Back to resultsSafety of Ataciguat in Patients With Moderate Calcific Aortic Valve Stenosis
Primary Purpose
Aortic Valve Stenosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ataciguat
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Aortic Valve Stenosis
Eligibility Criteria
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.
Sites / Locations
- Mayo Clinic in Rochester
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Placebo
Ataciguat
Arm Description
Placebo gel capsule, dosage matches number of Ataciguat capsules for each respective dose, capsules taken once daily with breakfast for 14 consecutive days.
Ataciguat, orally administered gel capsule, 50, 100, or 200 mg, once per day with breakfast for 14 consecutive days
Outcomes
Primary Outcome Measures
Number of patients experiencing orthostatic hypotension
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
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
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
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT02049203
First Posted
January 28, 2014
Last Updated
July 5, 2016
Sponsor
Jordan D. Miller, Ph.D.
Collaborators
National Center for Advancing Translational Sciences (NCATS), Sanofi-Synthelabo, National Center for Research Resources (NCRR)
1. Study Identification
Unique Protocol Identification Number
NCT02049203
Brief Title
Safety of Ataciguat in Patients With Moderate Calcific Aortic Valve Stenosis
Official Title
A Phase Ib Randomized, Placebo-controlled, Double-blinded Study Evaluating the Safety of Ataciguat (HMR1766) in Patients With Moderate Calcific Aortic Valve Stenosis
Study Type
Interventional
2. Study Status
Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
January 2014 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jordan D. Miller, Ph.D.
Collaborators
National Center for Advancing Translational Sciences (NCATS), Sanofi-Synthelabo, National Center for Research Resources (NCRR)
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aortic Valve Stenosis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo gel capsule, dosage matches number of Ataciguat capsules for each respective dose, capsules taken once daily with breakfast for 14 consecutive days.
Arm Title
Ataciguat
Arm Type
Active Comparator
Arm Description
Ataciguat, orally administered gel capsule, 50, 100, or 200 mg, once per day with breakfast for 14 consecutive days
Intervention Type
Drug
Intervention Name(s)
Ataciguat
Other Intervention Name(s)
HMR1766
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo gel capsule of identical composition to Active group, but does not have active compound.
Primary Outcome Measure Information:
Title
Number of patients experiencing orthostatic hypotension
Description
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.
Time Frame
Baseline - 14 days
Title
The change in blood pressure following the transition from sitting to standing
Description
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.
Time Frame
Baseline - 14 days
Title
The change in blood pressure following progressive head-up tilt
Description
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.
Time Frame
Baseline - 14 days
Title
Subject self-reports of light-headedness/orthostatic intolerance during the standing test and the head-up tilt testing
Description
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.
Time Frame
Baseline - 14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jordan Miller, PhD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety of Ataciguat in Patients With Moderate Calcific Aortic Valve Stenosis
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