Safety of Ataciguat in Patients With Moderate Calcific Aortic Valve Stenosis

Jordan D. Miller, Ph.D.

Status and phase: Completed; Phase 1

Conditions: Aortic Valve Stenosis

Treatments: Drug: Placebo; Drug: Ataciguat

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT02049203

UL1RR024150 (U.S. NIH Grant/Contract)

13-005387

Details and patient eligibility

About

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.

Enrollment: 44 patients

Sex: All

Ages: 50+ years old

Volunteers: No 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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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44 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo gel capsule, dosage matches number of Ataciguat capsules for each respective dose, capsules taken once daily with breakfast for 14 consecutive days.

Treatment:

Drug: Placebo

Ataciguat

Active Comparator group

Description:

Ataciguat, orally administered gel capsule, 50, 100, or 200 mg, once per day with breakfast for 14 consecutive days

Treatment:

Drug: Ataciguat