Clinical Trial: Bucillamine Phase 2 Trial in Patients With Cystinuria

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief 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.

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 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.

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 D
Sponsor: Revive Therapeutics, Ltd.

Current 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.


Original Primary Outcome: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Daily for 8-days ]

Number, type, and severity of AEs observed by the staff (dosing visit and end-of-study visit) or volunteered by the subject during telephone follow-up.


Current Secondary Outcome:

  • Cystine Excretion [ Time Frame: Day 0 and Day 8 ]
    Measurement of 24-hr urine cystine excretion.
  • Cystine Capacity [ Time Frame: Day 0 and Day 8 ]
    Measurement of 24-hr urine cystine capacity, i.e., the capacity of a patient's urine to solubilize or precipitate.


Original Secondary Outcome:

  • Cystine Excretion [ Time Frame: Over 24-hours ]
    Quantitative measure of cysteine excretion from a 24-hour urine volume (mcmol/24 hours) collected on days 0, 3 and 8 and determined by chromatography/mass spectroscopy.
  • Cystine Capacity [ Time Frame: Over 24-hours ]
    Quantitative measure of the ability of a patient's urine to solubilize or precipitate cystine


Information By: Revive Therapeutics, Ltd.

Dates:
Date Received: October 19, 2016
Date Started: May 1, 2017
Date Completion: March 2018
Last Updated: May 16, 2017
Last Verified: March 2017