CystinosisPhase 1/2NCT00872729

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

A Phase 1/2 study testing Cystagon® and RP103 in people with Cystinosis, run by Amgen at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Any age
Conditions the study is for: Cystinosis
What is being tested?: Cystagon® and RP103
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 9 participants
Where: 1 siteUnited States
Study dates: May 2009to Oct 2009
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Show all 9Show fewer

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.

Who cannot join

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.

Show all 10Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of California San Diego Medical Center
San Diego, California, 92103

Other trials in United States

About this study

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

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.

Read the 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

Conditions: Cystinosis
Being tested: Cystagon®, RP103
Keywords: cystinosis, cysteamine, inheritable disease, orphan disease, CTNS protein, human, nephropathic cystinosis
Medical subject headings: Cystinosis, Rare Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Cystagon®Drug
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
Duration of Treatment and Dose: Reference Period up to four doses Q6H.
RP103Drug
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.

Study groups in NCT00872729
Study group	Role	What they receive
Cystagon®	Active comparator	Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg Receives: Drug: Cystagon®
RP103	Experimental	Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg Receives: Drug: RP103

What is being measured

The primary outcome is the main question the study is designed to answer.

Plasma Pharmacokinetic Parameter: Cmax of Cysteamine
Measured: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing
Plasma Pharmacokinetic Parameter: Tmax of Cysteamine
Measured: 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.
Measured: 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.
Measured: up to 12 hours post Cystagon® dosing and RP103 dosing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2009Oct 2009

First posted31 Mar 2009 (estimated)
Study startMay 2009
Primary completionOct 2009
Study completionOct 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for CystinosisStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 9 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00872729
Sponsor's protocol ID: RP103-01
Status last verified: Nov 2024
First submitted: 27 Mar 2009
Last updated: 19 Dec 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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.
PubMed 16769383
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.
PubMed 17229040
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.
PubMed 16252107

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingObservational study
European Cystinosis Cohort 2
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RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 1/2
DFT383 in Pediatric Participants With Nephropathic Cystinosis
Nephropathic Cystinosis
Not yet recruitingPhase 2
Pilot Study of TTI-0102 in Cystinosis
Nephropathic Cystinosis, Cystinosis
RecruitingObservational study
Use of Cysteamine in the Treatment of Cystinosis
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All Cystinosis trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00872729
Acronym / sponsor ID: RP103-01
Conditions: Cystinosis
Keywords: cystinosis, cysteamine, inheritable disease, orphan disease, CTNS protein, human, nephropathic cystinosis
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 9 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: May 2009
Primary completion: Oct 2009 (actual)
Study completion: Oct 2009 (actual)
First posted: 31 Mar 2009 (estimated)
Results: Posted 28 Oct 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study with completed results acquired from Horizon in 2024

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Cystagon®	Active comparator	Drug: Cystagon®Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg
RP103	Experimental	Drug: RP103Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (9 listed)

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.

Key exclusion criteria (10 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Cystagon®Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg. Duration of Treatment and Dose: Reference Period up to four doses Q6H.	Drug	Cystagon®
RP103Test 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.	Drug	RP103

Primary outcome

Plasma Pharmacokinetic Parameter: Cmax of Cysteamine
Time frame: 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
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.
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.

Results and safety

Results posted to the registry on 28 Oct 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cystagon® and RP103	9	9

Primary outcome: Plasma Pharmacokinetic Parameter: Cmax of Cysteamine

Time frame: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing. Geometric mean (Geometric Coefficient of Variation). Unit: umol/L

Measure	Cystagon® n = 9	RP103 n = 9
Value	42.02 (51)	33.06 (55)

Primary outcome: Plasma Pharmacokinetic Parameter: Tmax of Cysteamine

Time frame: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing. Median (Full Range). Unit: hour

Measure	Cystagon® n = 9	RP103 n = 9
Value	1.00 (0.50 to 2.00)	3.00 (0.00 to 5.13)

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

Time frame: 12 hours post RP103 dosing and 6 hours post 1st Cystagon® dosing. Geometric mean (Geometric Coefficient of Variation). Unit: umol•h/L

Measure	Cystagon® n = 9	RP103 n = 9
Value	107.89 (58)	119.17 (46)

Population analysed: Subjects were enrolled sequentially according to the study design. A mixed-effects linear model was used to assess differences between the RP103 and Cystagon treatment groups. Sample size is based on feasibility rather than statistical considerations.

Primary outcome: Pharmacodynamic Parameter: Changes of White Blood Cell (WBC) Cystine Level From Baseline

Time frame: up to 12 hours post Cystagon® dosing and RP103 dosing. Mean (Standard Deviation). Unit: nmol 1/2 cystine/mg protein

Measure	Cystagon® (0.5 Hour) n = 6	RP103 (0.5 Hour) n = 0	Cystagon® (1 Hour) n = 3	RP103 (1 Hour) n = 3	Cystagon® (2 Hour) n = 6	RP103 (2 Hour) n = 0	Cystagon® (2.5 Hour) n = 0	RP103 (2.5 Hour) n = 6	Cystagon® (3 Hour) n = 3	RP103 (3 Hour) n = 3	Cystagon® (4 Hour) n = 6	RP103 (4 Hour) n = 6	Cystagon® (6 Hour) n = 9	RP103 (6 Hour) n = 6	Cystagon® (8 Hour) n = 0	RP103 (8 Hour) n = 3	Cystagon® (10 Hour) n = 0	RP103 (10 Hour) n = 3	Cystagon® (12 Hour) n = 3	RP103 (12 Hour) n = 6
Value	0.11 (0.24)	–	-0.10 (0.02)	0.87 (0.33)	-0.07 (0.28)	–	–	0.19 (0.48)	-0.14 (0.06)	0.43 (0.70)	-0.01 (0.15)	0.10 (0.50)	0.30 (0.34)	0.22 (0.41)	–	0.20 (0.31)	–	0.45 (0.36)	0.37 (0.18)	0.72 (0.47)

Population analysed: Sample size is based on feasibility rather than statistical considerations. Analysis time differences (0-6 hours) is due to different absorption characteristics of Cysteamine between RP103 and Cystagon. Cystagon is dosed every 6 hours and there is no measurement after 6 hours and up to 12 hours.

Adverse events

Time frame: After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cystagon®	0 of 9 (0%)	8 of 9 (88.9%)	Not reported
RP103	0 of 9 (0%)	2 of 9 (22.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16769383Dohil 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.
Background: PubMed 17229040Fidler 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.
Background: PubMed 16252107Levtchenko 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.
RP103 (marketed as PROCYSBI) is now approved by the US FDA for management of nephropathic cystinosis in patients 6 years and olderLink provided by the sponsor.
Click here for more information about UCSD's cystinosis programLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cystagon® and RP103 in people with Cystinosis, run by Amgen at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma Pharmacokinetic Parameter: Cmax of Cysteamine (time frame: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00872729, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2024.