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: 23.1Level: PTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Not possible to specify
- Registration Number
- EUCTR2018-001303-36-CZ
- Lead Sponsor
- Tricida Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 3000
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. Had heart failure with maximum New York Heart Association (NYHA)
Class IV symptoms during the 3 months prior to the Screening 1 Visit.
4. Had a heart, liver or kidney transplant.
5. 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): Progression of chronic kidney disease, defined by time to first occurrence of any event in the composite endpoint consisting of the following as adjudicated by the independent blinded Clinical Endpoint Adjudication Committee (CEAC):<br>• A confirmed = 40% reduction in eGFR<br>• End-stage renal disease (ESRD)<br>• Renal death;Timepoint(s) of evaluation of this end point: The time to first occurrence of any component of the composite endpoint as adjudicated by an independent blinded CEAC.;Main Objective: To evaluate the effect of TRC101 on the progression of chronic kidney disease and to evaluate the safety profile of TRC101 in CKD patients with metabolic acidosis.;Secondary Objective: Not applicable
- Secondary Outcome Measures
Name Time Method