Trial Outcomes & Findings for Study of Nintedanib and Chemotherapy for Advanced Pancreatic Cancer (NCT NCT02902484)

Last Updated: 2024-06-03

Results Overview

A standard 3+3 phase 1 trial design will be used for Nintedanib monotherapy for a two week period (Days 1-14) followed by combination therapy of nintedanib plus chemotherapy. Two dose levels of nintedanib will be explored 150 mg BID and 200 mg BID. The combination phase will include gemcitabine + nab-paclitaxel, and nintedanib. Treatment will be administered intravenously on days 1, 8, 15 every 28 days. One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 150 mg PO BID and 200mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days MTD assessed after combination therapy.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Each 28 day cycle for up to 2 years

Results posted on

2024-06-03

Participant Flow

14 subjects were consented in which 1 subject withdrew consent and was not assigned to treatment.

Participant milestones

Participant milestones
Measure	Nintedanib 150 mg One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 150 mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days Nintedanib: Nintedanib Monotherapy Followed by Combination Therapy of Nintedanib and Gemcitabine Plus nab-Paclitaxel	Nintedanib 200 mg One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 200 mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days Nintedanib: Nintedanib Monotherapy Followed by Combination Therapy of Nintedanib and Gemcitabine Plus nab-Paclitaxel
Nintedanib Monotherapy 150 mg STARTED	3	0
Nintedanib Monotherapy 150 mg COMPLETED	3	0
Nintedanib Monotherapy 150 mg NOT COMPLETED	0	0
Nintedanib Monotherapy 200 mg STARTED	0	10
Nintedanib Monotherapy 200 mg COMPLETED	0	10
Nintedanib Monotherapy 200 mg NOT COMPLETED	0	0
Nintedanib 150 mg + Chemotherapy STARTED	3	0
Nintedanib 150 mg + Chemotherapy COMPLETED	3	0
Nintedanib 150 mg + Chemotherapy NOT COMPLETED	0	0
Nintedanib 200 mg + Chemotherapy STARTED	0	10
Nintedanib 200 mg + Chemotherapy COMPLETED	0	10
Nintedanib 200 mg + Chemotherapy NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Nintedanib and Chemotherapy for Advanced Pancreatic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nintedanib 150mg n=3 Participants One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 150 mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days Nintedanib: Nintedanib Monotherapy Followed by Combination Therapy of Nintedanib and Gemcitabine Plus nab-Paclitaxel	Nintedanib 200mg n=10 Participants One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 200 mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days	Total n=13 Participants Total of all reporting groups
Age, Continuous	65 years n=5 Participants	63 years n=7 Participants	63 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants	10 participants n=7 Participants	13 participants n=5 Participants

PRIMARY outcome

Timeframe: Each 28 day cycle for up to 2 years

Outcome measures

Outcome measures
Measure	All Participants n=13 Participants Two dose levels of nintedanib will be explored 150 mg BID and 200 mg BID. The combination phase will include gemcitabine + nab-paclitaxel, and nintedanib. Treatment will be administered intravenously on days 1, 8, 15 every 28 days. One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 150 mg PO BID and 200mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days
Maximum Tolerated Dose (MTD)	200 mg

Adverse Events

Nintedanib 150 mg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Nintedanib 200 mg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Nintedanib 150 mg n=3 participants at risk One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 150mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days	Nintedanib 200 mg n=10 participants at risk One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 200 mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days Nintedanib: Nintedanib Monotherapy Followed by Combination Therapy of Nintedanib and Gemcitabine Plus nab-Paclitaxel
Investigations Neutropenia	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Investigations Leukopenia	66.7% 2/3 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.

Other adverse events

Additional Information

Dr. Salwan Al Mutar

UT Southwestern Medical Center

Phone: 214-648-4008

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Nintedanib 150 mg n=3 participants at risk One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 150mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days	Nintedanib 200 mg n=10 participants at risk One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 200 mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days Nintedanib: Nintedanib Monotherapy Followed by Combination Therapy of Nintedanib and Gemcitabine Plus nab-Paclitaxel
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.
Gastrointestinal disorders Abdominal Pain	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	40.0% 4/10 • Number of events 7 • Adverse event data were collected for 3 years, 1 month.
Musculoskeletal and connective tissue disorders Abscess of gluteal lesion	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Gastrointestinal disorders Acid reflux	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Skin and subcutaneous tissue disorders Rash acneiform	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.
Investigations Alkaline phosphatase increased	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 5 • Adverse event data were collected for 3 years, 1 month.
Metabolism and nutrition disorders Azotemia	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Blood and lymphatic system disorders Anemia	100.0% 3/3 • Number of events 28 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 5 • Adverse event data were collected for 3 years, 1 month.
Psychiatric disorders Anxiety	66.7% 2/3 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Metabolism and nutrition disorders Anorexia	66.7% 2/3 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 4 • Adverse event data were collected for 3 years, 1 month.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	40.0% 4/10 • Number of events 4 • Adverse event data were collected for 3 years, 1 month.
Investigations Weightloss	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	40.0% 4/10 • Number of events 4 • Adverse event data were collected for 3 years, 1 month.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
General disorders Burning sensation leg and head	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Eye disorders Blurred vision	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
General disorders Chest Pain	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Musculoskeletal and connective tissue disorders Muscle pain	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Eye disorders Cataract	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
General disorders chills	33.3% 1/3 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.
Hepatobiliary disorders Cholangitis	33.3% 1/3 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Renal and urinary disorders Chronic Kidney disease	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.
Gastrointestinal disorders Consipation	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 5 • Adverse event data were collected for 3 years, 1 month.
Investigations Creatinine increased	33.3% 1/3 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Investigations Creatinine decreased	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.	60.0% 6/10 • Number of events 11 • Adverse event data were collected for 3 years, 1 month.
Psychiatric disorders Depression	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Nervous system disorders Dizziness	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.
Gastrointestinal disorders Dry Mouth	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.
General disorders Edema Face	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Gastrointestinal disorders Edema limbs	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.
Respiratory, thoracic and mediastinal disorders Dyspena	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Investigations Elevated (Transamineses, AST/ALT, bilirubn)	66.7% 2/3 • Number of events 5 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 5 • Adverse event data were collected for 3 years, 1 month.
Reproductive system and breast disorders enlarged prostate	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
General disorders Fever	66.7% 2/3 • Number of events 5 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 6 • Adverse event data were collected for 3 years, 1 month.
Respiratory, thoracic and mediastinal disorders Epistaxis	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Hepatobiliary disorders Fistula	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Musculoskeletal and connective tissue disorders General weakness	33.3% 1/3 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 4 • Adverse event data were collected for 3 years, 1 month.
Skin and subcutaneous tissue disorders Hairloss	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.
Nervous system disorders Headache	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.
Metabolism and nutrition disorders hyperglycemia	33.3% 1/3 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Musculoskeletal and connective tissue disorders Hip/Spine Pain	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Metabolism and nutrition disorders Hyperlipidemia	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Vascular disorders Hypertension	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 5 • Adverse event data were collected for 3 years, 1 month.
Metabolism and nutrition disorders Hypoalbuminemia	33.3% 1/3 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.
Metabolism and nutrition disorders Hyperuncemia	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Metabolism and nutrition disorders Hypokalemia	33.3% 1/3 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.	40.0% 4/10 • Number of events 8 • Adverse event data were collected for 3 years, 1 month.
Endocrine disorders hypothyroid	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Metabolism and nutrition disorders Hyponatremia	33.3% 1/3 • Number of events 5 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Psychiatric disorders Insomnia	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.
Skin and subcutaneous tissue disorders Itchy Dry Skin	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.
Gastrointestinal disorders vomiting	33.3% 1/3 • Number of events 4 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.
General disorders Body Pain	33.3% 1/3 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.	60.0% 6/10 • Number of events 8 • Adverse event data were collected for 3 years, 1 month.
Musculoskeletal and connective tissue disorders Leg swelling	66.7% 2/3 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Gastrointestinal disorders Nausea	100.0% 3/3 • Number of events 4 • Adverse event data were collected for 3 years, 1 month.	70.0% 7/10 • Number of events 9 • Adverse event data were collected for 3 years, 1 month.
Metabolism and nutrition disorders Leukopenia	100.0% 3/3 • Number of events 61 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 4 • Adverse event data were collected for 3 years, 1 month.
Nervous system disorders neuropathy	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	80.0% 8/10 • Number of events 9 • Adverse event data were collected for 3 years, 1 month.
Respiratory, thoracic and mediastinal disorders Congestion	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.
Renal and urinary disorders Frequent Urination	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.
Infections and infestations Sepsis	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Respiratory, thoracic and mediastinal disorders Nasal congestion / drainage	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 4 • Adverse event data were collected for 3 years, 1 month.
Vascular disorders Lymphocytopenia	100.0% 3/3 • Number of events 53 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 7 • Adverse event data were collected for 3 years, 1 month.
Musculoskeletal and connective tissue disorders lower extremity cramps	66.7% 2/3 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Blood and lymphatic system disorders neutropenia	100.0% 3/3 • Number of events 27 • Adverse event data were collected for 3 years, 1 month.	40.0% 4/10 • Number of events 4 • Adverse event data were collected for 3 years, 1 month.
Blood and lymphatic system disorders Thrombocytopenia	100.0% 3/3 • Number of events 30 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 8 • Adverse event data were collected for 3 years, 1 month.
Skin and subcutaneous tissue disorders Night Sweats	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Skin and subcutaneous tissue disorders Tingling in finger tips left hand	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Renal and urinary disorders Proteinuria	33.3% 1/3 • Number of events 51 • Adverse event data were collected for 3 years, 1 month.	30.0% 3/10 • Number of events 3 • Adverse event data were collected for 3 years, 1 month.
Respiratory, thoracic and mediastinal disorders Oral Sensitivity	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	20.0% 2/10 • Number of events 2 • Adverse event data were collected for 3 years, 1 month.
Skin and subcutaneous tissue disorders Worsening of gluteal lesion	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Infections and infestations nail infection	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.
Skin and subcutaneous tissue disorders Rash on back of head, arms and groin area	33.3% 1/3 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.	0.00% 0/10 • Adverse event data were collected for 3 years, 1 month.
Gastrointestinal disorders Pale colored stool	0.00% 0/3 • Adverse event data were collected for 3 years, 1 month.	10.0% 1/10 • Number of events 1 • Adverse event data were collected for 3 years, 1 month.