Safety and Efficacy Study of LHW090 in Resistant Hypertension Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02515331
• Date of registration: 31/07/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Safety and Efficacy Study of LHW090 in Resistant Hypertension Patients
• Scientific 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
• Date of first enrolment: November 4, 2015
• Target sample size: 64
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02515331
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

Denmark, France, Germany, Netherlands, Switzerland, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion 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



Age minimum: 40 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Patients, Resistant Hypertension

Intervention(s)

Drug: LHW090

Drug: Placebo

Primary Outcome(s)

Change From Baseline in Mean Daytime Blood Pressure [Time Frame: Baseline, day 27]

Number of Participants With Reported Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths [Time Frame: 6 months]

Secondary Outcome(s)

Pharmacokinetics of LHW090/LHV527 in Plasma: Last Measurable Plasma Concentration (Clast) [Time Frame: 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 [Time Frame: 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) [Time Frame: 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: Observe Maximum Plasma Concentration Following LHW090 at Steady State in Patients (Cmax) [Time Frame: 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) [Time Frame: 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]

Secondary ID(s)

CLHW090X2202

2015-001890-42

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/07/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02515331