Study of the Safety, Tolerability, and Pharmacokinetics of LHW090 in Patients With Moderately Impaired Renal Function

NCT ID: NCT02678000

Last Updated: 2021-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-10
• Study Completion Date: 2018-10-11

Brief 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.

Conditions

Chronic Kidney Disease (CKD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

LHW090

For Part 1, patients will receive 3 doses of LHW090 once daily with escalating doses every 4 days for a total 12 days of treatment.

For Part 2, patients will receive LHW090 once daily for 4 weeks.

Group Type: EXPERIMENTAL

LHW090

Intervention Type: DRUG

LHW090 is orally administered

Placebo

For Part 1, patients will receive matching placebo once daily for 12 days. For Part 2, patients will receive matching placebo once daily for 4 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo of LHW090

Interventions

LHW090

LHW090 is orally administered

Intervention Type: DRUG

Placebo

Matching placebo of LHW090

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Anaheim, California, United States

Novartis Investigative Site

Lakewood, Colorado, United States

Novartis Investigative Site

Miami Lakes, Florida, United States

Novartis Investigative Site

Orlando, Florida, United States

Novartis Investigative Site

New Orleans, Louisiana, United States

Novartis Investigative Site

Minneapolis, Minnesota, United States

Novartis Investigative Site

Saint Paul, Minnesota, United States

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Elsterwerda, , Germany

Novartis Investigative Site

Erlangen, , Germany

Novartis Investigative Site

Hamburg, , Germany

Novartis Investigative Site

Mannheim, , Germany

Countries

United States; Germany

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=310

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Other Identifiers

CLHW090X2102

Identifier Type: -

Identifier Source: org_study_id