAT ou ASAT ≥ 2 * LSN ou
 • BT ≥ 2* LSN
- Et/ou, pour des prélèvements sanguins destinés à l’isolement de CMSP (cellules mononucléées du sang périphérique) :
 • Loi de Hy (>3*LSN pour les taux d’ALAT et >2*LSN pour la bilirubine totale) ou
 • Taux maximum d’ALAT >7*LSN

E.4

Principal exclusion criteria

1. Unwilling or unable to provide a blood sample.

1. Refus ou incapacité à fournir un échantillon sanguin pour des analyses de marqueurs génétiques/biomarqueurs.

E.5 End points

E.5.1

Primary end point(s)

The number of subjects who provide a blood sample out of the number of subjects eligible to provide a sample.

Nombre de patients ayant donné un échantillon sanguin sur le nombre de patients devant potentiellement fournir un échantillon.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 year of trial initiation.

1 an après le début de l'étude

E.5.2

Secondary end point(s)

Not applicable.

Sans objet

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable.

Sans objet

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

E.6.5

Efficacy

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

Yes

E.6.13.1

Other scope of the trial description

To complete the blood sample collection of subjects who were exposed to tolvaptan and experienced qualifying elevated liver enzymes in prior clinical trials to get the broadest patient representation for investigation of drug-induced liver injury i.e. for subsequent identification of potential genetic/biomarkers for increased risk of liver injury (later analysis under separate protocols).

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

non-treatment, exploratory study

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

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

Argentina

Belgium

France

Germany

Japan

United States

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

The last Date of Contact or the last Date of Final Contact Attempt for the last subject completing or withdrawing from the trial.

La date du dernier contact pour le dernier patient ayant complété ou ayant terminé prématurément l'essai.

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.1.1.1

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)

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2016-01-15.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

Information not present in EudraCT

F.3.3.4

Nursing women

Information not present in EudraCT

F.3.3.5

Emergency situation

Information not present in EudraCT

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

Not applicable.

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

2015-12-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-12-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-08-07

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