Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF

Sponsor

NS Pharma, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01423851

Collaborator

(none)

Enrollment

Locations

Arm

106.7

Duration (Months)

8.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and tolerability of orally administered NS-018 in patients with Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (post-PV MF), or Post-essential Thrombocythemia Myelofibrosis (post-ET MF)

Condition or Disease	Intervention/Treatment	Phase
Primary Myelofibrosis Post-Polycythemia Vera Myelofibrosis Post-Essential Thrombocythemia Myelofibrosis	Drug: NS-018	Phase 1/Phase 2

Detailed Description

This is a Phase 1/2 study that is currently enrolling Janus kinase 2 (JAK2) failures into the Phase 2 portion of the study.

Study Design

Study Type:

Interventional

Actual Enrollment :

77 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

Phase 1: 75, 125, 200, 300, 400 mg QD and 100, 200, 250, 300, 400 mg BID Phase 2: 300 mg QDPhase 1: 75, 125, 200, 300, 400 mg QD and 100, 200, 250, 300, 400 mg BID Phase 2: 300 mg QD

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2, Open-label, Dose-Escalation Multi-center Study to Assess the Safety, Tolerability, PK and PD of Orally Administered NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF

Study Start Date :

Jun 1, 2011

Actual Primary Completion Date :

Apr 22, 2020

Actual Study Completion Date :

Apr 22, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention: Drug: NS-018 In Phase 1 part, subjects were treated with oral NS-018 at a dose of 75 - 400 mg once daily or 100 - 400 mg twice daily. In Phase 2 part, subjects were treated with oral NS-018 at a dose of 300 mg once daily.	Drug: NS-018 Treatment will be administered continuously as oral daily therapy in cycles of 4 weeks in duration (28 day treatment cycles).

Arm

Intervention/Treatment

Experimental: Intervention: Drug: NS-018

In Phase 1 part, subjects were treated with oral NS-018 at a dose of 75 - 400 mg once daily or 100 - 400 mg twice daily. In Phase 2 part, subjects were treated with oral NS-018 at a dose of 300 mg once daily.

Drug: NS-018

Treatment will be administered continuously as oral daily therapy in cycles of 4 weeks in duration (28 day treatment cycles).

Outcome Measures

Primary Outcome Measures

Part 1 and Part 2: Number of Subjects With Adverse Events and Serious Adverse Event [From screening to until study discontinuation (approximate 8 years 10 months)]
AEs (non-serious, serious) as variables of safety and tolerability of NS-018 were assesed. The number of patients were presented as Overall summary of AEs including treatment-emergent AEs (TEAEs); Treatment-emergent SAEs; Drug-related TEAEs; Treatment-emergent AEs leading to permanent discontinuation of study drug; Hospitalization or prolongation of existing hospitalization; Death.
Part 2: Number of Patient With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) [Cycle 7 Day 1 (duration of cycle was 4 weeks)]
Six response categories are listed: complete remission (CR) and partial remission signify treatment effects that are consistent with disease modification, whereas drug-induced improvements in MF-symptomatic burden were annotated as clinical improvement, anemia response, spleen response, orsymptoms response. Additional criteria are provided for progressive disease, stable disease, and relapse. The objective response was defined as the number of patients with confirmed complete remission (CR) + partial response (PR) + clinical improvement (CI) during the treatment period.
Part 2: Change From Baseline in Spleen Size [From Baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)]
Change from baseline in spleen size was assessed by magnetic resonance imaging (MRI) (computed tomography [CT] scan for patients not able to tolerate MRI).
Part 2: Change From Baseline in Bone Marrow Assessment [From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)]
Bone marrow was assessed by aspiration and biopsy for grade changes in osteomyelofibrosis. Fibrosis was graded according to European Consensus Myelofibrosis Grading Criteria, ranging from grade 0, which corresponds to normal bone marrow, to grade 3, in which coarse bundles of collagen fibrosis are identifiable with significant osteosclerosis.

Secondary Outcome Measures

Part 1: Number of Patients With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) [Cycle 7 Day 1 (duration of cycle was 4 weeks)]
Six response categories are listed: complete remission (CR) and partial remission signify treatment effects that are consistent with disease modification, whereas drug-induced improvements in MF-symptomatic burden were annotated as clinical improvement, anemia response, spleen response, orsymptoms response. Additional criteria are provided for progressive disease, stable disease, and relapse. The objective response was defined as the number of patients with confirmed "complete remission (CR) + partial response (PR) + clinical improvement (CI)" during the treatment period.
Part 1: Change From Baseline in Spleen Size [From Baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)]
Change from baseline in spleen size was assessed by palpation.
Part 1: Change From Baseline in Bone Marrow Assessment [From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)]
Bone marrow was assessed by aspiration and biopsy for grade changes in osteomyelofibrosis. Fibrosis was graded according to European Consensus Myelofibrosis Grading Criteria, ranging from grade 0, which corresponds to normal bone marrow, to grade 3, in which coarse bundles of collagen fibrosis are identifiable with significant osteosclerosis.
Part 1: Change From Baseline in Quality of Life Assessments Using Myelofibrosis Symptom Assessment Form (MF-SAF) [From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)]
MF SAF is a 20-item instrument comprised of 4 subscales: 1) the Brief Fatigue Inventory [= average of 9 fatigue scores], 2) Splenomegaly associated symptoms [= average of 4 splenomegaly and associated scores], 3) Catabolic/proliferative Symptoms [= average of 3 catabolic/proliferative associated scores] and 4) Overall Quality of Life. The items were on a scale from 1 to 10 where 1= most favorable, and 10= least favorable.
Part 2: Change From Baseline in Quality of Life Assessments Using Myeloproliferative Neoplasm Symptom Assessment Form (MPN SAF (MPN 10) [From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)]
Symptoms are evaluated by the MPN-SAF Total Symptom Score (TSS). The MPN-SAF TSS is assessed by the patients themselves and this includes fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Scoring is from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be) for each item. The MPN-SAF TSS is the summation of all the individual scores (0-100 scale). Symptoms response requires >50% reduction in the MPN-SAF TSS.
Part 1 and Part 2: Change in Baseline in Janus Kinase 2 (JAK2) V617F Allele Burden Levels [Part 1 and Part 2: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)]
The JAK2 V617F allele burden mean changes from baseline (%) are presented as pharmacodynamics parameters.
Part 2: Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (Phospho-STAT3) [From Baseline to Pre-dose at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (duration of cycle was 4 weeks)]
The Phospho-STAT3 mean changes from baseline (%) are presented as pharmacodynamics parameters. For phospho-STAT3 values (Phase 2 only), study samples were incubated (± IL-6) and labeled with CD markers. Surface markers included CD3+ (CD4+ [helper T cells] and CD8+ [cytotoxic T cells]) and CD14+ (monocytes) to which intracellular phospho STAT3 was targeted. The levels of phospho-STAT3 in CD14+, CD3+CD4+ and CD3+CD8+ cell subtypes were quantified. Phosphorylated-STAT3 levels were evaluated in the cell types before and after IL-6 incubation (stimulation) and reported both as mean fluorescence intensity (MFI) and the percentage of positive cells. For each sample time point, the MFI was normalized to a fold change. The fold change was calculated by MFI after IL-6 treatment/MFI before IL-6 treatment. The percent positive cells were normalized by subtracting the percent positive cells before IL-6 treatment from the percent positive cells after IL-6 treatment.
Part1 and Part 2: Observed Maximum Concentration (Cmax) [Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (duration of cycle was 4 weeks)]
To determine the Cmax as pharmacokinetic parameters of NS-018.
Part 1 and Part 2: Time to Maximum Plasma Concentration (Tmax) [Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1, Cycle 2 Day 1 (duration of cycle was 4 weeks)]
To determine the Tmax as pharmacokinetic parameters of NS-018.
Part1 and Part 2: Area Under the Plasma Concentration-time Curve (AUC0-24) [Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1 (duration of cycle was 4 weeks)]
To determine the AUC0-24 as pharmacokinetic parameters of NS-018.
Part 1 and Part 2: Terminal Elimination Half-life (t½) [Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1, Cycle 2 Day 1 (duration of cycle was 4 weeks)]
To determine the t½ as pharmacokinetic parameters of NS-018.
Part1 and Part 2: Accumulation Ratio (AR) [Part 1 and Part 2: Cycle 2 Day 1 (duration of cycle was 4 weeks)]
To determine the AR as pharmacokinetic parameters of NS-018. AR was calculated as AR = (AUC0-24) Cycle 2 Day 1/ (AUC0-24) Cycle 1 Day 1.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Primary myelofibrosis, post-PV MF, or post-ET MF that requires therapy
MF patients must have received prior JAK2 inhibitor therapy, and been found to be intolerant, or refractory/relapsed from prior JAK2 inhibitor therapy, based on investigator assessment
≥18 years old
ECOG Performance Status of ≤ 3
Estimated life expectancy of ≥12 weeks
Male or non-pregnant, non-lactating female patients
Serum creatinine of ≤1.5 × the upper limit of normal (ULN)OR estimated creatinine clearance (CrCl) ≥ 40 ml/min/1.73 m2
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × the upper limit of normal (ULN) and total bilirubin ≤1.5 × ULN. If the total bilirubin is elevated between 1.5 x and 3 x ULN, patients with a direct bilirubin ≤ 1.5 X ULN are eligible during the Phase II portion.
Absolute neutrophil count (ANC) >1000/μL and Platelet count > 25,000/μL
QTcB ≤ 480 msec
No MF-directed treatment for at least 2 weeks prior to initiation of NS-018, including any use of corticosteroids for Myelofibrosis symptom or blood count management. Low dose corticosteroids ≤ 10 mg/day prednisone or equivalent is allowed for non-myelofibrosis purposes.

Exclusion Criteria:

Active, uncontrolled systemic infection
Patients with any unresolved toxicity greater than Grade 1 from previous anticancer therapy
Potentially curative therapy is available
Currently taking medication that is substantially metabolized by cytochrome P450 (CYP) 1A2 or CYP3A4 or taking medication known to be strong inhibitors or inducers of CYP3A4
Patients with a serious cardiac condition within the past 6 months
Pregnant or lactating
Radiation therapy for splenomegaly within 6 months prior to study entry
Splenectomy (Phase 2 portion of the study only)
Known HIV positive status
Known active hepatitis, a history of viral hepatitis B or hepatitis C

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale Recruiting	Scottsdale	Arizona	United States	85259-5499
2	UC San Diego Moores Cancer Center	San Diego	California	United States	92093-0698
3	Mayo Clinic, Jacksonville	Jacksonville	Florida	United States	32224
4	Northwestern University	Chicago	Illinois	United States	60611
5	University of Chicago	Chicago	Illinois	United States	60637
6	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
7	University of Michigan	Ann Arbor	Michigan	United States	48109
8	Weill Cornell Medical College	New York	New York	United States	10021
9	MD Anderson Cancer Center, Department of Leukemia	Houston	Texas	United States	77030

Sponsors and Collaborators

NS Pharma, Inc.

Investigators

Principal Investigator: Srdan Verstovsek, M.D., Ph.D., MD Anderson Cancer Center, Houston, TX, 77030

Study Documents (Full-Text)

Study Protocol and Statistical Analysis Plan - Apr 21, 2015

More Information

Publications

None provided.

Responsible Party:

NS Pharma, Inc.

ClinicalTrials.gov Identifier:

NCT01423851

Other Study ID Numbers:

NS-018-101

First Posted:

Aug 26, 2011

Last Update Posted:

Mar 9, 2022

Last Verified:

Feb 1, 2022

Keywords provided by NS Pharma, Inc.

Keywords provided by NS Pharma, Inc.:

JAK2 kinase inhibitor

NS-018

Myeloproliferative Neoplasms

Primary Myelofibrosis

post-Polycythemia Vera Myelofibrosis

post-Essential Thrombocythemia Myelofibrosis

Additional relevant MeSH terms:

Bone Marrow Diseases

Hematologic Diseases

Polycythemia Vera

Thrombocythemia, Essential

PMF

post-PV MF

post-ET MF

Additional relevant MeSH terms:

Polycythemia Vera

Primary Myelofibrosis

Polycythemia

Thrombocytosis

Thrombocythemia, Essential

Study Results

Participant Flow

Recruitment Details

Subjects who met all the inclusion and none of the exclusion criteria were enrolled at 09 sites in the USA. The conduct of this study started on 02 June 2011 (the first patient screened) and the last patient last visit was on 22 April 2020. A total of 48 and 29 patients were enrolled during Phase 1 and Phase 2 of the study respectively. Participants could be reduced or escalated to the noted dose at physician discretion.

Pre-assignment Detail

The screening period was from Day -14 to Day 0 for Phase I and Phase II. Informed consent form (ICF) was signed prior to screening procedures. All the study assessments were performed as per the schedule of assessment.

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 250 mg BID	Part 1: 300 mg BID	Part 1: 400 mg BID	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Period Title: Whole Study
STARTED	3	3	3	6	3	3	3	8	8	8	29
COMPLETED	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	3	3	3	6	3	3	3	8	8	8	29
Period Title: Whole Study
STARTED	0	1	4	4	0	0	2	0	1	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	1	4	4	0	0	2	0	1	0	0
Period Title: Whole Study
STARTED	0	0	3	5	1	2	8	0	3	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	3	5	1	2	8	0	3	0	0

Baseline Characteristics

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 250 mg BID	Part 1: 300 mg BID	Part 1: 400 mg BID	Part 2: 300 mg QD	Total
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Total of all reporting groups
Overall Participants	3	3	3	6	3	3	3	8	8	8	29	77
Age (Years) [Mean (Standard Deviation) ]
Part 1	72.7 (1.5)	70.3 (14.8)	63.7 (12.9)	67.3 (9.4)	67.3 (3.8)	65.0 (8.9)	69.0 (3.6)	63.0 (11.8)	62.4 (11.9)	69.3 (7.7)	66.4 (9.6)
Part 2	67.2 (9.3)	67.2 (9.3)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 33.3%	0 0%	3 50%	2 66.7%	1 33.3%	0 0%	3 37.5%	6 75%	3 37.5%	14 48.3%	33 42.9%
Male	3 100%	2 66.7%	3 100%	3 50%	1 33.3%	2 66.7%	3 100%	5 62.5%	2 25%	5 62.5%	15 51.7%	44 57.1%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian	3 100%	3 100%	2 66.7%	6 100%	2 66.7%	3 100%	2 66.7%	8 100%	8 100%	8 100%	26 89.7%	71 92.2%
Black/African Heritage	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%	1 3.4%	3 3.9%
Asian/Oriental	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 3.4%	2 2.6%
Other	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 3.4%	1 1.3%

Outcome Measures

1. Primary Outcome

Title	Part 1 and Part 2: Number of Subjects With Adverse Events and Serious Adverse Event
Description	AEs (non-serious, serious) as variables of safety and tolerability of NS-018 were assesed. The number of patients were presented as Overall summary of AEs including treatment-emergent AEs (TEAEs); Treatment-emergent SAEs; Drug-related TEAEs; Treatment-emergent AEs leading to permanent discontinuation of study drug; Hospitalization or prolongation of existing hospitalization; Death.
Time Frame	From screening to until study discontinuation (approximate 8 years 10 months)

Outcome Measure Data

Analysis Population Description
The safety population included all patients who received at least 1 dose of study drug. NS-018-101 study was dose-finding study, Principal investigator (PI) could increase or decrease dose-level per protocol. Totals are based on number of patients and not on dose-level cohort. Patients can appear in more than one dose-level cohort.

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 250 mg BID	Part 1: 300 mg BID	Part 1: 400 mg BID	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	3	4	10	15	4	5	13	8	12	8	29
Not TEAE	0 0%	0 0%	0 0%	0 0%	1 33.3%	2 66.7%	1 33.3%	3 37.5%	4 50%	2 25%	6 20.7%
Any AE	3 100%	4 133.3%	9 300%	14 233.3%	4 133.3%	4 133.3%	11 366.7%	8 100%	12 150%	8 100%	29 100%
Any Treatment Emergent AE	3 100%	4 133.3%	9 300%	14 233.3%	4 133.3%	4 133.3%	11 366.7%	8 100%	12 150%	8 100%	29 100%
Drug Related TEAE	1 33.3%	1 33.3%	8 266.7%	11 183.3%	4 133.3%	2 66.7%	4 133.3%	5 62.5%	10 125%	7 87.5%	24 82.8%
Any Serious TEAE	2 66.7%	2 66.7%	2 66.7%	6 100%	1 33.3%	1 33.3%	4 133.3%	3 37.5%	4 50%	3 37.5%	13 44.8%
TEAE Leading to Discontinuation of study drug	1 33.3%	0 0%	0 0%	4 66.7%	0 0%	0 0%	0 0%	3 37.5%	4 50%	2 25%	5 17.2%
Hospitalization or Prolongation of Existing Hospitalization	1 33.3%	2 66.7%	2 66.7%	6 100%	1 33.3%	1 33.3%	3 100%	2 25%	3 37.5%	1 12.5%	11 37.9%
Death	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 3.4%

2. Primary Outcome

Title	Part 2: Number of Patient With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN)
Description	Six response categories are listed: complete remission (CR) and partial remission signify treatment effects that are consistent with disease modification, whereas drug-induced improvements in MF-symptomatic burden were annotated as clinical improvement, anemia response, spleen response, orsymptoms response. Additional criteria are provided for progressive disease, stable disease, and relapse. The objective response was defined as the number of patients with confirmed complete remission (CR) + partial response (PR) + clinical improvement (CI) during the treatment period.
Time Frame	Cycle 7 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. Here, the overall number of subjects analyzed signifies only the subjects with available data that were analyzed evaluated on that specific cycle day.

Arm/Group Title	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	12
Count of Participants [Participants]	1 33.3%

3. Primary Outcome

Title	Part 2: Change From Baseline in Spleen Size
Description	Change from baseline in spleen size was assessed by magnetic resonance imaging (MRI) (computed tomography [CT] scan for patients not able to tolerate MRI).
Time Frame	From Baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. Here, the overall number of subjects analyzed signifies only the subjects with available data that were analyzed evaluated on that specific cycle day.

Arm/Group Title	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	16
Mean (Standard Deviation) [cubic millimeter (mm3)]	-335918.1 (558459.9)

4. Primary Outcome

Title	Part 2: Change From Baseline in Bone Marrow Assessment
Description	Bone marrow was assessed by aspiration and biopsy for grade changes in osteomyelofibrosis. Fibrosis was graded according to European Consensus Myelofibrosis Grading Criteria, ranging from grade 0, which corresponds to normal bone marrow, to grade 3, in which coarse bundles of collagen fibrosis are identifiable with significant osteosclerosis.
Time Frame	From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. Here, the overall number of subjects analyzed signifies only the subjects with available data that were analyzed evaluated on that specific cycle day.

Arm/Group Title	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	3
Increased by at least 1 grade level	1 33.3%
Increased by at least 2 grade level	0 0%
Decreased by at least 1 grade level	2 66.7%
Decreased by at least 2 grade level	0 0%

5. Secondary Outcome

Title	Part 1: Number of Patients With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
Description	Six response categories are listed: complete remission (CR) and partial remission signify treatment effects that are consistent with disease modification, whereas drug-induced improvements in MF-symptomatic burden were annotated as clinical improvement, anemia response, spleen response, orsymptoms response. Additional criteria are provided for progressive disease, stable disease, and relapse. The objective response was defined as the number of patients with confirmed "complete remission (CR) + partial response (PR) + clinical improvement (CI)" during the treatment period.
Time Frame	Cycle 7 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. NS-018-101 study was dose finding study, PI could increase or decrease dose-level per protocol. Patients can appear in more than one dose-level cohort. For 300 mg QD, data from 7 patients were available. 4 patients were enrolled originally and 2 patients were dose-reduced from 400 mg QD and 1 patient was dose-reduced from 250 mg BID.

Analysis Population Description

The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. NS-018-101 study was dose finding study, PI could increase or decrease dose-level per protocol. Patients can appear in more than one dose-level cohort. For 300 mg QD, data from 7 patients were available. 4 patients were enrolled originally and 2 patients were dose-reduced from 400 mg QD and 1 patient was dose-reduced from 250 mg BID.

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 250 mg BID	Part 1: 300 mg BID	Part 1: 400 mg BID
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	0	3	2	7	0	3	3	1	3	0
Count of Participants [Participants]	0 0%	0 0%	0 0%	2 33.3%	0 0%	0 0%	1 33.3%	0 0%	1 12.5%	0 0%

6. Secondary Outcome

Title	Part 1: Change From Baseline in Spleen Size
Description	Change from baseline in spleen size was assessed by palpation.
Time Frame	From Baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. NS-018-101 study was dose finding study, PI could increase or decrease dose-level per protocol. Patients can appear in more than one dose-level cohort. At 200 mg BID cohort, 3 patients were enrolled originally, 2 patients were dose-escalated from 100 mg BID cohort and 8 patients were dose-reduced from 300 mg BID or 400 mg BID cohort.

Analysis Population Description

The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. NS-018-101 study was dose finding study, PI could increase or decrease dose-level per protocol. Patients can appear in more than one dose-level cohort. At 200 mg BID cohort, 3 patients were enrolled originally, 2 patients were dose-escalated from 100 mg BID cohort and 8 patients were dose-reduced from 300 mg BID or 400 mg BID cohort.

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 250 mg BID	Part 1: 300 mg BID	Part 1: 400 mg BID
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	0	3	2	6	0	3	13	1	3	0
Mean (Standard Deviation) [cm]	-0.67 (2.89)	-8.25 (3.18)	-3.17 (3.97)	-3.00 (3.00)	-4.33 (6.66)	-7.00 (NA)	-2.00 (3.00)

7. Secondary Outcome

Title	Part 1: Change From Baseline in Bone Marrow Assessment
Description	Bone marrow was assessed by aspiration and biopsy for grade changes in osteomyelofibrosis. Fibrosis was graded according to European Consensus Myelofibrosis Grading Criteria, ranging from grade 0, which corresponds to normal bone marrow, to grade 3, in which coarse bundles of collagen fibrosis are identifiable with significant osteosclerosis.
Time Frame	From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. Here, the overall number of subjects analyzed signifies only the subjects with available data that were analyzed evaluated on that specific cycle day.

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 250 mg BID	Part 1: 300 mg BID	Part 1: 400 mg BID
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	0	1	0	4	0	1	0	0	2	0
Increased by at least 1 grade level	0 0%	1 33.3%	1 33.3%	2 33.3%
Increased by at least 2 grade level	0 0%	0 0%	0 0%	0 0%
Decreased by at least 1 grade level	1 33.3%	3 100%	0 0%	0 0%
Decreased by at least 2 grade level	0 0%	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Part 1: Change From Baseline in Quality of Life Assessments Using Myelofibrosis Symptom Assessment Form (MF-SAF)
Description	MF SAF is a 20-item instrument comprised of 4 subscales: 1) the Brief Fatigue Inventory [= average of 9 fatigue scores], 2) Splenomegaly associated symptoms [= average of 4 splenomegaly and associated scores], 3) Catabolic/proliferative Symptoms [= average of 3 catabolic/proliferative associated scores] and 4) Overall Quality of Life. The items were on a scale from 1 to 10 where 1= most favorable, and 10= least favorable.
Time Frame	From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. NS-018-101 study was dose finding study, PI could increase or decrease dose-level per protocol. Patients can appear in more than one dose-level cohort. For 300 mg QD, data from 7 patients were available. 4 patients were enrolled originally and 2 patients were dose-reduced from 400 mg QD and 1 patient was dose-reduced from 250 mg BID.

Analysis Population Description

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 250 mg BID	Part 1: 300 mg BID	Part 1: 400 mg BID
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	0	3	2	7	0	3	2	1	3	0
Brief Fatigue Inventory Score	0.1 (0.4)	-1.3 (2.0)	0.8 (1.3)	-1.9 (0.1)	0.4 (0.2)	0.7 (NA)	-0.8 (1.1)
Splenomegaly-associated Symptom Score	1.3 (1.3)	-0.5 (1.1)	0.5 (0.8)	-0.3 (1.8)	-1.1 (1.2)	-4.0 (NA)	-1.8 (1.5)
Catabolic/Proliferative Symptoms Score	1.2 (0.2)	-0.7 (0.5)	-0.4 (2.4)	-0.4 (1.0)	1.5 (1.6)	-8.0 (NA)	-0.6 (1.0)
Overall Quality of Life Score	0.3 (0.6)	-1.0 (1.4)	0.0 (3.6)	-1.7 (2.1)	-1.5 (2.1)	0.0 (NA)	-1.7 (1.5)

9. Secondary Outcome

Title	Part 2: Change From Baseline in Quality of Life Assessments Using Myeloproliferative Neoplasm Symptom Assessment Form (MPN SAF (MPN 10)
Description	Symptoms are evaluated by the MPN-SAF Total Symptom Score (TSS). The MPN-SAF TSS is assessed by the patients themselves and this includes fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Scoring is from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be) for each item. The MPN-SAF TSS is the summation of all the individual scores (0-100 scale). Symptoms response requires >50% reduction in the MPN-SAF TSS.
Time Frame	From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. Here, the overall number of subjects analyzed signifies only the subjects with available data that were analyzed evaluated on that specific cycle day.

Arm/Group Title	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	10
Mean (Standard Deviation) [score on a scale]	-0.7 (3.4)

10. Secondary Outcome

Title	Part 1 and Part 2: Change in Baseline in Janus Kinase 2 (JAK2) V617F Allele Burden Levels
Description	The JAK2 V617F allele burden mean changes from baseline (%) are presented as pharmacodynamics parameters.
Time Frame	Part 1 and Part 2: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The PD population included all patients who received at least one dose of study drug and had a baseline and at least one post-baseline PD assessment (for at least one PD parameter). Here, the overall number of subjects analyzed signifies only the subjects with available data that were analyzed evaluated on that specific cycle day.

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 250 mg BID	Part 1: 300 mg BID	Part 1: 400 mg BID	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	0	1	1	2	0	2	2	2	2	4	11
Mean (Standard Deviation) [Percentage of JAK2 V617F Level]	4.360 (NA)	-0.210 (NA)	7.410 (2.758)	-6.720 (10.479)	8.255 (4.320)	-4.900 (9.065)	-9.033 (5.352)	-4.368 (14.602)	1.782 (8.978)

11. Secondary Outcome

Title	Part 2: Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (Phospho-STAT3)
Description	The Phospho-STAT3 mean changes from baseline (%) are presented as pharmacodynamics parameters. For phospho-STAT3 values (Phase 2 only), study samples were incubated (± IL-6) and labeled with CD markers. Surface markers included CD3+ (CD4+ [helper T cells] and CD8+ [cytotoxic T cells]) and CD14+ (monocytes) to which intracellular phospho STAT3 was targeted. The levels of phospho-STAT3 in CD14+, CD3+CD4+ and CD3+CD8+ cell subtypes were quantified. Phosphorylated-STAT3 levels were evaluated in the cell types before and after IL-6 incubation (stimulation) and reported both as mean fluorescence intensity (MFI) and the percentage of positive cells. For each sample time point, the MFI was normalized to a fold change. The fold change was calculated by MFI after IL-6 treatment/MFI before IL-6 treatment. The percent positive cells were normalized by subtracting the percent positive cells before IL-6 treatment from the percent positive cells after IL-6 treatment.
Time Frame	From Baseline to Pre-dose at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The PD population included all patients who received at least one dose of study drug and had a baseline and at least one post-baseline PD assessment (for at least one PD parameter). Here, number analyzed reflects number of patients evaluated on that specific cycle day. Data from 17 out of 24 participants were available and contributed to the analysis. Samples from 7 patients were analyzed, but data were not available due to quantities not sufficient.

Analysis Population Description

The PD population included all patients who received at least one dose of study drug and had a baseline and at least one post-baseline PD assessment (for at least one PD parameter). Here, number analyzed reflects number of patients evaluated on that specific cycle day. Data from 17 out of 24 participants were available and contributed to the analysis. Samples from 7 patients were analyzed, but data were not available due to quantities not sufficient.

Arm/Group Title	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	24
Cycle 1 Day 1: Change percentage of Phospho-STAT3 Levels in CD14+ Positive cells	-9.406 (19.357)
Cycle 1 Day 15: Change percentage of Phospho-STAT3 Levels in CD14+ Positive cells	-2.738 (16.191)
Cycle 2 Day 1: Change percentage of Phospho-STAT3 Levels in CD14+ Positive cells	-0.422 (20.092)
Cycle 1 Day 1: Change percentage of Phospho-STAT3 Levels in CD3+ CD4+ Positive cells	-10.614 (11.178)
Cycle 1 Day 15: Change percentage of Phospho-STAT3 Levels in CD3+ CD4+ Positive cells	6.217 (20.717)
Cycle 2 Day 1: Change percentage of Phospho-STAT3 Levels in CD3+ CD4+ Positive cells	-5.878 (16.304)
Cycle 1 Day 1: Change percentage of Phospho-STAT3 Levels in CD3+ CD8+ Positive cells	-3.707 (11.222)
Cycle 1 Day 15: Change percentage of Phospho-STAT3 Levels in CD3+ CD8+ Positive cells	5.533 (14.513)
Cycle 2 Day 1: Change percentage of Phospho-STAT3 Levels in CD3+ CD8+ Positive cells	-1.644 (6.615)

12. Secondary Outcome

Title	Part1 and Part 2: Observed Maximum Concentration (Cmax)
Description	To determine the Cmax as pharmacokinetic parameters of NS-018.
Time Frame	Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The PK population include all patients who received at least one dose of study drug and have at least 50% of the planned samples above the limit of quantitation to provide evaluable PK profile, Here, number analyzed reflects number of patients evaluated on that specific cycle day. Part 2: 1 patient was completely excluded from PK Population due to critical samples missing, 1 patient was excluded from the analysis due to sample missing at timepoint, So the overall number of participants was 27.

Analysis Population Description

The PK population include all patients who received at least one dose of study drug and have at least 50% of the planned samples above the limit of quantitation to provide evaluable PK profile, Here, number analyzed reflects number of patients evaluated on that specific cycle day. Part 2: 1 patient was completely excluded from PK Population due to critical samples missing, 1 patient was excluded from the analysis due to sample missing at timepoint, So the overall number of participants was 27.

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 250 mg BID	Part 1: 300 mg BID	Part 1: 400 mg BID	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	3	3	3	6	3	3	3	6	8	8	27
Cycle 1 Day 1	66.5600 (79.0171)	404.5333 (26.4258)	377.8000 (184.2086)	726.0667 (232.0338)	1643.0333 (789.0036)	242.0333 (174.3374)	351.0000 (257.1729)	853.5833 (271.7900)	1077.4750 (366.9158)	1261.7000 (658.9141)	957.9852 (306.7937)
Cycle 1 Day 8 (Part 1 only)	30.6700 (13.3077)	324.8667 (57.3280)	539.6667 (160.0954)	805.4333 (236.8877)	1554.6667 (351.6765)	412.8000 (232.9342)	606.8333 (233.7812)	806.8333 (464.3206)	969.0167 (342.3090)	1352.2200 (307.1358)
Cycle 1 Day 15 (Part 2 only)	732.5000 (313.5822)
Cycle 2 Day 1	67.6467 (55.6250)	450.6667 (187.4735)	556.9000 (52.8463)	1066.0000 (271.1854)	1556.0000 (676.3941)	408.6000 (127.0765)	596.1333 (362.6751)	830.7333 (166.0701)	1272.5600 (420.7722)	1040.6500 (321.5215)	1035.3087 (445.9895)

13. Secondary Outcome

Title	Part 1 and Part 2: Time to Maximum Plasma Concentration (Tmax)
Description	To determine the Tmax as pharmacokinetic parameters of NS-018.
Time Frame	Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1, Cycle 2 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The PK population include all patients who received at least one dose of study drug and have at least 50% of the planned samples above the limit of quantitation to provide evaluable PK profile, Here, number analyzed reflects number of patients evaluated on that specific cycle day. Part 2: 1 patient was completely excluded from PK Population due to critical samples missing, 1 patient was excluded from the analysis due to sample missing at timepoint, So the overall number of participants was 27.

Analysis Population Description

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 250 mg BID	Part 1: 300 mg BID	Part 1: 400 mg BID	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	3	3	3	6	3	3	3	6	8	8	27
Cycle 1 Day 1	1.00	1.08	2.00	1.04	1.00	1.00	1.00	1.46	1.02	2.00	2.00
Cycle 1 Day 8 (Part 1 only)	0.78	1.00	1.00	1.54	2.00	1.00	1.00	1.98	1.52	2.03
Cycle 2 Day 1	1.00	1.00	1.00	1.05	1.00	1.00	1.00	2.07	2.08	2.00	1.08

14. Secondary Outcome

Title	Part1 and Part 2: Area Under the Plasma Concentration-time Curve (AUC0-24)
Description	To determine the AUC0-24 as pharmacokinetic parameters of NS-018.
Time Frame	Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The PK Population includes all patients who received at least one dose of study drug and have at least 50% of the planned samples above the limit of quantitation to provide evaluable PK profile, regardless of whether derived from parent drug or metabolites. Part 2: One patient was completely excluded from the PK Population due to critical samples missing; Two patients were excluded from the analysis due to sample missing at time point. so the overall number of participants analyzed was 26.

Analysis Population Description

The PK Population includes all patients who received at least one dose of study drug and have at least 50% of the planned samples above the limit of quantitation to provide evaluable PK profile, regardless of whether derived from parent drug or metabolites. Part 2: One patient was completely excluded from the PK Population due to critical samples missing; Two patients were excluded from the analysis due to sample missing at time point. so the overall number of participants analyzed was 26.

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 250 mg BID	Part 1: 300 mg BID	Part 1: 400 mg BID	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	3	3	3	5	3	3	3	4	8	7	26
Cycle 1 Day 1	246.3454 (325.7347)	1510.0507 (123.2939)	1326.3929 (815.0175)	2299.2216 (877.2554)	5162.4119 (2485.9489)	1022.0977 (521.6626)	1241.5005 (461.6010)	2117.1396 (449.2456)	5666.7063 (5182.5571)	7592.4070 (3031.4332)	3672.2041 (1551.7435)
Cycle 2 Day 1 (Part 1 only)	253.6953 (306.7728)	1905.2058 (938.2984)	1816.8251 (559.9071)	3175.6938 (794.6091)	5443.2874 (986.8497)	1561.1245 (621.5414)	3470.6269 (2587.3663)	5876.1106 (5133.4208)	6132.2596 (3393.0644)	3828.0995 (NA)

15. Secondary Outcome

Title	Part 1 and Part 2: Terminal Elimination Half-life (t½)
Description	To determine the t½ as pharmacokinetic parameters of NS-018.
Time Frame	Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1, Cycle 2 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The PK population include all patients who received at least one dose of study drug and have at least 50% of the planned samples above the limit of quantitation to provide evaluable PK profile, Here, number analyzed reflects number of patients evaluated on that specific cycle day. Part 2: 1 patient was completely excluded from PK Population due to critical samples missing, 1 patient was excluded from the analysis due to sample missing at timepoint, So the overall number of participants was 27.

Analysis Population Description

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 250 mg BID	Part 1: 300 mg BID	Part 1: 400 mg BID	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	3	3	3	6	3	3	3	6	7	7	27
Cycle 1 Day 1	2.4878 (2.1008)	5.1659 (0.5209)	3.6685 (2.2953)	4.4899 (1.5478)	6.0302 (2.4730)	9.7153 (5.2865)	10.0780 (1.3932)	5.9468 (3.8500)	30.0521 (42.0129)	13.4566 (7.3992)	5.4384 (1.7469)
Cycle 1 Day 8 (Part 1 only)	1.9170 (0.5066)	2.4735 (0.3469)	2.0217 (0.2653)	2.6237 (0.5050)	2.8480 (1.3889)	2.3007 (0.0899)	3.5204 (1.6584)	2.6280 (0.8577)	3.2062 (0.8054)	2.8287 (1.2416)
Cycle 2 Day 1	3.7488 (2.9554)	5.6743 (1.3845)	5.4356 (0.7253)	5.9316 (0.8500)	8.5232 (5.0118)	16.5535 (6.8417)	8.7138 (6.8781)	10.8357 (1.0282)	13.7574 (8.1372)	7.7683 (5.3755)	2.8030 (1.2594)

16. Secondary Outcome

Title	Part1 and Part 2: Accumulation Ratio (AR)
Description	To determine the AR as pharmacokinetic parameters of NS-018. AR was calculated as AR = (AUC0-24) Cycle 2 Day 1/ (AUC0-24) Cycle 1 Day 1.
Time Frame	Part 1 and Part 2: Cycle 2 Day 1 (duration of cycle was 4 weeks)

Outcome Measure Data

Analysis Population Description
The PK Population includes all patients who received at least one dose of study drug and have at least 50% of the planned samples above the limit of quantitation to provide evaluable PK profile (i.e. at least Cmax and AUC evaluable), regardless of whether derived from parent drug or metabolites.

Arm/Group Title	Part 1: 75 mg QD	Part 1: 125 mg QD	Part 1: 200 mg QD	Part 1: 300 mg QD	Part 1: 400 mg QD	Part 1: 100 mg BID	Part 1: 200 mg BID	Part 1: 300 mg BID	Part 1: 250 mg BID	Part 1: 400 mg BID	Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.	Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
Measure Participants	1	3	2	4	3	2	2	3	3	1	22
Mean (Standard Deviation) [Ratio]	0.9778 (NA)	1.2517 (0.5579)	1.1728 (0.0372)	1.3581 (0.3108)	1.2026 (0.4755)	1.9941 (0.6140)	3.3229 (0.3197)	3.0501 (2.6306)	1.5452 (0.4025)	1.2514 (NA)	1.0543 (0.2572)

Adverse Events

	Part 1: 75 mg QD		Part 1: 125 mg QD		Part 1: 200 mg QD		Part 1: 300 mg QD		Part 1: 400 mg QD		Part 1: 100 mg BID		Part 1: 200 mg BID		Part 1: 250 mg BID		Part 1: 300 mg BID		Part 1: 400 mg BID		Part 2: 300 mg QD
Time Frame	Part 1 and Part 2: From screening to until study discontinuation (approximate 8 years 10 months)
Adverse Event Reporting Description	Safety population: NS-018-101 study was dose finding study, PI could increase or decrease dose-level per protocol. Totals are based on number of patients and not on dose-level cohort. Patients can appear in more than one dose-level cohort.

Arm/Group Title	Part 1: 75 mg QD		Part 1: 125 mg QD		Part 1: 200 mg QD		Part 1: 300 mg QD		Part 1: 400 mg QD		Part 1: 100 mg BID		Part 1: 200 mg BID		Part 1: 250 mg BID		Part 1: 300 mg BID		Part 1: 400 mg BID		Part 2: 300 mg QD
Arm/Group Description	Patients self-administered orally 75 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.		Patients self-administered orally 125 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.		Patients self-administered orally 200 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.		Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.		Patients self-administered orally 400 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.		Patients self-administered orally 100 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.		Patients self-administered orally 200 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.		Patients self-administered orally 250 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.		Patients self-administered orally 300 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.		Patients self-administered orally 400 mg of NS-018 twice daily (BID) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.		Patients self-administered orally 300 mg of NS-018 once daily (QD) in cycles of 28 days in duration (4 weeks) for Cycles 1, 2, 3, 4, 5, 6, 7 and until the patient experiences unacceptable toxicity that precludes any further treatment, disease progression, and/or as long as the patient is benefiting from treatment.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Serious Adverse Events
	Part 1: 75 mg QD		Part 1: 125 mg QD		Part 1: 200 mg QD		Part 1: 300 mg QD		Part 1: 400 mg QD		Part 1: 100 mg BID		Part 1: 200 mg BID		Part 1: 250 mg BID		Part 1: 300 mg BID		Part 1: 400 mg BID		Part 2: 300 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		2/4 (50%)		2/10 (20%)		6/15 (40%)		1/4 (25%)		1/5 (20%)		4/13 (30.8%)		3/8 (37.5%)		4/12 (33.3%)		3/8 (37.5%)		13/29 (44.8%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)		1/4 (25%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		1/29 (3.4%)
Thrombocytopenia	1/3 (33.3%)		1/4 (25%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Haemolysis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Haemolytic anaemia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Splenic infarction	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Splenomegaly	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Splenic infarction	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Cardiac disorders
Angina pectoris	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Acute coronary syndrome	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Coronary artery occlusion	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Myocardial infarction	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Sinus node dysfunction	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Left ventricular failure	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Acute myocardial infarction	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Cardiac failure acute	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Cardiac failure congestive	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Gastrointestinal disorders
Abdominal pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Diarrhoea	0/3 (0%)		1/4 (25%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Dysphagia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Enterocolitis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Gastrointestinal haemorrhage	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Vomiting	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Mallory-Weiss syndrome	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Pancreatitis acute	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
General disorders
Chest pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Generalised oedema	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Non-cardiac chest pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Hepatobiliary disorders
Hepatosplenomegaly	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Infections and infestations
Pneumonia	0/3 (0%)		0/4 (0%)		0/10 (0%)		3/15 (20%)		0/4 (0%)		0/5 (0%)		2/13 (15.4%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Sepsis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Appendicitis perforated	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Arthritis infective	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Cellulitis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Influenza	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Urinary tract infection	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Urosepsis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Acute sinusitis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Bacteraemia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Bronchitis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Clostridium difficile infection	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Otitis externa	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Otitis media	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Parainfluenzae virus infection	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Upper respiratory tract infection	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Vulval cellulitis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Injury, poisoning and procedural complications
Postoperative ileus	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Tibia fracture	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Investigations
Lipase increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Alanine aminotransferase increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
N-terminal prohormone brain natriuretic peptide increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Metabolism and nutrition disorders
Steroid diabetes	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Tumour lysis syndrome	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Musculoskeletal and connective tissue disorders
Bursitis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Muscular weakness	1/3 (33.3%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Spinal stenosis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Groin pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Haematoma muscle	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Lumbar spinal stenosis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Osteoarthritis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioblastoma multiforme	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Lung adenocarcinoma	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Nervous system disorders
Dizziness	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Hypoaesthesia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Paraesthesia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Seizure	1/3 (33.3%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Syncope	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Encephalopathy	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Psychiatric disorders
Confusional state	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Suicide attempt	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Renal and urinary disorders
Renal failure	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Acute kidney injury	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Epistaxis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Lung infiltration	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Pulmonary oedema	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Acute respiratory failure	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Hypoxia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Vascular disorders
Hypertension	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Other (Not Including Serious) Adverse Events
	Part 1: 75 mg QD		Part 1: 125 mg QD		Part 1: 200 mg QD		Part 1: 300 mg QD		Part 1: 400 mg QD		Part 1: 100 mg BID		Part 1: 200 mg BID		Part 1: 250 mg BID		Part 1: 300 mg BID		Part 1: 400 mg BID		Part 2: 300 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		4/4 (100%)		9/10 (90%)		14/15 (93.3%)		4/4 (100%)		4/5 (80%)		11/13 (84.6%)		8/8 (100%)		12/12 (100%)		7/8 (87.5%)		29/29 (100%)
Blood and lymphatic system disorders
Anaemia	2/3 (66.7%)		0/4 (0%)		4/10 (40%)		3/15 (20%)		1/4 (25%)		2/5 (40%)		5/13 (38.5%)		2/8 (25%)		6/12 (50%)		3/8 (37.5%)		12/29 (41.4%)
Thrombocytopenia	1/3 (33.3%)		0/4 (0%)		1/10 (10%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		3/8 (37.5%)		3/12 (25%)		1/8 (12.5%)		4/29 (13.8%)
Increased tendency to bruise	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		1/29 (3.4%)
Hypoprothrombinaemia	0/3 (0%)		1/4 (25%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Lymphadenopathy	0/3 (0%)		1/4 (25%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Neutropenia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Lymphopenia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		3/29 (10.3%)
Cardiac disorders
Palpitations	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		2/13 (15.4%)		0/8 (0%)		3/12 (25%)		0/8 (0%)		3/29 (10.3%)
Arrhythmia	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Cardiac flutter	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Sinus bradycardia	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Tachycardia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Ear and labyrinth disorders
Tinnitus	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		1/12 (8.3%)		2/8 (25%)		3/29 (10.3%)
Vertigo	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		1/8 (12.5%)		1/29 (3.4%)
Ear pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Hypoacusis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Eye disorders
Vision blurred	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		1/12 (8.3%)		1/8 (12.5%)		0/29 (0%)
Cataract	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Glaucoma	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Blepharitis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Dry eye	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Eye swelling	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Eyelid irritation	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Lacrimation increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Meibomian gland dysfunction	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Photophobia	0/3 (0%)		0/4 (0%)		1/10 (10%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Strabismus	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Gastrointestinal disorders
Diarrhoea	0/3 (0%)		0/4 (0%)		3/10 (30%)		6/15 (40%)		1/4 (25%)		1/5 (20%)		3/13 (23.1%)		1/8 (12.5%)		4/12 (33.3%)		3/8 (37.5%)		11/29 (37.9%)
Nausea	0/3 (0%)		0/4 (0%)		2/10 (20%)		3/15 (20%)		1/4 (25%)		0/5 (0%)		2/13 (15.4%)		3/8 (37.5%)		7/12 (58.3%)		1/8 (12.5%)		10/29 (34.5%)
Abdominal pain	0/3 (0%)		0/4 (0%)		1/10 (10%)		3/15 (20%)		0/4 (0%)		1/5 (20%)		2/13 (15.4%)		3/8 (37.5%)		2/12 (16.7%)		0/8 (0%)		4/29 (13.8%)
Vomiting	0/3 (0%)		0/4 (0%)		4/10 (40%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		2/8 (25%)		2/12 (16.7%)		1/8 (12.5%)		4/29 (13.8%)
Abdominal distension	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		8/29 (27.6%)
Constipation	0/3 (0%)		1/4 (25%)		1/10 (10%)		1/15 (6.7%)		1/4 (25%)		0/5 (0%)		1/13 (7.7%)		2/8 (25%)		5/12 (41.7%)		1/8 (12.5%)		6/29 (20.7%)
Abdominal discomfort	0/3 (0%)		0/4 (0%)		0/10 (0%)		3/15 (20%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		2/12 (16.7%)		1/8 (12.5%)		1/29 (3.4%)
Gastrooesophageal reflux disease	0/3 (0%)		0/4 (0%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Dyspepsia	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		2/12 (16.7%)		0/8 (0%)		2/29 (6.9%)
Ascites	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Abdominal hernia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Abdominal pain upper	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Anal pruritus	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Anal sphincter atony	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Dysphagia	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Faeces discoloured	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Flatulence	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Haematochezia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Haemorrhoids	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Hypoaesthesia oral	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Oesophageal ulcer	1/3 (33.3%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Oral discomfort	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Oral pain	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Umbilical hernia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
General disorders
Fatigue	0/3 (0%)		0/4 (0%)		1/10 (10%)		6/15 (40%)		1/4 (25%)		2/5 (40%)		3/13 (23.1%)		2/8 (25%)		4/12 (33.3%)		2/8 (25%)		11/29 (37.9%)
Oedema peripheral	1/3 (33.3%)		0/4 (0%)		2/10 (20%)		5/15 (33.3%)		0/4 (0%)		2/5 (40%)		1/13 (7.7%)		2/8 (25%)		1/12 (8.3%)		0/8 (0%)		10/29 (34.5%)
Pyrexia	1/3 (33.3%)		1/4 (25%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		2/8 (25%)		2/12 (16.7%)		0/8 (0%)		3/29 (10.3%)
Chills	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		2/13 (15.4%)		0/8 (0%)		1/12 (8.3%)		1/8 (12.5%)		0/29 (0%)
Chest discomfort	0/3 (0%)		0/4 (0%)		1/10 (10%)		1/15 (6.7%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Influenza like illness	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		1/8 (12.5%)		2/29 (6.9%)
Asthenia	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Early satiety	0/3 (0%)		0/4 (0%)		1/10 (10%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Gait disturbance	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		2/8 (25%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Non-cardiac chest pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		3/29 (10.3%)
Oedema	0/3 (0%)		0/4 (0%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Thirst	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Adverse drug reaction	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Chest pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Cyst	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Drug withdrawal syndrome	0/3 (0%)		1/4 (25%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Face oedema	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Generalised oedema	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Localised oedema	0/3 (0%)		1/4 (25%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Malaise	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		3/29 (10.3%)
Nodule	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Peripheral swelling	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Hepatobiliary disorders
Hepatic pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Hepatomegaly	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Jaundice	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Infections and infestations
Upper respiratory tract infection	0/3 (0%)		0/4 (0%)		2/10 (20%)		5/15 (33.3%)		0/4 (0%)		1/5 (20%)		2/13 (15.4%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		2/29 (6.9%)
Urinary tract infection	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		1/4 (25%)		1/5 (20%)		2/13 (15.4%)		0/8 (0%)		1/12 (8.3%)		1/8 (12.5%)		1/29 (3.4%)
Nasopharyngitis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		2/5 (40%)		2/13 (15.4%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		3/29 (10.3%)
Bronchitis	0/3 (0%)		0/4 (0%)		1/10 (10%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Oral candidiasis	0/3 (0%)		0/4 (0%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		2/13 (15.4%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Influenza	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Pneumonia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		1/29 (3.4%)
Sinusitis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Acute sinusitis	0/3 (0%)		1/4 (25%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Body tinea	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Cellulitis	0/3 (0%)		1/4 (25%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Ear infection	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Fungal infection	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Genital abscess	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Hordeolum	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Infected seroma	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Lip infection	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Localised infection	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Molluscum contagiosum	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Otitis media	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Rectal abscess	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Rhinovirus infection	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Skin infection	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Subcutaneous abscess	1/3 (33.3%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Tinea pedis	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Wound infection	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Injury, poisoning and procedural complications
Contusion	0/3 (0%)		1/4 (25%)		1/10 (10%)		2/15 (13.3%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		1/8 (12.5%)		2/29 (6.9%)
Fall	0/3 (0%)		1/4 (25%)		2/10 (20%)		3/15 (20%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		2/29 (6.9%)
Animal bite	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Animal scratch	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Foreign body	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Incision site pain	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Ligament injury	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Muscle strain	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Rib fracture	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Skin abrasion	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Skin wound	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Ligament sprain	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Investigations
Platelet count decreased	0/3 (0%)		1/4 (25%)		1/10 (10%)		2/15 (13.3%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		1/8 (12.5%)		2/12 (16.7%)		1/8 (12.5%)		2/29 (6.9%)
Blood alkaline phosphatase increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		3/15 (20%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		2/8 (25%)		2/12 (16.7%)		0/8 (0%)		0/29 (0%)
Weight increased	0/3 (0%)		0/4 (0%)		2/10 (20%)		1/15 (6.7%)		1/4 (25%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		3/29 (10.3%)
Alanine aminotransferase increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		2/13 (15.4%)		0/8 (0%)		2/12 (16.7%)		1/8 (12.5%)		3/29 (10.3%)
Blood bilirubin increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		2/8 (25%)		2/12 (16.7%)		0/8 (0%)		0/29 (0%)
Lymphocyte count decreased	0/3 (0%)		1/4 (25%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
White blood cell count decreased	1/3 (33.3%)		0/4 (0%)		1/10 (10%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		2/29 (6.9%)
Amylase increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		2/12 (16.7%)		0/8 (0%)		3/29 (10.3%)
Blood creatinine increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		3/29 (10.3%)
Electrocardiogram QT prolonged	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		1/29 (3.4%)
Aspartate aminotransferase increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		2/12 (16.7%)		0/8 (0%)		4/29 (13.8%)
Blood potassium increased	0/3 (0%)		0/4 (0%)		1/10 (10%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Cardiac murmur	0/3 (0%)		1/4 (25%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Lipase increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Neutrophil count decreased	1/3 (33.3%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Physical examination abnormal	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Serum ferritin increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Blast cell count increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Blood cholesterol increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Blood urea increased	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Blood uric acid increased	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Gamma-glutamyltransferase increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Heart rate abnormal	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Red blood cell count increased	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Troponin I increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Vitamin B1 decreased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
White blood cell count increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Blood lactate dehydrogenase increased	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Weight decreased	0/3 (0%)		0/4 (0%)		0/10 (0%)		3/15 (20%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/3 (0%)		0/4 (0%)		0/10 (0%)		2/15 (13.3%)		1/4 (25%)		1/5 (20%)		4/13 (30.8%)		2/8 (25%)		1/12 (8.3%)		1/8 (12.5%)		7/29 (24.1%)
Hypocalcaemia	1/3 (33.3%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		2/8 (25%)		2/12 (16.7%)		0/8 (0%)		0/29 (0%)
Hyperkalaemia	0/3 (0%)		0/4 (0%)		1/10 (10%)		1/15 (6.7%)		0/4 (0%)		1/5 (20%)		1/13 (7.7%)		1/8 (12.5%)		0/12 (0%)		1/8 (12.5%)		2/29 (6.9%)
Hyperuricaemia	0/3 (0%)		0/4 (0%)		0/10 (0%)		3/15 (20%)		0/4 (0%)		1/5 (20%)		2/13 (15.4%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		4/29 (13.8%)
Hypokalaemia	0/3 (0%)		1/4 (25%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		2/8 (25%)		1/12 (8.3%)		1/8 (12.5%)		2/29 (6.9%)
Decreased appetite	0/3 (0%)		0/4 (0%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		1/29 (3.4%)
Dehydration	0/3 (0%)		0/4 (0%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Hypoalbuminaemia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		1/8 (12.5%)		0/12 (0%)		1/8 (12.5%)		2/29 (6.9%)
Hyponatraemia	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		2/12 (16.7%)		0/8 (0%)		3/29 (10.3%)
Hyperphosphataemia	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Hypomagnesaemia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Diabetes mellitus	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Gout	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Hyperlipidaemia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Hypermagnesaemia	1/3 (33.3%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Iron deficiency	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Steroid diabetes	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Fluid overload	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Hypoglycaemia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/3 (0%)		2/4 (50%)		2/10 (20%)		3/15 (20%)		0/4 (0%)		1/5 (20%)		1/13 (7.7%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		7/29 (24.1%)
Musculoskeletal pain	0/3 (0%)		0/4 (0%)		1/10 (10%)		3/15 (20%)		0/4 (0%)		1/5 (20%)		1/13 (7.7%)		1/8 (12.5%)		2/12 (16.7%)		0/8 (0%)		0/29 (0%)
Pain in extremity	0/3 (0%)		0/4 (0%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		1/5 (20%)		3/13 (23.1%)		1/8 (12.5%)		2/12 (16.7%)		0/8 (0%)		4/29 (13.8%)
Back pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		5/15 (33.3%)		0/4 (0%)		0/5 (0%)		2/13 (15.4%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		5/29 (17.2%)
Muscle spasms	0/3 (0%)		1/4 (25%)		1/10 (10%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		5/29 (17.2%)
Muscular weakness	1/3 (33.3%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		2/12 (16.7%)		0/8 (0%)		2/29 (6.9%)
Bone pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Musculoskeletal chest pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		1/13 (7.7%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Myalgia	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Flank pain	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Arthritis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Bursitis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Chondrocalcinosis pyrophosphate	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Fibromyalgia	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Joint effusion	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Limb discomfort	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Lumbar spinal stenosis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Musculoskeletal stiffness	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Neck pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Osteoarthritis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Rheumatoid arthritis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Soft tissue mass	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Spinal stenosis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Synovial cyst	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Bone neoplasm	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Muscle neoplasm	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Neoplasm	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Skin cancer	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Transitional cell carcinoma	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Nervous system disorders
Dizziness	0/3 (0%)		0/4 (0%)		1/10 (10%)		5/15 (33.3%)		2/4 (50%)		2/5 (40%)		3/13 (23.1%)		3/8 (37.5%)		6/12 (50%)		2/8 (25%)		8/29 (27.6%)
Headache	0/3 (0%)		1/4 (25%)		0/10 (0%)		4/15 (26.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		1/8 (12.5%)		5/12 (41.7%)		1/8 (12.5%)		11/29 (37.9%)
Dysgeusia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		2/12 (16.7%)		2/8 (25%)		0/29 (0%)
Paraesthesia	0/3 (0%)		1/4 (25%)		0/10 (0%)		1/15 (6.7%)		2/4 (50%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Neuropathy peripheral	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		2/12 (16.7%)		2/8 (25%)		3/29 (10.3%)
Balance disorder	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Disturbance in attention	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Hypoaesthesia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Memory impairment	0/3 (0%)		0/4 (0%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Dizziness postural	0/3 (0%)		0/4 (0%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Somnolence	0/3 (0%)		1/4 (25%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Aphasia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Ataxia	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Cognitive disorder	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Dysaesthesia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Dysarthria	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Lethargy	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Migraine	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Muscle contractions involuntary	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Neuralgia	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Peripheral sensory neuropathy	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Sciatica	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Sensory disturbance	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Transient ischaemic attack	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Tremor	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Pregnancy, puerperium and perinatal conditions
Pelvic girdle pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Psychiatric disorders
Insomnia	0/3 (0%)		0/4 (0%)		1/10 (10%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		4/8 (50%)		1/12 (8.3%)		0/8 (0%)		4/29 (13.8%)
Depression	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		2/29 (6.9%)
Agitation	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Anxiety	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		3/29 (10.3%)
Depressed mood	0/3 (0%)		0/4 (0%)		1/10 (10%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Mental disorder	1/3 (33.3%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Alcohol withdrawal syndrome	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Claustrophobia	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Confusional state	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Emotional distress	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Mental status changes	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Sleep terror	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Tobacco withdrawal symptoms	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Renal and urinary disorders
Chromaturia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		2/8 (25%)		0/29 (0%)
Dysuria	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Haematuria	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Nocturia	0/3 (0%)		0/4 (0%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Urinary retention	1/3 (33.3%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Acute kidney injury	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Pollakiuria	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Urinary incontinence	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Urinary tract pain	0/3 (0%)		1/4 (25%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Breast cyst	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Erectile dysfunction	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Menorrhagia	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Oedema genital	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Penis disorder	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)		1/4 (25%)		1/10 (10%)		5/15 (33.3%)		1/4 (25%)		1/5 (20%)		4/13 (30.8%)		4/8 (50%)		3/12 (25%)		2/8 (25%)		7/29 (24.1%)
Dyspnoea	0/3 (0%)		1/4 (25%)		2/10 (20%)		5/15 (33.3%)		0/4 (0%)		2/5 (40%)		2/13 (15.4%)		1/8 (12.5%)		4/12 (33.3%)		2/8 (25%)		13/29 (44.8%)
Dyspnoea exertional	0/3 (0%)		0/4 (0%)		1/10 (10%)		2/15 (13.3%)		1/4 (25%)		0/5 (0%)		1/13 (7.7%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		6/29 (20.7%)
Nasal congestion	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		1/8 (12.5%)		1/12 (8.3%)		1/8 (12.5%)		0/29 (0%)
Epistaxis	0/3 (0%)		0/4 (0%)		1/10 (10%)		3/15 (20%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		1/8 (12.5%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Pleural effusion	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Wheezing	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		1/5 (20%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Hypoxia	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		1/12 (8.3%)		1/8 (12.5%)		0/29 (0%)
Oropharyngeal pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Atelectasis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Bronchospasm	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Chronic obstructive pulmonary disease	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Dysphonia	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Interstitial lung disease	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Laryngeal inflammation	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Pleuritic pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Pulmonary mass	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Pulmonary oedema	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Rales	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Rhinorrhoea	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		1/29 (3.4%)
Sinus pain	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Sleep apnoea syndrome	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Upper-airway cough syndrome	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Skin and subcutaneous tissue disorders
Pruritus	0/3 (0%)		1/4 (25%)		2/10 (20%)		3/15 (20%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		4/29 (13.8%)
Hyperhidrosis	0/3 (0%)		0/4 (0%)		1/10 (10%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		2/12 (16.7%)		1/8 (12.5%)		3/29 (10.3%)
Night sweats	0/3 (0%)		1/4 (25%)		1/10 (10%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		4/29 (13.8%)
Ecchymosis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Rash maculo-papular	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		1/12 (8.3%)		0/8 (0%)		2/29 (6.9%)
Skin lesion	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		1/5 (20%)		2/13 (15.4%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Acne	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Petechiae	0/3 (0%)		0/4 (0%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Rash	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Decubitus ulcer	1/3 (33.3%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Dermatitis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Erythema	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Macule	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Madarosis	0/3 (0%)		0/4 (0%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Neurodermatitis	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Onychoclasis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Rash erythematous	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Rash pruritic	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Skin ulcer	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Urticaria	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Actinic keratosis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		3/29 (10.3%)
Blister	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		2/29 (6.9%)
Vascular disorders
Hypertension	0/3 (0%)		0/4 (0%)		0/10 (0%)		2/15 (13.3%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		2/12 (16.7%)		0/8 (0%)		2/29 (6.9%)
Haematoma	0/3 (0%)		1/4 (25%)		1/10 (10%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Flushing	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		1/8 (12.5%)		0/29 (0%)
Hot flush	0/3 (0%)		0/4 (0%)		0/10 (0%)		1/15 (6.7%)		1/4 (25%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Pallor	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		0/8 (0%)		1/12 (8.3%)		0/8 (0%)		0/29 (0%)
Peripheral arterial occlusive disease	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		1/13 (7.7%)		0/8 (0%)		0/12 (0%)		0/8 (0%)		0/29 (0%)
Thrombosis	0/3 (0%)		0/4 (0%)		0/10 (0%)		0/15 (0%)		0/4 (0%)		0/5 (0%)		0/13 (0%)		1/8 (12.5%)		0/12 (0%)		0/8 (0%)		0/29 (0%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

This confidential document is the property of NS Pharma, Inc. No unpublished information contained herein may be disclosed without prior written approval from NS Pharma, Inc. Access to this document must be restricted to relevant parties.

Results Point of Contact

Name/Title	Medical Affairs
Organization	NS Pharma, Inc.
Phone	201-986-3860 ext +1
Email	trialinfo@nspharma.com

Responsible Party:

NS Pharma, Inc.

ClinicalTrials.gov Identifier:

NCT01423851

Other Study ID Numbers:

NS-018-101

First Posted:

Aug 26, 2011

Last Update Posted:

Mar 9, 2022

Last Verified:

Feb 1, 2022

Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF

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