Phase 2b Study of KBP-5074 in Subjects With Uncontrolled Hypertension and Advanced Chronic Kidney Disease
Condition: Chronic Kidney Diseases; Hypertension
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Hypertension
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a Phase 2 randomized, double-blind, placebo-controlled, multi-center study to assess
      the efficacy, safety, and pharmacokinetics of KBP-5074 in patients with moderate-to-severe
      chronic kidney disease and uncontrolled hypertension.
    

Detailed description: 
      The study will enroll up to 165 patients, randomized in a 1:1:1 ratio to 1 of 3 treatment
      groups (55 patients in each group): KBP-5074 0.25 mg once daily (QD), KBP-5074 0.5 mg QD, or
      placebo QD. Randomization will be stratified to balance enrollment for key variables that may
      influence safety and/or efficacy evaluations, including estimated Glomerular Filtration Rate
      (eGFR) (30 versus 29 mL/min/1.73 m2) and Systolic Blood Pressure (SBP) (160 versus <160
      mmHg). The study will be approximately 5 months in duration with 84 days of double-blind
      treatment. The study will consist of an up to 4-week screening period; 2-week, open-label
      (placebo) run-in period; 84-day double-blind treatment period; and a 4-week post-treatment
      safety follow-up period. Patients will be sampled for plasma pharmacokinetics (PK). Total
      KBP-5074 levels will be assessed in patients treated with active drug. A total of 4 PK
      samples will be collected from each patient, including Day 1 (prior to discharge), Day 14
      pre-dose, Day 28 pre-dose, and End of Study Visit (Day 98)/Early Termination Visit. The
      pre-dose samples assume that patients will be dosed in the unit on those days above. If
      patients are not dosed in the unit on those days, a flexible PK sample will be collected
      during each of these visits.Safety will be assessed systematically, and an independent data
      monitoring committee will perform cumulative reviews of safety data at regular intervals
      during the study. Serum potassium levels, serum creatinine, and blood pressure will be
      closely monitored throughout the study. At Screening, patients must have uncontrolled
      hypertension, defined as resting trough cuff seated SBP 140 mmHg, based on the mean of the
      last 2 consecutive blood pressure readings at Screening in the clinic. In all cases, dose and
      frequency of concurrent antihypertensive medications are expected to be maintained without
      change for 30 days prior to randomization in order to ensure that blood pressure is stable.
      In general, patients should not add nor adjust dose and/or types of the antihypertensive
      medications they are receiving during the screening period and throughout the duration of the
      study (unless they develop hypertensive crisis or symptomatic hypotension). Patients will be
      advised to maintain their normal diet and avoid alcohol or potassium-rich foods/drinks during
      the study period. No potassium supplements are permitted, unless clinically indicated to
      treat hypokalemia until serum potassium values are within the normal range. Potassium-sparing
      agents are not permitted. After completion of the screening period and the qualifying
      Screening Visit, patients who meet all eligibility criteria (except those criteria scheduled
      to be assessed after the Screening Visit), will enter the 2-week, open-label (placebo) run-in
      period. At the end of the run-in period, patients will be re-assessed for eligibility,
      including compliance to study drug received during the run-in period, which must be >80% and
      120% (i.e. placebo and stable antihypertensive medication, i.e. no change in antihypertensive
      medication). If a patient is found to be ineligible during Screening, a 1-time re-screening
      is allowed if the Investigator believes that the patient's condition has changed and the
      patient may be eligible before the re-screening tests. Please note that a new patient number
      should be assigned to any re-screened patient, and all the procedures defined in the protocol
      for the Screening Visit and during the run-in period must be repeated. Patients who meet all
      eligibility criteria at the end of the screening period and run-in period will be randomized
      (stratified based on eGFR 30 versus 29 mL/min/1.73 m2 and SBP 160 versus <160 mmHg) into the
      study on Day 1. All randomized patients will receive double-blind treatment for 84 days.
      Patients will be followed for 4 weeks for safety assessments after the last dose of study
      drug. A subset of patients who still meet eligibility criteria at the end of the run-in
      period (Visit 3) will undergo 24-hour ambulatory blood pressure monitoring (ABPM) on Day 1,
      Day 40, and Day 82.
    

Intervention name(s): KBP-5074 0.25 mg tablet; KBP-5074 0.5 mg tablet
Intervention type(s): Drug; Drug
Intervention description(s): Oral administration, QD, 84 days; Oral administration, QD, 84 days
Other intervention name(s): MRA; MRA
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Chronic Kidney Disease; Hypertension