Pilot Study of Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of RP103 Compared to Cystagon® in Patients With Cystinosis

NCT00872729 | Completed Phase 1 Results

• 1 other identifier: RP103-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Cystinosis is an inheritable disease that if untreated, results in kidney failure as early as the first decade of life. The current marketed therapy is Cystagon® (cysteamine bitartrate) which must be taken every six hours for the rest of the patient's life to prevent complications of cystinosis. RP103 is a formulation of cysteamine bitartrate that is being studied to see if it may be able to be given less frequently, once every 12 hours, and have similar results.

Conditions

Cystinosis

Keywords

cystinosis; cysteamine; inheritable disease; orphan disease; CTNS protein, human; nephropathic cystinosis

Outcome Measures

Primary Outcomes (4)

• Plasma Pharmacokinetic Parameter: Cmax of Cysteamine

  12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing

• Plasma Pharmacokinetic Parameter: Tmax of Cysteamine

  12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing

• Plasma Pharmacokinetic Parameter: AUC(0-t) of Cysteamine

  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

  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

Study Arms (2)

Cystagon®

ACTIVE COMPARATOR

Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg

Drug: Cystagon®

RP103

EXPERIMENTAL

Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg

Drug: RP103

Interventions

Cystagon® DRUG

Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg. Duration of Treatment and Dose: Reference Period up to four doses Q6H.

Cystagon®

RP103 DRUG

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.

RP103

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (1)

University of California San Diego Medical Center

San Diego, California, 92103, United States

Location

Related Publications (3)

• 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.

  PMID: 16769383 BACKGROUND

• 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.

  PMID: 17229040 BACKGROUND

• 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.

  PMID: 16252107 BACKGROUND

Related Links

• RP103 (marketed as PROCYSBI) is now approved by the US FDA for management of nephropathic cystinosis in patients 6 years and older
• Click here for more information about UCSD's cystinosis program

MeSH Terms

Conditions

Cystinosis; Rare Diseases

Interventions

Cysteamine

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Mercaptoethylamines; Ethylamines; Amines; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds

Results Point of Contact

• Title: Evelyn Olson, Director
• Organization: Horizon Orphan LLC

clinicaltrials@horizonpharma.com

224-383-3000

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2009
• First Posted: March 31, 2009
• Study Start: May 1, 2009
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: December 19, 2024
• Results First Posted: October 28, 2014

Record last verified: 2024-11

Locations

US (1)