A Rollover Study of ARRY-371797 in Patients With LMNA-Related Dilated Cardiomyopathy

An Open-label Rollover Study of ARRY-371797 in Patients With Symptomatic Genetic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02351856

Enrollment

Registered

2015-01-30

Start date

2015-02-02

Completion date

2020-12-21

Last updated

2022-03-31

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

Conditions

LMNA-Related Dilated Cardiomyopathy

Keywords

laminopathy, ARRY-797

Brief summary

This is a rollover study designed to investigate the safety and effectiveness of investigational study drug ARRY-371797 in patients who previously received ARRY-371797 in a study for patients with LMNA-related dilated cardiomyopathy sponsored by Array BioPharma and may, in the Investigator's opinion, derive benefit from continued treatment.

Interventions

DRUGARRY-371797, p38 inhibitor, oral

multiple dose, single schedule

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: * Received ARRY-371797 as treatment for a genetic dilated cardiomyopathy secondary to LMNA mutations in a clinical study sponsored by Array BioPharma. * May, in the opinion of the Investigator, benefit from continued ARRY-371797 treatment. * Additional criteria exist. Key

Exclusion criteria

* Discontinued treatment in the parent study for any reason other than study completion or Sponsor termination of the study. * Additional criteria exist.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)	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.
Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value	Baseline, Post-Baseline (anytime from first dose of study drug to maximum duration of up to 282 weeks)	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.
Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value	Baseline, Post-Baseline (anytime from first dose of study drug to maximum duration of up to 282 weeks)	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.
Number of Participants With Abnormal Physical Examination Findings	Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)	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.
Number of Participants With Abnormalities in Vital Signs	Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)	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.
Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings	Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)	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.

Secondary

Measure	Time frame	Description
Change From Baseline in Right Ventricular Fractional Area at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit	Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)	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.
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	Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)	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.
Change From Baseline in Six Minute Walk Test (6MWT) Distance at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit	Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)	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.
Mean Plasma Concentration of ARRY-371797 and Metabolites (AR00420643, AR00428028, AR00486705)	Pre dose and post dose on Day 1, Weeks 12 and 24	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.
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	Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)	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.
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	Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)	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.
Change From Baseline in Left Ventricular Mass (LVM) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit	Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)	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.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit	Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)	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.
Change From Baseline in Left Ventricular Mass (LVM) to Volume Ratio at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit	Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)	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.
Change From Baseline in Right Ventricular End Diastolic Diameter at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit	Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)	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.

Countries

United States

Participant flow

Pre-assignment details

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.

Participants by arm

Arm	Count
ARRY-371797 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.	8
Total	8

Arm

Count

ARRY-371797

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.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	2
Overall Study	Physician Decision	5
Overall Study	Study terminated by sponsor	1

Baseline characteristics

Characteristic	ARRY-371797
Age, Continuous	51.0 Years STANDARD_DEVIATION 10.17
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	8 Participants
Sex: Female, Male Female	4 Participants
Sex: Female, Male Male	4 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 8
other Total, other adverse events	7 / 8
serious Total, serious adverse events	6 / 8

Outcome results

Primary

Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings

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.

Time frame: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
ARRY-371797	Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings	8 Participants

Primary

Number of Participants With Abnormalities in Vital Signs

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.

Time frame: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
ARRY-371797	Number of Participants With Abnormalities in Vital Signs	6 Participants

Primary

Number of Participants With Abnormal Physical Examination Findings

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.

Time frame: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
ARRY-371797	Number of Participants With Abnormal Physical Examination Findings	8 Participants

Primary

Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value

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.

Time frame: 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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	1 Participants
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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	3 Participants
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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

Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value

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.

Time frame: 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
ARRY-371797	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
ARRY-371797	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	3 Participants
ARRY-371797	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
ARRY-371797	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	1 Participants
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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
ARRY-371797	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	2 Participants
ARRY-371797	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
ARRY-371797	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	1 Participants
ARRY-371797	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	8 Participants

Primary

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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.

Time frame: 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
ARRY-371797	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	6 Participants
ARRY-371797	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	TEAEs	8 Participants

Secondary

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

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.