The objective of this pivotal study is to assess the long-term safety, tolerability, pharmacokinetics and pharmacodynamics of RP103 in pediatric and adult patients with nephropathic cystinosis. Results of this Phase 3 study will be used to support…
ID
Source
Brief title
Condition
- Metabolism disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess safety and tolerability of RP103 using safety data collected during
the study (adverse events, physical exams, vital signs, VAS swallowing
assessments, ECG and clinical laboratory testing).
Secondary outcome
To assess the steady-state pharmacokinetics (PK) of RP103 using trough plasma
cysteamine concentrations 0.5 hours post-dose and to assess the steady-state
pharmacodynamics (PD) of RP103 using WBC cystine content meastured 0.5 hours
post-dose.
Background summary
Cysteamine bitartrate is currently marketed for treatment of nephropathic
cystinosis under the trade name Cystagon® and is available for oral
administration as immediate-release 50 mg or 150 mg capsules with a dosing
interval of Q6H. Preliminary studies in healthy volunteers using a
delayed-release formulation have shown that an extemporaneously prepared
enteric-coated cysteamine product (i.e., EC-Cystagon, enteric-coated Cystagon®
Capsules) had a mean maximum concentration (Cmax) and area under the curve
(AUC) similar to Cystagon®. Compared to the study period with Cystagon® which
required dosing Q6H, the EC-Cystagon was taken only Q12H, eliminating the
problem of disrupting sleep with a Q6H dosing schedule while still maintaining
adequate reduction of WBC cystine levels. Raptor Pharmaceuticals (Raptor) is
developing Cysteamine Bitartrate Delayed-release Capsules (RP103), 75 mg and 25
mg. Cysteamine Bitartrate Delayed-release Capsules (RP103) are enteric-coated
beads that are further encapsulated and intended to be administered every 12
hours (Q12H).
Study objective
The objective of this pivotal study is to assess the long-term safety,
tolerability, pharmacokinetics and pharmacodynamics of RP103 in pediatric and
adult patients with nephropathic cystinosis. Results of this Phase 3 study
will be used to support the registration application for this new formulation
of cysteamine bitartrate.
Primary Objective: to assess safety and tolerability of long-term repeat dosing
of RP103 in patients with nephropathic cystinosis.
Secondary Objectives : to assess the steady-state pharmacokinetics (PK) and
pharmacodynamics (PD) of RP103.
To assess the long-term quality of life using either PedsQL* and SF-36®
instruments.
Study design
This is a long-term, open-label study of the safety, tolerability and
steady-state pharmacokinetics and pharmacodynamics of RP103 in pediatric and
adult patients with nephropathic cystinosis.
Intervention
This is an open-label study during which patients will receive RP103 for up to
8 years.
Study burden and risks
Up to 5 years of study participation, including up to 25 study visits; blood
withdrawal (total max. of 290 mL of blood) for clinical laboratory tests and
PK/PD analyses, ECG examinations, physical examinations, vital signs,
completion of at-home medications diary, completion of Quality of Life
questionnaires, and treatment with RP103.
Naritaweg 165
Amsterdam 1043 BW
NL
Naritaweg 165
Amsterdam 1043 BW
NL
Listed location countries
Age
Inclusion criteria
Male and female subjects must completed the last visit of Study RP103-03 and be willing to continue on RP103 treatment.;Or for patients who did not complete the RP103-03 study:;Male or female subject with a documented diagnosis of nephropathic cystinosis.
Subject must be on a stable dose of Cystagon® at least 21 days prior to Screening.
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.
Subject must have an estimated GFR (corrected for body surface area) > 30 mL/minute/1.73 m2.
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.
Subject must be willing and able to comply with the study restrictions and requirements.
Subject or their parent or guardian must provide written informed consent and assent (where applicable) prior to participation in the study.
Exclusion criteria
Patients enrolled in the previous Study RP103-03 who did not complete their last scheduled Study visit or who do not wish to continue on treatment with RP103.;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.
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.
Subjects with known hypersensitivity to cysteamine and penicillamine.
Female subjects who are nursing, planning a pregnancy, known or suspected to be pregnant, or with a positive serum pregnancy screen.
Subjects who have a made a blood donation within 30 days of Screening.
Subjects who, in the opinion of the Investigator, are not able or willing to comply with the protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-018365-34-NL |
| ClinicalTrials.gov | NCT01197378 |
| CCMO | NL33066.091.10 |