Use of Xtampza ER to Overcome Difficulties in Swallowing Opioid Pills
Phase: PHASE4
Conditions: Chronic Pain, Opioid Use, Deglutition
Sponsor: Ajay Wasan, MD, Msc

 
1
 
 
 
 
2018 
Use of Xtampza ER to 
overcome difficulties in 
swallowing opioid pills 
CLINICAL RESEARCH PROTOCOL 
DEPARTMENT OF ANESTHESIOLOGY 
UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 
IRB PRO17040444 
APPROVED 11/10/2017 

 
PRO17040444: Use of Xtampza ER to overcome difficulties in swallowing opioid pills 
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Table of Contents 
 
Study Information ................................................................................................................................................. 3 
Study Contacts ...................................................................................................................................................... 4 
Subjects .................................................................................................................................................................. 4 
Eligibility ............................................................................................................................................................................ 5 
Subject Groups/Treatment Arms .................................................................................................................................... 6 
Treatment Arm 1: Open Label ........................................................................................................................................ 6 
Study Schedule ...................................................................................................................................................... 7 
Overview of Schedule ........................................................................................................................................................ 7 
Recruitment and Screening .............................................................................................................................................. 7 
Compensation Schedule .................................................................................................................................................... 8 
Detailed Study Schedule with Checklists ........................................................................................................................ 9 
Clinic Visit 1 ................................................................................................................................................................... 9 
Clinic Visit 2 ................................................................................................................................................................... 9 
Clinic Visit 3 ................................................................................................................................................................... 9 
Clinic Visit 4 (End of Study) ........................................................................................................................................ 10 
Daily Texts .................................................................................................................................................................... 10 
Weekly Surveys ............................................................................................................................................................ 10 
Study Measures ................................................................................................................................................... 12 
Medical History ............................................................................................................................................................. 12 
Medication Diary .......................................................................................................................................................... 12 
Medication Satisfaction Questions ................................................................................................................................ 12 
Modified Baylor Dysphagia Questionnaire .................................................................................................................. 12 
Pain Diary...................................................................................................................................................................... 13 
Pill Swallowing Difficulty Questions ........................................................................................................................... 13 
PROMIS-29 Adult Profile v2.0 (Participant Version) .................................................................................................. 13 
Text Message Compliance ............................................................................................................................................ 14 
Urine Pregnancy Test .................................................................................................................................................... 14 
Weekly Survey .............................................................................................................................................................. 14 
Text Message Scripts .......................................................................................................................................... 15 
Statistical Analysis Plan ..................................................................................................................................... 16 
Outcomes to be Analyzed ................................................................................................................................................ 16 
Primary Outcome 
 Pain Intensity........................................................................................................................... 16 
Overview of Analysis Plan .............................................................................................................................................. 17 
Data Management ............................................................................................................................................... 17 
Scripts and Files Needed ................................................................................................................................................. 17 
Updating Data Files ......................................................................................................................................................... 17 
Mosio SMS Text Messaging System .................................................................................................................. 19 
Initial Set-up (at Clinic Visit 1) ...................................................................................................................................... 19 
Scheduling Appointment Reminders ............................................................................................................................. 20 
Study Medication ................................................................................................................................................ 18 
Prescribing Xtampza ER ................................................................................................................................................ 22 
 
 
 
 
 
 
 

 
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Study Information 
 
Principle  
Investigator:  
Ajay Wasan, MD, MSc 
 
Study Coordinators: Andrea G. Gillman, PhD 
 
Institution: 
 
University of Pittsburgh School of Medicine 
 
 
 
 
Department of Anesthesiology 
 
IRB Protocol: 
University of Pittsburgh PRO17040444 
 
 
 
Approved: 11/10/2017 
 
 
 
Expiration Date:  10/24/2018  
 
Study Location: 
UPMC Pain Medicine Clinic at Centre Commons 
 
 
 
5750 Centre Ave, Ste. 400 
 
 
 
Pittsburgh, PA 15206  
 
Sponsoring Agency: Collegium Pharmaceutical, Inc. 
 
780 Dedham Street, Suite 800 
 
Canton, MA 02021 
 
Study Objective: 
Xtampza ER is an oral opioid medication capsule that can be opened to allow the pellets 
to be added to food or drink. This study will investigate whether Xtampza ER can 
adequately address common quality of care deficits of opioid medications. 
 
Specific Aims: 
We hypothesize that the subjects in our study will report comparable pain relief and 
improved ability to take opioid medication through the dispersal of the microspheres in 
food or liquid. 
1. The primary hypothesis is that there will be a significant improvement in ratings of 
swallowing difficulties in comparing pre- vs. post-administration scores. 
2. The secondary hypothesis is that there will be a non-inferior difference between pre- 
and post-pain ratings. In other words, after being converted to Xtampza ER, there will be 
no reported meaningful differences in the degree of pain. 
 
 

 
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Study Contacts 
 
Principle Investigator 
Ajay D. Wasan, MD, MSc 
 
 
 
 
Dept. of Anesthesiology, University of Pittsburgh School of Medicine 
 
 
 
 
UPMC Pain Medicine 
 
 
 
 
(412) 665-8048 
 
 
 
 
wasanad@upmc.edu 
 
 
Study Coordinators  
Andrea G. Gillman, PhD 
 
 
 
 
Dept. of Anesthesiology, University of Pittsburgh School of Medicine 
 
 
 
 
(412) 665-2904 
 
 
 
 
gillmana@pitt.edu 
 
  
Sponsoring Agency  
Michael DeGeorge, PharmD 
 
 
VP, Medical Affairs 
 
 
Collegium Pharmaceutical, Inc. 
 
 
(631) 431-4507 
 
 
mdegeorge@collegiumpharma.com 
 
 
Danielle Ruch, MBA 
Manager, Medical Operations 
Collegium Pharmaceutical, Inc. 
(781) 232-0770 
druch@collegiumpharma.com 
 
Pharmacy 
Howard Brenner 
Avella of Orlando, Inc. 
100 Technology Park, Suite 1525 
Lake Mary, FL 32746 
Phone: (407) 792-7099 
Fax: (877) 430-4768 
howard.brenner@avella.com  
 
 
Text Messaging 
 
Noel Chandler, CEO 
Mosio Simple Support 
noel@mosio.com 
 
 
 
 
 
 
 
 
 
 
Charlotte Justice, Account Manager 
 
 
 
 
Mosio Simple Support 
 
 
 
 
charlotte@mosio.com  
 
 
 
 
 
 
 
 
 
 
Jay Sachdev, Software Developer 
 
 
 
 
Mosio Simple Support 
 
 
 
 
 
jay@mosio.com 
 
 
Subjects 
 

 
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Eligibility 
 
Inclusion Criteria: 
1. Adult subjects must have noncancer chronic pain for at least six months on a daily 
basis, 
2. Be prescribed opioids on a daily basis 
3. Have an upper dose limit of daily opioids of 200 mg of morphine equivalents. This is 
because at doses greater than 200 mg daily, in our experience it is much more difficult to 
convert completely to another opioid compound within a week. Fentanyl and methadone 
users will not be specifically excluded unless their dosages fall outside this range. 
4. Ages 21-70 
5. Reported difficulty swallowing their opioid medication on the screening form at a level 
detemrined significant by the PI. 
6. Having a mobile phone. A smart phone is not required to respond to the text messages. 
7. Having Internet access to be able to respond to the emailed weekly surveys. 
8. If sexually active and able to become pregnant, must agree to use an acceptable 
method 
of birth control (hormonal methods, barrier methods with spermicide, intrauterine device 
(IUD) or abstinence). 
9. Only Pain Medicine Clinic patients may participate in this study 
 
 
 
Exclusion Criteria: 1. Inability to understand the surveys and complete them. 
2. Pregnancy 
3. High risk for opioid addiction and/or abuse behaviors 
4. Any condition, physical or mental, that in the investigator’s judgment precludes 
optimal participation in the study procedures. This includes any documented current 
history of liver disease, renal insufficiency, delirium, alcohol use disorder, breast-feeding 
mothers, acute or severe asthma, COPD requiring home oxygen, GI obstruction, biliary 
tract disease, pancreatitis, cardiac arrhythmia, bladder or urethral obstruction, adrenal 
insufficiency, psychosis, or taking medications which are potent inhibitors of the 
CYP3A4 enzyme (such as protease inhibitors, macrolide antibiotics, or antifungals).  
5. Demonstartion of abusive alcohol behavior. For women, this is more than 3 drinks on 
any single day or more than 7 drinks per week. For men, more than 4 drinks on any single 
day or more than 14 drinks per week. 
6. Currently taking fentanyl or methadone 
7. Exhibiting the following contradidated conditions: (1) significant respiratory 
depression (2) acute or severe bronchial asthma in an unmonitored setting or in the 
absence of resuscitative equipment (3) known or suspected gastrointestinal obstruction, 
including paralytic ileus (4) hypersensitivity (e.g. anaphylaxis) to oxycodone (5) patients 
with chronic pulmonary disease (6) elderly, cachet, or debilitated patients (7) patients 
with evidence of increased intracranial pressure, brain tumors, head injury, or impaired 
consciousness (8) patients with seizure disorders (9) pregnant and breastfeeding women, 
due to risks to the fetus/baby  
 
 
 
 

 
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Subject Groups/Treatment Arms 
 
Treatment Arm 1: Open Label 
 
Target Enrollment: 20  
 
Description: 
Subjects will be prescribed Xtampza ER for the duration of the study. Dosage and side 
effects will be monitored by the PI.  
 
Treatment Protocol: Administration of Xtampza ER will begin at Clinic Visit 2 in Week 2 of the study. 
During this clinic visit, subjects will discuss with the investigator conversion of their 
current opioids to Xtampza ER. If subjects are on a mix of short and long acting opioids, 
they may elect to only convert the long-acting opioid if this is the medication giving them 
the swallowing difficulties. In other words, ideally we would convert both the long and 
short acting opioids to Xtampza ER. However, we realize that subjects may prefer to still 
have their current breakthrough medication, which may not be giving them swallowing 
difficulties, and thus the accommodation of only converting the long-acting opioids. We 
will use a standard conversion table to calculate the dose. But, due to the phenomenon of 
incomplete cross tolerance, we will only convert 75% of the calculated dose to Xtampza 
ER. Subjects are dispensed a 7-10 day supply of Xtampza ER at the end of the visit. As 
per manufacturer recommendations, subjects will be instructed to take each dose of 
Xtampza ER with the same amount of food. Subjects will be instructed to open the 
capsules, sprinkle the microspheres onto soft food such as pudding or applesauce, and 
then consume the food.  
 
 
 
 

 
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Study Schedule 
 
Overview of Schedule 
 
Week 0: 
 
Recruitment & Screening 
Week 1: 
 
Clinic Visit 1, Daily text messaging begins 
Week 2: 
 
Clinic Visit 2 
Week 3: 
 
Clinic Visit 3 
Week 4: 
 
Weekly Survey – Week 4 
Week 5: 
 
Weekly Survey – Week 5 
Week 6: 
End of Study. Clinic Visit 4, Daily text messaging ends 
 
Recruitment and Screening 
 
Recruitment: 
Patients will be recruited from the UPMC Pain Medicine Clinic at Centre Commons from 
the PI and clinic providers approaching their patients. Clinic providers include Drs. 
Wasan (the study PI), Ed Heres, Cheryl Bernstein, Trent Emerick, and Susan Jarquin. If a 
physician is aware of a potential participant, the physician will briefly inform the 
participant of the research study and ask the participant for permission to be approached 
or called by the research team and, if permission is given, this will be documented by the 
physician. 
 
Flyers will be posted in the clinic waiting rooms and exam rooms with instructions to 
call, email or text the study coordinators to indicate interest in their study. The research 
team will then contact the interested volunteer to perform the initial screening. 
 
We are also planning to use the University of Pittsburgh Pitt+Me Registry as a recruiting 
tool.  
 
Efforts will be made to attain a mix of study participants, in terms of gender and 
racial/ethnic representation reflective of the population of the greater metropolitan 
Pittsburgh area. According to the 2010 census, this distribution should be: 52% female, 
48% male, 66% White, 26% Black or African American, 4% Asian, 2% Hispanic or 
Latino, 2% Two or More Races. 
 
We will review our patient demographic distribution quarterly and if we find that our 
gender or minority recruitment is lagging we will initiate targeted recruitment strategies 
to increase gender or minority representation. For example, if minority recruitment is 
lagging, we may post flyers at other UPMC Pain Medicine clinics such as Montefiore and 
Mercy Hospital. 
 
Advertisements: 
110536A PAIN & SWALLOWING STUDY POSTER final.pdf 
 
Screening: 
 
Use the study’s Phone Screening Form. Enter data into the form during phone interview. 
 
 
 
 
File name: Wk0.PhoneScreeningForm.docx  
 
Post- 
Screening Tasks: 
 Confirm eligibility with Dr. Wasan 

 
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 Contact volunteer about eligibility status 
 If eligible, schedule Clinic Visit 1 
 
 
Compensation Schedule 
 
Full Study Participation: 
 
1. Clinic Visit 1: $20  
 
 
 
 
 
2. Clinic Visit 4: $100 
 
Partial Study Participation:  
1. Clinic Visit 1: $20  
 
 
 
 
 
2. If at least half of study activities are completed: $30 
 
Travel Reimbursement: 
 
Up to $25 for travel to and from Centre Commons. 
 
 

 
PRO17040444: Use of Xtampza ER to overcome difficulties in swallowing opioid pills 
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Detailed Study Schedule with Checklists 
 
Clinic Visit 1 
 
Scheduled: 
 
Week 1  
Location: 
 
UPMC Pain Medicine Clinic at Centre Commons, Suite 400 
Appt. Reminder: 
 Research staff should call to confirm 24 hrs before appointment 
 
Preparation Tasks: 
 Print/gather paper forms: 
 
 
 
 
 Informed Consent:  Wk1.1.ConsentForm.docx  
 Medical History:  Wk1.2.MedicalHistoryForm.docx 
 
 
 
 Set up Chromebook for REDCap data entry 
 
Visit Tasks:  
 PI – Obtain informed consent. Complete Medical History 
 
 
 
 Staff – Enrollment Information (REDCap) 
 Subject completes REDCap surveys: PROMIS-29 & Opioid Medication Satisfaction 
 
 
 
 Staff – Set up subject in Mosio text messaging system & WePay system.  
 Staff – Schedule Clinic Visit 2 
 
Tasks After Appt.:  
 Order Xtampza ER from pharmacy 
 
 
 
 Schedule appointment reminders for Clinic Visit 2 in Mosio text message system 
 Pay subject for clinic visit in WePay - $20 for Clinic Visit 1 & reimburse for  
    transportation/parking 
 
Clinic Visit 2 
 
Scheduled: 
 
Week 2 
Location: 
 
UPMC Pain Medicine Clinic at Centre Commons, Suite 400 
Appt. Reminder: 
Programmed into Mosio SMS schedule. Text Name: APPT_CLIN 
 
Preparation Tasks: 
 Set up Chromebook for REDCap data entry 
 
 
 
 Confirm study medication shipment with pharmacy 
 
Visit Tasks:  
 Physician – Xtampza ER administration instructions 
 Subject completes REDCap surveys:  
1. Modified Baylor Dysphagia Questionnaire 
2. PROMIS-29 
3. Pill Swallowing Difficulty Questions 
 Staff – Schedule Clinic Visits 3 & 4 (in weeks 3 & 6).  
 Staff – Reimburse subjects for transportation/parking in WePay 
 
Tasks After Appt.:  
 Schedule appointment reminders for Clinic Visits 3 & 4 in Mosio text message system 
 
 
Clinic Visit 3 
 
Scheduled: 
 
Week 3 
Location: 
 
UPMC Pain Medicine Clinic at Centre Commons, Suite 400 
Appt. Reminder: 
Programmed into Mosio SMS schedule. Text Name: APPT_CLIN 
 
Preparation Tasks: 
 Set up Chromebook for REDCap data entry 

 
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Visit Tasks:  
 Physician – monitor side effects & dosage 
 Subject completes REDCap surveys:  
1. Modified Baylor Dysphagia Questionnaire 
2. PROMIS-29 
3. Pill Swallowing Difficulty Questions 
4. Xtampza ER Satisfaction Question 
 Staff – Reimburse subjects for transportation/parking in WePay 
 
 
Clinic Visit 4 (End of Study) 
 
Scheduled: 
 
Week 6 
Location: 
 
UPMC Pain Medicine Clinic at Centre Commons, Suite 400 
Appt. Reminder: 
Programmed into Mosio SMS schedule. Text Name: APPT_CLIN 
 
Preparation Tasks: 
 Set up Chromebook for REDCap data entry 
 
Visit Tasks:  
 Physician – discuss options for future medication/dosage 
 Subject completes REDCap surveys:  
1. Modified Baylor Dysphagia Questionnaire 
2. PROMIS-29 
3. Pill Swallowing Difficulty Question 
4. Xtampza ER Satisfaction Question 
5. Patient Global Impression of Change 
 Staff – Turn off Mosio text messaging for subject 
 Staff – Pay subject $100 in WePay for study completion and reimburse for 
transportation/parking  
 
Tasks After Appt.:  
 Download final subject data from REDCap and Mosio 
 
 
Daily Texts 
 
Scheduled: 
 
Every day starting with Clinic Visit 1 – Weeks 1-6 
Collection Route: 
Mosio text message 
 
 
 
Text name: PAIN_DIARY, MED_DIARY 
 
Measures Taken: 
Pain Diary Questions 
 
 
 
Medication Diary Questions  
 
Researcher Tasks: 
 Check and download Mosio study data once each week 
 
 
Weekly Surveys 
 
Scheduled: 
 
Weeks 4 & 5 
Collection Route: 
REDCap survey. Survey link sent via Mosio text message. Text name: SURVEY_LINK 
 
Measures Taken: 
Pill Swallowing Difficulty Question 

 
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PROMIS-29 
 
 
 
Xtampza ER Satisfaction Question (Week 5 only) 
 
 
 
Patient Global Impression of Change (Week 5 only) 
 
Researcher Tasks: 
 Check and download REDCap study data once each week 
 
 

 
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Study Measures 
 
Medical History 
Description 
Short form to collect subject’s demographic information, medical and psychiatric history.  
 
Data Entry by 
Study Physician 
 
Data  
Collection Route 
Paper 
 
Equipment/Supplies Wk1.2.MedicalHistoryForm.docx 
 
Medication Diary 
Description 
One daily question to monitor Xtampza ER use and compliance.   
 
 
Data Entry by 
Subjects 
 
Data  
Collection Route 
Mosio SMS 
 
Data Collected 
Q1: Did you remember to take your study medication yesterday? Text Y or N. 
 
Medication Satisfaction Questions 
Description 
Brief questions to determine the subject’s satisfaction with their current opioid pain 
medication.  
 
 
 
Data Entry by 
Subjects 
 
Data  
Collection Route 
REDCap 
 
Data Collected 
Week 1 – Opioid Medication Satisfaction Question:  
How satisfied are you with your current opioid medication?  
0------------------------10 
 
 
 
 
 
Not satisfied at all 
Completely satisfied 
 
 
 
 
Weeks 3, 5 & 6 – Xtampza ER Satisfaction Question: 
 
 
 
 
How satisfied are you with the study medication, Xtampza ER? 
0------------------------10 
 
 
 
 
 
Not satisfied at all 
Completely satisfied 
 
Modified Baylor Dysphagia Questionnaire 
Description 
Swallowing difficulty questionnaire used at Baylor Medical Centers (questions 1-11) 
 
 
Data Entry by 
Subjects  
 
Data  
Collection Route 
REDCap  
 
Data Collected 
1. Complaints regarding swallowing 
 
 
 
2. Date of onset of swallowing problems 
 
 
 
3. Swallowing problems currently experienced 
 
 
 
4. Food intake information   
 
 

 
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Original  
Documentation 
https://www.baylorhealth.com/ 
 
Pain Diary 
Description 
Two daily questions about the subject’s pain; questions #5 and 6 from the Brief Pain 
Inventory.  
 
Data Entry by 
Subjects 
 
Data  
Collection Route 
Mosio SMS texts 
 
Data Collected 
Q1: What is your level of pain now? Text 0-10. 0 = no pain, 10 = pain as bad as you can 
imagine. 
 
Q2: What was your average level of pain over the last 24 hours? Text 0-10. 0 = no pain, 
10 = pain as bad as you can imagine. 
 
Pill Swallowing Difficulty Questions 
Description 
Brief question to determine current level of swallowing difficulty  
 
Data Entry by 
Subjects  
 
Data  
Collection Route 
REDCap  
 
Data Collected 
Week 1: Do you have difficulty swallowing medications?  
If yes, how would you rate the difficulty swallowing your current opioid pain 
medications?   
0------------------------10 
 
 
 
 
 
No trouble at all 
The greatest difficulty possible 
 
Weeks 2-6: How would you rate the difficulty swallowing this study pain medication?  
0------------------------10 
 
 
 
 
 
No trouble at all 
The greatest difficulty possible 
 
PROMIS-29 Adult Profile v2.0 (Participant Version) 
Description 
Adult Profile 29-item instrument that contains a fixed collection of short forms measuring 
several physical and emotional domains.  
 
 
 
Data Entry by 
Subjects 
 
Data  
Collection Route 
REDCap 
 
Data Collected 
Physical Function Score = sum of q1 - q4 (range 4-20) 
 
 
 
Anxiety Score = sum of q5 - q8 (range 4-20) 
 
 
 
Depression Score = sum of q9 - q12 (range 4-20) 
 
 
 
Fatigue Score = sum of q13 - q16 (range 4-20) 
 
 
 
Sleep Disturbance Score = sum of q17 - q20 (range 4-20) 
 
 
 
Social Roles Score = sum of q21 – q24 (range 4-20) 
 
 
 
Pain Interference Score = sum of q25 – q28 (range 4-20) 
 
 
 
Pain Intensity Score = answer to q29 (range 0-10) 
 
 
 
See PROMIS Profile Scoring Manual for more information. 

 
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Original  
Documentation 
https://www.assessmentcenter.net  
 
 
References 
Cella, D., et al. (2010). "The Patient-Reported Outcomes Measurement Information 
System (PROMIS) developed and tested its first wave of adult self-reported health 
outcome item banks: 2005-2008." J Clin Epidemiol 63(11): 1179-1194. 
 
Text Message Compliance 
Description 
Record of whether and when subjects answered text message questions.   
 
 
Data  
Collection Route 
Mosio SMS 
 
Data Collected 
Answer received (y/n), time of receipt 
 
 
Urine Pregnancy Test 
Description 
“Dipstick” test for pregnancy in female subjects of child-bearing age 
 
Data  
Collection Route 
Urine Pregnancy Tests 
 
How to Administer Administer during the collection for the urine toxicology test listed above. Place dipstick 
in specimen cup and check for results before sealing cup for shipment pick-up. 
 
Weekly Survey 
Description 
Weekly survey; includes pain, psychological evaluations & swallowing difficulty  
 
 
Data Entry by 
Subjects  
 
Data  
Collection Route 
REDCap (link send via Mosio SMS) 
 
Data Collected 
Pill Swallowing Difficulty Question 
PROMIS-29 – full survey 
 
 

 
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Text Message Scripts 
 
TEST 
Text Contents 
<Welcome to the research study! Did you receive this message? Text Y or N> 
 
 
Allowed Answer Types 
Yes or No 
 
Branching 
 
 
If Y, text <Thank you!> 
 
Compliance Data 
 
Time sent, Time received, Did subject respond 
 
APPT_CLIN 
Text Contents 
<You have a research appointment at UPMC Pain Medicine at Centre Commons  
 
tomorrow, [DATE], at [TIME]. Text Y to confirm or N to cancel.>  
 
Allowed Answer Types 
Yes or No 
 
Branching 
 
 
If Y, text <Thank you. See you tomorrow!> 
 
 
 
 
If N, text <OK. A researcher will be in touch shortly to re-schedule your  
appointment.> 
 
Notes  
 
 
Mosio will notify research coordinator of subject cancellation 
 
PAIN_DIARY 
Question 1 
Text Contents 
<What is your level of pain now? Text 0-10. 0 = no pain, 10 = pain as bad as you  
 
can imagine.> 
 
Allowed Answer Types 
Numeric: 0-10 scale 
 
Compliance Data 
 
Time sent, Time responded, Did subject respond 
 
Question 2 
Text Contents 
<What was your average level of pain over the last 24 hours? Text 0-10. 0 = no  
 
pain, 10 = pain as bad as you can imagine.> 
Allowed Answer Types 
Numeric: 0-10 scale 
 
Compliance Data 
 
Time sent, Time responded, Did subject respond 
 
MED_DIARY 
Text Contents 
<Did you remember to take your study medication yesterday? Text Y or N.> 
 
Allowed Answer Types 
Yes or No 
 
Branching 
 
 
If Y, text <Thank you.> 
 
 
 
 
If N, text <Remember to take all of your prescribed medication. This is an  
important part of your treatment.> 
 
Compliance Data 
 
Time sent, Time responded, Did subject respond 
 

 
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Statistical Analysis Plan 
 
Outcomes to be Analyzed 
 
Primary Outcome 
 
Pain Intensity 
• Weekly average pain: PROMIS-29 Pain Intensity 
• Daily average pain: Text Message Pain Diary Questions 
 
 
 
 
 
  
Secondary Outcomes 
Swallowing Satisfaction 
• Pill Swallowing Difficulty Questions 
 
Pain Interference 
• PROMIS-29 Pain Interference 
 
Medication Satisfaction 
• Opioid Medication Satisfaction Question 
• Xtampza ER Satisfaction Question 
 
Swallowing Difficulty  
• Modified Baylor Dysphagia Questionnaire 
 
Mental Health Outcomes 
• PROMIS-29 Depression 
• PROMIS-29 Anxiety 
• PROMIS-29 Satisfaction with Social Roles 
• PROMIS-29 Sleep Disturbance 
• PROMIS-29 Fatigue 
 
Physical Health Outcomes 
• PROMIS-29 Physical Function 
 
Impression of Change 
• Patient Global Impression of Change 
 
 
 
 

 
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Overview of Analysis Plan 
 
The primary outcome of changes in pain is calculated by comparing average pain level at baseline to the 
average of the last four weeks of treatment (i.e., after the two week conversion period). This is a comparison of 
the average of the seven days of average pain ratings between weeks 1 and 2 to the average of the weekly 
average pain intensity ratings collected on the PROMIS-29 questionnaires (pre vs. post). The comparisons of 
pre vs post will be done with an analysis of covariance (ANCOVA), which permits inclusion of relevant 
covariates, such as the baseline level of pain. The primary hypothesis is that there will be a non-inferior 
difference between pre-and post-pain ratings. In other words, after being converted to Xtampza ER, there will 
be no reported meaningful differences in the degree of pain. 
 
The main secondary outcome is change in swallowing difficulty of opioid medication. The Pre vs Post 
comparisons are calculated in a similar fashion to the primary pain outcome, and compared using ANCOVA. 
This is a comparison between the baseline ratings of swallowing difficulties versus the average of these ratings 
in the last four weeks of study. The secondary hypothesis is that there will be a significant improvement in 
ratings of swallowing difficulties in comparing pre- vs. post scores.  
 
The same statistical approach is taken for the other secondary outcomes, such as global impression of change, 
satisfaction with pain care, and side effects. We anticipate that subjects will report on average greater 
satisfaction with pain care, ‘improved’ or ‘much improved’ global impression of change, and comparable side 
effects. For any outcome, in the event of greater than 20% missing data, we will first determine if this data is 
missing at random. If it does appear that this is the case then we will analyze that outcome with mixed linear 
modeling, which produces more reliable estimates of effect sizes with such missing data. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Study Medication 
 
Instructions for Prescribing Xtampza ER (from Collegium & Avella) 
 
• Avella will provide your site with pre-paid UPS envelopes. 
• Your site will place the patient enrollment form (Wk1.3.PharmacyEnrollmentForm.docx) in the pre-paid 
envelope and send it to Avella.  
• The PI will prescribe the study drug via EPIC using Avella Orlando as the pharmacy. 
• Avella will contact the PI to confirm the prescription dosage and instructions prior to dispensing 
• Please inform your subjects that they will receive a telephone call from Avella to complete a 5-
minute consultation prior to dispensing the study drug.  This consultation is important to ensure that 
the subject takes the medication as prescribed and that Avella will address any questions that the subject 
may have. This consultation is required for all subjects.  
• After Avella confirms the prescription with the PI and completes a 5-minute consultation with the 
subject, then Avella will dispense the study drug to the subject.  
• Avella also requested that we remind your site that they are located on the East coast, which is Eastern 
Standard Time (EST).