Evaluation of Risk Minimization, Assessment and Outcomes in Patients With Chronic Pain Taking Avinza (ACCESS 2008)

AVINZA Control of Chronic Pain, Effectiveness and Safety Study (ACCESS 2008) A Multi-Center Study to Evaluate the Effectiveness and Tolerability of AVINZA for Chronic Moderate-Severe Pain: A Focus on Risk Minimization Assessment, Intervention and Outcomes

The purpose of this study is to provide information in a broad, "real world" population of chronic pain patients assessing both pain control with AVINZA as well as the potential risk for misuse and abuse.

Pain affects more Americans than diabetes, heart disease and cancer combined and although it is one of the earliest known ailments, pain is still without a universal cure. It is estimated that only about 25% of patients with chronic pain receive adequate analgesia. Long-term treatment of chronic pain with opioids is recognized as an important treatment option for patients with moderate-severe pain related to cancer and other chronic serious illnesses. AVINZA (morphine sulfate extended-release capsules) was approved for marketing by the Food and Drug Administration (FDA) in 2002 as a once daily treatment for the relief of moderate to severe pain requiring continuous opioid therapy for an extended period of time. While opioids, such as AVINZA, are beneficial in the management of chronic pain, they are sometimes associated with illicit activities. Misuse, abuse and diversion of controlled prescription drugs, particularly opioids, are problems that have increased dramatically in the United States (U.S.) since the 1990s. This study will follow the Federation of State Medical Boards Model Policy for the Use of Controlled Substances for the Treatment of Pain. Patients will be counseled on the proper storage and destruction of unused AVINZA in accordance with federal and applicable state laws. A universal precautions approach to chronic pain management (KAIR) will be utilized in this study. Although not validated as a risk assessment and management instrument, KAIR is designed to assist clinicians with responsibly managing chronic moderate-severe pain patients prescribed AVINZA. The KAIR tools will be used by the Investigator to determine the level of monitoring required based on the patient's potential risk for opioid misuse or abuse (KAIR level). Investigators and staff participating in this study will be required to participate in a training program on the counseling to be given, procedures to be followed and tools to be used in this study.

pain, opioid, abuse, moderate-severe pain requiring continuous, around-the-clock opioid therapy for an extended period of time

30 mg, 60 mg, 90 mg, 120 mg morphine will be prescribed by the Investigator in accordance with the AVINZA prescribing information.

Average pain intensity over last 24 hours rated by the subject using an 11 point numeric rating scale (ranging from 0=no pain to 10=worst pain) at Visit 3

Average pain intensity over last 24 hours rated by the subject using an 11 point numeric rating scale (ranging from 0=no pain to 10=worst pain) at Visit 4

Average pain intensity over last 24 hours rated by the subject using an 11 point numeric rating scale (ranging from 0=no pain to 10=worst pain) at Visit 5 / End of Study

Risk level was determined by the investigator using the subject's SOAPP-R (Screener and Opioid Assessment for Patients with Pain® - Revised Questionnaire) score, reports/ evidence of aberrant behavior and clinical judgment. Low Risk: SOAPP-R score <= 9 and no signals of aberrant behavior; Moderate Risk: SOAPP-R score <= 9 with positive signals of aberrant behavior OR SOAPP-R score = 10-21 with or without positive signals of aberrant behavior OR SOAPP-R score >= 22; High Risk: SOAPP-R score >= 22 with positive signals of aberrant behavior.

Risk level was determined by the investigator using the subject's SOAPP-R score, reports/ evidence of aberrant behavior and clinical judgment. Low Risk: SOAPP-R score <= 9 and no signals of aberrant behavior; Moderate Risk: SOAPP-R score <= 9 with positive signals of aberrant behavior OR SOAPP-R score = 10-21 with or without positive signals of aberrant behavior OR SOAPP-R score >= 22; High Risk: SOAPP-R score >= 22 with positive signals of aberrant behavior.

Number of Cases in Which Investigators Were Satisfied or Very Satisfied With the Utility of the Risk Minimization Program in This Study.

After each subject completed participation in the study, investigators reported satisfaction with the utility of the risk minimization program in handling each subject's particular case. The risk minimization program is a set of tools used to assist clinicians in responsibly managing pain patients prescribed Avinza. The tools include SOAPP-R, treatment agreement, urine drug test, pill counts, PPAFT (Pain Patient Follow-up Tool), Investigator Assessment and Plan and prescription card data. These tools were used at each visit to assess subject risk and to aid in the management of subject's pain.

Number of Investigators Who Reported Continued Use of One or More Risk Minimization Tools Within 3 Months Post Study Completion.

The risk minimization tools include SOAPP-R, treatment agreement, urine drug test, pill counts, PPAFT, Investigator Assessment and Plan and prescription card information.

Number of Investigators Who Reported Continued Use of One or More Risk Minimization Tools Within 3 to 6 Months Post Study Completion.

The risk minimization tools include SOAPP-R, treatment agreement, urine drug test, pill counts, PPAFT, Investigator Assessment and Plan and prescription card information.

Inclusion Criteria: Patient is an adult (greater than or equal to 21 years old Patient has chronic (greater than or equal to 3 months) moderate-severe pain who, at the discretion of the Investigator, requires an around-the-clock opioid for optimal analgesia. Patients may be opioid naïve (not currently on an opioid) or opioid tolerant. Opioid naïve patients with a pain score of greater than or equal to 4 on an 11-point NRS (numerical rating scale. OR Opioid tolerant patients experiencing suboptimal response (i.e. pain score of greater than or equal to 4) or unacceptable side effects to sustained release opioids or short-acting opioids. Patient is able to read and understand English and comply with protocol requirements. Exclusion Criteria: A patient who meets ANY of the following exclusion criteria will not be enrolled: Hypersensitivity to morphine, morphine salts, or any components of AVINZA Respiratory depression (slowed breathing) Acute or severe bronchial asthma or severe chronic obstructive pulmonary disease (COPD) Currently has or is suspected of having paralytic ileus Requires a daily dose of AVINZA greater than 1600mg/day Patient is abusing alcohol Pregnancy or breast feeding Currently taking AVINZA Patient unwilling to sign the Treatment Agreement Life expectancy is less than 2 months Migraine as the primary pain score Patient resides in a hospital or nursing home Patient has had more than 2 surgeries for low back pain Patient is anticipated to require major surgery or steroid injections for chronic pain over the next 12 weeks

The American Pain Foundation. Pain Facts & Figures. January 2007. Available from http://www.painfoundation.org/print.asp?file=Newsroom/PainFacts.htm.

Joranson DE, Berger JW. Regulatory issues in pain management. J Am Pharm Assoc (Wash). 2000 Sep-Oct;40(5 Suppl 1):S60-1.

Caldwell JR, Rapoport RJ, Davis JC, Offenberg HL, Marker HW, Roth SH, Yuan W, Eliot L, Babul N, Lynch PM. Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial. J Pain Symptom Manage. 2002 Apr;23(4):278-91. doi: 10.1016/s0885-3924(02)00383-4.

Rauck RL, Bookbinder SA, Bunker TR, Alftine CD, Ghalie R, Negro-Vilar A, de Jong E, Gershon S. The ACTION study: a randomized, open-label, multicenter trial comparing once-a-day extended-release morphine sulfate capsules (AVINZA) to twice-a-day controlled-release oxycodone hydrochloride tablets (OxyContin) for the treatment of chronic, moderate to severe low back pain. J Opioid Manag. 2006 May-Jun;2(3):155-66. doi: 10.5055/jom.2006.0025. Erratum In: J Opioid Manag. 2006 Sep-Oct;2(5):276.

Rauck RL, Bookbinder SA, Bunker TR, Alftine CD, Ghalie R, Negro-Vilar A, de Jong E, Gershon S. A randomized, open-label study of once-a-day AVINZA (morphine sulfate extended-release capsules) versus twice-a-day OxyContin (oxycodone hydrochloride controlled-release tablets) for chronic low back pain: the extension phase of the ACTION trial. J Opioid Manag. 2006 Nov-Dec;2(6):325-8, 331-3. doi: 10.5055/jom.2006.0048.

Rosenthal M, Moore P, Groves E, Iwan T, Schlosser LG, Dziewanowska Z, Negro-Vilar A. Sleep improves when patients with chronic OA pain are managed with morning dosing of once a day extended-release morphine sulfate (AVINZA): findings from a pilot study. J Opioid Manag. 2007 May-Jun;3(3):145-54. doi: 10.5055/jom.2007.0052.

Katz NP, Adams EH, Chilcoat H, Colucci RD, Comer SD, Goliber P, Grudzinskas C, Jasinski D, Lande SD, Passik SD, Schnoll SH, Sellers E, Travers D, Weiss R. Challenges in the development of prescription opioid abuse-deterrent formulations. Clin J Pain. 2007 Oct;23(8):648-60. doi: 10.1097/AJP.0b013e318125c5e8.

Ives TJ, Chelminski PR, Hammett-Stabler CA, Malone RM, Perhac JS, Potisek NM, Shilliday BB, DeWalt DA, Pignone MP. Predictors of opioid misuse in patients with chronic pain: a prospective cohort study. BMC Health Serv Res. 2006 Apr 4;6:46. doi: 10.1186/1472-6963-6-46.

Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005 Mar-Apr;6(2):107-12. doi: 10.1111/j.1526-4637.2005.05031.x.

Setnik B, Roland CL, Pixton GC, Sommerville KW. Prescription opioid abuse and misuse: gap between primary-care investigator assessment and actual extent of these behaviors among patients with chronic pain. Postgrad Med. 2017 Jan;129(1):5-11. doi: 10.1080/00325481.2017.1245585. Epub 2016 Oct 26.