This is a randomized, double-blind, placebo-controlled study in patients with dilated cardiomyopathy (DCM) due to a mutation of the gene encoding the lamin A/C protein (LMNA). The study will further evaluate a dose level of study drug (ARRY-371797) that has shown preliminary efficacy and safety in this patient population. After the primary analysis has been performed, eligible patients may receive open-label treatment with ARRY-371797.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
77
400 mg twice daily (BID)
BID
Change From Baseline in Six-Minute Walk Test (6 MWT) at Week 24
The 6 MWT was an assessment where the distance that a participant could walk on a flat and hard surface in 6 minutes was measured. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed, and under supervision of a qualified professional. Study discontinuation \& death were incorporated into endpoint definition through ranking in hypothesis testing of treatment difference. Missing data resulting from study discontinuation were imputed using control-based multiple imputation method to estimate treatment effect.
Time frame: Baseline, Week 24
Change From Baseline in 6 MWT at Weeks 4 and 12
The 6 MWT was an assessment where the distance that a participant could walk on a flat and hard surface in 6 minutes was measured. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed, and under supervision of a qualified professional.
Time frame: Baseline, Week 4, Week 12
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24
The KCCQ measured the effects of symptoms, functional (physical) limitations, and psychological distress on an individual's health-related quality of life. It contains 23 items, which assessed the ability to perform activities of daily living, frequency and severity of symptoms, the impact of these symptoms, and health-related quality of life. PL was a single questionnaire with score range of 0 to 100, where higher scores reflected better physical functioning status. TSS included frequency and severity of symptoms, and the impact of these symptoms. TSS scores were transformed to a range of 0 to 100, where higher scores reflected better health status.
Time frame: Baseline, Week 12, Week 24
Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University of Alabama at Birmingham Hospital
Birmingham, Alabama, United States
University of Alabama at Birmingham the Kirklin Clinic
Birmingham, Alabama, United States
IDS Pharmacy at UAB Hospital
Birmingham, Alabama, United States
Cardiovascular Clinical Trials Unit
Birmingham, Alabama, United States
CB Flock Research Corporation
Mobile, Alabama, United States
Chandler Regional Medical Center
Chandler, Arizona, United States
Valley Heart Rhythm Specialists, PLLC
Chandler, Arizona, United States
Cardiovascular and Stem Cell Consultants
Gilbert, Arizona, United States
Cardiovascular Research Clinic
Gilbert, Arizona, United States
Dignity Health, Mercy Gilbert Medical Center
Gilbert, Arizona, United States
...and 97 more locations
PGI-S is a global index that rate the severity of the disease using a 5-point scale. In this outcome the number of participants with improvements in PGI-S the severity of their heart failure symptoms and in the severity of their PL were reported. Measured by the scale of: none, mild, moderate, severe or very severe (listed from better to worse).
Time frame: Week 12, Week 24
Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24
PGI-C is a global index that rate the severity of the disease using a 7-point scale. In this outcome the number participants with improvements in their heart failure symptoms and "in their physical activity limitations?", were reported. Measured by the scale of: very much better, moderately better, a little better, no change, a little worse, moderately worse, very much worse (listed from better to worse).
Time frame: Week 12, Week 24
Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Weeks 4, 12, and 24
NT pro-BNP is a cardiac biomarker that is released in the blood in response to changes in the pressure inside of the heart. Levels go up when heart failure develops or gets worse, and levels go down when heart failure is stable or improves. This biomarker helps to measure the changes in the severity of heart failure over time in response to therapy.
Time frame: Baseline, Week 4, Week 12, Week 24
Composite Time to First Occurrence of All-Cause Mortality or Worsening Heart Failure (WHF)
Defined as the time from randomization to the first occurrence of any event of death due to any cause, or worsening heart failure (HF-related hospitalization or HF-related urgent care visit). Kaplan-Meier method and cox regression model were used for analysis.
Time frame: Maximum up to 212.28 weeks (maximum exposure was 208 weeks)
Overall Survival (OS)
OS was defined as time from randomization to death due to any cause. Participants who did not have a death date were censored for OS at their last contact date. Kaplan-Meier method and cox regression model were used for analysis.
Time frame: From randomization up to death due to any cause or censored date, maximum up to 212.28 weeks (maximum exposure was of 208 weeks)
Number of Participants With Treatment Emergent Adverse Events (AEs) and by Severity
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and all Non-SAEs. Grade \>=3 AEs meant severe AEs.
Time frame: Maximum up to 212.28 weeks (maximum exposure was of 208 weeks)
Number of Participants With Laboratory Test Abnormalities
Following parameters were analyzed for laboratory examination: hematology (eosinophils, erythrocytes, hemoglobin, hematocrit, granulocytes, leukocytes, lymphocytes, monocytes, platelets, neutrophils, nucleated erythrocytes); blood chemistry (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, C-reactive protein, calcium, chloride, creatinine, creatine kinase, epidermal growth factor receptor, follicle stimulating hormone, gamma glutamyl transferase, glucose, magnesium, N-Terminal ProB-type natriuretic peptide, phosphate, potassium, protein, sodium, potassium, thyrotropin, troponin I, troponin T, urate).
Time frame: Maximum up to 212.28 weeks (maximum exposure was of 208 weeks)
Number of Participants According to Categorization of Abnormal Vital Signs
Following vital sign parameters were assessed: diastolic blood pressure, systolic blood pressure, heart rate, and body weight. Vital sign abnormalities criteria included: a) systolic blood pressure (mmHg): decrease (change \<= -20, or value \<90) and increase (change \>=20, or value \>140); b) diastolic blood pressure (mmHg): decrease (change \<= -15, or value \<60) and increase (change \>=15, or value \>90); c) heart Rate (bpm) decrease: (change \<= -15, or value \<50) and increase (change \>=15, or value \>100); d) weight: (kg) decrease (Change \<= -7%) and increase (Change \> =7%).
Time frame: Maximum up to 212.28 weeks (maximum exposure was of 208 weeks)
Number of Participants According to Categorization of Electrocardiogram (ECG) Data
Following parameters were analyzed: heart rate, QT interval, corrected QT (QTc) interval, Bazett's correction QT (QTcB) interval, and Fridericia's correction (QTcF) interval. Criteria for notable ECG values were as follows: QT interval (in millisecond \[msec\]) new (newly occurring post-baseline value) greater than (\>) 450, 480, 500, increase from baseline \>30, increase from baseline \>60; corrected QT interval by Fredericia formula (QTcF) in msec new (newly occurring post-baseline value) \> 450, 480, 500, increase from baseline \>30, increase from baseline \>60; corrected QT interval by Bazett's formula (QTcB) in msec new (newly occurring post-baseline value) \> 450, 480, 500, increase from baseline \>30, increase from baseline \>60; heart rate in bpm new (newly occurring post-baseline value) \<60 and \>100.
Time frame: Maximum up to 212.28 weeks (maximum exposure was of 208 weeks)
Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias
Arrhythmia assessment: incidence of new and clinically significant ventricular or atrial arrhythmias was assessed by an implantable cardioverter defibrillator (ICD) or CRT defibrillator (CRT-D) applicable device interrogations.
Time frame: Baseline, Week 12, Week 24