Moderate renal impairment MedDRA version: 20.0 Level: PT Classification code 10062237 Term: Renal impairment System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: LHW090
Product Code: LHW090
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not established
Current Sponsor code:
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent must be obtained before any assessment is performed. 2. 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/1.73m2 (inclusive) using the 4 variable MDRD Study equation for at least 3 months. 3. 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 4. 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 - 40kg/m2. BMI = Body weight (kg) / [Height (m)]2. 5. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 42 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 42
Exclusion criteria
Exclusion criteria: 1. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or until the expected PD effect has returned to baseline, whichever is longer; or longer if required by local regulations. 2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes. 3. History of angioedema, drug-related or otherwise, as reported by the patient. 4. 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). 5. History of a renal transplant. 6. Known current significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or significant severe valvular disease on prior or current echocardiogram. 7. A history of clinically significant ECG abnormalities, as determined by the Investigator, or any of the following ECG abnormalities at screening? •?QTcF > 480 msec 8. Known history or current clinically significant arrhythmias. 9. History within the previous 6 months of myocardial infarction, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), stroke, transient ischemic attack (TIA) or acute kidney injury. 10. Hemoglobin levels below 9.0 g/dL at screening. 11. A serum potassium = 3.5 mmol/l or = 5.5 mmol/l at screening. 12. A previous history or previously diagnosed kidney disorder, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study or is likely to confound the interpretation of the study results. Such kidney disorders may include 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. 13. Donation or loss of 400 mL or more of blood within 8 weeks prior to initial dosing, or longer if required by local regulations. 14. Significant illness which has not resolved within two (2) weeks prior to initial dosing. 15. History of immunodeficiency diseases, including a positive HIV test result. 16. A positive Hepatitis B surface antigen or Hepatitis C test result. 17. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 18. Pregnant or nursing (lactating) women. 19. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. 20. Sexually active males unwilling to use a condom during intercourse while taking
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This is a 2 parts study to determine whether LHW090 displays the clinical safety profile to support further development in patients with moderately impaired renal function. Objective of Part 1 of the study : To assess the safety and tolerability of doses of LHW090 in patients with moderate renal impairment to inform design of Part 2. - Objective of Part 2 of the study : To assess the renal safety of LHW090 in patients with moderate renal impairment ;Secondary Objective: To evaluate the pharmacokinetics of LHW090 and its active metabolite, LHV527, in patients with moderate renal impairment. To assess the safety and tolerability of LHW090 relative to placebo in patients with moderate renal impairment; Primary end point(s): - Part 1 of the study : Safety endpoints (including adverse events and serious adverse events) will be measured up to and including the EOS; plasma pharmacokinetic parameters, and serum creatinine will be measured - Part 2: Proportion of patients who develop a renal event as defined by a =0.3 mg/dL increase in serum creatinine from baseline ; Timepoint(s) of evaluation of this end point: Part1: safety parameters will be routinely evaluated over the maximum 12 days of treatment as defined in the protocol Upon completion of at least 10 patients in Part 1 through the end of study visit, an interim analysis of all safety and PK data as applicable will be pursued to confirm dosing with 100 mg or to choose another dose for Part 2. -Part 2: as defined in the protocol An interim analysis will be conducted after 36 patients in Part 2 (randomized in 3:1 ratio) of the study have received the last treatment and all safety/tolerability data up to and including 24 hours post last dose are available for analysis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For all parts of the study: - Plasma pharmacokinetic parameters (Cmax, Tmax, AUC) - Safety endpoints (including adverse events and serious adverse events) up to and including the EOS ;Timepoint(s) of evaluation of this end point: As defined in the protocol on a routine basis over the 12 days max (part 1) and 4 weeks of treatement ( part 2) | — |
Countries
Germany, Romania, United States
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed