Tapentadol IR vs Oxycodone IR vs Placebo in Acute Pain From Vertebral Compression Fracture Associated With Osteoporosis

A Randomized, Double-Blind, Placebo- and Oxycodone Immediate Release (IR)-Controlled Study of Tapentadol IR for the Treatment of Acute Pain Caused by Vertebral Compression Fractures Associated With Osteoporosis

The purpose of this study is to determine the effectiveness and safety of tapentadol immediate release (IR) as compared with placebo and oxycodone IR in patients with acute pain caused by vertebral compression fractures (VCF) associated with assumed osteoporosis for whom treatment with oral opioid analgesics is appropriate.

This is a randomized (study drug assigned by chance), multicenter, double-blind (neither the patient nor the physician know the study drug administered) study to determine the efficacy and safety of tapentadol immediate release (IR) as compared with placebo and oxycodone IR in approximately 625 patients with acute pain caused by vertebral compression fractures (VCFs) associated with assumed osteoporosis for whom treatment with oral opioid analgesics is appropriate. Patients will be randomized to receive multiple doses of tapentadol IR 50 or 75 milligrams (mg) or oxycodone IR 5 or 10 mg or placebo for up to 10 days. Screening/Randomization Visit (Visit 1): Potential patients with acute thoracolumbar pain with either new onset of pain or acute exacerbation of previous pain associated with a VCF will be identified. The acute pain episode must have started within 14 days of Visit 1. The study will be explained and informed consent will be obtained. Patients will either have had a radiographic procedure to confirm diagnosis of a VCF within 3 months prior to Visit 1 or will have a radiographic procedure (e.g., lateral vertebral x-ray or magnetic resonance imaging, etc) performed at Visit 1 as standard of care. Patients must have moderate to severe acute vertebral pain and must be appropriate candidates for pain management with an oral opioid analgesic. At Visit 1, patients must report both a qualifying average back pain intensity score in the last 24 hours related to the current episode and a qualifying current back pain intensity on an 11-point numerical rating scale (NRS) where 0=no pain and 10=pain as bad as you can imagine. Patients must also have a qualifying score on the Mini-Mental State Examination (MMSE) to be eligible for study participation. At Visit 1, patients will have laboratory assessments (including a urine drug screen), physical and back examinations and an electrocardiogram (ECG). Patients will also complete paper copies of the sleep quality, functionality and vomiting assessments (i.e., morning (AM) and evening (PM) Interactive Voice Response [IVR] system questions except satisfaction with treatment). In addition, patients will have physical performance assessed. Patients who have taken long-acting or controlled-release opioid therapy or immediate release CII opioid formulations (e.g., Opana IR, Percocet, Percodan, oxycodone IR, Dilaudid) within the 1 month prior to Visit 1 are not eligible for the study. Patients taking a CIII opioid formulation (e.g., Tylenol with Codeine) or any other analgesic medication (e.g., Non-steroidal anti-inflammatory drugs (NSAIDs) not previously described above will be eligible for study participation if they meet all study criteria (e.g., pain intensity score), unless they take the CIII > 5 days/week in the 1 month prior to Visit 1. After randomization all analgesic medications other than the study drug are prohibited except for NSAIDs taken for a condition other than chronic back pain, provided the patient has been taking a stable regimen for at least one month before screening and plans to continue throughout the study. Patients may take up to 2 pills (any form) of acetaminophen (e.g., Tylenol Extra-Strength) for pain other than back pain (e.g., headache, joint pain) once per day only. Subjects who take up to 325 mg/day aspirin for cardiovascular prevention will be permitted to enter the study provided they are on a stable dose for at least 1 month prior to study entry and plan to continue the same dose during the study. Double-Blind Treatment: Patients may be enrolled and randomized with laboratory and ECG results pending. If the results of any of these tests suggest the patient is not in good health, the patient will immediately be discontinued from the study. Patients meeting study entry criteria will be randomized in a double-blind fashion in a 2:2:1 ratio to receive tapentadol IR, oxycodone IR, or matching placebo every 4-6 hours during waking hours as needed for pain. The first dose of study drug will be one capsule of tapentadol IR 50 mg, oxycodone IR 5 mg or placebo. Most patients will take the first dose of study drug in the office at Visit 1. All patients will be instructed to call the IVR system to complete another assessment of current back pain intensity immediately before taking the first dose of study drug. This call will be made by the patient from the study site unless the first dose cannot be taken in the office, in which case the patient will make the call from home. Patients will be instructed to call the IVR system every morning and each evening to complete assessments related to back pain intensity and pain relief. Patients will also respond to IVR system questions related to sleep quality, patient satisfaction with treatment and functionality (AM only) and vomiting (PM only). Patients who discontinue prematurely for any reason will be instructed to contact the study site to complete final assessments, prior to taking supplemental pain medication if applicable, and to schedule a final study visit. During this call, site personnel will obtain current pain intensity and pain relief scores from the patient; these scores will be documented. Patients will begin treatment on Day 1 with one "lower dose" capsule of study drug (tapentadol IR 50 mg, oxycodone IR 5 mg, or matching placebo). For subsequent doses, patients may remain at the "lower dose" capsule (tapentadol IR 50 mg, oxycodone IR 5 mg, or matching placebo) or may choose to take the "higher dose" (tapentadol IR 75 mg, oxycodone IR 10 mg, or matching placebo) every 4 to 6 hours during waking hours as needed depending on their level of pain and tolerability of the study drug. The duration of treatment with study drug will be up to 10 days. Tapentadol IR 450 mg or oxycodone IR 60 mg is the maximum daily dose allowed. Patients who require supplemental medication for insufficient analgesia will be discontinued from the study and will be treated at the investigator's discretion. All patients will receive a telephone call from the study staff on Day 3. During this telephone call, site personnel will inquire about the patient's overall status. Patients will return to the study site on Day 10/End of Study for the final visit (Visit 2). Patients who have not discontinued from the study prior to the final visit will complete a final assessment of current pain intensity and pain relief (on paper). In addition, all patients will have physical functionality assessed. Patients and investigators will each complete a global assessment of study drug. The investigator will also respond to two ease-of-care questions. Vital signs will be obtained, safety assessments will be completed and study drug will be collected. All patients will have their post-study analgesia prescribed at the investigator's discretion. Tapentadol IR 50 or 75 mg, oxycodone IR 5 or 10 mg, or placebo for up to 10 days. The dose is every 4-6 hours, as needed for pain. Maximum dosage is 450 mg tapentadol or 60 mg oxycodone per day.

Inclusion Criteria:

• Female (non-pregnant, non-lactating) and male
• new onset of pain or acute exacerbation of previous pain associated with a VCF within 14 days prior to Visit 1
• Radiographic confirmation of a VCF within 3 months prior to Visit 1 or a radiographic procedure performed at Visit 1
• Average back pain intensity score in the last 24 hours related to the current episode and a qualifying current back pain intensity score
• Qualifying score on the Mini-Mental Status Exam
• Able to verbalize and differentiate with regard to location and intensity of pain
• Medically stable
• Sexually active women must be postmenopausal for at least 1 year, surgically sterile, or practicing an effective method of birth control at study entry and throughout the trial
• Women of childbearing potential must have a negative urine pregnancy test at Visit 1
• Physically and mentally willing and able to adhere to the protocol requirements and its prohibitions and restrictions
• Sign an informed consent document

Exclusion Criteria:

• Neurological symptoms or deficits, or radiculopathy related to the VCF
• Taken any of the following in the month before Visit 1: long-acting or controlled-release opioid, immediate release Class II opioid formulations or Class III opioid formulation (e.g., Tylenol with Codeine) > 5 days/week
• Systemic steroid therapy within 3 months before Visit 1
• Anticonvulsants, monoamine oxidase inhibitors, tricyclic antidepressants, neuroleptics, or serotonin norepinephrine reuptake inhibitor within 2 weeks before randomization
• Major trauma to or infection in the fractured vertebrae in the 6 months preceding study
• Pain due to herniated nucleus pulposus, high energy trauma, severe spinal stenosis, bone tumor at the level(s) of pathology or known canal compromise causing clinical manifestations of cord, neural foramen, or nerve root compression with an ongoing pain level of >= 5
• Severe cardiopulmonary deficiencies
• Active systemic or local infection
• History of alcohol or drug abuse in the investigator's judgment based on medical history and physical examination
• Malignancy within the past 2 years, with the exception of basal cell carcinoma
• Concomitant autoimmune inflammatory conditions
• History of laboratory values reflecting severe renal insufficiency
• History of moderately or severely impaired hepatic function or alanine aminotransaminase or aspartate aminotransferase greater than 3 times the upper limit of normal.