Study of the Safety, Tolerability, and Pharmacokinetics of LHW090 in Patients With Moderately Impaired Renal Function
Condition: Chronic Kidney Disease (CKD)
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
Intervention: LHW090; Placebo
Intervention description: LHW090 is orally administered; Matching placebo of LHW090
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 84.0
Sex: All
Minimum age: 40 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This was a randomized, double-blind, parallel group, placebo-controlled study, in two
      sequential parts that evaluated the renal safety, tolerability and pharmacokinetics of LHW090
      in patients with moderately impaired renal function.
    

Eligibility criteria:

        Inclusion Criteria (all Parts):

          -  Written informed consent must be obtained before any assessment is performed.

          -  Male and female patients, age 40 to 85 years of age (inclusive) on a stable (at least
             1 month) dose of an angiotensin receptor blocker (ARB) and stable moderately impaired
             renal function, defined here as an eGFR 30-59 mL/min/1.73m^2 (inclusive) using the 4
             variable MDRD Study equation for at least 3 months.

          -  At screening, vital signs (systolic and diastolic blood pressure and pulse rate) will
             be assessed in the sitting position after the patient has rested for at least five
             minutes, and again after three minutes in the standing position. Sitting vital signs
             should be within the following ranges:

               -  oral body temperature between 35.0-37.5 °C

               -  systolic blood pressure, 100-170 mm Hg

               -  diastolic blood pressure, 50-100 mm Hg

               -  pulse rate, 50 - 95 bpm

          -  Patients should be excluded if their standing vital signs (relative to sitting) show
             findings which, in the opinion of the Investigator, are associated with clinical
             manifestation of postural hypotension (i.e. absence of any other cause). The
             Investigator should carefully consider enrolling patients with either a > 20 mm Hg
             decrease in systolic or a >10 mm Hg decrease in diastolic blood pressure, accompanied
             by a > 20 bpm increase in heart-rate (comparing standing to sitting results).

          -  Patients must weigh at least 50 kg to participate in the study, and must have a body
             mass index (BMI) within the range of 18 - 38 kg/m^2. BMI = Body weight (kg) / [Height
             (m)]^2.

          -  Able to communicate well with the investigator, to understand and comply with the
             requirements of the study.

        Exclusion criteria:

          -  History of angioedema, drug-related or otherwise, as reported by the patient.

          -  Use of angiotensin converting enzyme inhibitors (ACE inhibitors), mineralocorticoid
             receptor antagonists (e.g. spironolactone or eplerenone), aliskiren, vasopressin
             receptor antagonists (e.g. tolvaptan), or oral alkalinizing agents (e.g. sodium and
             potassium citrate or Shohl's solution). Note: Patients who discontinue their
             ACE-inhibitor and substitute with an angiotensin receptor blocker (ARB) may be
             eligible to be rescreened provided their medication regimen has been stable for at
             least 1 month and their renal function has been stable for at least 3 months. Any
             substitutions or changes to a patient's medication regimen must be done under the
             guidance of the patient's treating physician.

          -  History of a renal transplant.

          -  Known current significant left ventricular outflow obstruction, such as obstructive
             hypertrophic cardiomyopathy or significant severe valvular disease on prior or current
             echocardiogram.

          -  A serum potassium ≤ 3.5 mmol/l or ≥ 5.2 mmol/l at screening.

          -  A previous history or previously diagnosed renal cystic disease such as autosomal
             dominant polycystic kidney disease (history of an incidental asymptomatic acquired
             renal cyst(s) is excepted); obstructive uropathy; renal stone(s) in the past 2 years;
             chronic interstitial nephropathy; drug induced nephropathy; residual renal
             insufficiency following an episode of acute kidney injury or acute tubular necrosis
             related to renal atheroembolic disease, septic shock or ischemic nephropathy; renal
             tubular acidosis requiring treatment; nephrotic syndrome or nephrotic range
             proteinuria; or renal artery stenosis.