Clinical Trials Register

Summary
EudraCT Number:	2012-002582-35
Sponsor's Protocol Code Number:	MCI-196-E16
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-10-23
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

UK - MHRA

A.2

EudraCT number

2012-002582-35

A.3

Full title of the trial

A Multi-centre, Open-label Study Evaluating the Safety and Tolerability of Colestilan (MCI-196) in Paediatric Subjects with Chronic Kidney Disease Stages 3b to 5 and with Hyperphosphataemia 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 different doses of MCI-196 lower phosphate levels in patients suffering from a condition called hyperphosphatemia (high levels of phosphorus in the blood), who have stage 3b to 5 chronic kidney disease and are not on dialysis.

A.4.1

Sponsor's protocol code number

MCI-196-E16

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® 1g 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.3.9.3	Other descriptive name	Colestimide, Colestilan chloride
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® 2g 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.3.9.3	Other descriptive name	Colestimide, Colestilan chloride
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® 3g 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.3.9.3	Other descriptive name	Colestimide, Colestilan chloride
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 safety and tolerability of colestilan (MCI-196) in paediatric subjects (aged 2 years to <18 years) with CKD stages 3b to 5, diagnosed with hyperphosphataemia, who are not on dialysis.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Main inclusion criteria for enrolment into this study:
• Children aged 2 years to <18 years with CKD stages 3b to 5, not on dialysis (stage 3b is defined as a glomerular filtration rate below 45 mL/min/1.73 m²).
• The subject has a documented diagnosis of hyperphosphataemia, as demonstrated by serum phosphorus (P) levels above the age-related upper limit of normal (ULN) (Kidney Disease Outcomes Quality Initiative [KDOQI] Clinical Practice Guidelines for Nutrition in Children with CKD updated 2008).
• The subject is on a stable P diet at baseline (as judged by the Investigator).

Inclusion criteria for subjects not currently treated with phosphate binders:
• The subject, with serum P not controlled despite being on an appropriate P diet, must demonstrate serum P levels >1.5 standard deviation (SD) above the KDOQI 2008 age-related mean value at any time during the screening period.
Such subjects do not require wash-out and should proceed to baseline for the next visit if additional screening visits are not required.

Baseline inclusion criteria for subjects treated with phosphate binders:
• The subject must have demonstrated serum P levels >1.5 SD above the KDOQ 2008 age-related mean value at any time during the wash-out period (after stopping phosphate binders), and;
• The subject must demonstrate an increase in serum P levels by at least 10% above the pre wash-out level (after stopping phosphate binders).

Note: should a subject fail to meet any of the above criteria, the subject is permitted to be re-screened once after an interval of at least three months.

Refer to protocol for a complete list of inclusion criteria.

E.4

Principal exclusion criteria

A subject meeting any of the following criteria is ineligible to participate in this study:
• The subject has been diagnosed with hypocholesterolaemia (i.e., cholesterol levels below age-related normal ranges, per local practices)
• The subject has current clinically significant medical comorbidities, which may substantially compromise subject safety, or expose him/her 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 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 cannot stop treatment (prescription or over-the-counter) of any of the following orally taken medications during the wash-out period: any product containing calcium (Ca), magnesium (Mg), aluminium compounds, sevelamer, lanthanum, ketosteril
• The subject is receiving immunosuppressant treatment for any medical condition at the baseline visit or is expected to receive such treatment during the course of the study
• The subject is considered as unstable on his/her current treatment for CKD within one month prior to screening (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 Ca levels]

Exclusion criteria for subjects treated with phosphate binders:
• The subject was treated with a combination of two or more phosphate binders within one month prior to screening

Refer to protocol for a complete list of exclusion criteria.

E.5 End points

E.5.1

Primary end point(s)

The percentage of subjects who, due to hyperphosphataemia, require rescue treatment and/or discontinuation of therapy with colestilan (MCI-196).

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 17 or last observation carried forward (LOCF) for all subjects. For further information, please refer to the protocol.

E.5.2

Secondary end point(s)

Safety endpoints:
1) The incidence and profile of treatment-emergent adverse events (TEAEs)
2) The incidence of TEAEs of hypercalcaemia and hypocalcaemia
3) Laboratory safety assessments:
o Morphology parameters: complete blood count (CBC), platelet count
o Biochemistry
- Electrolytes, mineral parameters, and acid-base balance – sodium (Na), potassium (K), chloride (Cl), magnesium (Mg), calcium (Ca), P, calcium phosphorus ion product (CaxP), bicarbonate (HCO3), pH
- Lipids – low density lipoprotein cholesterol (LDL-C), total cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides (TG)
- Liver Function Tests (LFTs) – aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), bilirubin, alkaline phosphatase (ALP)
- Vitamins and microelements – iron and iron-related parameters (total iron-binding capacity [TIBC], unsaturated iron-binding capacity[UIBC]), folate, 25-(OH)-vitamin D3, 1,25-(OH)2-vitamin D3, vitamin K
- Other - blood urea nitrogen (BUN), serum creatinine, serum albumin, intact parathyroid hormone (iPTH), C-reactive protein (CRP), creatine kinase (CK), serum glucose, HbA1c, and uric acid
o Other parameters:
- Coagulation: prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalised ratio (INR)
- Fibroblast Growth Factor 23 (FGF23)

Efficacy endpoints
1)The mean absolute change in serum P levels from baseline to Week 17 or last observation carried forward (LOCF) in subjects receiving colestilan (MCI-196) only.
2) The proportion of responders at Week 17 or LOCF (responders are defined as subjects demonstrating serum P levels ≤1.5 standard deviation [SD] above the age-related KDOQI 2008 mean value at Week 17 or LOCF.

LOCF will be applied at the time of rescue or withdrawal. A sensitivity analysis will also be performed where LOCF is taken at time of withdrawal only.

The other/exploratory endpoint is the acceptability and palatability of colestilan (MCI-196) formulation (tablets and granules)

E.5.2.1

Timepoint(s) of evaluation of this end point

As defined in 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

Yes

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

Acceptability and palatability of colestilan (MCI-196) formulation (tablets and granules)

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

Yes

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

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

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

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

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:

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

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)

Normal treatment for this condition

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 (MCRN)
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

2012-11-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-14

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2014-12-17

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