Trial Outcomes & Findings for Phase I Dose Escalation Study of VS-6063 in Japanese Subjects With Non-Hematologic Malignancies (NCT NCT01943292)

NCT ID: NCT01943292

Last Updated: 2017-03-09

Results Overview

A composite by dose level to include incidence of AEs, SAEs, dose interruptions and dose reductions as a measure of safety and tolerability. Abnormal Clinical significant laboratory results, ECG measurements, vital signs measurement, physical examination findings, and ECOG performance status were captured as adverse events. The severity of AEs were evaluated according to CTCAE (Common Toxicity Criteria for Adverse Effects) 4.03

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

9 participants

Primary outcome timeframe

From start of treatment to end of treatment, an expected average of 12 weeks

Results posted on

2017-03-09

Participant Flow

First subject enrolled 02Sep2013; Last subject enrolled 07Jan2014; all patients enrolled at one site in Japan.

There were no significant events and approaches for overall study. There was one screen failure.

Participant milestones

Participant milestones
Measure	Defactinib 200 mg Bid 200 mg bid (twice a day) po (by mouth) defactinib	Defactinib 400 mg Bid 400 mg bid po defactinib	Defactinib 600 mg Bid 600 mg bid po defactinib
Overall Study STARTED	3	3	3
Overall Study Completed Cycle 1	3	3	3
Overall Study Completed Treatment	3	3	3
Overall Study Completed Follow-Up	2	3	3
Overall Study COMPLETED	2	3	3
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Defactinib 200 mg Bid 200 mg bid (twice a day) po (by mouth) defactinib	Defactinib 400 mg Bid 400 mg bid po defactinib	Defactinib 600 mg Bid 600 mg bid po defactinib
Overall Study Withdrawal by Subject	1	0	0

Baseline Characteristics

Phase I Dose Escalation Study of VS-6063 in Japanese Subjects With Non-Hematologic Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Defactinib 200 mg Bid n=3 Participants 200 mg po bid defactinib	Defactinib 400 mg Bid n=3 Participants 400 mg po bid defactinib	Defactinib 600 mg Bid n=3 Participants 600 mg po bid defactinib	Total n=9 Participants Total of all reporting groups
Age, Continuous	60.7 years STANDARD_DEVIATION 6.51 • n=5 Participants	67.0 years STANDARD_DEVIATION 7.21 • n=7 Participants	53.7 years STANDARD_DEVIATION 16.56 • n=5 Participants	60.4 years STANDARD_DEVIATION 11.20 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: From start of treatment to end of treatment, an expected average of 12 weeks

Outcome measures

Outcome measures
Measure	Defactinib 200 mg Bid n=3 Participants 200 mg po bid defactinib	Defactinib 400 mg Bid n=3 Participants 400 mg po bid defactinib	Defactinib 600 mg Bid n=3 Participants 600 mg po bid defactinib
Assess the Safety and Tolerability of Defactinib (VS-6063) in Japanese Subjects With Non-hematologic Malignancies At least 1 TEAE (treatment emergent AE)	3 participants	3 participants	3 participants
Assess the Safety and Tolerability of Defactinib (VS-6063) in Japanese Subjects With Non-hematologic Malignancies Lab TEAE with Severity ≥ Grade 3	1 participants	0 participants	0 participants
Assess the Safety and Tolerability of Defactinib (VS-6063) in Japanese Subjects With Non-hematologic Malignancies Dose Interruptions	1 participants	1 participants	0 participants
Assess the Safety and Tolerability of Defactinib (VS-6063) in Japanese Subjects With Non-hematologic Malignancies At least 1 TEAE related to study drug	3 participants	3 participants	3 participants
Assess the Safety and Tolerability of Defactinib (VS-6063) in Japanese Subjects With Non-hematologic Malignancies Non-Lab TEAE with Severity ≥ Grade 3	0 participants	0 participants	0 participants
Assess the Safety and Tolerability of Defactinib (VS-6063) in Japanese Subjects With Non-hematologic Malignancies At least 1 Serious TEAE	0 participants	0 participants	0 participants
Assess the Safety and Tolerability of Defactinib (VS-6063) in Japanese Subjects With Non-hematologic Malignancies Dose Reductions	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: From start of treatment to end of cycle 1 (21 day cycles)

The RP2D will be determined based on the MTD of defactinib (VS-6063) as determined by number of participants with dose limiting toxicities (DLTs) related to defactinib.

Outcome measures

Outcome measures
Measure	Defactinib 200 mg Bid n=3 Participants 200 mg po bid defactinib	Defactinib 400 mg Bid n=3 Participants 400 mg po bid defactinib	Defactinib 600 mg Bid n=3 Participants 600 mg po bid defactinib
Define the Maximum Tolerated Dose (MTD), if Achieved, and Establish the Recommended Phase 2 Dose (RP2D) of Defactinib (VS-6063) in Japanese Subjects.	NA mg There were no DLTs. MTD was not reached. RP2D is 400 mg bid.	NA mg There were no DLTs. MTD was not reached. RP2D is 400 mg bid.	NA mg There were no DLTs. MTD was not reached. RP2D is 400 mg bid.

SECONDARY outcome

Timeframe: Time points at Day 1 and Day 15 in Cycle 1

PK parameters, including but not limited to plasma concentration, AUC (Area Under Curve) 0-t, Cmax, Tmax, and T1/2. Total 24-hour urine output will be collected in conjunction with PK sampling to assess the elimination of defactinib (VS-6063) and its potential metabolites.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 8 weeks up to end of treatment, an expected average of 12 weeks

Response rate and progression-free survival, as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1

Outcome measures

Outcome data not reported

Adverse Events

Defactinib 200 mg Bid

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Defactinib 400 mg Bid

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Defactinib 600 mg Bid

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Lou Vaickus, MD, FACP/Chief Medical Officer

Verastem

Phone: 781-292-4200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The site is not able to publish any clinical trial results without first seeking permission from Verastem.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Defactinib 200 mg Bid n=3 participants at risk 200 mg po bid defactinib	Defactinib 400 mg Bid n=3 participants at risk 400 mg po bid defactinib	Defactinib 600 mg Bid n=3 participants at risk 600 mg po bid defactinib
Investigations Blood Bilirubin Increased	100.0% 3/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	66.7% 2/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	66.7% 2/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Investigations Aspartate Aminotransferase Increased	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Investigations Blood Alkaline Phosphatase Increased	66.7% 2/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Decreased Appetite	66.7% 2/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Diarrhea	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	66.7% 2/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Nausea	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
General disorders Fatigue	66.7% 2/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	100.0% 3/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Nervous system disorders Headache	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Anemia	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	66.7% 2/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer Pain	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Thrombocytopenia	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Abdominal Distension	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Abdominal Pain	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Stomatitis	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
General disorders Oedema Peripheral	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Infections and infestations Nasopharyngitis	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Injury, poisoning and procedural complications Lower Limb Fracture	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Investigations Alanine Aminotransferase Increased	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Investigations Blood Creatinine Increased	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Investigations Blood Phosphorus Increased	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Investigations Blood Pressure Increased	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Hyperuricaemia	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Hypouricaemia	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Musculoskeletal and connective tissue disorders Pain in Extremity	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Nervous system disorders Dizziness	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Nervous system disorders Peripheral Sensory Neuropathy	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Renal and urinary disorders Proteinuria	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Pain of Skin	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	33.3% 1/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.	0.00% 0/3 • Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment The systematic method was through regular investigator assessment and regular laboratory testing.