Trial Outcomes & Findings for A Rollover Study of ARRY-371797 in Patients With LMNA-Related Dilated Cardiomyopathy (NCT NCT02351856)
NCT ID: NCT02351856
Last Updated: 2022-03-31
Results Overview
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. Treatment-emergent AEs were events between baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
8 participants
Primary outcome timeframe
Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)
Results posted on
2022-03-31
Participant Flow
Total 8 participants signed the informed consent form (ICF). All were enrolled into the study and assigned to a study treatment. None of them were screen failure.
Participant milestones
| Measure |
ARRY-371797
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA (Gene encoding the Lamin A/C protein) mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 milligram (mg) twice a day (BID) until treatment discontinuation criteria \[withdrawal of consent, unacceptable adverse events (AE) or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
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Overall Study
STARTED
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8
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Overall Study
COMPLETED
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0
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Overall Study
NOT COMPLETED
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8
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Reasons for withdrawal
| Measure |
ARRY-371797
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA (Gene encoding the Lamin A/C protein) mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 milligram (mg) twice a day (BID) until treatment discontinuation criteria \[withdrawal of consent, unacceptable adverse events (AE) or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
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Overall Study
Adverse Event
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2
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|
Overall Study
Physician Decision
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5
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Overall Study
Study terminated by sponsor
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1
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Baseline Characteristics
A Rollover Study of ARRY-371797 in Patients With LMNA-Related Dilated Cardiomyopathy
Baseline characteristics by cohort
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
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Age, Continuous
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51.0 Years
STANDARD_DEVIATION 10.17 • n=5 Participants
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Sex: Female, Male
Female
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4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=5 Participants
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|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
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8 Participants
n=5 Participants
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|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
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|
Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)Population: Safety analysis set included all enrolled participants who received at least 1 dose of study drug.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. Treatment-emergent AEs were events between baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
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Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
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6 Participants
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|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
TEAEs
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8 Participants
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PRIMARY outcome
Timeframe: Baseline, Post-Baseline (anytime from first dose of study drug to maximum duration of up to 282 weeks)Population: Safety analysis set included all enrolled participants who received at least 1 dose of study drug. Here, "Number Analyzed" signifies participants evaluable for specific parameter.
In this outcome measure, number of participants with baseline laboratory hematology values as per National Cancer Institute Common Terminology Criteria (NCI-CTC) grade (Grade 0= within normal limits, Grade 1=Mild, Grade 2=Moderate, Grade 3= Severe, Grade 4= Life-threatening) and corresponding changes/shift to the worst CTC grades post baseline were presented. Shift data have been reported for hematology parameters: hemoglobin (g/L), platelets (10\^9/L), leukocytes (10\^9/L), neutrophils (10\^9/L), lymphocytes (10\^9/L) and eosinophils (10\^9/L). Baseline was defined as last non-missing value before the initial administration of study treatment in parent study and worst post-baseline value defined as worst value between first dose of study drug up to the maximum of 282 weeks. Only those categories in which at least 1 participant had data were reported.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
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Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Hemoglobin: grade 0 (baseline grade) to post baseline grade 1
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3 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Hemoglobin: grade 0 (baseline grade) to post baseline grade 2
|
4 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Hemoglobin: grade 0 (baseline grade) to post baseline grade 3
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1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Platelets: grade 0 (baseline grade) to post baseline grade 0
|
6 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Platelets: grade 0 (baseline grade) to post baseline grade 1
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Platelets: grade 1 (baseline grade) to post baseline grade 3
|
1 Participants
|
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Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Leukocytes: grade 0 (baseline grade) to post baseline grade 0
|
6 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Leukocytes: grade 1 (baseline grade) to post baseline grade 1
|
2 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Neutrophils: grade 0 (baseline grade) to post baseline grade 0
|
6 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Neutrophils: grade 0 (baseline grade) to post baseline grade 1
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2 Participants
|
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Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Lymphocytes: grade 0 (baseline grade) to post baseline grade 0
|
6 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Lymphocytes: grade 0 (baseline grade) to post baseline grade 2
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Lymphocytes: grade 1 (baseline grade) to post baseline grade 2
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1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value
Eosinophils: grade 0 (baseline grade) to post baseline grade 0
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8 Participants
|
PRIMARY outcome
Timeframe: Baseline, Post-Baseline (anytime from first dose of study drug to maximum duration of up to 282 weeks)Population: Safety analysis set included all enrolled participants who received at least 1 dose of study drug. Here, "Number Analyzed" signifies participants evaluable for specific parameter.
In this outcome measure, number of participants with baseline laboratory chemistry values as per NCI-CTC grade (Grade 0= within normal limits, Grade 1=Mild, Grade 2=Moderate, Grade 3= Severe, Grade 4= Life-threatening) and corresponding changes/shift to the worst CTC grades post baseline were presented. Shift data have been reported for laboratory parameters: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, international unit per liter (IU/L), albumin, bilirubin, urea nitrogen, calcium, creatinine, glucose, magnesium, protein and phosphate grams per deciliter (g/dL), potassium and sodium, millimol per liter (mmol/L). Baseline was defined as last non-missing value before the initial administration of study treatment in parent study and worst post-baseline value defined as worst value between first dose of study drug up to the maximum of 282 weeks. Only those categories in which at least 1 participant had data were reported.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
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Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Protein: grade 0 (baseline grade) to post baseline grade 0
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3 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Alanine aminotransferase: grade 0 (baseline grade) to post baseline grade 0
|
6 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Alanine aminotransferase: grade 0 (baseline grade) to post baseline grade 1
|
1 Participants
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Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Alanine aminotransferase: grade 1 (baseline grade) to post baseline grade 1
|
1 Participants
|
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Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Albumin: grade 0 (baseline grade) to post baseline grade 0
|
7 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Albumin: grade 0 (baseline grade) to post baseline grade 1
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1 Participants
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Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Alkaline phosphatase: grade 0 (baseline grade) to post baseline grade 0
|
8 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Aspartate aminotransferase: grade 0 (baseline grade) to post baseline grade 0
|
3 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Aspartate aminotransferase: grade 0 (baseline grade) to post baseline grade 1
|
2 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Aspartate aminotransferase: grade 1 (baseline grade) to post baseline grade 0
|
3 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Bilirubin: grade 0 (baseline grade) to post baseline grade 0
|
5 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Bilirubin: grade 0 (baseline grade) to post baseline grade 1
|
2 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Bilirubin: grade 0 (baseline grade) to post baseline grade 3
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Urea nitrogen: grade 0 (baseline grade) to post baseline grade 0
|
4 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Urea nitrogen: grade 0 (baseline grade) to post baseline grade 1
|
3 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Urea nitrogen: grade 0 (baseline grade) to post baseline grade 3
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Calcium: grade 0 (baseline grade) to post baseline grade 0
|
6 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Calcium: grade 0 (baseline grade) to post baseline grade 1
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Calcium: grade 0 (baseline grade) to post baseline grade 2
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Creatinine: grade 0 (baseline grade) to post baseline grade 0
|
7 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Creatinine: grade 0 (baseline grade) to post baseline grade 2
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Glucose: grade 0 (baseline grade) to post baseline grade 0
|
3 Participants
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|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Glucose: grade 0 (baseline grade) to post baseline grade 1
|
2 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Glucose: grade 0 (baseline grade) to post baseline grade 2
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Glucose: grade 1 (baseline grade) to post baseline grade 0
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Glucose: grade 2 (baseline grade) to post baseline grade 1
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Magnesium: grade 0 (baseline grade) to post baseline grade 0
|
8 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Phosphate: grade 0 (baseline grade) to post baseline grade 0
|
5 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Phosphate: grade 0 (baseline grade) to post baseline grade 1
|
2 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Phosphate: grade 0 (baseline grade) to post baseline grade 3
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Potassium: grade 0 (baseline grade) to post baseline grade 0
|
6 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Potassium: grade 0 (baseline grade) to post baseline grade 1
|
2 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Protein: grade 0 (baseline grade) to post baseline grade 1
|
3 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Protein: grade 0 (baseline grade) to post baseline grade 3
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Protein: grade 1 (baseline grade) to post baseline grade 1
|
1 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Sodium: grade 0 (baseline grade) to post baseline grade 0
|
5 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Sodium: grade 0 (baseline grade) to post baseline grade 1
|
2 Participants
|
|
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value
Sodium: grade 2 (baseline grade) to post baseline grade 2
|
1 Participants
|
PRIMARY outcome
Timeframe: Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)Population: Safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Physical examination included the assessment of skin, head, ears, eyes, nose, throat, cardiovascular system, abdomen and lungs. Abnormality in physical examination were based on investigator's discretion.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
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Number of Participants With Abnormal Physical Examination Findings
|
8 Participants
|
PRIMARY outcome
Timeframe: Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)Population: Safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Following vital signs parameters were analyzed using prespecified range of results for signs of clinical significance: systolic blood pressure in millimeters of mercury (mmHg): \<90 mmHg and ≥160 mmHg, diastolic blood pressure: \<60 mmHg and ≥100 mmHg, heart rate in beats per minute (bpm): \<40bpm and \>120 bpm, temperature in degree Celsius (C): \<36.1 and \> 37.2 degree C.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
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Number of Participants With Abnormalities in Vital Signs
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6 Participants
|
PRIMARY outcome
Timeframe: Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)Population: Safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Following ECG parameters were analyzed using prespecified range of results for signs of clinical significance: heart rate: \<40bpm and \>120 bpm; QT/QTcF (QT interval corrected using Fridericia's formula) criteria: QT interval \>500 ms; QTcF interval \>450 ms; or change from baseline in QTcF \>30 ms.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
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Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings
|
8 Participants
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)Population: Efficacy analysis set included participants who had at least 1 post-baseline efficacy evaluation. Here, "Number Analyzed" signifies participants evaluable for specific time point.
6MWT was the distance that a participant could quickly walk on a flat, hard surface in a period of 6 minutes. Participants were asked to walk a set course of 30 meters for 6 minutes (timed), and the distance walked (in meters) was recorded. Change from baseline in 6MWT distance at specified time points were reported. Baseline was defined as last non-missing value before the initial administration of study treatment in parent study.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
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Change From Baseline in Six Minute Walk Test (6MWT) Distance at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Baseline
|
319.5 Meters
Standard Deviation 48.48
|
|
Change From Baseline in Six Minute Walk Test (6MWT) Distance at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Day 1
|
55.3 Meters
Standard Deviation 51.92
|
|
Change From Baseline in Six Minute Walk Test (6MWT) Distance at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 24
|
32.2 Meters
Standard Deviation 62.31
|
|
Change From Baseline in Six Minute Walk Test (6MWT) Distance at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 48
|
55.8 Meters
Standard Deviation 63.76
|
|
Change From Baseline in Six Minute Walk Test (6MWT) Distance at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 72
|
42.6 Meters
Standard Deviation 74.92
|
|
Change From Baseline in Six Minute Walk Test (6MWT) Distance at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 96
|
10.8 Meters
Standard Deviation 113.12
|
|
Change From Baseline in Six Minute Walk Test (6MWT) Distance at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Early Termination Visit
|
-14.3 Meters
Standard Deviation 68.78
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)Population: Efficacy analysis set included participants who had at least 1 post-baseline efficacy evaluation. Here, "Number Analyzed" signifies participants evaluable for specific time point.
LVESVI and LVEDVI were echocardiographic assessment of left ventricular remodeling. Baseline was defined as last non-missing value before the initial administration of study treatment in parent study.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
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Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVESVI: Baseline
|
45.25 Milliliter per meter square
Standard Deviation 12.766
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVESVI: change at Day 1
|
1.83 Milliliter per meter square
Standard Deviation 7.932
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVESVI: change at Week 24
|
-0.01 Milliliter per meter square
Standard Deviation 5.403
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVESVI: change at Week 48
|
-1.31 Milliliter per meter square
Standard Deviation 11.707
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVESVI: change at Week 72
|
-1.36 Milliliter per meter square
Standard Deviation 14.374
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVESVI: change at Week 96
|
-0.39 Milliliter per meter square
Standard Deviation 4.090
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVESVI: change at Early Termination Visit
|
-0.26 Milliliter per meter square
Standard Deviation 4.447
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVEDVI: Baseline
|
70.41 Milliliter per meter square
Standard Deviation 13.933
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVEDVI: change at Day 1
|
2.31 Milliliter per meter square
Standard Deviation 11.504
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVEDVI: change at Week 24
|
1.19 Milliliter per meter square
Standard Deviation 12.320
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVEDVI: change at Week 48
|
-1.13 Milliliter per meter square
Standard Deviation 9.338
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVEDVI: change at Week 72
|
-2.99 Milliliter per meter square
Standard Deviation 14.063
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVEDVI: change at Week 96
|
-1.54 Milliliter per meter square
Standard Deviation 13.236
|
|
Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
LVEDVI: change at Early Termination Visit
|
6.36 Milliliter per meter square
Standard Deviation 7.089
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)Population: Efficacy analysis set included participants who had at least 1 post-Baseline efficacy evaluation. Here, "Number Analyzed" signifies participants evaluable for specific time point.
LVM is the weight of the left ventricle in grams estimated by echocardiography. For this outcome measure, Baseline is the pre-dose baseline of parent study.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
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Change From Baseline in Left Ventricular Mass (LVM) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Baseline
|
169.97 Grams
Standard Deviation 65.592
|
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Change From Baseline in Left Ventricular Mass (LVM) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Day 1
|
4.38 Grams
Standard Deviation 39.217
|
|
Change From Baseline in Left Ventricular Mass (LVM) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 24
|
12.39 Grams
Standard Deviation 31.789
|
|
Change From Baseline in Left Ventricular Mass (LVM) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 48
|
7.46 Grams
Standard Deviation 32.190
|
|
Change From Baseline in Left Ventricular Mass (LVM) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 72
|
20.87 Grams
Standard Deviation 43.152
|
|
Change From Baseline in Left Ventricular Mass (LVM) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 96
|
15.25 Grams
Standard Deviation 33.332
|
|
Change From Baseline in Left Ventricular Mass (LVM) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Early Termination Visit
|
8.97 Grams
Standard Deviation 14.194
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)Population: Efficacy analysis set included participants who had at least 1 post-Baseline efficacy evaluation. Here, "Number Analyzed" signifies participants evaluable for specific time point.
LVEF was the fraction of the end-diastolic volume (EDV) that was ejected out of left ventricle with each contraction, estimated by echocardiography. EDV was the volume of blood within a ventricle immediately before a contraction. Baseline was defined as last non-missing value before the initial administration of study treatment in parent study.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
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|---|---|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Baseline
|
37.88 Percentage of EDV
Standard Deviation 10.633
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Day 1
|
0.10 Percentage of EDV
Standard Deviation 5.322
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 24
|
1.50 Percentage of EDV
Standard Deviation 5.032
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 48
|
0.10 Percentage of EDV
Standard Deviation 7.195
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 72
|
4.27 Percentage of EDV
Standard Deviation 7.882
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 96
|
1.71 Percentage of EDV
Standard Deviation 3.538
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Early Termination Visit
|
2.11 Percentage of EDV
Standard Deviation 4.137
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)Population: Efficacy analysis set included participants who had at least 1 post-Baseline efficacy evaluation. Here, "Number Analyzed" signifies participants evaluable for specific time point.
LVM divided by the end diastolic volume, estimated by echocardiography. Baseline was defined as last non-missing value before the initial administration of study treatment in parent study.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
|
|---|---|
|
Change From Baseline in Left Ventricular Mass (LVM) to Volume Ratio at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Baseline
|
1.32 Grams per milliliter
Standard Deviation 0.568
|
|
Change From Baseline in Left Ventricular Mass (LVM) to Volume Ratio at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Day 1
|
-0.04 Grams per milliliter
Standard Deviation 0.357
|
|
Change From Baseline in Left Ventricular Mass (LVM) to Volume Ratio at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 24
|
0.03 Grams per milliliter
Standard Deviation 0.259
|
|
Change From Baseline in Left Ventricular Mass (LVM) to Volume Ratio at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 48
|
0.05 Grams per milliliter
Standard Deviation 0.137
|
|
Change From Baseline in Left Ventricular Mass (LVM) to Volume Ratio at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 72
|
0.14 Grams per milliliter
Standard Deviation 0.295
|
|
Change From Baseline in Left Ventricular Mass (LVM) to Volume Ratio at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 96
|
0.21 Grams per milliliter
Standard Deviation 0.442
|
|
Change From Baseline in Left Ventricular Mass (LVM) to Volume Ratio at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Early Termination Visit
|
0.08 Grams per milliliter
Standard Deviation 0.378
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)Population: Efficacy analysis set included participants who had at least 1 post-Baseline efficacy evaluation. Here, "Number Analyzed" signifies participants evaluable for specific time point.
The internal diameter of the right ventricle at the end of diastole, measured by echocardiography. Baseline was defined as last non-missing value before the initial administration of study treatment in parent study.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
|
|---|---|
|
Change From Baseline in Right Ventricular End Diastolic Diameter at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Baseline
|
3.79 Centimeter
Standard Deviation 0.686
|
|
Change From Baseline in Right Ventricular End Diastolic Diameter at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Day 1
|
0.30 Centimeter
Standard Deviation 0.329
|
|
Change From Baseline in Right Ventricular End Diastolic Diameter at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 24
|
0.02 Centimeter
Standard Deviation 0.635
|
|
Change From Baseline in Right Ventricular End Diastolic Diameter at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 48
|
0.59 Centimeter
Standard Deviation 0.462
|
|
Change From Baseline in Right Ventricular End Diastolic Diameter at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 72
|
0.14 Centimeter
Standard Deviation 0.604
|
|
Change From Baseline in Right Ventricular End Diastolic Diameter at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 96
|
0.26 Centimeter
Standard Deviation 0.853
|
|
Change From Baseline in Right Ventricular End Diastolic Diameter at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Early Termination Visit
|
1.15 Centimeter
Standard Deviation 1.909
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)Population: Efficacy analysis set included participants who had at least 1 post-Baseline efficacy evaluation. Here, "Number Analyzed" signifies participants evaluable for specific time point.
Right ventricular fractional area change is a measure of global right ventricular systolic function estimated by echocardiography. For this outcome measure, Baseline is the pre-dose baseline of parent study.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
|
|---|---|
|
Change From Baseline in Right Ventricular Fractional Area at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 72
|
8.22 Percentage
Standard Deviation 12.059
|
|
Change From Baseline in Right Ventricular Fractional Area at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Baseline
|
22.14 Percentage
Standard Deviation 6.896
|
|
Change From Baseline in Right Ventricular Fractional Area at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Day 1
|
8.25 Percentage
Standard Deviation 10.252
|
|
Change From Baseline in Right Ventricular Fractional Area at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 24
|
8.67 Percentage
Standard Deviation 13.358
|
|
Change From Baseline in Right Ventricular Fractional Area at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 48
|
7.85 Percentage
Standard Deviation 13.051
|
|
Change From Baseline in Right Ventricular Fractional Area at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Week 96
|
1.95 Percentage
Standard Deviation 6.945
|
|
Change From Baseline in Right Ventricular Fractional Area at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Change at Early Termination Visit
|
0.51 Percentage
Standard Deviation 8.004
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)Population: Efficacy analysis set included participants who had at least 1 post-Baseline efficacy evaluation. Here, "Number Analyzed" signifies participants evaluable for specific time point.
The SF-36 health survey is a participant-reported survey to measure participant's health. It is a 36-item questionnaire used to measure 8 various aspects of health (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health). The score range for each of the 8 aspects was from 0 (maximum disability) to 100 (no disability), higher scores indicating good health condition. For this analysis, baseline was defined as last non-missing value before the initial administration of study treatment in parent study.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
|
|---|---|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical functioning: change at Week 72
|
0.77 Units on a scale
Standard Deviation 5.347
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Vitality: Baseline
|
39.97 Units on a scale
Standard Deviation 11.858
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Vitality: change at Day 1
|
-0.74 Units on a scale
Standard Deviation 7.901
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Vitality: change at Week 24
|
-0.50 Units on a scale
Standard Deviation 8.491
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Vitality: change at Week 48
|
-2.97 Units on a scale
Standard Deviation 8.405
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Vitality: change at Week 72
|
-3.57 Units on a scale
Standard Deviation 8.246
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Vitality: change at Week 96
|
-5.94 Units on a scale
Standard Deviation 8.403
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Vitality: change at Early Termination Visit
|
-1.78 Units on a scale
Standard Deviation 7.462
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical functioning: Baseline
|
35.77 Units on a scale
Standard Deviation 9.540
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical functioning: change at Day 1
|
-0.24 Units on a scale
Standard Deviation 6.508
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical functioning: change at Week 24
|
0.96 Units on a scale
Standard Deviation 6.929
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical functioning: change at Week 48
|
-1.15 Units on a scale
Standard Deviation 10.539
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical functioning: change at Week 96
|
1.53 Units on a scale
Standard Deviation 7.944
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical functioning: change at Early Termination Visit
|
-6.51 Units on a scale
Standard Deviation 5.512
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Bodily pain: Baseline
|
51.11 Units on a scale
Standard Deviation 8.635
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Bodily pain: change at Day 1
|
-1.92 Units on a scale
Standard Deviation 9.561
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Bodily pain: change at Week 24
|
-3.97 Units on a scale
Standard Deviation 10.195
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Bodily pain: change at Week 48
|
2.72 Units on a scale
Standard Deviation 8.076
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Bodily pain: change at Week 72
|
3.06 Units on a scale
Standard Deviation 4.648
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Bodily pain: change at Week 96
|
-4.27 Units on a scale
Standard Deviation 5.991
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Bodily pain: change at Early Termination Visit
|
-5.56 Units on a scale
Standard Deviation 10.725
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
General health: Baseline
|
36.37 Units on a scale
Standard Deviation 8.372
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
General health: change at Day 1
|
1.78 Units on a scale
Standard Deviation 5.637
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
General health: change at Week 24
|
0 Units on a scale
Standard Deviation 3.669
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
General health: change at Week 48
|
-2.09 Units on a scale
Standard Deviation 8.717
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
General health: change at Week 72
|
-1.43 Units on a scale
Standard Deviation 8.057
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
General health: change at Week 96
|
-1.62 Units on a scale
Standard Deviation 8.612
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
General health: change at Early Termination Visit
|
1.90 Units on a scale
Standard Deviation 4.801
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role physical: Baseline
|
32.74 Units on a scale
Standard Deviation 8.691
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role physical: change at Day 1
|
5.61 Units on a scale
Standard Deviation 8.315
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role physical: change at Week 24
|
4.49 Units on a scale
Standard Deviation 9.420
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role physical: change at Week 48
|
5.62 Units on a scale
Standard Deviation 6.982
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role physical: change at Week 72
|
9.43 Units on a scale
Standard Deviation 4.316
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role physical: change at Week 96
|
2.25 Units on a scale
Standard Deviation 8.249
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role physical: change at Early Termination Visit
|
4.94 Units on a scale
Standard Deviation 12.339
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role emotional: Baseline
|
43.98 Units on a scale
Standard Deviation 11.772
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role emotional: change at Day 1
|
1.74 Units on a scale
Standard Deviation 8.325
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role emotional: change at Week 24
|
0.00 Units on a scale
Standard Deviation 7.940
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role emotional: change at Week 48
|
-3.48 Units on a scale
Standard Deviation 14.773
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role emotional: change at Week 72
|
5.57 Units on a scale
Standard Deviation 12.696
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role emotional: change at Week 96
|
-6.96 Units on a scale
Standard Deviation 18.095
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Role emotional: change at Early Termination Visit
|
0.00 Units on a scale
Standard Deviation 8.532
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social functioning: Baseline
|
41.05 Units on a scale
Standard Deviation 9.936
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social functioning: change at Day 1
|
-1.26 Units on a scale
Standard Deviation 12.778
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social functioning: change at Week 24
|
1.67 Units on a scale
Standard Deviation 11.285
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social functioning: change at Week 48
|
-2.51 Units on a scale
Standard Deviation 8.683
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social functioning: change at Week 72
|
3.01 Units on a scale
Standard Deviation 7.605
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social functioning: change at Week 96
|
-3.01 Units on a scale
Standard Deviation 9.106
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social functioning: change at Early Termination Visit
|
-4.01 Units on a scale
Standard Deviation 9.641
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Mental health: Baseline
|
47.60 Units on a scale
Standard Deviation 14.378
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Mental health: change at Day 1
|
2.94 Units on a scale
Standard Deviation 3.816
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Mental health: change at Week 24
|
-0.43 Units on a scale
Standard Deviation 7.654
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Mental health: change at Week 48
|
-5.23 Units on a scale
Standard Deviation 7.702
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Mental health: change at Week 72
|
-2.09 Units on a scale
Standard Deviation 15.405
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Mental health: change at Week 96
|
-4.71 Units on a scale
Standard Deviation 14.373
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Mental health: change at Early Termination Visit
|
0 Units on a scale
Standard Deviation 7.623
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Mental Classification System (MCS): Baseline
|
46.96 Units on a scale
Standard Deviation 13.995
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
MCS: change at Day 1
|
1.19 Units on a scale
Standard Deviation 6.558
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
MCS: change at Week 24
|
-0.27 Units on a scale
Standard Deviation 8.294
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
MCS: change at Week 48
|
-7.07 Units on a scale
Standard Deviation 10.751
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
MCS: change at Week 72
|
-0.24 Units on a scale
Standard Deviation 15.610
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
MCS: change at Week 96
|
-7.70 Units on a scale
Standard Deviation 14.765
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
MCS: change at Early Termination Visit
|
-0.10 Units on a scale
Standard Deviation 7.394
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical Classification System (PCS): Baseline
|
36.32 Units on a scale
Standard Deviation 8.201
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
PCS: change at Day 1
|
0.71 Units on a scale
Standard Deviation 7.519
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
PCS: change at Week 24
|
0.79 Units on a scale
Standard Deviation 7.552
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
PCS: change at Week 48
|
6.19 Units on a scale
Standard Deviation 1.535
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
PCS: change at Week 72
|
3.52 Units on a scale
Standard Deviation 5.672
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
PCS: change at Week 96
|
1.90 Units on a scale
Standard Deviation 5.656
|
|
Change From Baseline in 36-Item Short-Form (SF-36) Health Survey Score at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
PCS: change at Early Termination Visit
|
-2.34 Units on a scale
Standard Deviation 6.730
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)Population: Efficacy analysis set was included participants who had at least 1 post-Baseline efficacy evaluation. Here, "Number Analyzed" signifies participants evaluable for specific time point.
KCCQ was a 23-item heart failure specific questionnaire quantified into following 10 summary scores: physical limitation score, symptom frequency score, symptom severity score, symptom stability score, total symptoms score, quality of life score, social interference score, self-efficacy score, overall summary score and clinical summary score. These scores ranged from 0 to 100, where higher scores indicated better functioning, fewer symptoms, and better disease specific quality of life. For this analysis, baseline was defined as last non-missing value before the initial administration of study treatment in parent study.
Outcome measures
| Measure |
ARRY-371797
n=8 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
|
|---|---|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical limitation score: Baseline
|
60.42 Units on a scale
Standard Deviation 27.186
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical limitation score: change at Day 1
|
0.60 Units on a scale
Standard Deviation 15.296
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical limitation score: change at Week 24
|
8.33 Units on a scale
Standard Deviation 19.365
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical limitation score: change at Week 48
|
-0.83 Units on a scale
Standard Deviation 27.386
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical limitation score: change at Week 72
|
13.83 Units on a scale
Standard Deviation 23.204
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical limitation score: change at Week 96
|
12.17 Units on a scale
Standard Deviation 23.545
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Physical limitation score: change at Early Termination Visit
|
-8.33 Units on a scale
Standard Deviation 6.804
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom stability score: Baseline
|
53.13 Units on a scale
Standard Deviation 8.839
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom stability score: change at Day 1
|
0 Units on a scale
Standard Deviation 13.363
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom stability score: change at Week 24
|
4.17 Units on a scale
Standard Deviation 24.580
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom stability score: change at Week 48
|
-5.00 Units on a scale
Standard Deviation 11.180
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom stability score: change at Week 72
|
5.00 Units on a scale
Standard Deviation 27.386
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom stability score: change at Week 96
|
-15.00 Units on a scale
Standard Deviation 13.693
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom stability score: change at Early Termination Visit
|
-5.00 Units on a scale
Standard Deviation 11.180
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom frequency score: Baseline
|
73.18 Units on a scale
Standard Deviation 20.334
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom frequency score: change at Day 1
|
-1.30 Units on a scale
Standard Deviation 10.018
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom frequency score: change at Week 24
|
-4.86 Units on a scale
Standard Deviation 18.942
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom frequency score: change at Week 48
|
-19.17 Units on a scale
Standard Deviation 27.418
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom frequency score: change at Week 72
|
-3.33 Units on a scale
Standard Deviation 13.060
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom frequency score: change at Week 96
|
-17.50 Units on a scale
Standard Deviation 21.123
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom frequency score: change at Early Termination Visit
|
-7.92 Units on a scale
Standard Deviation 9.592
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom burden score: Baseline
|
72.92 Units on a scale
Standard Deviation 21.708
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom burden score: change at Day 1
|
-1.04 Units on a scale
Standard Deviation 10.387
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom burden score: change at Week 24
|
-2.78 Units on a scale
Standard Deviation 11.386
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom burden score: change at Week 48
|
-16.67 Units on a scale
Standard Deviation 17.678
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom burden score: change at Week 72
|
5.00 Units on a scale
Standard Deviation 20.069
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom burden score: change at Week 96
|
-15.00 Units on a scale
Standard Deviation 29.107
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Symptom burden score: change at Early Termination Visit
|
-6.67 Units on a scale
Standard Deviation 14.907
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Total symptom score: Baseline
|
73.05 Units on a scale
Standard Deviation 20.672
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Total symptom score: change at Day 1
|
-1.17 Units on a scale
Standard Deviation 9.858
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Total symptom score: change at Week 24
|
-3.82 Units on a scale
Standard Deviation 15.004
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Total symptom score: change at Week 48
|
-17.92 Units on a scale
Standard Deviation 22.467
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Total symptom score: change at Week 72
|
0.83 Units on a scale
Standard Deviation 15.084
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Total symptom score: change at Week 96
|
-16.25 Units on a scale
Standard Deviation 24.358
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Total symptom score: change at Early Termination Visit
|
-7.29 Units on a scale
Standard Deviation 10.725
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Self-efficacy score: Baseline
|
85.94 Units on a scale
Standard Deviation 12.388
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Self-efficacy score: change at Day 1
|
6.25 Units on a scale
Standard Deviation 11.573
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Self-efficacy score: change at Week 24
|
2.08 Units on a scale
Standard Deviation 16.615
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Self-efficacy score: change at Week 48
|
5.00 Units on a scale
Standard Deviation 11.180
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Self-efficacy score: change at Week 72
|
7.50 Units on a scale
Standard Deviation 14.252
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Self-efficacy score: change at Week 96
|
10.00 Units on a scale
Standard Deviation 10.458
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Self-efficacy score: change at Early Termination Visit
|
7.50 Units on a scale
Standard Deviation 11.180
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Quality of life score: Baseline
|
52.08 Units on a scale
Standard Deviation 28.781
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Quality of life score: change at Day 1
|
7.29 Units on a scale
Standard Deviation 16.925
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Quality of life score: change at Week 24
|
4.17 Units on a scale
Standard Deviation 13.693
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Quality of life score: change at Week 48
|
-13.33 Units on a scale
Standard Deviation 21.731
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Quality of life score: change at Week 72
|
10.00 Units on a scale
Standard Deviation 25.954
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Quality of life score: change at Week 96
|
-5.00 Units on a scale
Standard Deviation 28.626
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Quality of life score: change at Early Termination Visit
|
13.33 Units on a scale
Standard Deviation 33.124
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social limitation score: Baseline
|
57.81 Units on a scale
Standard Deviation 29.267
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social limitation score: change at Day 1
|
10.16 Units on a scale
Standard Deviation 21.635
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social limitation score: change at Week 24
|
3.47 Units on a scale
Standard Deviation 26.506
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social limitation score: change at Week 48
|
-9.38 Units on a scale
Standard Deviation 10.825
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social limitation score: change at Week 72
|
9.17 Units on a scale
Standard Deviation 18.669
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social limitation score: change at Week 96
|
-11.46 Units on a scale
Standard Deviation 18.980
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Social limitation score: change at Early Termination Visit
|
1.56 Units on a scale
Standard Deviation 29.920
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Overall summary score: Baseline
|
60.84 Units on a scale
Standard Deviation 25.603
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Overall summary score: change at Day 1
|
4.74 Units on a scale
Standard Deviation 13.906
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Overall summary score: change at Week 24
|
3.04 Units on a scale
Standard Deviation 14.082
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Overall summary score: change at Week 48
|
-12.64 Units on a scale
Standard Deviation 21.030
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Overall summary score: change at Week 72
|
8.46 Units on a scale
Standard Deviation 19.155
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Overall summary score: change at Week 96
|
-3.76 Units on a scale
Standard Deviation 22.697
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Overall summary score: change at Early Termination Visit
|
2.55 Units on a scale
Standard Deviation 19.283
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Clinical summary score: Baseline
|
66.73 Units on a scale
Standard Deviation 23.833
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Clinical summary score: change at Day 1
|
0.33 Units on a scale
Standard Deviation 11.729
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Clinical summary score: change at Week 24
|
2.26 Units on a scale
Standard Deviation 13.955
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Clinical summary score: change at Week 48
|
-9.38 Units on a scale
Standard Deviation 22.619
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Clinical summary score: change at Week 72
|
7.33 Units on a scale
Standard Deviation 18.803
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Clinical summary score: change at Week 96
|
-2.04 Units on a scale
Standard Deviation 22.629
|
|
Change From Baseline in Quality of Life by Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit
Clinical summary score: change at Early Termination Visit
|
-5.10 Units on a scale
Standard Deviation 9.521
|
SECONDARY outcome
Timeframe: Pre dose and post dose on Day 1, Weeks 12 and 24Population: Pharmacokinetic (PK) analysis set included all participants who had at least 1 plasma sample with associated PK concentration results. Here, "Number Analyzed" signifies participants evaluable at specific time points.
Plasma concentrations of ARRY-371797 and its metabolites (AR00420643, AR00428028 and AR00486705) was summarized on Day 1, Weeks 12 and 24 at both pre and post dose.
Outcome measures
| Measure |
ARRY-371797
n=7 Participants
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
|
|---|---|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
ARRY-371797 Day 1 (Pre-dose)
|
4.7136 Nanogram per milliliter
Geometric Coefficient of Variation 209.88
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
ARRY-371797 Day 1 (Post-dose)
|
54.053 Nanogram per milliliter
Geometric Coefficient of Variation 643.32
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
ARRY-371797 Week 12 (Pre-dose)
|
3.9258 Nanogram per milliliter
Geometric Coefficient of Variation 155.51
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
ARRY-371797 Week 12 (Post-dose)
|
109.10 Nanogram per milliliter
Geometric Coefficient of Variation 205.28
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
ARRY-371797 Week 24 (Pre-dose)
|
4.9345 Nanogram per milliliter
Geometric Coefficient of Variation 300.53
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
ARRY-371797 Week 24 (Post-dose)
|
41.653 Nanogram per milliliter
Geometric Coefficient of Variation 691.82
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00420643 Day 1 (Pre-dose)
|
80.859 Nanogram per milliliter
Geometric Coefficient of Variation 171.38
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00420643 Day 1 (Post-dose)
|
348.45 Nanogram per milliliter
Geometric Coefficient of Variation 281.51
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00420643 Week 12 (Pre-dose)
|
33.749 Nanogram per milliliter
Geometric Coefficient of Variation NA
Per the decision rules written in the Statistical Analysis Plan (SAP), the number of below the limit of quantitation (BLQ) values for the -643 analyte resulted in geometric coefficient of variation (CV), being not reportable.
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00420643 Week 12 (Post-dose)
|
432.99 Nanogram per milliliter
Geometric Coefficient of Variation 189.13
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00420643 Week 24 (Pre-dose)
|
73.737 Nanogram per milliliter
Geometric Coefficient of Variation 219.07
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00420643 Week 24 (Post-dose)
|
258.80 Nanogram per milliliter
Geometric Coefficient of Variation 411.34
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00428028 Day 1 (Pre-dose)
|
44.453 Nanogram per milliliter
Geometric Coefficient of Variation 134.15
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00428028 Day 1 (Post-dose)
|
47.392 Nanogram per milliliter
Geometric Coefficient of Variation 110.81
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00428028 Week 12 (Pre-dose)
|
24.003 Nanogram per milliliter
Geometric Coefficient of Variation 131.07
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00428028 Week 12 (Post-dose)
|
27.213 Nanogram per milliliter
Geometric Coefficient of Variation 96.919
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00428028 Week 24 (Pre-dose)
|
32.625 Nanogram per milliliter
Geometric Coefficient of Variation 69.620
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00428028 Week 24 (Post-dose)
|
32.102 Nanogram per milliliter
Geometric Coefficient of Variation 80.353
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00486705 Day 1 (Pre-dose)
|
6.1025 Nanogram per milliliter
Geometric Coefficient of Variation 256.23
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00486705 Day 1 (Post-dose)
|
14.541 Nanogram per milliliter
Geometric Coefficient of Variation 256.54
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00486705 Week 12 (Pre-dose)
|
4.0176 Nanogram per milliliter
Geometric Coefficient of Variation NA
Per the decision rules written in the SAP, the number of BLQ values for the -643 analyte resulted in geometric CV being not reportable.
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00486705 Week 12 (Post-dose)
|
13.909 Nanogram per milliliter
Geometric Coefficient of Variation 237.85
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00486705 Week 24 (Pre-dose)
|
6.8860 Nanogram per milliliter
Geometric Coefficient of Variation 97.778
|
|
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)
AR00486705 Week 24 (Post-dose)
|
13.389 Nanogram per milliliter
Geometric Coefficient of Variation 177.04
|
Adverse Events
ARRY-371797
Serious events: 6 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ARRY-371797
n=8 participants at risk
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
|
|---|---|
|
Cardiac disorders
Cardiac failure acute
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Cardiac disorders
Cardiac failure congestive
|
25.0%
2/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Cardiac disorders
Ventricular tachycardia
|
50.0%
4/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Gastrointestinal disorders
Colitis
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
General disorders
Non-cardiac chest pain
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Clostridium difficile infection
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Metabolism and nutrition disorders
Iron deficiency
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Renal and urinary disorders
Acute kidney injury
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Surgical and medical procedures
Heart transplant
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Vascular disorders
Orthostatic hypotension
|
25.0%
2/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
Other adverse events
| Measure |
ARRY-371797
n=8 participants at risk
Participants with symptomatic genetic dilated cardiomyopathy due to a LMNA mutation, and who received ARRY-371797 in the parent study, NCT02057341, were enrolled in this rollover study ARRAY-797-001. Participants received ARRY-371797 at the same dose and schedule they were administered at the end of parent study: ARRY-371797 tablet or capsules 400 mg BID until treatment discontinuation criteria \[withdrawal of consent, unacceptable AE or failure to tolerate ARRY-371797, pregnancy or initiation of breastfeeding, lost to follow-up\] were met, (up to a maximum of 282 weeks). If participant had tolerability concerns at 400 mg BID, they were down-titrated to 200 mg BID (400 mg total daily dose). If participant had tolerability concerns at 200 mg BID, they were down-titrated to 100 mg BID (200 mg total daily dose). Participants were followed up to 30 days for safety after last dose of study drug.
|
|---|---|
|
Cardiac disorders
Bradycardia
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Cardiac disorders
Cardiac failure
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Cardiac disorders
Congestive cardiomyopathy
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Cardiac disorders
Ventricular tachycardia
|
37.5%
3/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Gastrointestinal disorders
Abdominal pain
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Gastrointestinal disorders
Ascites
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
2/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Gastrointestinal disorders
Gastritis
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Gastrointestinal disorders
Haemorrhoids
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Gastrointestinal disorders
Nausea
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Gastrointestinal disorders
Peptic ulcer
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Gastrointestinal disorders
Stomatitis
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
General disorders
Fatigue
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
General disorders
Pyrexia
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Bronchitis
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Clostridium difficile infection
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
External ear cellulitis
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Furuncle
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Gastroenteritis viral
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Influenza
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Lyme disease
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Nasopharyngitis
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Pharyngitis
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Sinusitis
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Upper respiratory tract infection
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Urinary tract infection
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Vaginal infection
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Infections and infestations
Viral infection
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
50.0%
4/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Investigations
Blood creatinine increased
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Investigations
Coronavirus test positive
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Investigations
International normalised ratio increased
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Investigations
Liver function test increased
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Nervous system disorders
Dizziness
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Nervous system disorders
Headache
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Nervous system disorders
Syncope
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Psychiatric disorders
Insomnia
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Renal and urinary disorders
Dysuria
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Renal and urinary disorders
Haematuria
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
25.0%
2/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Skin and subcutaneous tissue disorders
Acute febrile neutrophilic dermatosis
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Skin and subcutaneous tissue disorders
Onychoclasis
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Vascular disorders
Flushing
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
|
Vascular disorders
Hypotension
|
12.5%
1/8 • Baseline up to 30 days after last dose of study drug (maximum up to 282 weeks)
Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER