Clinical Trials Register

Summary
EudraCT Number:	2009-017882-42
Sponsor's Protocol Code Number:	RP103-03
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-06-25
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

Netherlands - Competent Authority

A.2

EudraCT number

2009-017882-42

A.3

Full title of the trial

A Randomized, Crossover, Pharmacokinetic and Pharmacodynamic
Study to Determine the Safety and Efficacy of Cysteamine Bitartrate
Delayed-release Capsules (RP103), Compared to Cystagon® in Patients
with Nephropathic Cystinosis

A.4.1

Sponsor's protocol code number

RP103-03

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	Raptor Therapeutics 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
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	Cysteamine bitartrate (INN: mercaptamine bitartrate
D.3.2	Product code	RP103
D.3.4	Pharmaceutical form	Capsule, hard
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	mercaptamine bitartrate
D.3.9.1	CAS number	CAS 27761-19
D.3.9.2	Current sponsor code	RP103
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	25, 75
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	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Cystagon
D.2.1.1.2	Name of the Marketing Authorisation holder	Orphan Europe
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	Capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.11 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	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

Cystinosis

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10011777
E.1.2	Term	Cystinosis

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate that at steady-state, patients receiving every 6 hour
(Q6H) treatment of Cystagon® can maintain a comparable depletion
of white blood cell (WBC) cystine levels after receiving every 12
hour (Q12H) treatment regimen of RP103

E.2.2

Secondary objectives of the trial

To assess safety and tolerability of RP103.
To assess the steady-state pharmacokinetics (PK) and
pharmacodynamics (PD) of RP103 compared to Cystagon®.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Male or female subject with a documented diagnosis of
nephropathic cystinosis.
2. Subject must be on a stable dose of Cystagon® sufficient to
maintain their white blood cell (WBC) cystine level at ≤ 1.0
nmol/half-cystine/mg protein.
3. Subject must be able to swallow their typically administered
Cystagon® capsule with the capsule intact.
4. Within the last 6 months, no clinically significant change from
normal in liver function tests [i.e., 1.5 times ULN for ALT and
AST, and/or 1.5 times ULN for total bilirubin] and renal function
[i.e., estimated GFR (corrected for body surface area)] at
Screening as determined by the Investigator.
5. Subject must have an estimated GFR (corrected for body surface
area) > 30 mL/minute/1.73 m2.
6. Sexually active female subjects of childbearing potential (i.e., not
surgically sterile [tubal ligation, hysterectomy, or bilateral
oophorectomy] or at least 2 years naturally postmenopausal)
must agree to utilize the same acceptable form of contraception
from Screening through completion of the study. The acceptable
forms of contraception for this study include hormonal
contraceptives (oral, implant, transdermal patch, or injection) at a
stable dose for at least 3 months prior to Screening, barrier
(spermicidal condom, diaphragm with spermicide), IUD, or a
partner who has been vasectomized for at least 6 months. For
pre-pubescent children, a documented attestation of abstinence
from their parent or guardian will be acceptable.
7. Subject must be willing and able to comply with the study
restrictions and requirements.
8. Subject or their parent or guardian must provide written informed
consent and assent (where applicable) prior to participation in the
study.

E.4

Principal exclusion criteria

1. Subject’s age < 6 years old or subjects weight < 21 kg.
2. Subjects with current history of the following conditions or any
other health issues that make it, in the opinion of the Investigator,
unsafe for them to participate:
- Inflammatory bowel disease (if currently active) or prior
resection of small intestine;
- Heart disease (e.g., myocardial infarction, heart failure,
unstable arrhythmias, or poorly controlled hypertension)
90 days prior to Screening;
- Active bleeding disorder 90 days prior to Screening;
- History of malignant disease within the last 2 years.
3. Subject with a hemoglobin level of < 10 g/dL at Screening or, in
the opinion of the Investigator, a hemoglobin level that would
make it unsafe for the subject to participate.
4. Subjects receiving any form of cysteamine medication through a
gastric tube.
5. Subjects who are receiving maintenance dialysis or who have
had a kidney transplant.
6. Subjects who are on an active kidney transplant list or who are
planning to receive a kidney transplant within 3 months of
Screening.
7. Subjects with known hypersensitivity to cysteamine and
penicillamine.
8. Female subjects who are nursing, planning a pregnancy, known
or suspected to be pregnant, or with a positive serum pregnancy
screen.
9. Subjects who have a made a blood donation within 30 days of
Screening.
10. Subjects who, in the opinion of the Investigator, are not able or
willing to comply with the protocol.

E.5 End points

E.5.1

Primary end point(s)

Comparable depletion of steady-state cysteamine-trough WBC
cystine levels (Days 5, 6 and 7 of Week 6 (Period 1) and Week 9
(Period 2) between Cystagon® and RP103. If the one-sided test
of non-inferiority, conducted at the nominal level of 0.02104, is
rejected at a non-inferiority margin of 0.3, we will conclude that
RP103 is non-inferior to Cystagon® with an overall significance
level of 0.025.

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

Yes

E.6.9

Dose response

Yes

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

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

Yes

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

E.8.2.3.1

Comparator description

Cystagon

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.8.4.1

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

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.1.1.1

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.1.1.6

Adolescents (12-17 years)

Yes

F.1.2

Adults (18-64 years)

Yes

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

Children

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

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

2010-07-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-10-19

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

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