CystinosisPhase 3NCT01000961
Phase 3 Study of Cysteamine Bitartrate Delayed-release (RP103) Compared to Cystagon® in Patients With Cystinosis
A Phase 3 study testing Cystagon® (Cysteamine Bitartrate) and Cysteamine Bitartrate Delayed-release Capsules (RP103) in people with Cystinosis, run by Amgen at 8 sites in 3 countries.
Trial summary
Cystinosis is an inherited 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. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Cystinosis
- What is being tested?
- Cystagon® (Cysteamine Bitartrate) and Cysteamine Bitartrate Delayed-release Capsules (RP103)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 8 sitesin 3 countries
- Study dates
- Jun 2010to Aug 2011
- Phase
- Phase 3
- 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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male and female subjects must have nephropathic cystinosis.
- Subjects must be on a stable dose of Cystagon® sufficient to maintain their white blood cell (WBC) cystine level at ≤ 1.0 nmol/half-cystine/mg protein.
- Subjects must be able to swallow their typically administered Cystagon® capsule with the capsule intact.
- Within the last 6 months, no clinically significant change in liver function [i.e., ALT, AST, total bilirubin] and renal function [i.e., estimated GFR] at Screening as determined by the Investigator.
- Subjects with an estimated GFR (corrected for body surface area) > 30 mL/min/1.73m2.
- 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 must be willing and able to comply with the study restrictions and requirements.
- Subjects or their or their parent or guardian must provide written informed consent and assent (where applicable) prior to participation in the study.
Who cannot join
- Subject's age < 6 years old or subject's weight < 21 kg.
- Subjects with a known history, currently of the following conditions or other health issues that make it, in the opinion of the investigator, unsafe for them to participate: inflammatory bowel disease (if currently active) or have had prior resection of small intestine; Heart disease (e.g., myocardial infarction, heart failure, arrhythmias or poorly controlled hypertension) 90 days prior to Screening; Active bleeding disorder 90 days prior to Screening; Malignant disease within the last 2 years.
- Patients with a hemoglobin level < 10 g/dL at Screening or a level that, in the opinion of the investigator, makes it unsafe for the subject to participate.
- Subjects receiving any form of cysteamine medication through a gastric tube.
- Subjects who are receiving maintenance dialysis or who have had a kidney transplant.
- Subjects who are on an active kidney transplant list or who are planning to receive a kidney transplant within 3 months of Screening.
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- Subjects with known hypersensitivity to cysteamine or penicillamine.
- Female subjects who are nursing, planning a pregnancy, known or suspected to be pregnant, or have 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.
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
France4 sites
Hospices Civils de Lyon
Lyon
Villeneuve-Lapeyronie Hospital
Montpellier
Necker Hospital
Paris
Robert Debre Hospital
Paris
United States3 sites
Emory Children's Center
Atlanta, Georgia, 30322
Ann & Robert H. Lurie Children's Hospital of Chicago (formerly Children's Memorial Hospital)
Chicago, Illinois, 60614
Stanford University Medical School
Stanford, California, 94305
About this study
Official title: A Randomized, Crossover Pharmacokinetic and Pharmacodynamic Study to Determine the Safety and Efficacy of Cysteamine Bitartrate Delayed-release Capsules (RP103), Compared to Cystagon® in Patients With Nephropathic Cystinosis
Cystinosis is an inherited 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 to four times a day Cystagon®.
Read the detailed description
This is a multi-center, open-label, randomized, cross-over study to determine whether steady-state, twice a day treatment with Cysteamine Bitartrate Delayed-release Capsules(RP103) results in comparable depletion of white blood cell (WBC) cystine levels compared to the existing four times a day cysteamine treatment. It will involve up to 20 clinic visits plus intermittent home use of the RP103. Most of these clinic visits occur in clusters of 3-4 consecutive days. Eligible patients will be offered enrollment into a long-term follow up study.
Study with completed results acquired from Horizon in 2024.
- Conditions
- Cystinosis
- Being tested
- Cystagon® (Cysteamine Bitartrate), Cysteamine Bitartrate Delayed-release Capsules (RP103)
- Keywords
- cystinosis, cysteamine, inheritable disease, orphan disease, CTNS protein, human, metabolic disease, nephropathic cystinosis
- Medical subject headings
- Cystinosis, Rare Diseases, Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cystagon® (Cysteamine Bitartrate)Drug
Run-in Period (Weeks 1, 2, 3) and Period 1 (Weeks 4, 5, 6) or Period 2 (Weeks 7, 8, 9); Immediate crossover to opposite treatment than taken during Period 1:
Every 6H, supplied in 150 and 50mg capsules/Duration of Treatment: 3 weeks each period used
Cysteamine Bitartrate Delayed-release Capsules (RP103)Drug
Period 1 (Weeks 4, 5, 6) or Period 2 (Weeks 7, 8, 9); Immediate crossover to opposite treatment than taken during Period 1:
Every 12H, supplied in 75 and 25mg capsules/Duration of Treatment: 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| RP103 Q12H | Experimental | Not described Receives: Drug: Cysteamine Bitartrate Delayed-release Capsules (RP103) |
| Cystagon® Q6H | Active comparator | Not described Receives: Drug: Cystagon® (Cysteamine Bitartrate) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Steady-state White Blood Cell Cystine Levels of RP103 Compared to Cystagon®
Measured: 4 weeks after the last subject has completed the study
Secondary outcomes (3)
Comparison of Cysteamine PK Profiles, Steady State Cmax, Between RP103 and Cystagon®.
Measured: 4 weeks after the last subject has completed the study
Comparison of Cysteamine PK Profiles, Steady State Tmax, Between RP103 and Cystagon®.
Measured: 4 weeks after the last subject has completed the study
Comparison of Cysteamine PK Profiles, AUC(0-t), Between RP103 and Cystagon®.
Measured: 6 hours post dosing for Cystagon®; 12 hours post dosing for RP103.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2009 (estimated)
- Study startJun 2010
- Primary completionJun 2011
- Study completionAug 2011
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01000961
- Sponsor's protocol ID
- RP103-03
- Status last verified
- Nov 2024
- First submitted
- 22 Oct 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 16769383Fidler 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 17229040Levtchenko 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
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 Randomized, Crossover Pharmacokinetic and Pharmacodynamic Study to Determine the Safety and Efficacy of Cysteamine Bitartrate Delayed-release Capsules (RP103), Compared to Cystagon® in Patients With Nephropathic Cystinosis
- ClinicalTrials.gov ID
- NCT01000961
- Acronym / sponsor ID
- RP103-03
- Conditions
- Cystinosis
- Keywords
- cystinosis, cysteamine, inheritable disease, orphan disease, CTNS protein, human, metabolic disease, nephropathic cystinosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- Jun 2010
- Primary completion
- Jun 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 23 Oct 2009 (estimated)
- Results
- Posted 19 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cystinosis is an inherited 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 to four times a day Cystagon®.
Detailed description
This is a multi-center, open-label, randomized, cross-over study to determine whether steady-state, twice a day treatment with Cysteamine Bitartrate Delayed-release Capsules(RP103) results in comparable depletion of white blood cell (WBC) cystine levels compared to the existing four times a day cysteamine treatment. It will involve up to 20 clinic visits plus intermittent home use of the RP103. Most of these clinic visits occur in clusters of 3-4 consecutive days. Eligible patients will be offered enrollment into a long-term follow up study.
Study with completed results acquired from Horizon in 2024.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RP103 Q12H | Experimental | Drug: Cysteamine Bitartrate Delayed-release Capsules (RP103) |
| Cystagon® Q6H | Active comparator | Drug: Cystagon® (Cysteamine Bitartrate) |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female subjects must have nephropathic cystinosis.
- Subjects must be on a stable dose of Cystagon® sufficient to maintain their white blood cell (WBC) cystine level at ≤ 1.0 nmol/half-cystine/mg protein.
- Subjects must be able to swallow their typically administered Cystagon® capsule with the capsule intact.
- Within the last 6 months, no clinically significant change in liver function [i.e., ALT, AST, total bilirubin] and renal function [i.e., estimated GFR] at Screening as determined by the Investigator.
- Subjects with an estimated GFR (corrected for body surface area) > 30 mL/min/1.73m2.
Key exclusion criteria (10 listed)
- Subject's age < 6 years old or subject's weight < 21 kg.
- Subjects with a known history, currently of the following conditions or other health issues that make it, in the opinion of the investigator, unsafe for them to participate: inflammatory bowel disease (if currently active) or have had prior resection of small intestine; Heart disease (e.g., myocardial infarction, heart failure, arrhythmias or poorly controlled hypertension) 90 days prior to Screening; Active bleeding disorder 90 days prior to Screening; Malignant disease within the last 2 years.
- Patients with a hemoglobin level < 10 g/dL at Screening or a level that, in the opinion of the investigator, makes it unsafe for the subject to participate.
- Subjects receiving any form of cysteamine medication through a gastric tube.
- Subjects who are receiving maintenance dialysis or who have had a kidney transplant.
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® (Cysteamine Bitartrate)Run-in Period (Weeks 1, 2, 3) and Period 1 (Weeks 4, 5, 6) or Period 2 (Weeks 7, 8, 9); Immediate crossover to opposite treatment than taken during Period 1: Every 6H, supplied in 150 and 50mg capsules/Duration of Treatment: 3 weeks each period used | Drug | Cystagon® Q6H |
| Cysteamine Bitartrate Delayed-release Capsules (RP103)Period 1 (Weeks 4, 5, 6) or Period 2 (Weeks 7, 8, 9); Immediate crossover to opposite treatment than taken during Period 1: Every 12H, supplied in 75 and 25mg capsules/Duration of Treatment: 3 weeks | Drug | RP103 Q12H |
Primary outcome
The Steady-state White Blood Cell Cystine Levels of RP103 Compared to Cystagon®
Time frame: 4 weeks after the last subject has completed the study
3 secondary outcomes
Comparison of Cysteamine PK Profiles, Steady State Cmax, Between RP103 and Cystagon®.
Time frame: 4 weeks after the last subject has completed the study
Comparison of Cysteamine PK Profiles, Steady State Tmax, Between RP103 and Cystagon®.
Time frame: 4 weeks after the last subject has completed the study
Comparison of Cysteamine PK Profiles, AUC(0-t), Between RP103 and Cystagon®.
Time frame: 6 hours post dosing for Cystagon®; 12 hours post dosing for RP103.
Results and safety
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.
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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
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cystagon® (Cysteamine Bitartrate) and Cysteamine Bitartrate Delayed-release Capsules (RP103) in people with Cystinosis, run by Amgen at 8 sites in 3 countries.
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 8 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 8 sites in France, United States, Netherlands. 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 19 Nov 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?
The Steady-state White Blood Cell Cystine Levels of RP103 Compared to Cystagon® (time frame: 4 weeks after the last subject has completed the study). 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 NCT01000961, 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.