Safety of Ataciguat in Patients With Moderate Calcific Aortic Valve Stenosis

A Phase Ib Randomized, Placebo-controlled, Double-blinded Study Evaluating the Safety of Ataciguat (HMR1766) in Patients With Moderate Calcific Aortic Valve Stenosis

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02049203

Enrollment

Registered

2014-01-30

Start date

2014-01-31

Completion date

2015-03-31

Last updated

2016-07-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Aortic Valve Stenosis

Brief summary

This study will determine whether Ataciguat (HMR1766) is well-tolerated in patients with mild to moderate calcific aortic valve stenosis. The primary focus of these studies will be on changes in blood pressure and orthostatic tolerance (i.e., ability to stand up without passing out), and determining whether treatment with Ataciguat results in significant reductions in blood pressure in this patient population.

Interventions

DRUGAtaciguat

DRUGPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

Inclusion criteria

* Age \> 50 years * Male or female sex * Aortic valve area greater than 1.0 cm2 but less than 2.0 cm2 * Aortic valve calcium levels greater than 300 arbitrary units from chest CT * Ejection fraction \>50%

Exclusion criteria

* History of orthostatic intolerance or symptomatic hypotension * Positive pregnancy test during screening visit * Nitrate use or α-antagonist medication use within 24 hours * Systolic blood pressure \<110 mm Hg * Mean systemic arterial pressure \<75 mm Hg * Severe mitral or aortic regurgitation * Retinal or optic nerve problems * Recent (≤30 days) acute coronary syndrome * Oxygen saturation \<90% on room air * Congenital valve disease * Hepatic dysfunction/elevated liver enzymes * Prescription of drugs known to alter nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling (sildenafil, nitrates, etc.) * History of orthostatic intolerance * Concomitant participation in other trials at Mayo Clinic or elsewhere.

Design outcomes

Primary

Measure	Time frame	Description
Number of patients experiencing orthostatic hypotension	Baseline - 14 days	The primary objective of the current study is to determine whether Ataciguat (HMR1766) is well-tolerated by patients with moderate calcific aortic valve stenosis. In this particular patient population, incidence of orthostatic intolerance/symptomatic hypotension is a potential concern.
The change in blood pressure following the transition from sitting to standing	Baseline - 14 days	The primary objective of the current study is to determine whether Ataciguat (HMR1766) is well-tolerated by patients with moderate calcific aortic valve stenosis. In this particular patient population, incidence of orthostatic intolerance/symptomatic hypotension is a potential concern. Transitioning from sitting to standing is a functional test that will allow us to examine the effects of Ataciguat on blood pressure regulation in response to a relevant orthostatic stress.
The change in blood pressure following progressive head-up tilt	Baseline - 14 days	The primary objective of the current study is to determine whether Ataciguat (HMR1766) is well-tolerated by patients with moderate calcific aortic valve stenosis. In this particular patient population, incidence of orthostatic intolerance/symptomatic hypotension is a potential concern. Tilt table testing will allow us to examine the effects of Ataciguat on blood pressure regulation in response to a tightly controlled orthostatic stress.
Subject self-reports of light-headedness/orthostatic intolerance during the standing test and the head-up tilt testing	Baseline - 14 days	The primary objective of the current study is to determine whether Ataciguat (HMR1766) is well-tolerated by patients with moderate calcific aortic valve stenosis. In this particular patient population, incidence of orthostatic intolerance/symptomatic hypotension is a potential concern. Evaluating subject perceptions of light-headedness/orthostatic intolerance will help us to understand the relationship between changes in blood pressure and changes in symptoms in this patient population before and after treatment with Ataciguat.

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026