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

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2009-017882-42-FR
• Date of registration: 14/06/2010
• Prospective Registration: Yes
• Primary sponsor: Raptor Therapeutics Inc.
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 12/08/2010
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-017882-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: yes Other: yes Other trial design description: sequential If controlled, specify comparator, Other Medicinial Product: Placebo: Other: yes Other specify the comparator: Cystagon
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Netherlands

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? yes
Number of subjects for this age range:
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) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystinosis
MedDRA version: 12.1 Level: LLT Classification code 10011777 Term: Cystinosis

Intervention(s)

Product Name: Cysteamine bitartrate (INN: mercaptamine bitartrate )
Product Code: RP103
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: mercaptamine bitartrate
CAS Number: CAS 27761-19
Current Sponsor code: RP103
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
INN or Proposed INN: mercaptamine bitartrate
CAS Number: CAS 27761-19
Current Sponsor code: RP103
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Cystagon
Pharmaceutical Form: Capsule, hard

Primary Outcome(s)

Secondary Objective: To assess safety and tolerability of RP103.

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

Main Objective: 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

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.

Secondary ID(s)

RP103-03