A study evaluating the safety and efficacy of LHW090 in patients with resistant hypertension

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2015-001890-42-FR
• Date of registration: 07/12/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A study evaluating the safety and efficacy of LHW090 in patients with resistant hypertension
• 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: 15/12/2015
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001890-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: sponsor open study If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Information&Communication Médicales
• Affiliation: Novartis Pharma S.A.S

• Name: Information&Communication Médicales
• Affiliation: Novartis Pharma S.A.S

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent must be obtained before any assessment is performed.
2. Male and female patients, age 40 to 85 years inclusive.
3. Demonstrating a = 80% medication compliance rate during the single-blind run-in period.
4. Patients with uncontrolled hypertension (here defined as having a daytime BP = 135/85 by ABPM) despite treatment with a stable (at least 2 months) regimen that includes an optimal dose of an ARB plus optimal doses of two or more of the following classes of anti-hypertensive medications: thiazide diuretics, loop diuretics, beta-blockers, and calcium channel blockers.
For the purposes of this trial, optimal doses of anti-hypertensive medications are defined as:
? a) the highest dose listed in the clinical practice guideline from the American Society for Hypertension and the International Society for Hypertension [Weber, et al. 2014] or
? b) the highest allowable prescribed dose per the manufacturer's label or
? c) the highest dose tolerated by an individual patient or
? d) the highest dose appropriate for an individual patient in the judgment of the Investigator
5. Subjects must weigh at least 45 kg to participate in the study and must have a body mass index
(BMI) within the range of 18-36 kg/m2.
6. Able to communicate well with the investigator, to understand and comply with the requirements of
the study.

Other protocol defined inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion criteria:
Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives
of enrollment, whichever is longer; or longer if required by local regulations, and for
any other limitation of participation in an investigational trial based on local regulations.
2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical
classes.
3. Patients with an estimated GFR <60 ml/min/1.73m2 at screening using the MDRD
equation.
4. 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 2 months. Any substitutions or changes to a patient's
anti-hypertensive regimen should be done under the guidance of the patient's treating
physician.
5. Clinically significant ECG abnormalities at screening as determined by the Investigator.
6. Severe hypertension as defined by systolic blood pressure =180 mmHg or diastolic blood
pressure =110 mmHg at screening.
7. 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.
8. Known current significant left ventricular outflow obstruction, such as obstructive
hypertrophic cardiomyopathy or significant severe valvular disease on prior or current
echocardiogram).
9. 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).
10. To facilitate ABPM assessment of daytime readings, an upper arm circumference greater
than 42 cm or third shift or overnight workers.
11. 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).
12. Hemoglobin levels below 9.0 g/dL at screening.
13. History of malignancy of any organ system (other than localized basal cell carcinoma of
the skin or in-situ cervical cancer), treated or untreated, within the past 1 year, regardless
of whether there is evidence of local recurrence or metastases.
14. Donation or loss of 400 mL or more of blood within 8 weeks prior to initial dosing, or
longer if required by local regulation.
15. 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.
16. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 1 week after stopping study medication.
17. Sexually active males must use a condom during intercourse while taking drug and for
1 week after stopping study medication and should not father a child in this period.
A condom is required to be used also by vasectomized men in order to prevent delivery of
the drug via seminal fluid.
18. Any surgical or medical condition, which in the opinion of the investigator, may place the
patient

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Resistant hypertension
MedDRA version: 18.1 Level: LLT Classification code 10015491 Term: Essential hypertension, unspecified System Organ Class: 100000004866

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: LHW090
Product Code: LHW090
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not established
Current Sponsor code: LHW090
Other descriptive name: LHW090-NXA and NVP-LHW090
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Safety endpoints (adverse events, serious adverse events) will be measured up to and including end of study assessments

The primary efficacy variable will be the change in the 12 hour average of systolic blood pressure
measured by ambulatory blood pressure monitoring (ABPM) 28 days following the start of treatment

Main Objective: To determine whether LHW090 displays the clinical safety and efficacy profile to support further development in patients with resistant hypertension: i.e
-? To assess the safety and tolerability of LHW090 for 4 weeks on a background of conventional anti-hypertensive medications in patients with resistant hypertension.
-? To evaluate the effect of LHW090 on placebo-adjusted mean daytime systolic blood pressure (SBP) after 4 weeks in patients with resistant hypertension.

Secondary Objective: To evaluate the pharmacokinetics (PK) of LHW090 and its active metabolite LHV527 in patients with resistant hypertension.

Timepoint(s) of evaluation of this end point: -Efficacy and Safety parameters will be routinely evaluated over the 4 weeks of treatment as defined in the protocol
-ABPM measured at baseline and at the end of the treatment at day 28

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: As defined in the protocol : PK parameters will be measured on Day 28 (Cmax, Tmax, AUClast, AUC0-t)

Secondary end point(s): Pharmacokinetics (PK) parameters of LHW090 and its active metabolite LHV527 in patients with resistant hypertension.

Secondary ID(s)

CLHW090X2202

2015-001890-42-DE

Source(s) of Monetary Support

Novartis Pharma Services AG