Clinical trial NCT00872729: Pilot Study of Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of RP103 Compared to Cystagon® in Patients With Cystinosis
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cystinosis
Keywords: cystinosis
cysteamine
inheritable disease
orphan disease
CTNS protein, human
nephropathic cystinosis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2009-03-31
Enrollment: 9
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This is a single-dose, open-labeled, non-randomized, two-period study of Cysteamine Bitartrate Delayed-release Capsules (RP103) and Cystagon® in up to 10 patients (male or female) with nephropathic cystinosis under fasting conditions. It will involve a 4 night check-in to a clinical research center.

Study with completed results acquired from Horizon in 2024

Eligibility criteria: 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.

Primary outcomes:
measure: Plasma Pharmacokinetic Parameter: Cmax of Cysteamine
timeFrame: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing
measure: Plasma Pharmacokinetic Parameter: Tmax of Cysteamine
timeFrame: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing
measure: Plasma Pharmacokinetic Parameter: AUC(0-t) of Cysteamine
timeFrame: 12 hours post RP103 dosing and 6 hours post 1st Cystagon® dosing
measure: Pharmacodynamic Parameter: Changes of White Blood Cell (WBC) Cystine Level From Baseline
timeFrame: up to 12 hours post Cystagon® dosing and RP103 dosing
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.