untitled h1
grade ecog

0 Fully active, able to carry on all pre-disease performance without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light house work, office work)
2 Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.  
3 Capable of only limited self-care, confined to bed or chair more than 50% of waking hours 4 Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 5 Dead STU022016-083, Al Mutar, FormA3-ResearchProtocol-V8-05.03.22, Mod_27, 06-06-22 71  
| In general, how would you rate your physical          |
|-------------------------------------------------------|
| health?…                                              |
| In general, how would you rate your mental health,    |
| including your mood and your ability to think?...     |
| In general, how would you rate your satisfaction with |
| your social activities and relationships?...          |
| In general, please rate how well you carry out your   |
| usual social activities and roles. (This includes     |
| activities at home, at work and in your community,    |
| and responsibilities as a parent, child, spouse,      |
| employee, friend, etc.)...                            |
| To what extent are you able to carry out your         |
| everyday physical activities such as walking,         |
| climbing stairs, carrying groceries, or moving a      |
| chair?...                                             |
appendix b - promis qol
please respond to each item

In general, would you say your health is:… In general, would you say your quality of life is:...  
STU022016-083, Al Mutar, FormA3-ResearchProtocol-V8-05.03.22, Mod_27, 06-06-22  
| 1) 5 Excellent   |
|------------------|
| 4 Very good      |
| O 3 Good         |
| O 2 Fair         |
| O 1 Poor         |
|                  |
| O 4 Very good    |
| O 3 Good
O 2 Fair
O 1 Poor                  |
| O 5 Excellent    |
| O 4 Very good
O 3 Good                  |
| O 2 Fair
O 1 Poor                  |
| O 5 Excellent    |
| O 4 Very good
O  2 Fair
O  1 Poor                  |
| ❏ 5 Excellent    |
| O 4 Very good
O  3 Good
O  2 Fair                  |
| 1 Poor           |
| ❏ 5 Excellent    |
|                  |
| O 3 Good
O 2 Fair                  |
| O 1 Poor         |
| 5   5            |
| O 4 Mostly       |
| O 3 Moderately   |
| O 2 A little     |
| c 1 Not at all   |
promis global - qol (v
in the past 7 days...

How often have you been bothered by emotional problems such as feeling anxious, depressed or irritable? ... How would you rate your fatigue on average?...  
| 0 1 Never   |
|-------------|
| 0 2 Rarely
0 3 Sometimes             |
| O 4 Often
O 5 Always             |  
| O 1 None
O  3 Moderate
O  4 Severe                 |
|-----------------|
| O 5 Very severe |  
How would you rate you pain on average?…
00  
| 0 0 No pain   |
|---------------|  
| 0 9   |
|-------|  
O
10 Worst imaginable pain Form Completed by:
Date:
Form Reviewed by:
Date:
Information and materials contained herein are ©2010 PROMIS Health Organization or other individuals/entities that have contributed information and materials to Assessment Center, and are being used with the permission of the copyright.  
STU022016-083, Al Mutar, FormA3-ResearchProtocol-V8-05.03.22, Mod_27, 06-06-22
promis global - qol (v
appendix c - pharmacodynamic studies

Blood samples will be obtained using BD Vacutainer CPTTM Cell Preparation Tubes. A total of 16 mL (8 mL x 2 tubes) of blood will be collected at each time point as indicated in the study calendar. After collection, store CPT upright at room temperature until centrifugation. Sample should be centrifuged within 2 hours of collection. Remix the blood sample immediately prior to centrifugation by gently inverting several times.  
1. Centrifuge CPT at room temperature for 30 minutes at 1700 g (RCF). After centrifugation, mononuclear cells will be in the layer above the gel and below the plasma layer.  
2. Remove approximately half of the plasma, without disturbing the cell layer.  
3. Transfer the cell layer to a 15-ml polypropylene conical tube: It is difficult to pipet out just the cell layer, so transfer the entire remainder of the contents above the gel into the 15-ml conical tube. Add cold PBS to bring volume to 14 ml. Mix by inverting several times.  
4. Centrifuge at 300 g for 15 min. at 4°. 5. Aspirate as much supernatant as possible without disturbing the cell pellet. Resuspend cell pellet in 10 ml of cold PBS.  
6. Centrifuge at 300 g for 10 min. at 4°. 7. Aspirate off supernatant. RESUSPEND CELL PELLET in 1 ml of cold PBS and count cell number. *
*When cells are counted, remove 10 µl of cells for counting. Add 90µl trypan blue. To determine the cell number using a hemocytometer, count the number of cells in 4 large squares. To determine the count of cells/ml, the number counted in 4 large squares is divided by 4 and then multiplied by 104. This number must then be multiplied by 10 to account for the dilution in trypan blue.  
cells/ml = \# cells counted in 4 large squares /4 x 104 x 10 (dilution factor)
8. PBMCs can be placed at -80°C for use in western blotting at a later date. 9. Samples should be delivered to the Biomarker Research Core at the Harold C. Simmons Cancer Center at UT Southwestern or other designated vendors on dry ice or room temperature as appropriate. Contact information for the Simmons Biomarker Research Core:
Simmons Cancer Center Biomarker Research Core Harold C. Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center 5323 Harry Hines Blvd., ND2. 210K Dallas, Texas 75390-8807 Phone: (214) 645-6371 Fax: (214) 645-6347 STU022016-083, Al Mutar, FormA3-ResearchProtocol-V8-05.03.22, Mod_27, 06-06-22 74
promis global - qol (v
appendix d - safety assessment

A Phase 1b and Pharmacodynamic Study of Nintedanib Monotherapy Followed by Combination Therapy of Nintedanib and Gemcitabine Plus nab-Paclitaxel for Advanced Pancreatic Cancer h Study Center
promis global - qol (v
safety assessment during cycle 2

Cohort Submit this form upon completion of Cycle 2 (dosing day 1 of cycle 3) or in the event of early discontinuation during the first two cycles. One form per patient; please maintain a copy of this document with the patient's case report Assigned Dose: (mg, bid)
□ 150 mg forms.  
200 mg Nintedanib administered during Cycle 2:
Study Status for this Patient:
Date of first dose (mm/dd/yy):
Date of last dose(mm/dd/yy): _
□ Continuing on study
□ Continuing at a reduced dose:
□ Off study due to disease status
□ Off study due to toxicity m Did the patient experience a DLT?   □ No    □ Yes DLT will be defined by the occurrence of any of the following toxicities possibly or probably related to drug during cycle 2 (combination phase). AE occurring during the monotherapy phase (cycle 1) will not be considered DLT.  
lf yes, describe below and check the DLT criterion that was met Any drug related grade 3 or grade 4 non-hematological toxicity, except alopecia, or asymptomatic elevation a of hepatic transaminases thought to be secondary to gemcitabine or as defined below.  
o Grade ≥ 3 diarrhea, vomiting, or nausea that persists for > 3 days despite optimal supportive care. Hematological toxicity o
- CTCAE Grade 4 neutropenia that is uncomplicated (not associated with fever ≥38.5°C) only if continuing for > 7 Days  
- CTCAE Grade 4 febrile neutropenia of any duration if associated with fever ≥  38.58C
- Platelet decrease to CTCAE Grade 4, or decrease to CTCAE grade 3 associated with bleeding or requiring
transfusions.  
□ Nintedanib related liver toxicity except GGT*** as specified below:
AST/ALT > 5x ULN*  independent of  bilirubin  
  
  
  
  
AST/ALT > 2.5 x ULN together with total bilirubin > 1.5 ULN
** isolated GGT elevation with no corresponding ALT/AST increase will not be considered as DLT
□ Missing two consecutive weekly doses of gemcitabine and nab-paclitaxel because of unresolved toxicity  
□ Inability to resume Nintedanib|dosing within 14 days of stopping due to treatment related toxicity
□ Any other toxicity possibly or probably related to treatment in the view of the investigator that represents a clinically significant hazard to the patient (please attach a detailed report).
Describe details of toxicity:
Created: 1/12/16 Revised: 8/27/18 Consider both clinical and laboratory events when answering the following questions.  
Did the patient experience an SAE during Cycle 2?  
Did the patient experience any other significant toxicity during cycle 2?  
□ No
*Please comment on relationship to Nintedanib Person providing assessment (print):
Signature:
Date:
I have reviewed this completed safety assessment and certify that the information is correct and accurate to the best of my knowledge.  
Investigator (print):
Signature:
promis global - qol (v
date give completed form to

/ Patient This is cohort of
□ No safety concerns noted; accrual to continue
□ No safety concerns noted; dose escalation authorized/ Next dose level to be evaluated:
□ Safety concerns noted; additional patients to be added to this cohort □ Safety concerns noted; dose escalation to cease mg/m²
¤ Other comments:
Study Manager (print):  
| Date:                                                                                                 |       |
|-------------------------------------------------------------------------------------------------------|-------|
| Signature:                                                                                            |       |
| Principal Investigator (print):                                                                       |       |
| Signature:                                                                                            | Date: |
| Evaluations of all subjects in a cohort must be completed before the next cohort can begin enrolling. |       |  
Created: 1/12/16 Revised: 8/27/18
appendix e procedures for the
introduction

Drug-induced liver *injury* Drug-induced liver injury (DILI) has been the most frequent single cause of safety-related drug marketing withdrawals for the past 50 years (e.g., iproniazid), continuing to the present (e.g., ticrynafen, benoxaprofen, bromfenac, troglitazone, nefazodone). Accordingly, detection of drug-induced liver injury of an investigational compound has become an important aspect of patient´s safety guarding in drug development. The US-FDA has published a Guidance for Industry entitled, "Drug-Induced Liver Injury: Premarketing Clinical Evaluation" which outlines the detection, evaluation, follow-up and reporting of drug-induced liver injury in clinical trials. Drugs that have the potential for inducing severe liver injury may be identified by marked peak aminotransferase elevations (10x-, 15xULN), or the combination of hepatocellular injury (aminotransferase elevation ≥3xULN) and altered liver function (hyperbilirubinemia ≥2xULN) which is defined as potential "Hy´s law case" if not explained by other causes including evidence of biliary obstruction (i.e., significant elevation of alkaline phosphatase, ALP, >2X ULN) or some other explanation of the injury (e.g., viral hepatitis, alcohol hepatitis, concomitant use of other known hepatotoxic drugs). This constellation predicts a poor outcome and although very rare, these potential cases have to be well characterized as soon as being identified as other confounding conditions may be the cause. In further consideration of this FDA Guidance, any potential "Hy's Law case" has to be reported in an expedited manner to the FDA (i.e., even before all other possible causes of liver injury have been excluded) and be followed-up appropriately. The follow-up includes a detailed clinical evaluation and identification of possible alternative etiologies for the "Hy´s Law case" constellation such as concomitant diseases (e.g. Hepatitis B) and/or other concomitant therapies that might potentially be hepatotoxic.  
Although rare, a potential for drug-induced liver injury is under constant surveillance by sponsors and regulators. Therefore, this study requires timely detection, evaluation, and follow-up of laboratory alterations of selected liver laboratory parameters to ensure patients´ safety. The concept below has been worked out by Boehringer Ingelheim (BI) in order to guard patient´s safety and to respond to regulatory requirements. It is the basis for all clinical studies and should be applied as appropriate.
appendix e procedures for the
definition

The following changes in the laboratory values are considered to be a protocol-specific significant adverse event for all patients with normal values for ALT/AST at baseline:
- an elevation of ALT and / or AST > 5x ULN without bilirubin elevation measured in the same blood draw sample
- an elevation of AST and/or ALT >2.5 fold ULN combined with an elevation of bilirubin to >1.5 fold ULN measured in the same blood draw sample.  
STU022016-083, Al Mutar, FormA3-ResearchProtocol-V8-05.03.22, Mod_27, 06-06-22 77 These definitions are in line with the current dose reduction recommendations as outlined in all study protocols for BIBF 1120. Patients showing these laboratory abnormalities need to be followed up until the protocol specific retreatment criteria have been met.  
For patients with elevated ALT/AST values at baseline special considerations apply, if they are eligible for inclusion into the trial, e.g. if liver metastasis are present and do not qualify as exclusion criterion. For those special cases, the BI contact person should be involved.
appendix e procedures for the
procedures

1. Protocol-specified significant events are to be reported in an expedited manner similar as Serious Adverse Events, even if they do not meet any of the seriousness criteria and documented in the eCRF.  
2. Replication of the following laboratory tests for confirmation within 48 hours:
The results of these repeated laboratory tests must be documented on the eCRF /CRF forms and reported immediately via the SAE form to BI.  
3. An evaluation of the patient within 48 hours with respect to but not limited to:  
- Abdominal ultrasound or clinically appropriate other imaging and investigations adequate to rule out biliary tract, pancreatic, intra- or extrahepatic pathology, e.g. bile duct stones, neoplasm, hepatic tumor involvement, biliary tract, pancreatic or intrahepatic pathology, vascular hepatic conditions such as portal vein thrombosis or right heart failure. These data need to be collected, documented in the respective field of the eCRF / CRF / additional documentation form, and the respective SAE form has to be updated and forwarded to BI
- detailed history of current symptoms and concurrent diagnoses and medical history - detailed history of concomitant drug use (including non-prescription medications, herbal and dietary supplement preparations and eg steroids as concomitant, supportive treatment), alcohol use, recreational drug use, and special diets detailed history of exposure to environmental chemical agents
4. In case that both imaging and laboratory value did not unequivocally confirm cholestasis as the reason of ALT / AST increase, in particular if AP < 2x ULN, then please complete the following laboratory tests:
- AST, ALT
- Bilirubin measurement (total and direct bilirubin)
- Alkaline Phosphatase - Haptoglobin - Complete blood count and cell morphology - Reticulocyte count
- CK
- LDH
STU022016-083, Al Mutar, FormA3-ResearchProtocol-V8-05.03.22, Mod_27, 06-06-22 78
appendix e procedures for the
- clinical chemistry

alkaline phosphatase, cholinesterase (either plasma or red blood cell), albumin, PT or INR, CK, CK-MB, coeruloplasmin*, α-1 antitrypsin*, transferrin, ferritin, amylase*, lipase*, fasting glucose*, cholesterol, triglycerides
- Serology Hepatitis A (Anti-IgM, Anti-IgG), Hepatitis B (HbsAg, Anti-HBs, DNA), Hepatitis C (AntiHCV, RNA if Anti-HCV positive), Hepatitis D (Anti-IgM, Anti-IgG)*, Hepatitis E (AntiHEV, Anti-HEV IgM, RNA if Anti-HEV IgM positive)*, Anti-Smooth Muscle antibody
(titer)*, Anti-nuclear antibody (titer)*, Anti-LKM (liver-kidney microsomes) antibody*,
Anti-mitochondrial antibody*, Epstein Barr Virus (VCA IgG, VCA IgM), cytomegalovirus (IgG, IgM), herpes simplex virus (IgG, IgM), varicella (IgG, IgM), parvovirus (IgG, IgM)
appendix e procedures for the
- hormones tumor marker tsh

*If clinically indicated and in case additional investigations are needed (e.g immunocompromised patients.)  
5. Initiate close observation of all patients with elevated liver enzyme and bilirubin elevations by repeat testing of ALT, AST, bilirubin (with fractionation into total and direct) and AP at least weekly until the laboratory values return to normal or to the values as defined in the protocol.  
6. In case that transaminases and/or bilirubin increase despite cessation of the experimental therapy, more frequent intervals will be warranted.  
Depending on further laboratory changes, additional parameters identified e.g. by reflex testing will be followed up based on medical judgement and Good Clinical Practices
STU022016-083, Al Mutar, FormA3-ResearchProtocol-V8-05.03.22, Mod_27, 06-06-22 79
appendix e procedures for the
appendix f monotherapy patient diary

| Subject ID:                     |                |                                       |
|---------------------------------|----------------|---------------------------------------|
| Cycle Number:                   |                |                                       |
| Current Cycle Day 1 Visit Date: | Assigned Dose: | Number of Capsule(s):                 |
| Study Drug:                     | Ninted anib    | Take same dose twice (2 times) a day. |  
- Please be sure to ask the research study staff if you have any questions during this process. - Store your study drug in a safe place out of the reach of children. - Take your study drug at or around the same time every day about 12 hours apart.  
- Please record the date, time and the actual number of capsules you take or the reason why any capsules were not taken - if you forget or you miss a dose, make sure you report it and make note of it on this dosing diary.  
- Please bring your study drug bottle(s) (including empty bottles) and this dosing diary with you to each clinic visit.  
- Please keep your study drug tablets in their bottle until you are ready to take them.  
- If you experience any ill feelings or side effects after taking your study drug please write down how you are feeling and discuss with your physician and study staff at your next visit.  
- If you have any questions about your study drug please contact the study staff.
appendix e procedures for the
treatment will have two phases

Nintedanib monotherapy (you will only take the study drug) for a two week period (days 1-14)
followed by a combination phase of nintedanib plus chemotherapy (cycle 2+)
Patient Initials:
nntedanib patient dosing diary Patient number:  
| Nintedanib Daily Dose:   | Cycle number:         |            |                        |     |     |          |
|--------------------------|-----------------------|------------|------------------------|-----|-----|----------|
| Nintedanib               | Number of             |            |                        |     |     |          |
| Dose                     | Date Nintedanib Taken | Time Taken | Comments               |     |     |          |
| Taken?                   | Capsules              |            |                        |     |     |          |
| Example                  | 1 2                   | MAR        | 2016                   | 15  | 3 0 | Example: |
| Yes                      | e                     | No         | Example: no drug taken |     |     |          |
| D                        | MM                    | YYY        | HR                     | MIN | 2   |          |
| 1 st Dose                | Yes                   | L          | No                     |     |     |          |
| MM                       | hr                    | MIN        |                        |     |     |          |
| DD                       | YYY                   |            |                        |     |     |          |
| Day                      | l                     |            |                        |     |     |          |
| 2 " Dose                 | Yes                   | No         | MIN                    |     |     |          |
| DD                       | MM                    | YYY        | HR                     |     |     |          |
| Yes                      | l                     | No         |                        |     |     |          |
| 1 1 1 Dose               |                       |            |                        |     |     |          |
| 2                        | D                     | MM         | YYY                    | hr  | MIN |          |
| Day                      | 2" Dose               | Yes        | No                     |     |     |          |
| D                        | MM                    | YYY        | HR                     | MIN |     |          |
| No                       |                       |            |                        |     |     |          |
| 1 " Dose                 | Yes                   | L          |                        |     |     |          |
| 3                        | DD                    | MM         | YYY                    | HR  | MIN |          |
| Day                      | 2 Dose                | Yes        | L                      | No  |     |          |
| MM                       | YYY                   | HR         | MIN                    |     |     |          |
| DD                       |                       |            |                        |     |     |          |
| 1 st Dose                | Yes                   | No         |                        |     |     |          |
| 4                        | MM                    | YYY        | HR                     | MIN |     |          |
| D                        |                       |            |                        |     |     |          |
| Day                      | Yes                   | No         |                        |     |     |          |
| 2 " Dose                 | D                     | MM         | YYY                    | HR  | MIN |          |
| 1 st Dose                | Yes                   | L          | No                     |     |     |          |
| 5                        | MM                    | HR         | MIN                    |     |     |          |
| DD                       | YYYY                  |            |                        |     |     |          |
| I av                     | 2 " Dose              | Yes        | L                      | No  | HR  | MIN      |
| DD                       | MM                    | YYY        |                        |     |     |          |
| 151 Dose                 | Yes                   | l          | No                     |     |     |          |
| g                        | D                     | MM         | YYY                    | HR  | MIN |          |
| Day                      | 2 " Dose              | Yes        | No                     |     |     |          |
| DD                       | MM                    | YYY        | hr                     | MIN |     |          |
| 1 st Dose                | Yes                   | L          | No                     |     |     |          |
| 7                        | MM                    | YYY        | hr                     | MIN |     |          |
| DD                       |                       |            |                        |     |     |          |
| lav                      | 2 " Dose              | Yes        | L                      | No  |     |          |
| D                        | MM                    | YYY        | HR                     | MIN |     |          |  
STU022016-083, Al Mutar, FormA3-ResearchProtocol-V8-05.03.22, Mod_27, 06-06-22  
| Nintedanib   | Number of              |            |          |     |     |
|--------------|------------------------|------------|----------|-----|-----|
| Dose         | Date Nintedanib Taken  | Time Taken | Comments |     |     |
| Taken?       | Capsules               |            |          |     |     |
| Example      | 1 2                    | MAR        | 2 0 1 6  | 15  | 3 0 |
|              | No                     | Example:   |          |     |     |
| Yes          | Example: no drug taken |            |          |     |     |
| 2            |                        |            |          |     |     |
| D            | MMM                    | YYY        | HR       | MIN |     |
| 1 st Dose    | L                      | No         |          |     |     |
| Yes          |                        |            |          |     |     |
| 8            | DD                     | MM         | YYY      | HR  | MIN |
| Day          | 2 Dose                 | Yes        | L        | No  |     |
| DD           | MM                     | YYY        | HR       | MIN |     |
| L            |                        |            |          |     |     |
| 1 st Dose    | Yes                    | No         |          |     |     |
| 6            | D                      | MM         | YYY      | HR  | MIN |
| Day          | r                      |            |          |     |     |
| 2 " Dose     | Yes                    | No         |          |     |     |
| D            | MM                     | HR         | MIN      |     |     |
| YYY          |                        |            |          |     |     |
| 1 " Dose     | Yes                    | L          | No       |     |     |
| 10           | D                      | MM         | YYYY     | hr  | MIN |
| Day          | L                      |            |          |     |     |
| 2 d Dose     | Yes                    | No         |          |     |     |
| DD           | MM                     | YYYY       | HR       | MIN |     |
| 1 5 Dose     |                        |            |          |     |     |
| Yes          | No l                   |            |          |     |     |
| 11           | D                      | MM         | YYY      | HR  | MIN |
| Day          | 2 " Dose               | Yes        | No       |     |     |
| D            | MM                     | YYY        | HR       | MIN |     |
| 151          | L                      |            |          |     |     |
| Yes          | No                     |            |          |     |     |
| 12           | DD                     | MM         | YYY      | hr  | MIN |
| Day          | 2 Dose                 | Yes        | L        | No  |     |
| DD           | MM                     | YYY        | HR       | MIN |     |
| L            |                        |            |          |     |     |
| 1 1 ' Dose   | Yes                    | No         |          |     |     |
| 13           | DD                     | MM         | YYY      | HR  | MIN |
| Day          | l                      |            |          |     |     |
| 2 " Dose     | Yes                    | No         |          |     |     |
| D            | MM                     | YYY        | HR       | MIN |     |
| 1 st Dose    | L                      |            |          |     |     |
| 14           | Yes                    | No         |          |     |     |
| D            | MM                     | YYY        | hr       | MIN |     |
| Day          | 2" Dose                | Yes        | No       |     |     |
| D            | MM                     | YYY        | HR       | MIN |     |  
Patient Initials:
Nintedanib Daily Dose:
NINTEDANIB PATIENT DOSING DIARY
Patient number:
Cycle number:
STU022016-083, Al Mutar, FormA3-ResearchProtocol-V8-05.03.22, Mod_27, 06-06-22
appendix e procedures for the
appendix g combination therapy patient

| Subject ID:                     |                |                                       |
|---------------------------------|----------------|---------------------------------------|
| Cycle Number:                   |                |                                       |
| Current Cycle Day 1 Visit Date: | Assigned Dose: | Number of Capsule(s):                 |
| Study Drug:                     | Nintedanib     | Take same dose twice (2 times) a day. |
appendix e procedures for the
|combination dosing diary - days

- Please be sure to ask the research study staff if you have any questions during this process.  
- Store your study drug in a safe place out of the reach of children.
- Take your study drug at or around the same time twice daily about 12 hours apart.  
- Please record the date, time and the actual number of capsules you take or the reason why any capsules were not taken - if you forget or you miss a dose, make sure you report it and make note
of it on this dosing diary.  
- On clinic visit days please do not take your study drug at home.  
- Please bring your study drug bottle(s) (including empty bottles) and this dosing diary with you to each clinic visit.  
- Please keep your study drug capsules in their bottle until you are ready to take them.  
- If you experience any ill feelings or side effects after taking your study drug please write down how you are feeling and discuss with your physician and study staff at your next visit.  
- If you have any questions about your study drug please contact the study staff.
appendix e procedures for the
treatment will have two phases

Nintedanib monotherapy (you will only take the study drug) for a two week period (days 1-14)
followed by a combination phase of nintedanib plus chemotherapy (cycle 2+)
Patient Initials:
Nintedanib Daily Dose:
NINTEDANIB PATIENT DOSING DIARY
Patient number:
Cycle number:  
| Nintedanib   | Number of                       |                        |          |     |     |     |          |
|--------------|---------------------------------|------------------------|----------|-----|-----|-----|----------|
| Dose         | Date Nintedanib Taken           | Time Taken             | Comments |     |     |     |          |
| Taken?       | Capsules                        |                        |          |     |     |     |          |
| Example      | 1 2                             | MAR                    | 2016     | e   | 15  | 3 0 | Example: |
| Yes          | No                              | Example: no drug taken |          |     |     |     |          |
| D            | MM                              | YYY                    | HR       | 2   |     |     |          |
| l            |                                 |                        |          |     |     |     |          |
| Day          | DO NOT TAKE Nintedanib capsules |                        |          |     |     |     |          |
| Yes          |                                 | No                     |          |     |     |     |          |
| 1 1 Dose     |                                 |                        |          |     |     |     |          |
| 2            | D                               | MM                     | YYY      | HR  | MIN |     |          |
| Day          | l                               | No                     |          |     |     |     |          |
| 2 nd Dose    | Yes                             |                        |          |     |     |     |          |
| D            | MM                              | YYY                    | HR       | MIN |     |     |          |
| No           |                                 |                        |          |     |     |     |          |
| 1" Dose      | Yes                             |                        |          |     |     |     |          |
| 3            | D                               | MM                     | YYY      | HR  | MIN |     |          |
| Day          | 2 nd Dose                       | Yes                    | No       |     |     |     |          |
| DD           | MM                              | YYY                    | HR       | MIN |     |     |          |
| 1" Dose      | Yes                             | l                      | No L     |     |     |     |          |
| t            | D                               | MM                     | YYY      | HR  | MIN |     |          |
| Day          | 2 Dose                          | Yes                    | No       |     |     |     |          |
| D            | MM                              | YYY                    | HR       | MIN |     |     |          |
| 1" Dose      | Yes                             | AAA                    | No L     |     |     |     |          |
| s            | DD                              | MM                     | YYY      | hr  | MIN |     |          |
| Day          | 2 Dose                          | Yes                    | l        | No  |     |     |          |
| D            | MM                              | YYY                    | HR       | MIN |     |     |          |
| 1 1 Dose     | Yes                             | l                      | No       |     |     |     |          |
| 9            | D                               | MM                     | YYY      | HR  | MIN |     |          |
| Day          | 2 Dose                          | No                     |          |     |     |     |          |
| Yes          |                                 |                        |          |     |     |     |          |
| D            | MM                              | YYY                    | HR       | MIN |     |     |          |
| 1 1 Dose     | Yes                             | L                      | No L     |     |     |     |          |
| 2            | MM                              | hr                     | MIN      |     |     |     |          |
| DD           | YYY                             |                        |          |     |     |     |          |
| Day          | No                              |                        |          |     |     |     |          |
| 2 nd Dose    | Yes                             | HR                     | MIN      |     |     |     |          |
| D            | MM                              | YYY                    |          |     |     |     |          |  
STU022016-083, Al Mutar, FormA3-ResearchProtocol-V8-05.03.22, Mod_27, 06-06-22  
| Nintedanib   | Number of                       |            |          |     |     |
|--------------|---------------------------------|------------|----------|-----|-----|
| Dose         | Date Nintedanib Taken           | Time Taken | Comments |     |     |
| Taken?       | Capsules                        |            |          |     |     |
| 1 2          | MAR                             | 2 0 1 6    | 15       | 3 0 |     |
| Example      | M                               | No         | Example: |     |     |
| res          | Example: no drug taken          |            |          |     |     |
| x            | :                               | 2          |          |     |     |
| D            | MM                              | YYY        | HR       | MIN |     |
| 8            |                                 |            |          |     |     |
| Day          | DO NOT TAKE Nintedanib capsules |            |          |     |     |
| Yes          | No L                            |            |          |     |     |
| 1" Dose      |                                 |            |          |     |     |
| 6            | DD                              | MM         | YYY      | hr  | MIN |
| Day          | 2 2 Dose                        | Yes        | NO NO    |     |     |
| DD           | MMM                             | YYY        | HR       | MIN |     |
| No _         |                                 |            |          |     |     |
| 1" Dose      | Yes                             |            |          |     |     |
| 0            | D                               | MM         | YYY      | HR  | MIN |
| Day          | 2 2 Dose                        | Yes        | No       |     |     |
| D            | MM                              | YYY        | HR       | MIN |     |
| 1 st Dose    | Yes                             | No L       |          |     |     |
| MM           | HR                              | MIN        |          |     |     |
| DD           | YYY                             |            |          |     |     |
| Day          | 2 Dose                          | Yes        | No       |     |     |
| MM           | YYY                             | HR         | MIN      |     |     |
| DD           |                                 |            |          |     |     |
| 1st Dose     | Yes                             | L          | No L     |     |     |
| r            | D                               | MM         | YYY      | HR  | MIN |
| Day          | 2 2 Dose                        | Yes        | NO       | HR  | MIN |
| D            | MM                              | YYY        |          |     |     |
| 1 st Dose    | Yes                             | No L       |          |     |     |
| 13           | D                               | MM         | YYY      | h   | MIN |
| Day          | 2 2 Dose                        | Yes        | No       |     |     |
| DD           | MM                              | YYY        | hr       | MIN |     |
| 1* Dose      | Yes                             | No _       |          |     |     |
| 14           | D                               | MM         | YYY      | HR  | MIN |
| Day          | 2 2 Dose                        | Yes        | NO       |     |     |
| D            | MM                              | YYY        | HR       | MIN |     |  
NINTEDANIB PATIENT DOSING DIARY
Patient number:
Cycle number:
Patient Initials:
Nintedanib Daily Dose:  
| NINTEDANIB PATIENT DOSING DIARY   |                                 |            |          |       |     |     |
|-----------------------------------|---------------------------------|------------|----------|-------|-----|-----|
| Patient Initials:                 | Patient number:                 |            |          |       |     |     |
| Nintedanib Daily Dose:            | Cycle number:                   |            |          |       |     |     |
| Nintedanib                        | Number of                       |            |          |       |     |     |
| Dose                              | Date Nintedanib Taken           | Time Taken | Comments |       |     |     |
| Taken?                            | Capsules                        |            |          |       |     |     |
| Example:                          | 1 2                             | MAR        | 2016     | 15    | 3 0 |     |
|                                   | No                              | Example:   |          |       |     |     |
| Yes                               | Example: no drug taken          |            |          |       |     |     |
| 2                                 |                                 |            |          |       |     |     |
| D                                 | MMM                             | YYY        | HR       | MIN   |     |     |
| 15                                |                                 |            |          |       |     |     |
| Day                               | DO NOT TAKE Nintedanib capsules |            |          |       |     |     |
| Yes                               | l                               | No _       |          |       |     |     |
| 16                                | 1 5 ' Dose                      | D          | MM       | YYY   | HR  | MIN |
| Day                               | 2 " Dose                        | Yes        | No       |       |     |     |
| D                                 | MM                              | YYY        | HR       | MIN   |     |     |
| L                                 | No                              |            |          |       |     |     |
| 15' Dose                          | Yes                             |            |          |       |     |     |
| 17                                | DD                              | MM         | YYY      | HR    | MIN |     |
| Day                               | 2 nd Dose                       | No         |          |       |     |     |
| Yes                               | l                               |            |          |       |     |     |
| MM                                | YYY                             | HR         | MIN      |       |     |     |
| DD                                | L                               |            |          |       |     |     |
| 1 " Dose                          | Yes                             |            |          |       |     |     |
| 18                                | No                              | HR         | MIN      |       |     |     |
| D                                 | MM                              | YYY        |          |       |     |     |
| Day                               | Yes                             |            |          |       |     |     |
| 2 " Dose                          | No                              | HR         | MIN      |       |     |     |
| D                                 | MM                              | YYY        |          |       |     |     |
| 1 st Dose                         | Yes                             | L          | No L     |       |     |     |
| 19                                | DD                              | MM         | YYYY     | HR    | MIN |     |
| Day                               | 2 " Dose                        | Yes        | l        | No No |     |     |
| DD                                | MM                              | YYY        | hr       | MIN   |     |     |
| 1 51 Dose                         | l                               |            |          |       |     |     |
| Yes                               | No _                            |            |          |       |     |     |
| 20                                | MM                              | YYY        | HR       | MIN   |     |     |
| D                                 |                                 |            |          |       |     |     |
| lay                               |                                 |            |          |       |     |     |
| D                                 | 2 " Dose                        | Yes        | No       | HR    | MIN |     |
| D                                 | MM                              | YYY        |          |       |     |     |
| 1" Dose                           | Yes                             | L          | No _     |       |     |     |
| 21                                | D                               | MM         | YYY      | HR    | MIN |     |
| Day                               | 2 d Dose                        | Yes        | No       |       |     |     |
| D                                 | MM                              | YYY        | HR       | MIN   |     |     |  
Patient Initials:
Nintedanib Daily Dose:
nintedanib patient dosing diary Patient number:
Cycle number:  
| Nintedanib Daily Dose:   | Cycle number:   |                        |     |     |     |
|--------------------------|-----------------|------------------------|-----|-----|-----|
| Nintedanib               | Number of       |                        |     |     |     |
| Date Nintedanib Taken    | Time Taken      |                        |     |     |     |
| Dose                     | Taken?          | Comments               |     |     |     |
| Capsules                 |                 |                        |     |     |     |
| 1 2                      | M A R           | 2016                   | 15  | 3 0 |     |
| Example:                 |                 | Example:               |     |     |     |
| Yes                      | No              | Example: no drug taken |     |     |     |
| 2                        |                 |                        |     |     |     |
| D                        | MM              | YYY                    | HR  | MIN |     |
| 1 111                    | Yes             | _ No [                 |     |     |     |
| 2                        | D               | MM                     | YYY | HR  | MIN |
| lay                      | 2" Dose         | Yes                    | No  |     |     |
| D                        | MM              | YYY                    | HR  | MIN |     |
| 1 st Dose                | Yes             | __                     |     |     |     |
| 23                       | D               | MM                     | YYY | HR  | MIN |
| Day                      | 2 nd Dose       | Yes                    | l   | No  |     |
| DD                       | MM              | YYY                    | HR  | MIN |     |
| Yes                      | _ No _          |                        |     |     |     |
| 1" Dose                  |                 |                        |     |     |     |
| 24                       | D               | MM                     | YYY | HR  | MIN |
| Day                      | 2 nd Dose       | Yes                    | No  | HR  | MIN |
| D                        | MM              | YYY                    |     |     |     |
| 1 st Dose                | Yes             | No [                   |     |     |     |
| 25                       | MIN             |                        |     |     |     |
| DD                       | MMM             | YYY                    | HR  |     |     |
| Day                      | No              |                        |     |     |     |
| 2 n Dose                 | Yes             |                        |     |     |     |
| D                        | MM              | YYY                    | HR  | MIN |     |
| 1 51 Dose                |                 |                        |     |     |     |
| 26                       | Yes             | _ No L                 |     |     |     |
| D                        | MM              | YYY                    | HR  | MIN |     |
| lay                      | 2 Dose          | Yes                    | No  |     |     |
| D                        | MM              | YYY                    | HR  | MIN |     |
| 1 st Dose                | Yes             | No                     |     |     |     |
| 27                       | DD              | MM                     | YYY | HR  | MIN |
| Day                      | 2" Dose         | Yes                    | No  |     |     |
| D                        | MM              | YYY                    | hr  | MIN |     |
| 1 51 Dose                | Yes             | No                     |     |     |     |
| 28                       | D               | MM                     | YYY | HR  | MIN |
| Day                      | 2 " Dose        | Yes                    | No  |     |     |
| D                        | MM              | YYY                    | HR  | MIN |     |