Inclusion Criteria:
1. Subjects of any gender and of any race ≥18 and ≤80 years of age
2. 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
3. Subjects must be able to reliably urinate in a collection vessel and measure urine volume
4. Subjects must have documentation of a stable complete blood count (CBC) and urinalysis (UA) in the 6 months prior to date of enrollment
5. Subjects may have a history of but not currently active CNS disorders or symptoms/effects (e.g., headache)
6. 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
7. 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
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
9. Subjects must be willing and able to give written informed consent
Exclusion Criteria:
1. Subjects with renal colic
2. Subjects who are scheduled to undergo a surgical procedure
3. Subjects on D-penicillamine (see page 35 for explanation)
4. Subjects with cancer
5. Subjects with acute or chronic infections including HIV, tuberculosis, hepatitis B or hepatitis C
6. Patients with proteinuria ≥30 mg that is confirmed on repeat laboratory assessment within 24 hours
7. Subjects with QTc interval >450 ms
8. A history of, hypokalemia and family history of Long QT syndrome
9. Use of concomitant medications that may prolong QT/QTc interval
10. Patients with significant heart failure and activity impairment (Class III-IV of the New York Heart Association (NYHA)
11. Subjects with serious hepatic disorder (Child-Pugh scores B or C)
12. Subjects with a history of alcohol or substance abuse within the 12 months prior to enrollment
13. Subjects with history of or active blood dyscrasia such as myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia.
14. Subjects with Coagulopathy (regardless if controlled by pharmacotherapy or not)
15. 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
16. Use of any investigational drug within 30 days prior to enrollment
17. Subjects currently participating in another research study or anticipated to enroll in such during participation in this study
18. Subjects for whom informed consent cannot be obtained