Safety and Efficacy Study of LHW090 in Resistant Hypertension Patients

NCT02515331 | Completed Phase 2 Results

• 2 other identifiers: CLHW090X22022015-001890-42
• Study Type: interventional
• Target: 64
• Locations: 6 countries
• Sites: 16

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.

Conditions

Patients, Resistant Hypertension

Keywords

resistant hypertension

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Pharmacokinetics of LHW090/LHV527 in Plasma: Observe Maximum Plasma Concentration Following LHW090 at Steady State in Patients (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)

  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)

  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)

  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

  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

Study Arms (3)

LHW090 100 mg

EXPERIMENTAL

LHW090 100 mg once daily for 28 days

Drug: LHW090

LHW090 200 mg

EXPERIMENTAL

LHW090 200 mg once daily for 28 days

Drug: LHW090

Placebo

PLACEBO COMPARATOR

Matching placebo to LHW090 oral dose for 28 days

Drug: Placebo

Interventions

LHW090 DRUG

Capsule - oral dose

LHW090 100 mg; LHW090 200 mg

Placebo DRUG

Capsule - oral dose

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (16)

Novartis Investigative Site

Birmingham, Alabama, 35294, United States

Location

Novartis Investigative Site

North Hollywood, California, 91606, United States

Location

Novartis Investigative Site

Atlantis, Florida, 33462, United States

Location

Novartis Investigative Site

Daytona Beach, Florida, 32117, United States

Location

Novartis Investigative Site

Jacksonville, Florida, 32216, United States

Location

Novartis Investigative Site

Honolulu, Hawaii, 96814, United States

Location

Novartis Investigative Site

Knoxville, Tennessee, 37920, United States

Location

Novartis Investigative Site

Gentofte Municipality, DK 2820, Denmark

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Berlin, 10098, Germany

Location

Novartis Investigative Site

Düsseldorf, 40225, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Homburg, 66421, Germany

Location

Novartis Investigative Site

Meibergdreef 9, Netherlands, 1105 AZ, Netherlands

Location

Novartis Investigative Site

Basel, 4031, Switzerland

Location

Novartis Investigative Site

Lausanne, 1011, Switzerland

Location

Related Links

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartisemail@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2015
• First Posted: August 4, 2015
• Study Start: November 4, 2015
• Primary Completion: August 17, 2017
• Study Completion: August 17, 2017
• Last Updated: January 5, 2021
• Results First Posted: July 5, 2018

Record last verified: 2018-06

Locations

NL (1); US (7); DE (4); FR (1); CH (2); DK (1)