Clinical Trials Register

Summary
EudraCT Number:	2012-002583-27
Sponsor's Protocol Code Number:	MCI-196-E15
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-12-19
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2012-002583-27

A.3

Full title of the trial

A Multi-centre, Flexible Dose, Parallel Group, Open-label, Active Control (Calcium-based Phosphate Binder), Long-term Extension Study Evaluating the Efficacy, Safety and Tolerability of Colestilan (MCI-196) in Paediatric Subjects With Hyperphosphataemia and With Either Chronic Kidney Disease Stage 5 on Dialysis or Chronic Kidney Disease Stages 3b to 5 Not on Dialysis

A.3.1

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

A clinical study to investigate how MCI-196 lowers phosphate levels in patients over a long period of time, who have previously participated in the short-term MCI-196 studies and suffer from hyperphosphatemia (high levels of phopshorus in the blood), who have stage 5 chronic kidney disease and are on dialysis or who have stages 3b to 5 chronic kidney disease and are not on dialysis. MCI-196 phosphate-lowering effect will be compated to patients taking calcium-based phosphate binders.

A.4.1

Sponsor's protocol code number

MCI-196-E15

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/207/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Mitsubishi Tanabe Pharma Corporation (MTPC)
B.1.3.4	Country	Japan
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	Mitsubishi Tanabe Pharma Corporation (MTPC)
B.4.2	Country	Japan
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Mitsubishi Tanabe Pharma Europe Ltd (MTPE)
B.5.2	Functional name of contact point	General Information
B.5.3	Address:
B.5.3.1	Street Address	Dashwood House, 69 Old Broad Street
B.5.3.2	Town/ city	London
B.5.3.3	Post code	EC2M 1QS
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44(0)20 7065 5017
B.5.5	Fax number	+44(0)20 7065 5050
B.5.6	E-mail	regulatory@mt-pharma-eu.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	BindRen® 1 g Film-coated Tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Mitsubishi Tanabe Pharma 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.3.2	Product code	MCI-196
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Nasogastric use (Noncurrent) Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COLESTILAN
D.3.9.1	CAS number	95522-45-5
D.3.9.2	Current sponsor code	MCI-196
D.3.9.4	EV Substance Code	SUB06795MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(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.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.2.1.1.1	Trade name	BindRen® 2 g Granules
D.2.1.1.2	Name of the Marketing Authorisation holder	Mitsubishi Tanabe Pharma 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.3.2	Product code	MCI-196
D.3.4	Pharmaceutical form	Granules
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Nasogastric use (Noncurrent) Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COLESTILAN
D.3.9.1	CAS number	95522-45-5
D.3.9.2	Current sponsor code	MCI-196
D.3.9.4	EV Substance Code	SUB06795MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
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	No
D.IMP: 3
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	BindRen® 3 g Granules
D.2.1.1.2	Name of the Marketing Authorisation holder	Mitsubishi Tanabe Pharma 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.3.2	Product code	MCI-196
D.3.4	Pharmaceutical form	Granules
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Nasogastric use (Noncurrent) Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COLESTILAN
D.3.9.1	CAS number	95522-45-5
D.3.9.2	Current sponsor code	MCI-196
D.3.9.4	EV Substance Code	SUB06795MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
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

Hyperphosphataemia

E.1.1.1

Medical condition in easily understood language

Abnormally elevated levels of phosphorus in the blood

E.1.1.2

Therapeutic area

Diseases [C] - Symptoms and general pathology [C23]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10020711
E.1.2	Term	Hyperphosphataemia
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 assess the long-term efficacy of treatment with colestilan (MCI-196) (including combination therapy)

To assess the long-term safety of treatment with colestilan (MCI-196) (including combination therapy).

E.2.2

Secondary objectives of the trial

To assess the long-term efficacy profile for colestilan (MCI-196) (monotherapy and combination therapy) versus a standard calcium-based phosphate binder (CBPB) therapy.

To assess the long-term safety profile for colestilan (MCI-196)(monotherapy and combination therapy) versus a standard CBPB therapy.

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

Title: Ultrasound Measurement of Intima Media Thickness
Objectives: Ultrasound measurement of intima media thickness of the common carotid artery is planned as a measure of arterial calcification in this sub-study.

E.3

Principal inclusion criteria

• The subject and/or parent(s)/guardian(s) must be capable of providing informed consent, and assent when applicable, in agreement with regional requirements.

• The subject has completed either of the short-term studies, MCI-196-E14 or MCI-196-E16

or

• The subject has been withdrawn from MCI-196-E14, but is eligible to enter this study according to the following rules, as defined in MCI-196-E14:

1.Hyperphosphataemia: Subjects who experienced hyperphosphataemia, defined as any increase in serum phosphorus [P] levels above the age-related ULN on two consecutive occasions, and was withdrawn by the Investigator in order to proceed to this study, where flexible dosing with colestilan (MCI-196) is available. Subjects withdrawn from MCI-196-E14 due to hyperphosphataemia may only enter this study after Week 6 of the short-term study, following two consecutive out-of-range P values (one obtained at Week 3 and one obtained at Week 6). After Week 6, subjects meeting the above criteria may enter this study at any time (the two consecutive out-of-range P values having been obtained any time after Week 6 from a scheduled or unscheduled visit).

2.Hypercalcaemia: Subjects treated with CBPB and experiencing hypercalcaemia may be withdrawn from the short-term study at the discretion of the Investigator in order to proceed to this study at any time, where flexible dosing with colestilan (MCI-196) is available.

E.4

Principal exclusion criteria

• The subject has current clinically significant medical co-morbidities, which may substantially compromise subject safety, or expose them to undue risk, or interfere significantly with study procedures and which, in the opinion of the Investigator, make the subject unsuitable for inclusion in the study (e.g., the subject currently has or has had a history of seizure disorders, dysphagia, swallowing disorders, predisposition to or current bowel obstruction, ileus or severe gastrointestinal [GI] disorders such as chronic or severe constipation (as judged by the Investigator), intestinal stenosis, intestinal diverticulum, sigmoid colitis, GI ulcers, current or a history of GI bleeding, or major GI tract surgery).

• The subject is expected to receive immunosuppressant treatment during the course of the study.

• The subject is considered unstable on his/her current treatment for CKD within one month prior to enrolment (e.g., subjects starting treatment with vitamin D or its analogues, or other agents/procedures that may influence bone mineral metabolism [i.e., serum P and calcium (Ca) levels]).

• The subject is considered to be non-compliant with study procedures in the opinion of the Investigator.

• The subject has a temporary catheter as a vascular access and is showing active signs of inflammation as a result of this, which would significantly interfere with dialysis.

• If on peritoneal dialysis, the subject has a recent history of peritonitis (as judged by the Investigator).

Refer to the protocol for a complete list of the exclusion criteria.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint of this study is the proportion of responders at Week 52 or last observation carried forward (LOCF). (Responders are defined as subjects demonstrating serum P levels ≤1.5 standard deviation above the Kidney Disease Outcomes Quality Initiative (KDOQI) 2008 age-related mean value at Week 52 or LOCF.)

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 52 or last observation carried forward (LOCF).

E.5.2

Secondary end point(s)

The following secondary efficacy endpoints are to be assessed:

Change from baseline in the short-term study (MCI-196-E14 or MCI-196-E16) to Week 25, Week 41, and Week 52 of treatment exposure for the following efficacy parameters:

• The mean absolute change from baseline for serum P, Ca and calcium phosphorus ion product (CaxP), intact parathyroid hormone (iPTH), serum glucose, glycosylated haemoglobin (HbA1c), and uric acid

• The mean percentage change from baseline for lipid parameters (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol, and triglycerides [TG])

• The incidence and profile of treatment-emergent adverse events (TEAEs).

• The incidence of TEAEs of hypercalcaemia and hypocalcaemia.

• Laboratory safety assessments as defined in the protocol.

The exploratory substudy endpoint is:

High resolution ultrasound measurement of intima media thickness of the common carotid artery as a measure of arterial calcification measured at the baseline visit of the short-term study and at the end of this study.

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary efficacy endpoints are to be assessed Week 25, Week 41, and Week 52 of treatment exposure.

The exploratory endpoint of this study is to be assessed at the end of this study. For further information, please refer to the protocol.

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

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

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

Yes

E.8.2.3.1

Comparator description

Standard of care (Calcium-based phosphate binder)

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

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

Turkey

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

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

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

Yes

F.1.1

Number of subjects for this age range:

100

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Paediatric subjects

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

100

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)

The subject should be returned to his/her standard care/therapy, as appropriate.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	The Medicines for Children Research Network
G.4.3.4	Network Country	United Kingdom

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-02-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-07-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials