A clinical study with patients who have increased acid in their blood because of chronic kidney disease that is testing if the experimental drug TRC101, compared to placebo (a substance that does not contain medicine), is safe and if it slows down worsening of kidney disease.
- Conditions
- Chronic kidney diseaseMedDRA version: 21.1Level: PTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Not possible to specify
- Registration Number
- EUCTR2018-001303-36-PL
- Lead Sponsor
- Tricida Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 2000
1. Have provided written informed consent prior to participation in the study.
2. Male or female subjects 18 to 85 years of age, inclusive, at Screening 1 Visit.
3. The mean of two Screening eGFR measurements, drawn at least 2 weeks apart and both within 6 weeks of the first day of Part A, is 20 to 40 mL/min/1.73m2, inclusive, calculated using the CKD-EPI equation as reported by the central laboratory.
• Note: If more than two eGFR values were measured at the central laboratory during the Screening Period, the Screening eGFR will be based on the most recent two values that are at least 2 weeks apart and within 6 weeks of the first day of Part A.
Enrollment of patients with Screening eGFR in the range 15 to 20 mL/min/1.73m2 may be allowed in the future with notification to the sites by Tricida and will not require a protocol amendment. Subjects with a Screening eGFR value in the range of 15 to <20 mL/min/1.73m2 may not be enrolled until Tricida has authorized this change in writing.
4. Have stable renal function as defined by eGFR Screening values that are not different by > 20% (the higher of the two Screening eGFR values will be used as the denominator to calculate the 20% allowable difference).
• Note: If more than two eGFR values were measured at the central laboratory during the Screening Period, the first and last values must be used for calculation of the allowable eGFR difference.
5. Based on onsite measurement using an i STAT point of care device, have three serum bicarbonate values, each = 2 weeks apart from each other and all within 6 weeks of the A1 Visit, in the range from 12 to 20 mEq/L, inclusive. One of these three values must be from the A1 Visit, pre-dose.
One retest (which can be performed on the same day as the test being
repeated) using the i-STAT point of care device is allowed from Screening 1 Visit through the A1 Visit.
Subjects with Baseline Bicarbonate (defined as the average of the serum bicarbonate values at Screening 1, Screening 2 and the A1 Visit [predose]) values of 12 to 18 mEq/L are eligible without restriction. Once approximately half of study subjects have been randomized with Baseline Bicarbonate > 18 to 20 mEq/L, randomization may be closed to additional subjects with Baseline Bicarbonate in this range.
6. Mean systolic and diastolic blood pressure (determined as the average of three replicates) must be < 160/92 mmHg at the Screening 2 Visit.
7. Receiving treatment with an ACE inhibitor and/or ARB at the maximum tolerated (for the individual subject) dose within the country-specific labeled dose range, without adjustments, for = 4 weeks prior to the Screening 1 Visit and during the Screening Period. The maximum tolerated dose for an individual subject may be less than the maximum labeled dose or may be zero if the medical reason is documented.
Subjects not treated with an ACE inhibitor or ARB must be approved by the Medical Monitor following a review of the medical justification.
Non-diabetic subjects with urine ACR < 30 mg/g (< 3.39 mg/mmol) are not required to be receiving treatment with an ACE inhibitor and/or ARB.
8. If receiving an oral alkali supplement, the dose must be stable for = 2 weeks prior to Screening 1 Visit and during the Screening Period.
If not receiving alkali treatment, there must be no such treatment within the 2 weeks prior to Screening 1 Visit or during the Screening Period.
9. Have a hemoglobin A1c (HbA1c) value of = 11.0% (0.11 fraction; 97 mmol/mol) at the Screenin
1. Have any level of low serum bicarbonate at either Screening Visit that, in the opinion of the Investigator, requires emergency intervention or evaluation for an acute acidotic process.
2. Have had anuria, dialysis, or acute kidney injury/acute renal failure in the 3 months prior to the Screening 1 Visit.
3. Have chronic obstructive pulmonary disease (COPD) that is treated with chronic oral steroids, that requires the subject to be on oxygen, or that required hospitalization within the previous 6 months.
4. Had heart failure with maximum New York Heart Association (NYHA) Class IV symptoms during the 3 months prior to the Screening 1 Visit.
5. Had a heart, liver or kidney transplant.
Note: Subjects on the cadaveric transplant list or being evaluated for a future living donor transplant may be enrolled.
6. Have planned initiation of renal replacement (RRT) therapy (dialysis or transplantation) within 6 months following randomization.
7. Have had a stroke or transient ischemic attack within the 6 months prior to Screening 1 Visit.
8. Have had a cardiac event within 3 months prior to Screening 1 Visit, including: myocardial infarction, acute coronary syndrome, coronary bypass grafting, percutaneous coronary intervention, valve procedure, inpatient or outpatient treatment for acute decompensated heart failure.
9. Have been hospitalized for any reason during the 2 months prior to the Screening 1 Visit, other than for pre-planned diagnostic or minor invasive procedures (e.g., placement of dialysis access).
Note 1: Subjects who had major cardiovascular procedures or percutaneous cardiac interventional or therapeutic procedures during this time frame are excluded, even if the procedures were pre-planned.
Note 2: Subjects hospitalized during this time frame for <48 hours or for self-limited conditions (e.g., hypoglycemia, hyperkalemia, nausea) may be enrolled with approval of the Medical Monitor.
10. Have had a bowel resection or bariatric surgery. Subjects who have
had gastric lap band procedures (no gastric resection) are allowed.
11. Have liver enzyme (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) or total bilirubin values > 3× the upper limit of normal (ULN) at the Screening 2 Visit based on central laboratory measurements.
12. Have a corrected serum calcium < 8.0 mg/dL (80 mg/L; 2 mmol/L) at the Screening 1 Visit, based on central laboratory measurement.
13. Have active cancer during the 1 year prior to the Screening 1 Visit or cancer that is currently being treated or will be treated during the study, other than non-melanoma skin cancer or low-grade cervical carcinoma. Subjects with cancers that are being treated with hormonal therapy only may be permitted with approval of the Medical Monitor.
14. Have received any investigational drug during the last month (28 days or = 5 half-lives [if known], whichever is longer) preceding the Screening 1 Visit or during Screening Period.
15. Have a known allergy to placebo (microcrystalline cellulose).
16. Have an inability to consume the study drug or otherwise comply with the protocol.
17. Has received cytotoxic therapy, immunosuppressive therapy, or other immunotherapy for renal disease within 6 months prior to the Screening 1 Visit or during the Screening Period.
Note: Glucocorticoid use is allowed.
18. Have a history of alcoholism or drug/chemical abuse, as defined by The Diagnostic and Statistical Manual of Mental Disorders (DSM-5), within 6 months prior to the Scr
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method