CystinuriaPhase 2NCT02942420
Bucillamine Phase 2 Trial in Patients With Cystinuria
A Phase 2 study testing Bucillamine in people with Cystinuria, run by Revive Therapeutics, Ltd. at 5 sites in United States.
Trial summary
Subjects on a standard regimen of tiopronin (cystine binding thiol drug; CBTD) plus prescribed first-line therapy (i.e. on a hydration, alkali therapy and dietary restriction) who are failing therapy will be selected for this trial. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cystinuria
- What is being tested?
- Bucillamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 5 sitesUnited States
- Study dates
- 1 May 2017to Mar 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects of any gender and of any race ≥18 and ≤80 years of age
- Subjects with proven cystinuria who are failing their standard drug therapy of tiopronin plus first-line therapy (hydration, alkali and diet restriction) and who meet the following criteria.
- formed new stones while taking a thiol.
- had increase in stone size of pre-existing stones while taking a thiol.
- had a urologic intervention for stones while taking a thiol
- Subjects must be able to reliably urinate in a collection vessel and measure urine volume
Show all 28Show fewer
- Subjects must have documentation of a stable complete blood count (CBC) and urinalysis (UA) in the 6 months prior to date of enrollment
- Subjects may have a history of but not currently active CNS disorders or symptoms/effects (e.g., headache)
- Subjects must have adequate organ function, evidenced by the following laboratory results within 30 days prior to enrollment:
- Absolute neutrophil count >2000 cells/mm
- Platelet count >140,000 cells/mm3
- Hemoglobin >11.0 g/dl
- Albumin ≥2.5 g/dl
- Total bilirubin ≤1.5 upper limit of normal (ULN)
- SGOT (aspartate aminotransferase [AST]), SGPT (alanine aminotransferase [ALT]), and alkaline phosphatase (ALP)
- ≤ 2.5 x ULN
- eGFR >60 ml/min/173m 2 based on Modification of Diet and Renal Disease (MDRD) Study equation which includes the variables of creatinine, age, sex and race
- Female subject who has been post-menopausal for at least 24 consecutive months, or women who have undergone surgical sterilization, (e.g. hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy) is eligible without requiring the use of a contraceptive methods described in Inclusion #8
- For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception:
- Acceptable forms of should include two of the following:
- Placement of intrauterine device (IUD) or intrauterine system (IUS)
- Condom with spermicidal foam/gel/film/cream/suppository
- Diaphragm or cervical/vault caps with spermicidal foam/gel/film/cream/suppository
- The above contraception is not a requirement in the case of any of the following:
- Subject is surgically sterilized
- Subject has had no menstrual period for 12 consecutive months
- Contraception use should continue for the duration of the study treatment and for at least 3 months after the last dose of study treatment Periodic abstinence (e.g., calendar ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
- Subjects must be willing and able to give written informed consent
Who cannot join
- Subjects with renal colic
- Subjects who are scheduled to undergo a surgical procedure
- Subjects on D-penicillamine (see page 35 for explanation)
- Subjects with cancer
- Subjects with acute or chronic infections including HIV, tuberculosis, hepatitis B or hepatitis C
- Patients with proteinuria ≥30 mg that is confirmed on repeat laboratory assessment within 24 hours
Show all 18Show fewer
- Subjects with QTc interval >450 ms
- A history of, hypokalemia and family history of Long QT syndrome
- Use of concomitant medications that may prolong QT/QTc interval
- Patients with significant heart failure and activity impairment (Class III-IV of the New York Heart Association (NYHA)
- Subjects with serious hepatic disorder (Child-Pugh scores B or C)
- Subjects with a history of alcohol or substance abuse within the 12 months prior to enrollment
- Subjects with history of or active blood dyscrasia such as myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia.
- Subjects with Coagulopathy (regardless if controlled by pharmacotherapy or not)
- Subjects who have any concomitant illness (including active significant infection) or other finding that, in the opinion of the Investigator, would confound the study data or place the subject at unacceptable risk if the subject were to participate in the study, or that would require frequent adjustments in concomitant medications during the course of the study
- Use of any investigational drug within 30 days prior to enrollment
- Subjects currently participating in another research study or anticipated to enroll in such during participation in this study
- Subjects for whom informed consent cannot be obtained
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
University of Alabama - Department of Urology
Birmingham, Alabama, 35294
Lisa Harvey, 205-996-2613, lharvey@uabmc.edu
Dean Assimos, MD
- Recruiting
Massachusette General Hospital
Boston, Massachusetts, 02114
Sagar Uday Nigwekar, MD, 617-726-7872, snigwekar@mgh.harvard.edu
- Recruiting
University of Wisconsin School of Medicane and Public Health
Madison, Wisconsin, 53705,
Stephen Nakada, MD, 360-252-2500, nakada@urology.wisc.edu
- Recruiting
New York University School of Medicine
New York, New York, 10016
Frank Moderstizki, 212-686-7500 ext. 6379, Frank.Moderstizki@nyumc.org
Lama Nazzal, MD
- Recruiting
Omega Medical Research
Warwick, Rhode Island, 02886
Johnna Pezzullo, 401-739-9350, Johnna@omegamedicalresearch.com
Gyan Pareek, MD
About this study
Official title: Phase 2 Multi-Center, Dose Escalation Trial To Assess The Safety And Effectiveness Of Bucillamine On Urinary Cystine Excretion And Cystine Capacity In Patients With Cystinuria
Subjects on a standard regimen of tiopronin (cystine binding thiol drug; CBTD) plus prescribed first-line therapy (i.e. on a hydration, alkali therapy and dietary restriction) who are failing therapy will be selected for this trial.
After completing informed consent, the subject will have Screening consisting of medication history and physical examination with vital signs. Samples of blood and urine will be taken for clinical laboratory and urinalysis. Patients will undergo a 12-lead ECG test. A history of side effects with current CBTD as well as laboratory recordings of abnormalities attributable to treatment will also be recorded.
Read more
Subjects will be dosed in a sequential manner, starting with the low dose group (300 mg/day), then proceeding to the 600 mg.day dose group.. Safety and tolerability will be monitored closely by an Independent Medical Monitor (IMM) and based on the IMM's assessment that it is safe to proceed to the higher dose (600 mg/day), subsequent subjects will be enrolled into that group. Up to 15 subjects each will be enrolled into either Group A or Group B.
After 7 days on the assigned bucillamine dose, a 24-hour urine sample will be taken and after completing the Day 8 safety visit, subjects will undergo a 7 day washout where no CBTDs will be taken. Thereafter, subjects will be allowed to resume their originally prescribed CBTDs under Investigator's supervision.
One week following study drug discontinuation, subjects will return to the clinic for follow-up safety assessments.
Read the detailed description
Subjects on a standard regimen of tiopronin (cystine binding thiol drug; CBTD) plus prescribed first-line therapy (i.e. on a hydration, alkali therapy and dietary restriction) who are failing therapy will be selected for this trial.
Subjects will be encouraged to continue their usual self-selected ad-lib diets, fluid and alkali regimen and keep this regimen consistent throughout the duration of the study. Study diaries will be kept to assess consistency and drug compliance.
After completing informed consent, the enrolled subject will have an initial Screening interview. During the interview the patient will be assessed for symptoms of renal colic as well as asked about any scheduled urological procedures (a positive indication is an exclusionary criteria). At the Screening visit, a medication history will be taken and a complete physical examination, including vital signs will be done. Samples of blood and urine will be taken for clinical laboratory and urinalysis. Patients will then undergo a 12-lead ECG test.
A history of side effects with current CBTD as well as laboratory recordings of abnormalities attributable to treatment will also be recorded.
Enrolled subjects will be dosed in a sequential manner, starting with the low dose group (300 mg/day). Safety and tolerability will be monitored closely by an Independent Medical Monitor (IMM) and based on the IMM's assessment that it is safe to proceed to the higher dose (600 mg/day), subsequent subjects will be enrolled into that group. Up to 15 subjects each will be enrolled into either Group A or Group B.
Subjects will stop taking their current CBTDs for 7 days and perform a 24-hour urine collection on Day-7 and report for Day 1 Visit .
Subjects enrolled into Group A will start taking bucillamine tablets orally, three times a day preferably 1hr before or 2hrs after meals in the following sequence; 100 mg (1 tab) in the morning; 100 mg (1 tab) at noon and 100 mg (1 tab) at night. This drug regimen will continue for 7 days. Safety Visits are scheduled on Day 3 and Day 8 (End of Study Visit). Furthermore, on Day 7 a 24-hour urine collection will be performed. Instructions for handling this sample will be provided in a separate manual.
Subjects enrolled into Group B, will start taking bucillamine tablets orally, three times a day preferably 1hr before or 2hrs after meals in the following sequence; 200 mg (2 tabs) in the morning; 200 mg (2 tabs) at noon and 200 mg (2 tabs) at night. This drug regimen will continue for 7 days. Safety Visits are scheduled on Day 3 and Day 8 (End of Study Visit). Furthermore, on Day 7 a 24-hour urine collection will be performed. Instructions for handling this sample will be provided in a separate manual.
After 7 days on the assigned bucillamine dose and after providing the 24-hour urine sample, and after completing the Day 8 safety visit, subjects will undergo a 7 day washout where no CBTDs will be taken. Thereafter, subjects will be allowed to resume their originally prescribed CBTDs under Investigator's supervision.
One week following study drug discontinuation, subjects will return to the clinic for follow-up safety assessments.
- Conditions
- Cystinuria
- Being tested
- Bucillamine
- Medical subject headings
- Cystinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BucillamineDrug
Thiol donor which results in a cysteine-bucillamine complex for removing excess cysteine from the urine
| Study group | Role | What they receive |
|---|---|---|
| Dose Group A | Experimental | Bucillamine 300 mg/day Receives: Drug: Bucillamine |
| Dose Group B | Experimental | Bucillamine 600 mg/day Receives: Drug: Bucillamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Number, type, and severity of AEs observed by the staff during visits on Days 0 (dosing), 3, 8 and +1 week post-study or volunteered by the subject during telephone follow-up on Days 2 and 7.
Measured: Days 0, 2, 3, 7, 8 and + 1 wk post study
Secondary outcomes (2)
Cystine Excretion
Measurement of 24-hr urine cystine excretion.
Measured: Day 0 and Day 8
Cystine Capacity
Measurement of 24-hr urine cystine capacity, i.e., the capacity of a patient's urine to solubilize or precipitate.
Measured: Day 0 and Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2016 (estimated)
- Study start1 May 2017
- Primary completionMar 2018 (estimated)
- Study completionMar 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CystinuriaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dosing will occur sequentially from low to high dose: The 600 mg bucillamine dose group (Arm A) will enroll first, then after safety is assured, the 900 mg bucillamine dose group will enroll.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Revive Therapeutics, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02942420
- Sponsor's protocol ID
- REV401
- Status last verified
- Mar 2017
- First submitted
- 19 Oct 2016
- Last updated
- 18 May 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Multi-Center, Dose Escalation Trial To Assess The Safety And Effectiveness Of Bucillamine On Urinary Cystine Excretion And Cystine Capacity In Patients With Cystinuria
- ClinicalTrials.gov ID
- NCT02942420
- Acronym / sponsor ID
- REV401
- Conditions
- Cystinuria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Revive Therapeutics, Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 May 2017 (actual)
- Primary completion
- Mar 2018 (estimated)
- Study completion
- Mar 2018 (estimated)
- First posted
- 24 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Subjects on a standard regimen of tiopronin (cystine binding thiol drug; CBTD) plus prescribed first-line therapy (i.e. on a hydration, alkali therapy and dietary restriction) who are failing therapy will be selected for this trial.
After completing informed consent, the subject will have Screening consisting of medication history and physical examination with vital signs. Samples of blood and urine will be taken for clinical laboratory and urinalysis. Patients will undergo a 12-lead ECG test. A history of side effects with current CBTD as well as laboratory recordings of abnormalities attributable to treatment will also be recorded.
Subjects will be dosed in a sequential manner, starting with the low dose group (300 mg/day), then proceeding to the 600 mg.day dose group.. Safety and tolerability will be monitored closely by an Independent Medical Monitor (IMM) and based on the IMM's assessment that it is safe to proceed to the higher dose (600 mg/day), subsequent subjects will be enrolled into that group. Up to 15 subjects each will be enrolled into either Group A or Group B.
After 7 days on the assigned bucillamine dose, a 24-hour urine sample will be taken and after completing the Day 8 safety visit, subjects will undergo a 7 day washout where no CBTDs will be taken. Thereafter, subjects will be allowed to resume their originally prescribed CBTDs under Investigator's supervision.
One week following study drug discontinuation, subjects will return to the clinic for follow-up safety assessments.
Detailed description
Subjects on a standard regimen of tiopronin (cystine binding thiol drug; CBTD) plus prescribed first-line therapy (i.e. on a hydration, alkali therapy and dietary restriction) who are failing therapy will be selected for this trial.
Subjects will be encouraged to continue their usual self-selected ad-lib diets, fluid and alkali regimen and keep this regimen consistent throughout the duration of the study. Study diaries will be kept to assess consistency and drug compliance.
After completing informed consent, the enrolled subject will have an initial Screening interview. During the interview the patient will be assessed for symptoms of renal colic as well as asked about any scheduled urological procedures (a positive indication is an exclusionary criteria). At the Screening visit, a medication history will be taken and a complete physical examination, including vital signs will be done. Samples of blood and urine will be taken for clinical laboratory and urinalysis. Patients will then undergo a 12-lead ECG test.
A history of side effects with current CBTD as well as laboratory recordings of abnormalities attributable to treatment will also be recorded.
Enrolled subjects will be dosed in a sequential manner, starting with the low dose group (300 mg/day). Safety and tolerability will be monitored closely by an Independent Medical Monitor (IMM) and based on the IMM's assessment that it is safe to proceed to the higher dose (600 mg/day), subsequent subjects will be enrolled into that group. Up to 15 subjects each will be enrolled into either Group A or Group B.
Subjects will stop taking their current CBTDs for 7 days and perform a 24-hour urine collection on Day-7 and report for Day 1 Visit .
Subjects enrolled into Group A will start taking bucillamine tablets orally, three times a day preferably 1hr before or 2hrs after meals in the following sequence; 100 mg (1 tab) in the morning; 100 mg (1 tab) at noon and 100 mg (1 tab) at night. This drug regimen will continue for 7 days. Safety Visits are scheduled on Day 3 and Day 8 (End of Study Visit). Furthermore, on Day 7 a 24-hour urine collection will be performed. Instructions for handling this sample will be provided in a separate manual.
Subjects enrolled into Group B, will start taking bucillamine tablets orally, three times a day preferably 1hr before or 2hrs after meals in the following sequence; 200 mg (2 tabs) in the morning; 200 mg (2 tabs) at noon and 200 mg (2 tabs) at night. This drug regimen will continue for 7 days. Safety Visits are scheduled on Day 3 and Day 8 (End of Study Visit). Furthermore, on Day 7 a 24-hour urine collection will be performed. Instructions for handling this sample will be provided in a separate manual.
After 7 days on the assigned bucillamine dose and after providing the 24-hour urine sample, and after completing the Day 8 safety visit, subjects will undergo a 7 day washout where no CBTDs will be taken. Thereafter, subjects will be allowed to resume their originally prescribed CBTDs under Investigator's supervision.
One week following study drug discontinuation, subjects will return to the clinic for follow-up safety assessments.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Dosing will occur sequentially from low to high dose: The 600 mg bucillamine dose group (Arm A) will enroll first, then after safety is assured, the 900 mg bucillamine dose group will enroll.
| Arm | Type | Receives |
|---|---|---|
| Dose Group A | Experimental | Drug: BucillamineBucillamine 300 mg/day |
| Dose Group B | Experimental | Drug: BucillamineBucillamine 600 mg/day |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Subjects of any gender and of any race ≥18 and ≤80 years of age
- Subjects with proven cystinuria who are failing their standard drug therapy of tiopronin plus first-line therapy (hydration, alkali and diet restriction) and who meet the following criteria.
- Subjects must be able to reliably urinate in a collection vessel and measure urine volume
- Subjects must have documentation of a stable complete blood count (CBC) and urinalysis (UA) in the 6 months prior to date of enrollment
- Subjects may have a history of but not currently active CNS disorders or symptoms/effects (e.g., headache)
Key exclusion criteria (18 listed)
- Subjects with renal colic
- Subjects who are scheduled to undergo a surgical procedure
- Subjects on D-penicillamine (see page 35 for explanation)
- Subjects with cancer
- Subjects with acute or chronic infections including HIV, tuberculosis, hepatitis B or hepatitis C
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 |
|---|---|---|
| BucillamineThiol donor which results in a cysteine-bucillamine complex for removing excess cysteine from the urine | Drug | Dose Group A, Dose Group B |
Primary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: Days 0, 2, 3, 7, 8 and + 1 wk post study
Number, type, and severity of AEs observed by the staff during visits on Days 0 (dosing), 3, 8 and +1 week post-study or volunteered by the subject during telephone follow-up on Days 2 and 7.
2 secondary outcomes
Cystine Excretion
Time frame: Day 0 and Day 8
Cystine Capacity
Time frame: Day 0 and Day 8
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2017.
- Individual participant dataSharing planned: No
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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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bucillamine in people with Cystinuria, run by Revive Therapeutics, Ltd. at 5 sites 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 28 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 18 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 phase mean?
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fabio Chianelli (905-605-5535 ext. 10, fabio@revivethera.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (time frame: Days 0, 2, 3, 7, 8 and + 1 wk post study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 May 2017; AzTrials last refreshed its copy on 6 Nov 2026.