Safety and Efficacy Study of LHW090 in Resistant Hypertension Patients

A Randomized, Sponsor Open, Site and Subject Double Blind, Parallel Group, Placebo-controlled Study to Evaluate the Safety and Efficacy of LHW090 After 4 Weeks Treatment in Patients With Resistant Hypertension

The purpose of the present study was to determine whether LHW090 displays the clinical safety and efficacy profile to support further development in patients with resistant hypertension.

Study Overview

• Status: Completed
• Conditions: Patients, Resistant Hypertension
• Intervention / Treatment: Drug: LHW090; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Gentofte, Denmark, DK 2820
    • Novartis Investigative Site
• France
  • Paris, France, 75015
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10098
    • Novartis Investigative Site
  • Duesseldorf, Germany, 40225
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
• Netherlands
  • Meibergdreef 9, Netherlands, 1105 AZ
    • Novartis Investigative Site
• Switzerland
  • Basel, Switzerland, 4031
    • Novartis Investigative Site
  • Lausanne, Switzerland, 1011
    • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Novartis Investigative Site
  • California
    • North Hollywood, California, United States, 91606
      • Novartis Investigative Site
  • Florida
    • Atlantis, Florida, United States, 33462
      • Novartis Investigative Site
    • Daytona Beach, Florida, United States, 32117
      • Novartis Investigative Site
    • Jacksonville, Florida, United States, 32216
      • Novartis Investigative Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Novartis Investigative Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients, age 40 to 85 years inclusive.
• • Patients with uncontrolled hypertension (here defined as having a mean daytime systolic BP ≥ 135 mmHg by ABPM at screening) despite treatment with a stable (at least 1 month) regimen that includes an optimal dose of an ARB plus a diuretic plus at least one additional class of anti-hypertensive medication.

For the purposes of this trial, optimal doses of anti-hypertensive medications are defined as:

• the highest dose listed in the clinical practice guideline from the American Society for Hypertension and the International Society for Hypertension or
• the highest allowable prescribed dose per the manufacturer's label or
• the highest dose tolerated by an individual patient or
• the highest dose appropriate for an individual patient in the judgment of the Investigator
• Subjects must weigh at least 45 kg to participate in the study and must have a body mass index (BMI) within the range of 18-38 kg/m^2.

Exclusion Criteria:

• Patients with an estimated GFR <60 ml/min/1.73m^2.
• Use of angiotensin converting enzyme inhibitors (ACE-inhibitors). Note: Patients who discontinue their ACE-inhibitor and substitute with an angiotensin receptor blocker may be eligible to be re-screened provided their anti-hypertensive regimen has been stable for at least 1 month. Any substitutions or changes to a patient's anti-hypertensive regimen should be done under the guidance of the patient's treating physician.
• Severe hypertension as defined by systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg at screening.
• A history of secondary hypertension of any etiology including but not limited to unilateral or bilateral renal artery stenosis, polycystic kidney disease, coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, and drug-induced hypertension.
• Known current significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or significant severe valvular disease on prior or current echocardiogram).
• A history of known moderate or malignant retinopathy defined as moderate (retinal signs of hemorrhage), microaneurysms, cotton-wool spots, hard exudates, or a combination thereof) or malignant (signs of moderate retinopathy plus swelling of the optic disk). Patients with a stable ophthalmologic history in the past 6 months are eligible.
• To facilitate ABPM assessment, an upper arm circumference greater than 42 cm.
• History within the previous 6 months of myocardial infarction, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), hypertensive encephalopathy, stroke, or transient ischemic attack (TIA).

Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

• Women of child-bearing potential

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LHW090 100 mg; LHW090 100 mg once daily for 28 days	Drug: LHW090; Capsule - oral dose
Experimental: LHW090 200 mg; LHW090 200 mg once daily for 28 days	Drug: LHW090; Capsule - oral dose
Placebo Comparator: Placebo; Matching placebo to LHW090 oral dose for 28 days	Drug: Placebo; Capsule - oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Reported Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths	Number of participants with AEs, SAEs and deaths were assessed.	6 months
Change From Baseline in Mean Daytime Blood Pressure	Change in the 12 hour average of systolic blood pressure (SBP) measured by ambulatory blood pressure was defined as the 12 hour daytime average SBP on Day 28 minus the 12 hour daytime average SBP on Day -1. monitoring (ABPM). A negative change from baseline indicates improvement.	Baseline, day 27

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of LHW090/LHV527 in Plasma: Observe Maximum Plasma Concentration Following LHW090 at Steady State in Patients (Cmax)	Blood samples were collected to assess Cmax.	Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28
Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (Tmax)	Blood samples were collected to assess Tmax.	Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28
Pharmacokinetics of LHW090/LHV527 in Plasma: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast)	Blood samples were collected to assess AUClast.	Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28
Pharmacokinetics of LHW090/LHV527 in Plasma: Last Measurable Plasma Concentration (Clast)	Blood samples were collected to assess Clast.	Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28
Pharmacokinetics of LHW090/LHV527 in Plasma:Tlast	Blood samples were collected to assess Tlast.	Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs up to 12 hrs on Day 1 and Day 28

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2015
• Primary Completion (Actual): August 17, 2017
• Study Completion (Actual): August 17, 2017

Study Registration Dates

• First Submitted: July 31, 2015
• First Submitted That Met QC Criteria: July 31, 2015
• First Posted (Estimate): August 4, 2015

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: resistant hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: CLHW090X2202; 2015-001890-42 (EudraCT Number)