Safety And Efficacy Evaluation Of Fx-1006A In Subjects With Transthyretin Amyloidosis

NIS-LL: a subscale (of 37-item NIS questionnaire) that provided a total neuropathic deficit score for the lower limbs. It assess muscle weakness, reflexes, sensation; scored separately for left, right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0=normal, 1=decreased, or 2=absent. Total possible NIS-LL score range 0-88, high score=more impairment.

NIS-LL: a subscale (of 37-item NIS questionnaire) that provided a total neuropathic deficit score for the lower limbs. It assess muscle weakness, reflexes, sensation; scored separately for left, right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0=normal, 1=decreased, or 2=absent. Total possible NIS-LL score range 0-88, high score=more impairment.

NIS-LL: a subscale (of 37-item NIS questionnaire) that provided a total neuropathic deficit score for the lower limbs. It assess muscle weakness, reflexes, sensation; scored separately for left, right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0=normal, 1=decreased, or 2=absent. Total possible NIS-LL score range 0-88, high score=more impairment.

NIS-LL: a subscale (of 37-item NIS questionnaire) that provided a total neuropathic deficit score for the lower limbs. It assess muscle weakness, reflexes, sensation; scored separately for left, right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0=normal, 1=decreased, or 2=absent. Total possible NIS-LL score range 0-88, high score=more impairment.

NIS-LL: a subscale (of 37-item NIS questionnaire) that provided a total neuropathic deficit score for the lower limbs. It assess muscle weakness, reflexes, sensation; scored separately for left, right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0=normal, 1=decreased, or 2=absent. Total possible NIS-LL score range 0-88, high score=more impairment.

NIS-LL: a subscale (of 37-item NIS questionnaire) that provided a total neuropathic deficit score for the lower limbs. It assess muscle weakness, reflexes, sensation; scored separately for left, right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0=normal, 1=decreased, or 2=absent. Total possible NIS-LL score range 0-88, high score=more impairment.

Norfolk QOL-DN: 35-item participant-rated questionnaire; assessed impact of DN on health related QOL of participants with DN. Scoring was based on 35 questions that yield a TQOL as well as 5 subscale scores: symptoms, activities of daily living (ADLs), large fiber neuropathy/physical functioning, small fiber neuropathy, and autonomic neuropathy. TQOL score: sum of all items, total possible score range= -2 to 138, where higher score=worse QOL.

Norfolk QOL-DN: 35-item participant-rated questionnaire; assessed impact of DN on health related QOL of participants with DN. Scoring was based on 35 questions that yield a TQOL as well as 5 subscale scores: symptoms, activities of daily living (ADLs), large fiber neuropathy/physical functioning, small fiber neuropathy, and autonomic neuropathy. TQOL score: sum of all items, total possible score range= -2 to 138, where higher score=worse QOL.

Norfolk QOL-DN: 35-item participant-rated questionnaire; assessed impact of DN on health related QOL of participants with DN. Scoring was based on 35 questions that yield a TQOL as well as 5 subscale scores: symptoms, activities of daily living (ADLs), large fiber neuropathy/physical functioning, small fiber neuropathy, and autonomic neuropathy. TQOL score: sum of all items, total possible score range= -2 to 138, where higher score=worse QOL.

Norfolk QOL-DN: 35-item participant-rated questionnaire; assessed impact of DN on health related QOL of participants with DN. Scoring was based on 35 questions that yield a TQOL as well as 5 subscale scores: symptoms, activities of daily living (ADLs), large fiber neuropathy/physical functioning, small fiber neuropathy, and autonomic neuropathy. TQOL score: sum of all items, total possible score range= -2 to 138, where higher score=worse QOL.

Norfolk QOL-DN: 35-item participant-rated questionnaire; assessed impact of DN on health related QOL of participants with DN. Scoring was based on 35 questions that yield a TQOL as well as 5 subscale scores: symptoms, activities of daily living (ADLs), large fiber neuropathy/physical functioning, small fiber neuropathy, and autonomic neuropathy. TQOL score: sum of all items, total possible score range= -2 to 138, where higher score=worse QOL.

Norfolk QOL-DN: 35-item participant-rated questionnaire; assessed impact of DN on health related QOL of participants with DN. Scoring was based on 35 questions that yield a TQOL as well as 5 subscale scores: symptoms, activities of daily living (ADLs), large fiber neuropathy/physical functioning, small fiber neuropathy, and autonomic neuropathy. TQOL score: sum of all items, total possible score range= -2 to 138, where higher score=worse QOL.

KPS: used for rating participant activities of daily living on 11-step scale from 0-100, higher score=participant is better able to carry out daily activities. Score range: 100=normal no complaints; no disease evidence, 90=able to carry normal activity; minor signs/symptoms of disease, 80=normal activity with effort; some signs/symptoms, 70=cares for self; unable to carry on normal activity, 60=requires occasional assistance, but able to care for most personal needs, 50=requires considerable assistance and frequent medical care, 40=disabled; requires special care, assistance, 30=severely disabled; hospital admission is indicated although death not imminent, 20=very sick; hospital admission necessary, 10=moribund; fatal processes progressing rapidly and 0=dead. The lower the score the worse is survival for most serious illnesses. Data for KPS score was not collected in parent studies Fx-005 and Fx-006, therefore not reported for any time points from parent studies.

KPS: used for rating participant activities of daily living on 11-step scale from 0-100, higher score=participant is better able to carry out daily activities. Score range: 100=normal no complaints; no disease evidence, 90=able to carry normal activity; minor signs/symptoms of disease, 80=normal activity with effort; some signs/symptoms, 70=cares for self; unable to carry on normal activity, 60=requires occasional assistance, but able to care for most personal needs, 50=requires considerable assistance and frequent medical care, 40=disabled; requires special care, assistance, 30=severely disabled; hospital admission is indicated although death not imminent, 20=very sick; hospital admission necessary, 10=moribund; fatal processes progressing rapidly and 0=dead. The lower the score the worse is survival for most serious illnesses. Data for KPS score was not collected in parent studies Fx-005 and Fx-006, therefore not reported for any time points from parent studies.

Karnofsky performance scale was used for rating participant activities of daily living. It rated participant on 11-step scale ranged from 0-100, higher score=participant is better able to carry out daily activities. The lower the score, the worse the survival for most serious illnesses. Score range: 100=normal no complaints; no evidence of disease, 90=able to carry on normal activity; minor signs/symptoms of disease, 80=normal activity with effort; some signs or symptoms, 70=cares for self; unable to carry on normal activity or to do active work, 60=requires occasional assistance, but able to care for most personal needs, 50=requires considerable assistance and frequent medical care, 40=disabled; requires special care and assistance, 30=severely disabled; hospital admission is indicated although death not imminent, 20=very sick; hospital admission necessary, 10=moribund; fatal processes progressing rapidly and 0=dead, where lower score=worse survival for most serious illnesses.

Karnofsky performance scale was used for rating participant activities of daily living. It rated participant on 11-step scale ranged from 0-100, higher score=participant is better able to carry out daily activities. The lower the score, the worse the survival for most serious illnesses. Score range: 100=normal no complaints; no evidence of disease, 90=able to carry on normal activity; minor signs/symptoms of disease, 80=normal activity with effort; some signs or symptoms, 70=cares for self; unable to carry on normal activity or to do active work, 60=requires occasional assistance, but able to care for most personal needs, 50=requires considerable assistance and frequent medical care, 40=disabled; requires special care and assistance, 30=severely disabled; hospital admission is indicated although death not imminent, 20=very sick; hospital admission necessary, 10=moribund; fatal processes progressing rapidly and 0=dead, where lower score=worse survival for most serious illnesses.

Karnofsky performance scale was used for rating participant activities of daily living. It rated participant on 11-step scale ranged from 0-100, higher score=participant is better able to carry out daily activities. The lower the score, the worse the survival for most serious illnesses. Score range: 100=normal no complaints; no evidence of disease, 90=able to carry on normal activity; minor signs/symptoms of disease, 80=normal activity with effort; some signs or symptoms, 70=cares for self; unable to carry on normal activity or to do active work, 60=requires occasional assistance, but able to care for most personal needs, 50=requires considerable assistance and frequent medical care, 40=disabled; requires special care and assistance, 30=severely disabled; hospital admission is indicated although death not imminent, 20=very sick; hospital admission necessary, 10=moribund; fatal processes progressing rapidly and 0=dead, where lower score=worse survival for most serious illnesses.

Ambulatory status for each Val30Met participant was collected using ambulatory data collection forms in [B3461020 (Fx-005), B3461021 (Fx-006)] or forms based on modified polyneuropathy disability (mPND) score in B3461023 (after protocol amendment 1.1). The data were categorized to 3 ambulation stages: Stage 1 (normal), Stage 2 (some assistance required), or Stage 3 (not ambulatory).

Ambulatory status for each Val30Met participant was collected using ambulatory data collection forms in [B3461020 (Fx-005), B3461021 (Fx-006)] or forms based on mPND score in B3461023 (after protocol amendment 1.1). The data were categorized to 3 ambulation stages: Stage 1 (normal), Stage 2 (some assistance required), or Stage 3 (not ambulatory).

Ambulatory status for each Val30Met participant was collected using ambulatory data collection forms in [B3461020 (Fx-005), B3461021 (Fx-006)] or forms based on mPND score in B3461023 (after protocol amendment 1.1). The data were categorized to 3 ambulation stages: Stage 1 (normal), Stage 2 (some assistance required), or Stage 3 (not ambulatory).

Ambulatory status for each NonVal30Met participant was collected using ambulatory data collection forms in B3461022 (Fx1A-201) or forms based on mPND score in B3461023 (after protocol amendment 1.1). The data were categorized to 3 ambulation stages: Stage 1 (normal), Stage 2 (some assistance required), or Stage 3 (not ambulatory).

Ambulatory status for each NonVal30Met participant was collected using ambulatory data collection forms in B3461022 (Fx1A-201) or forms based on mPND score in B3461023 (after protocol amendment 1.1). The data were categorized to 3 ambulation stages: Stage 1 (normal), Stage 2 (some assistance required), or Stage 3 (not ambulatory).

Ambulatory status for each NonVal30Met participant was collected using ambulatory data collection forms in B3461022 (Fx1A-201) or forms based on mPND score in B3461023 (after protocol amendment 1.1). The data were categorized to 3 ambulation stages: Stage 1 (normal), Stage 2 (some assistance required), or Stage 3 (not ambulatory).

NIS-LL: a subscale (of 37-item NIS questionnaire) that provided a total neuropathic deficit score for the lower limbs. It assess muscle weakness, reflexes, sensation; scored separately for left, right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0=normal, 1=decreased, or 2=absent. Total possible NIS-LL score range 0-88, high score=more impairment.

NIS-LL: a subscale (of 37-item NIS questionnaire) that provided a total neuropathic deficit score for the lower limbs. It assess muscle weakness, reflexes, sensation; scored separately for left, right limbs with a total possible NIS-LL score range of 0 to 88, higher score=greater impairment. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0=normal, 1=decreased, or 2=absent. NIS-LL Muscle Weakness score range is 0 to 64, high score=more impairment. NIS-LL Sensation score range is 0 to 16, high score=more impairment. NIS-LL Reflexes score range is 0 to 8, high score=more impairment.

NIS-LL: a subscale (of 37-item NIS questionnaire) that provided a total neuropathic deficit score for the lower limbs. It assess muscle weakness, reflexes, sensation; scored separately for left, right limbs with a total possible NIS-LL score range of 0 to 88, higher score=greater impairment. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0=normal, 1=decreased, or 2=absent. NIS-LL Muscle Weakness score range is 0 to 64, high score=more impairment. NIS-LL Sensation score range is 0 to 16, high score=more impairment. NIS-LL Reflexes score range is 0 to 8, high score=more impairment.

NIS-LL: a subscale (of 37-item NIS questionnaire) that provided a total neuropathic deficit score for the lower limbs. It assess muscle weakness, reflexes, sensation; scored separately for left, right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0=normal, 1=decreased, or 2=absent. Total possible NIS-LL score range 0-88, high score=more impairment.

NIS-LL: a subscale (of 37-item NIS questionnaire) that provided a total neuropathic deficit score for the lower limbs. It assess muscle weakness, reflexes, sensation; scored separately for left, right limbs with a total possible NIS-LL score range of 0 to 88, higher score=greater impairment. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0=normal, 1=decreased, or 2=absent. NIS-LL Muscle Weakness score range is 0 to 64, high score=more impairment. NIS-LL Sensation score range is 0 to 16, high score=more impairment. NIS-LL Reflexes score range is 0 to 8, high score=more impairment.

NIS-LL: a subscale (of 37-item NIS questionnaire) that provided a total neuropathic deficit score for the lower limbs. It assess muscle weakness, reflexes, sensation; scored separately for left, right limbs with a total possible NIS-LL score range of 0 to 88, higher score=greater impairment. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0=normal, 1=decreased, or 2=absent. NIS-LL Muscle Weakness score range is 0 to 64, high score=more impairment. NIS-LL Sensation score range is 0 to 16, high score=more impairment. NIS-LL Reflexes score range is 0 to 8, high score=more impairment.

Norfolk QOL-DN: 35-item participant-rated questionnaire; assessed impact of DN on health related QOL of participants with DN. Scoring was based on 35 questions that yield a TQOL as well as 5 subscale scores: symptoms, activities of daily living (ADLs), large fiber neuropathy/physical functioning, small fiber neuropathy, and autonomic neuropathy. TQOL score: sum of all items, total possible score range= -2 to 138, where higher score=worse QOL.

Norfolk QOL-DN: 35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1 to 7: scored as 1=symptom present, 0=symptom absent. Items 8 to 35: scored on 5-point Likert scale: 0=no problem to 4=severe problem (except item 32, where -1="somewhat better", -2=much better, 0=about the same, 1=somewhat worse, 2=much worse). Norfolk QOL-DN summarized in 5 domains (score range): physical functioning/large fiber neuropathy (-2 to 58), activities of daily living (ADLs) (0 to 20), symptoms (0 to 32), small fiber neuropathy (0 to 16), autonomic neuropathy (0 to 12); higher score=greater impairment, for each. Total score= -2 to 138 (higher score=worse QOL).

Norfolk QOL-DN: 35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1 to 7: scored as 1=symptom present, 0=symptom absent. Items 8 to 35: scored on 5-point Likert scale: 0=no problem to 4=severe problem (except item 32, where -1="somewhat better", -2=much better, 0=about the same, 1=somewhat worse, 2=much worse). Norfolk QOL-DN summarized in 5 domains (score range): physical functioning/large fiber neuropathy (-2 to 58), activities of daily living (ADLs) (0 to 20), symptoms (0 to 32), small fiber neuropathy (0 to 16), autonomic neuropathy (0 to 12); higher score=greater impairment, for each. Total score= -2 to 138 (higher score=worse QOL).

Norfolk QOL-DN: 35-item participant-rated questionnaire; assessed impact of DN on health related QOL of participants with DN. Scoring was based on 35 questions that yield a TQOL as well as 5 subscale scores: symptoms, activities of daily living (ADLs), large fiber neuropathy/physical functioning, small fiber neuropathy, and autonomic neuropathy. TQOL score: sum of all items, total possible score range= -2 to 138, where higher score=worse QOL.

Norfolk QOL-DN: 35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1 to 7: scored as 1=symptom present, 0=symptom absent. Items 8 to 35: scored on 5-point Likert scale: 0=no problem to 4=severe problem (except item 32, where -1="somewhat better", -2=much better, 0=about the same, 1=somewhat worse, 2=much worse). Norfolk QOL-DN summarized in 5 domains (score range): physical functioning/large fiber neuropathy (-2 to 58), activities of daily living (ADLs) (0 to 20), symptoms (0 to 32), small fiber neuropathy (0 to 16), autonomic neuropathy (0 to 12); higher score=greater impairment, for each. Total score= -2 to 138 (higher score=worse QOL).

Norfolk QOL-DN: 35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1 to 7: scored as 1=symptom present, 0=symptom absent. Items 8 to 35: scored on 5-point Likert scale: 0=no problem to 4=severe problem (except item 32, where -1="somewhat better", -2=much better, 0=about the same, 1=somewhat worse, 2=much worse). Norfolk QOL-DN summarized in 5 domains (score range): physical functioning/large fiber neuropathy (-2 to 58), activities of daily living (ADLs) (0 to 20), symptoms (0 to 32), small fiber neuropathy (0 to 16), autonomic neuropathy (0 to 12); higher score=greater impairment, for each. Total score= -2 to 138 (higher score=worse QOL).

Karnofsky performance scale was used for rating participant activities of daily living. It rated participant on 11-step scale ranged from 0-100, higher score=participant is better able to carry out daily activities. The lower the score, the worse the survival for most serious illnesses. Score range: 100=normal no complaints; no evidence of disease, 90=able to carry on normal activity; minor signs/symptoms of disease, 80=normal activity with effort; some signs or symptoms, 70=cares for self; unable to carry on normal activity or to do active work, 60=requires occasional assistance, but able to care for most personal needs, 50=requires considerable assistance and frequent medical care, 40=disabled; requires special care and assistance, 30=severely disabled; hospital admission is indicated although death not imminent, 20=very sick; hospital admission necessary, 10=moribund; fatal processes progressing rapidly and 0=dead, where lower score=worse survival for most serious illnesses.

Karnofsky performance scale was used for rating participant activities of daily living. It rated participant on 11-step scale ranged from 0-100, higher score=participant is better able to carry out daily activities. The lower the score, the worse the survival for most serious illnesses. Score range: 100=normal no complaints; no evidence of disease, 90=able to carry on normal activity; minor signs/symptoms of disease, 80=normal activity with effort; some signs or symptoms, 70=cares for self; unable to carry on normal activity or to do active work, 60=requires occasional assistance, but able to care for most personal needs, 50=requires considerable assistance and frequent medical care, 40=disabled; requires special care and assistance, 30=severely disabled; hospital admission is indicated although death not imminent, 20=very sick; hospital admission necessary, 10=moribund; fatal processes progressing rapidly and 0=dead, where lower score=worse survival for most serious illnesses.

Ambulatory status for each Val30Met participant was collected using ambulatory data collection forms in [B3461020 (Fx-005), B3461021 (Fx-006)] or forms based on mPND score in B3461023 (after protocol amendment 1.1). The data were categorized to 3 ambulation stages: Stage 1 (normal), Stage 2 (some assistance required), or Stage 3 (not ambulatory).

Ambulatory status for each NonVal30Met participant was collected using ambulatory data collection forms in B3461022 (Fx1A-201) or forms based on mPND score in B3461023 (after protocol amendment 1.1). The data were categorized to 3 ambulation stages: Stage 1 (normal), Stage 2 (some assistance required), or Stage 3 (not ambulatory).

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. 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; medically important events. Treatment-emergent AEs were events that emerged after enrollment in B3461023 (Fx1A-303) or which worsened during the course of B3461023 (Fx1A-303) relative to the pretreatment state. AEs included both SAEs and non-SAEs.

Complete physical examination included examination of the general appearance, head and neck, ears, eyes, nose, throat, respiratory, genitourinary, endocrine, cardiovascular, abdomen, skin, musculoskeletal, neurological, immunologic/allergies, hematologic/lymphatic. Abnormality in physical findings were based on investigator's decision.

Abnormalities criteria: Serum chemistry (bilirubin>1.5*upper limit normal [ULN]; aspartate aminotransferase; alanine aminotransferase; alkaline phosphatase; gamma glutamyl transferase >3.0*ULN; albumin<0.8*lower limit normal [LLN],>1.2*ULN; blood urea nitrogen, creatinine>1.3*ULN; free T4, thyrotropin, thyroxine <0.8*LLN,>1.2*ULN; glucose<0.6*LLN,>1.5*ULN); Coagulation (prothrombin time, prothrombin int. normalized ratio >1.1*ULN); Hematology(basophils; eosinophils, monocytes >1.2*ULN; leukocytes <0.6*LLN,>1.5*ULN; lymphocytes, neutrophils <0.8*LLN, >1.2*ULN).

Twelve-lead ECGs were obtained for all participants. Criteria for QT interval, Bazett's correction formula (QTcB) and Fridericia's correction formula (QTcF): greater than (>) 450-480 millisecond (msec), >480-500 msec and >500 msec. Findings were considered to be abnormal based on investigator's decision.

Criteria for clinically significant changes: Supine and standing systolic blood pressure (BP): decrease from baseline of less than or equal to (<=) -20 millimeter of mercury (mmHg), increase from baseline of greater than or equal to (>=) 20 mmHg, systolic BP <90 mmHg or >180 mmHg; Supine and standing diastolic BP: decrease from baseline of <=-15 mmHg, increase from baseline of >= 15 mmHg, diastolic BP <50 mmHg or >105 mmHg; Supine and standing pulse rate: decrease from baseline of <=-15 beats per minute (bpm), increase from baseline of >=15 bpm, pulse rate <50 bpm or >120 bpm; Weight: decrease from baseline of <=-7 percentage (%) or increase from baseline of >=7%.

Number of participants with any concomitant medications usage are reported.