E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Uncontrolled hypertension in patients who have Stage 3b/4 chronic kidney disease
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E.1.1.1 | Medical condition in easily understood language |
Uncontrolled hypertension in patients who have Stage 3b/4 chronic kidney disease
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066860 |
E.1.2 | Term | Uncontrolled hypertension |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076410 |
E.1.2 | Term | Chronic kidney disease stage 3 |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076411 |
E.1.2 | Term | Chronic kidney disease stage 4 |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the efficacy and durability of KBP-5074 in reducing systolic blood pressure (SBP).
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: • To evaluate the effect of KBP-5074 on diastolic blood pressure (DBP) and urine albumin:creatinine ratio (UACR); • To evaluate the safety and tolerability of KBP-5074.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject must be ≥18 years of age at the Screening Visit (Visit 1). • Body mass index (BMI) must be ≥19 to <45 kg/m2at the Screening Visit (Visit 1). • Subject must have uncontrolled hypertension defined as meeting both of the following criteria: - The subject has a resting seated trough cuff SBP ≥140 mm Hg at the Screening Visit (Visit 1), and at the start (Visit 2) and end (Visit 3) of the Run-In Period. - The subject is taking 2 or more antihypertensive medications that have been titrated upward as tolerated to hypertension target doses per local SoC and have been stable (i.e., without any dose adjustments) from 4 weeks before the Screening Visit (Visit 1) through the end of the Run-In Period (Visit 3). ◦ The antihypertensive medications must include at least 1 loop, thiazide, or thiazide-like diuretic unless the subject has a documented intolerance to or contraindication for diuretic therapy. ◦ A subject on 1 antihypertensive medication that has been titrated upward as tolerated to a hypertension target dose per local SoC and has been stable during the 4 weeks prior to the Screening Visit (Visit 1) may be enrolled in the study if the subject has a documented history of intolerance to multiple antihypertensive medications. • The subject must have Stage 3b (eGFR ≥30 and ≤44 mL/min/1.73 m2) or Stage 4 (eGFR ≥15 and <30 mL/min/1.73 m2) CKD.
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E.4 | Principal exclusion criteria |
Subject has a serum potassium level >4.8 mmol/L according to central laboratory results during the Screening or Run-In Periods. • Subject has had a serum potassium level >5.6 mmol/L within 2 weeks before the Screening Visit (Visit 1). • Subject has been hospitalized for hyperkalemia within the 3 months before the Randomization Visit (Visit 3). • Subject was not compliant with taking placebo during the Run-in Period (defined as taking <80% or >120% of planned placebo doses) or the Investigator determines that the subject was not compliant with background antihypertensive medications during the Run-in Period as assessed at the Randomization Visit (Visit 3). • Subject has taken a mineralocorticoid receptor antagonist (MRA), a potassium-sparing diuretic, or chronic potassium supplements during the 4 weeks before the Screening Visit (Visit 1). • Subject has taken potassium binders for the treatment of hyperkalemia during the 3 months before the Screening Visit (Visit 1). • Subject has taken a strong CYP3A4 inducer or strong CYP3A4 inhibitor during the 7 days before the Randomization Visit (Visit 3).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for efficacy is change in seated trough cuff SBP from baseline to Week 12. The second key endpoint for durability is change in seated trough cuff SBP from Week 48 to Week 52.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to Week 12 From Week 48 to Week 52 |
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E.5.2 | Secondary end point(s) |
The key secondary efficacy endpoints for the study are: • Change in seated trough cuff SBP from baseline to Week 24; • Changes in seated trough cuff DBP from baseline to Week 12 and Week 24; • Changes in UACR from baseline to Week 12 and Week 24 for subjects with UACR ≥30 mg/g at baseline. Other secondary efficacy endpoints for the study are: • Changes in seated trough cuff SBP and DBP from baseline to Week 48; • Percentage changes in UACR from baseline to Week 12 and Week 24 for subjects with UACR ≥30 mg/g at baseline; • Changes and percentage changes in UACR from baseline to Week 12, Week 24, and Week 48 for subjects with macroalbuminuria (defined as UACR ≥300 mg/g) at baseline; • Changes and percentage changes in UACR from baseline to Week 12, Week 24, and Week 48 for subjects with microalbuminuria (defined as UACR ≥30 and <300 mg/g) at baseline; • Change in seated trough cuff DBP from Week 48 to Week 52; • Change and percentage change in UACR from Week 48 to Week 52 for subjects with UACR ≥30 mg/g at baseline; • Change and percentage change in UACR from Week 48 to Week 52 for subjects with macroalbuminuria (defined as UACR ≥300 mg/g) at baseline; • Change and percentage change in UACR from Week 48 to Week 52 for subjects with microalbuminuria (defined as UACR ≥30 and <300 mg/g) at baseline. Safety assessments include evaluation of AEs, vital signs, clinical laboratory findings, 12-lead electrocardiograms (ECGs), and physical examination findings. Safety endpoints for this study are: • Incidences of SAEs, non-serious AEs, AEs leading to discontinuation of study drug, and AEs leading to discontinuation from the study; • Incidences of AEs of hyperkalemia, hypertension, hypotension and eGFR decrease; • Incidences of serum potassium >5.0 to <5.6 mmol/L, ≥5.6 to <6.0 mmol/L, and ≥6.0 mmol/L by central laboratory results; • Changes in serum potassium levels from baseline to Week 12, Week 24, and Week 48 by central laboratory results; • Changes in eGFR from baseline to Week 12, Week 24, and Week 48 by central laboratory results; • Incidence of sustained decreases in eGFR of ≥30% from baseline by central laboratory results (an eGFR decrease of ≥30% from baseline will be considered sustained if the eGFR reduction is still ≥30% from baseline at least 4 weeks after the initial measurement); • Change in serum potassium levels from Week 48 to Week 52 by central laboratory results; • Change in eGFR from Week 48 to Week 52 by central laboratory results.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Malaysia |
Bosnia and Herzegovina |
Hong Kong |
Taiwan |
Canada |
China |
Georgia |
Korea, Republic of |
Serbia |
South Africa |
United States |
Bulgaria |
Croatia |
Czechia |
Germany |
Hungary |
Latvia |
Lithuania |
Poland |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 15 |