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

Chronic Kidney Disease (CKD) Clinical Trial

— LHW090  

Official title:

A Two Part Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Renal Safety, Tolerability and Pharmacokinetics of LHW090 in Patients With Moderately Impaired Renal Function on Angiotensin Receptor Blockers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02678000
• Other study ID #: CLHW090X2102
• Status: Completed
• Phase: Phase 2
• Start date: March 10, 2017
• Est. completion date: October 11, 2018

Study information

• Verified date: October 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: October 11, 2018
• Est. primary completion date: October 11, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Disease (CKD)
• Kidney Diseases
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• LHW090
LHW090 is orally administered
• Placebo
Matching placebo of LHW090

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Elsterwerda
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Mannheim
United States	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	Minneapolis	Minnesota
United States	Novartis Investigative Site	New Orleans	Louisiana
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Saint Paul	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1)	Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. For LHW090, incidence of AEs by primary organ class presented	Adverse events were collected from first dose of study treatment until end of study treatment, (12 days dosing period + 9 days follow up (PART 1) plus 30 days post treatment, up to maximum duration of approximately 20 months
Primary	Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' Where t is a Defined Time Point After Administration (AUC0-t) (PART 1)	The area under the plasma concentration-time curve from time zero to 24 hours. Area Under the Curve (AUC0-t) after 4 days dosing will be reported for PART 1. LHW090 and LHV527 (its active metabolite)	Within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs.
Primary	Number of Patients Who Developed a Renal Event (PART 2)	Patients who developed a renal event will be reported (defined as a =0.3 mg/dL increase in serum creatinine from baseline within 24-48 hours post dose )	Baseline, within 24 to 48 hours of post-dose weekly for up to 8 weeks
Secondary	Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2)	The observed maximum plasma (or serum or blood) concentration following drug administration for PART 1 and PART 2	PART 1: within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs. PART 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing.
Secondary	AUC0-t: Pharmacokinetics of LHW090/LHV527 (Active Metabolite)in Plasma: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' Where t is a Defined Time Point After Administration (PART 2)	The area under the plasma concentration-time curve from time zero to 24 hours	PART 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing
Secondary	Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2)	The time to reach the maximum concentration after drug administration	Part 1: within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs. Part 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com