- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00872729
Pilot Study of Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of RP103 Compared to Cystagon® in Patients With Cystinosis
A Pilot Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Cysteamine Bitartrate Delayed-release Capsules (RP103), Compared to Cysteamine Bitartrate (Cystagon®) in Patients With Nephropathic Cystinosis
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
San Diego, California, United States, 92103
- University of California San Diego Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- ADULT
- OLDER_ADULT
- CHILD
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male and female subjects must have nephropathic cystinosis.
- Children less than 22.5 kg will only be included in the study if the investigator feels they can safely participate in the study including the required blood draw volume for the safety and PK/PD assessments.
- Subjects must be on a stable dose of Cystagon® at least 21 days prior to Screening.
- Subjects must be able to swallow a 150 mg Cystagon® capsule with the capsule intact.
- Within the last 2 months, no clinically significant change in liver function [i.e., ALT, AST, alkaline phosphatase, bilirubin (total and direct)] and renal function [i.e., serum creatinine, albumin, total protein] at Screening as determined by the Investigator.
- 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.
- Subjects or their authorized caregiver must provide written informed consent and assent (where applicable) prior to participation in the study.
- If in the opinion of the investigator, patients can safely provide the study required blood draw volume.
- Subjects must be willing and able to comply with the study restrictions and requirements.
Exclusion Criteria:
- If, in the opinion of the investigator, the planned study dose would exceed the patient's tolerability of cysteamine based on their prior Cystagon® steady state drug requirements.
- Evidence of or verbal attestation of Helicobacter pylori infection, presently, or within the last 90 days prior to Screening.
- Subjects with a known history, currently or within the past 90 days prior to Screening, of the following conditions or other health issues that make it, in the opinion of the investigator, unsafe for them to participate, or whose concomitant medical problems preclude them from committing to the study schedule including the following: Crohn's disease, inflammatory bowel disease (if currently active) or have had prior resection of small intestine; • History of heart disease, e.g., myocardial infarction, heart failure, arrhythmias; Any bleeding disorder; Malignant disease; Severe liver disease as defined as ALT or AST > 2 times the upper limit of normal.
- Subjects who have had a kidney transplant.
- Subjects who are planning or are a registered candidate for a kidney transplant within 3 months of the Screening or have a serum creatinine > 2.4.
- Subjects with known hypersensitivity to cysteamine.
- If female (of child-bearing potential), are nursing, planning a pregnancy, known or suspected to be pregnant, or have a positive urine pregnancy screen.
- Patients with a hemoglobin level < 10.5.
- Subjects who have a made a blood donation within 60 days prior to study initiation.
- Subjects who, in the opinion of the Investigator, are not able or willing to comply with the protocol.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Cystagon®
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg
|
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg. Duration of Treatment and Dose: Reference Period up to four doses Q6H. |
EXPERIMENTAL: RP103
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg
|
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg. Duration of treatment and Dose: Single dose of Test Product at dose equivalent to Reference Product. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma Pharmacokinetic Parameter: Cmax of Cysteamine
Time Frame: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing
|
12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing
|
|
Plasma Pharmacokinetic Parameter: Tmax of Cysteamine
Time Frame: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing
|
12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing
|
|
Plasma Pharmacokinetic Parameter: AUC(0-t) of Cysteamine
Time Frame: 12 hours post RP103 dosing and 6 hours post 1st Cystagon® dosing
|
t = 6 for Cystagon and t = 12 for RP103.
Cystagon is dosed every 6 hours and there is no measurement after 6 hours and up to 12 hours.
|
12 hours post RP103 dosing and 6 hours post 1st Cystagon® dosing
|
Pharmacodynamic Parameter: Changes of White Blood Cell (WBC) Cystine Level From Baseline
Time Frame: up to 12 hours post Cystagon® dosing and RP103 dosing
|
The pharmacodynamic (PD) parameter measures the changes of WBC cystine level from the baseline. Cystine is a disulfide amino acid formed through oxidation of two molecules of cysteine; hence, cystine's concentration is commonly given in half-cystine equivalents to avoid confusion. The level of cystine in WBC/leukocytes is expressed in units of nmol half-cystine/mg protein (nmol ½ cystine/mg protein). Half-cystine is quantified by a reduction of cystine followed by an assay for cysteine, which is then normalized by the total cellular protein content within the sample using methods of such as Lowry assay, bicinchoninic acid assay, or Bradford. |
up to 12 hours post Cystagon® dosing and RP103 dosing
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Dohil R, Fidler M, Barshop BA, Gangoiti J, Deutsch R, Martin M, Schneider JA. Understanding intestinal cysteamine bitartrate absorption. J Pediatr. 2006 Jun;148(6):764-9. doi: 10.1016/j.jpeds.2006.01.050.
- Fidler MC, Barshop BA, Gangoiti JA, Deutsch R, Martin M, Schneider JA, Dohil R. Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion. Br J Clin Pharmacol. 2007 Jan;63(1):36-40. doi: 10.1111/j.1365-2125.2006.02734.x.
- Levtchenko EN, van Dael CM, de Graaf-Hess AC, Wilmer MJ, van den Heuvel LP, Monnens LA, Blom HJ. Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis. Pediatr Nephrol. 2006 Jan;21(1):110-3. doi: 10.1007/s00467-005-2052-0. Epub 2005 Oct 27.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- RP103-01
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cystinosis
-
University of California, San DiegoRaptor Pharmaceuticals Corp.CompletedCystinosis | Nephropathic CystinosisUnited States
-
Eloxx Pharmaceuticals, Inc.TerminatedGenetic Disease | Cystinosis | Nonsense MutationCanada
-
Nacuity Pharmaceuticals, Inc.Recruiting
-
Cystinose StiftungLabor Becker & Kollegen, Munich, Germany; Screening Labor Hannover; Genetikum... and other collaboratorsCompletedSpinal Muscular Atrophy | Cystinosis | Cystinosis, NephropathicGermany
-
Chiesi SA/NVEnrolling by invitationNephropathic CystinosisBelgium
-
National Human Genome Research Institute (NHGRI)Recruiting
-
University of California, San DiegoCalifornia Institute for Regenerative Medicine (CIRM); Cystinosis Research...Active, not recruiting
-
Universitaire Ziekenhuizen KU LeuvenCompleted
-
Centre Hospitalier Universitaire de NiceCompleted
-
National Eye Institute (NEI)CompletedCystinosisUnited States
Clinical Trials on Cystagon®
-
Horizon Pharma USA, Inc.CompletedCystinosisFrance, United States, United Kingdom, Belgium, Italy, Netherlands
-
Horizon Pharma USA, Inc.CompletedCystinosisFrance, United States, Netherlands
-
University of AberdeenNHS Grampian; University of Huddersfield; Cystic Fibrosis TrustCompleted
-
Augusta UniversityTerminatedSchizophrenia | SchizoaffectiveUnited States
-
University of California, San DiegoRaptor Pharmaceuticals Corp.CompletedCystinosis | Nephropathic CystinosisUnited States
-
Eunice Kennedy Shriver National Institute of Child...CompletedInfantile Neronal Ceroid LipofuscinosisUnited States
-
Nacuity Pharmaceuticals, Inc.Recruiting
-
Dong-A ST Co., Ltd.CompletedFunctional DyspepsiaKorea, Republic of
-
Chong Kun Dang PharmaceuticalCompleted
-
Galderma R&DCompletedAtopic DermatitisPhilippines, China