Clinical trial NCT02515331: Safety and Efficacy Study of LHW090 in Resistant Hypertension Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Patients, Resistant Hypertension
Keywords: resistant hypertension
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-08-04
Enrollment: 64
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Reported Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths
timeFrame: 6 months
measure: Change From Baseline in Mean Daytime Blood Pressure
timeFrame: Baseline, day 27
Secondary outcomes:
measure: Pharmacokinetics of LHW090/LHV527 in Plasma: Observe Maximum Plasma Concentration Following LHW090 at Steady State in Patients (Cmax)
timeFrame: 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
measure: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (Tmax)
timeFrame: 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
measure: Pharmacokinetics of LHW090/LHV527 in Plasma: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast)
timeFrame: 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
measure: Pharmacokinetics of LHW090/LHV527 in Plasma: Last Measurable Plasma Concentration (Clast)
timeFrame: 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
measure: Pharmacokinetics of LHW090/LHV527 in Plasma:Tlast
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: North Hollywood
country: United States
facility: Novartis Investigative Site
state: California
city: Atlantis
country: United States
facility: Novartis Investigative Site
state: Florida
city: Daytona Beach
country: United States
facility: Novartis Investigative Site
state: Florida
city: Jacksonville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Honolulu
country: United States
facility: Novartis Investigative Site
state: Hawaii
city: Knoxville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Gentofte
country: Denmark
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Homburg
country: Germany
facility: Novartis Investigative Site
city: Meibergdreef 9
country: Netherlands
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: