NUCYNTA (Tapentadol Immediate Release) Versus Oxycodone Immediate Release in the Treatment of Acute Low Back Pain

Study Overview
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Brief Summary
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Evaluate how NUCYNTA (tapentadol) immediate release (IR) compares with oxycodone IR in the treatment of acute low back pain.

Detailed Description
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This is a randomized, outpatient, multicenter, double-blind study (blinded to patient and to study doctor) comparing NUCYNTA to oxycodone IR in the treatment of patients with acute (new onset) low back pain who also have associated leg pain that radiates (travels down) below the knee. Patients will be screened for study eligibility at Visit 1. The study will be explained and informed consent will be obtained. Potential patients must satisfy all eligibility criteria to be enrolled in the study. Eligible candidates will proceed to the Double-Blind Treatment Phase. At the time of study entry, all prohibited medications will be discontinued and will be disallowed throughout the study. All patients will call into an interactive voice response system (IVRS) to complete a pain assessments twice daily throughout the study. Patients who discontinue early 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. All patients will return to the study site on Day 5 (Visit 2) where they will be evaluated by study personnel and, as appropriate, continue with study treatment for an additional 5 days. Patients will return to the study site for the final visit on Day 10/End of Study (Visit 3) when they will have all final study assessments. The treatment duration will be up to 10 days. The sponsor will collect adverse events starting with the signing of the informed consent form. Adverse events will be reported by the subject for the duration of the study. Any clinically significant abnormalities persisting at the end of the study will be followed by the investigator until resolution or until a clinically stable endpoint is reached. Blood samples for serum chemistry and hematology and a urine sample for urinalysis will be collected. The investigator will review the laboratory report, document this review, and record any clinically relevant changes occurring during the study. The following tests will be performed by the central laboratory: Urine Pregnancy Testing for women of childbearing potential only, Urine Drug Screen, Vital Signs (pulse rate and blood pressure), Physical Examination, Neurological Examination, and Vomiting Assessment. The study will be conducted at approximately 80 sites in the United States (US). Patients will be randomized to one of the two following treatment groups: NUCYNTA 50, 75 or 100 mg every 4 to 6 hours up to 10 days as needed for pain. Oxycodone IR 5, 10 or 15 mg every 4 to 6 hours as needed for pain. Patients will begin treatment on Day 1 with one lower dose capsule of study drug (NUCYNTA 50 mg or oxycodone IR 5 mg). Subsequent dose adjustments will be made by study patients, as needed, to achieve a dose that provides a meaningful improvement in their pain intensity

Official Title
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A Randomized, Double-Blind, Parallel-Group Study of NUCYNTA (Tapentadol) Immediate Release vs. Oxycodone Immediate Release for the Treatment of Acute Low Back Pain

Conditions
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Pain, Back Pain, Low Back Pain, Back Pain With Radiation

Intervention / Treatment
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* Drug: NUCYNTA
* Drug: Oxycodone IR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At Visit 1 (study entry) patients must have a medical history and physical and neurological examinations that support a clinical diagnosis of acute low back pain that is felt down to the lower leg below the knee with the onset no longer than 30 days before Visit 1 At Visit 1 patients must report qualifying pain intensity scores Patients must be appropriate candidates for treatment with oral opioid pain medication in the investigator's clinical judgment Patients must be able to appropriately verbalize pain characteristics and to complete all protocol required measurements/assessments without assistance Patients must be medically stable on the basis of physical examination, medical history, vital signs, and clinical laboratory tests performed at screening Exclusion Criteria: History of back (cervical, thoracic or lumbosacral) pain =50% of the time in the 1 year prior to the first visit History of any low back pain episode, with the exception of the current acute low back pain episode, within 3 months prior to the first visit that was greater than mild in pain intensity, or was associated with disability (e.g., loss of time from work, family, or activities of daily living), or necessitated the use of an opioid (narcotic) analgesic including tramadol Medical history or physical examination results that suggest the acute low back pain or any of the neurological symptoms or signs are caused by a serious medical condition (e.g., fever, chills, unexplained weight loss, bowel or urinary bladder dysfunction or incontinence, bilateral leg weakness, progressive weakness, paralysis) There is a high probability for surgical intervention for the back pain during the projected time on the study or that there will be an increase in the severity of the leg pain or deficits Had either a surgical procedure involving the spine or intervertebral discs in the lower back region within 1 year prior to Visit 1 or had >1 surgical procedure(s) involving the spine or intervertebral discs in the lower back region has any painful condition that could interfere with the study assessments or with the patient's ability to differentiate the pain associated with the acute low back pain episode from pain associated with another condition History of severe lumbar spinal stenosis, fibromyalgia, or ankylosing spondylitis history of epilepsy or recurrent seizures Unable or unwilling to discontinue all prohibited medications at the time of randomization and during the time of their participation in the study Known or suspected history of alcohol or drug abuse based on medical history, physical examination, urine drug screening, or the investigator's clinical judgment History of cancer malignancy within 2 years prior to the first visit, with the exception of basal cell skin carcinoma Have filed or plan to file a worker's compensation claim for any issue related to the current acute low back pain episode Currently involved in litigation or plan to seek legal recourse for any issue related to their acute low back pain Known allergies, hypersensitivity, or intolerance to tapentadol or the comparator (oxycodone) or any excipients used in their manufacture Had previously been enrolled in a tapentadol clinical study is pregnant or are breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>NUCYNTA 50 75 or 100 mg every 4 to 6 hours for up to 10 days as needed for pain | Drug: NUCYNTA<br>* 50, 75, or 100 mg every 4 to 6 hours for up to 10 days as needed for pain<br>|
| Active Comparator: 002<br>Oxycodone IR 5 10 or 15 mg every 4 to 6 hours for up to 10 days as needed for pain | Drug: Oxycodone IR<br>* 5, 10, or 15 mg every 4 to 6 hours for up to 10 days as needed for pain<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Pain Intensity Difference (SPID) for Low Back Pain - Summary Statistics at 120 Hours (With Imputation) | Pain intensity is an 11-point numerical rating scale (NRS). 0=no pain, 10=Pain as bad as you can imagine. The pain intensity difference (PID) was to be calculated as baseline pain minus current pain at each assessment time point. SPID is a weighted sum of PID over a specified time period, say 120 hours. | 0 hour (prior to first dose) and 120 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Pain Intensity Difference (SPID) for Low Back Pain - Summary Statistics at 2 Days (With Imputation) | Pain intensity is an 11-point numerical rating scale (NRS). 0=no pain, 10=Pain as bad as you can imagine. The pain intensity difference (PID) was to be calculated as baseline pain minus current pain at each assessment time point. SPID is a weighted sum of PID over a specified time period, say 2 days. | Day 0 and Day 2 | 
| SPID for Low Back Pain - Summary Statistics at 3 Days (With Imputation) | Pain intensity is an 11-point numerical rating scale (NRS). 0=no pain, 10=Pain as bad as you can imagine. The pain intensity difference (PID) was to be calculated as baseline pain minus current pain at each assessment time point. SPID is a weighted sum of PID over a specified time period, say 3 days. | Day 0 and Day 3 | 
| SPID for Low Back Pain - Summary Statistics at 10 Days (With Imputation) | Pain intensity is an 11-point numerical rating scale (NRS). 0=no pain, 10=Pain as bad as you can imagine. The pain intensity difference (PID) was to be calculated as baseline pain minus current pain at each assessment time point. SPID is a weighted sum of PID over a specified time period, say 10 days. | Day 0 and Day 10 | 
| SPID for Index Leg Pain - Summary Statistics at 2 Days (With Imputation) | Pain intensity is an 11-point numerical rating scale (NRS). 0=no pain, 10=Pain as bad as you can imagine. The pain intensity difference (PID) was to be calculated as baseline pain minus current pain at each assessment time point. SPID is a weighted sum of PID over a specified time period, say 2 days. | Day 0 and Day 2 | 
| SPID for Index Leg Pain - Summary Statistics at 3 Days (With Imputation) | Pain intensity is an 11-point numerical rating scale (NRS). 0=no pain, 10=Pain as bad as you can imagine. The pain intensity difference (PID) was to be calculated as baseline pain minus current pain at each assessment time point. SPID is a weighted sum of PID over a specified time period, say 3 days. | Day 0 and Day 3 | 
| SPID for Index Leg Pain - Summary Statistics at 5 Days (With Imputation) | Pain intensity is an 11-point numerical rating scale (NRS). 0=no pain, 10=Pain as bad as you can imagine. The pain intensity difference (PID) was to be calculated as baseline pain minus current pain at each assessment time point. SPID is a weighted sum of PID over a specified time period, say 5 days. | Day 0 and Day 5 | 
| SPID for Index Leg Pain - Summary Statistics at 10 Days (With Imputation) | Pain intensity is an 11-point numerical rating scale (NRS). 0=no pain, 10=Pain as bad as you can imagine. The pain intensity difference (PID) was to be calculated as baseline pain minus current pain at each assessment time point. SPID is a weighted sum of PID over a specified time period, say 10 days. | Day 0 and Day 10 | 
| Total Pain Relief (TOTPAR) for Low Back Pain - Summary Statistics at 5 Days | Pain Relief - 5-Point Numerical Rating Scale, 0=None, 4=Complete. Total Pain Relief (TOTPAR) is a weighted sum of pain relieve over a specified time period, say 5 days. | Day 0 and Day 5 | 
| SF-MPQ-2 - Change From Baseline Values: Subscale and Total Scores - Continuous Pain Day 5 | Short-Form McGill Pain Questionnaire - 2 (SF-MPQ-2) is a 22-question instrument. Each item lists different qualities of pain or related symptoms and is scored using an 11-point NRS ranging from (pain or symptom is not present) to 10 (worst possible pain). Subscale scores are calculated as the mean of the items in that subscale ranged from 0 to 10. Continuous pain subscale descriptors include: throbbing pain, cramping pain, gnawing pain, aching pain, heavy pain, and tender. | Day 0 and Day 5 | 
| SF-MPQ-2 - Change From Baseline Values: Subscale and Total Scores - Continuous Pain Day 10/Last Visit | Short-Form McGill Pain Questionnaire - 2 (SF-MPQ-2) is a 22-question instrument. Each item lists different qualities of pain or related symptoms and is scored using an 11-point NRS ranging from (pain or symptom is not present) to 10 (worst possible pain). Subscale scores are calculated as the mean of the items in that subscale ranged from 0 to 10. Continuous pain subscale descriptors include: throbbing pain, cramping pain, gnawing pain, aching pain, heavy pain, and tender. | Day 0 and Day 10 | 
| SF-MPQ-2 - Change From Baseline Values: Subscale and Total Scores - Intermittent Pain Day 5 | Short-Form McGill Pain Questionnaire - 2 (SF-MPQ-2) is a 22-question instrument. Each item lists different qualities of pain or related symptoms and is scored using an 11-point NRS ranging from (pain or symptom is not present) to 10 (worst possible pain). Subscale scores are calculated as the mean of the items in that subscale ranged from 0 to 10. Intermittent pain subscale descriptors include: shooting pain, stabbing pain, sharp pain, splitting pain, electric-shock pain, and piercing. | Day 0 and Day 5 | 
| SF-MPQ-2 - Change From Baseline Values: Subscale and Total Scores - Intermittent Pain Day 10/Last Visit | Short-Form McGill Pain Questionnaire - 2 (SF-MPQ-2) is a 22-question instrument. Each item lists different qualities of pain or related symptoms and is scored using an 11-point NRS ranging from (pain or symptom is not present) to 10 (worst possible pain). Subscale scores are calculated as the mean of the items in that subscale ranged from 0 to 10. Intermittent pain subscale descriptors include: shooting pain, stabbing pain, sharp pain, splitting pain, electric-shock pain, and piercing. | Day 0 and Day 10 | 
| SF-MPQ-2 - Change From Baseline Values: Subscale and Total Scores - Neuropathic Pain Day 5 | Short-Form McGill Pain Questionnaire - 2 (SF-MPQ-2) is a 22-question instrument. Each item lists different qualities of pain or related symptoms and is scored using an 11-point NRS ranging from (pain or symptom is not present) to 10 (worst possible pain). Subscale scores are calculated as the mean of the items in that subscale ranged from 0 to 10. Predominantly neuropathic pain subscale descriptors include: hot-burning pain, cold-freezing pain, pain caused by light touch, itching, tingling or pins and needles and numbness. | Day 0 and Day 5 | 
| SF-MPQ-2 - Change From Baseline Values: Subscale and Total Scores - Neuropathic Pain Day 10/Last Visit | Short-Form McGill Pain Questionnaire - 2 (SF-MPQ-2) is a 22-question instrument. Each item lists different qualities of pain or related symptoms and is scored using an 11-point NRS ranging from (pain or symptom is not present) to 10 (worst possible pain). Subscale scores are calculated as the mean of the items in that subscale ranged from 0 to 10. Predominantly neuropathic pain subscale descriptors include: hot-burning pain, cold-freezing pain, pain caused by light touch, itching, tingling or pins and needles and numbness. | Day 0 and Day 10 | 
| SF-MPQ-2 - Change From Baseline Values: Subscale and Total Scores - Affective Descriptors Day 5 | Short-Form McGill Pain Questionnaire - 2 (SF-MPQ-2) is a 22-question instrument. Each item lists different qualities of pain or related symptoms and is scored using an 11-point NRS ranging from (pain or symptom is not present) to 10 (worst possible pain). Subscale scores are calculated as the mean of the items in that subscale ranged from 0 to 10. Affective subscale descriptors include: tiring-exhausting, sickening, fearful, and punishing-cruel. | Day 0 and Day 5 | 
| SF-MPQ-2 - Change From Baseline Values: Subscale and Total Scores - Affective Descriptors Day 10/Last Visit | Short-Form McGill Pain Questionnaire - 2 (SF-MPQ-2) is a 22-question instrument. Each item lists different qualities of pain or related symptoms and is scored using an 11-point NRS ranging from (pain or symptom is not present) to 10 (worst possible pain). Subscale scores are calculated as the mean of the items in that subscale ranged from 0 to 10. Affective subscale descriptors include: tiring-exhausting, sickening, fearful, and punishing-cruel. | Day 0 and Day 10 | 
| SF-MPQ-2 - Change From Baseline Values: Subscale and Total Scores - Total Score Day 5 | Short-Form McGill Pain Questionnaire - 2 (SF-MPQ-2) is a 22-question instrument. Each item lists different qualities of pain or related symptoms and is scored using an 11-point NRS ranging from (pain or symptom is not present) to 10 (worst possible pain). The total SF-MPQ-2 scale score is calculated as the mean of all 22 items. The range of the total score is 0 to 10. | Day 0 and Day 5 | 
| SF-MPQ-2 - Change From Baseline Values: Subscale and Total Scores - Total Score Day 10/Last Visit | Short-Form McGill Pain Questionnaire - 2 (SF-MPQ-2) is a 22-question instrument. Each item lists different qualities of pain or related symptoms and is scored using an 11-point NRS ranging from (pain or symptom is not present) to 10 (worst possible pain). The total SF-MPQ-2 scale score is calculated as the mean of all 22 items. The range of the total score is 0 to 10. | Day 0 and Day 10 | 
| Patient Global Impression of Change at End of Study | Patient Global Impression of Change (PGIC) assesses the subject's global improvement since starting study treatment using a 7-point NRS (1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse). | Day 0 and Day 10/last visit | 
| Patient Global Impression of Change at End of Study | Patient Global Impression of Change (PGIC) assesses the subject's global improvement since starting study treatment using a 7-point NRS (1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse). | Day 0 and Day 10/lst visit | 
| Clinician Global Impression of Change at End of Study | Clinician Global Impression of Change (CGIC) assesses the subject's global improvement since starting study treatment using a 7-point NRS (1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse). | Day 0 and Day 10/last visit | 
| Satisfaction With Treatment at Day 5 | The subject's satisfaction with treatment was assessed using a 7-point scale (1=Very satisfied, 2=Somewhat satisfied, 3=Slightly satisfied, 4=Neither satisfied nor dissatisfied, 5=Slightly dissatisfied, 6=Somewhat dissatisfied, 7=Very dissatisfied). | Day 0 and Day 5 | 
| Satisfaction With Treatment at End of Study | The subject's satisfaction with treatment was assessed using a 7-point scale (1=Very satisfied, 2=Somewhat satisfied, 3=Slightly satisfied, 4=Neither satisfied nor dissatisfied, 5=Slightly dissatisfied, 6=Somewhat dissatisfied, 7=Very dissatisfied). | Day 0 and Day 10/last visit | 
| Incidence of 30% Responders Without Nausea or Vomiting at Day 5 | Number of subjects had ≥ 30% reduction from baseline in low back pain intensity without nausea or vomiting reported. | Day 0 and Day 5 | 
| Incidence of 50% Responders Without Nausea or Vomiting at Day 5 | Number of subjects had ≥ 50% reduction from baseline in low back pain intensity without nausea or vomiting reported. | Day 0 and Day 5 | 
| Summary of Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation |  | Day 0 and Day 10/last visit | 
| Summary of Subjects Having Nausea as a Treatment-Emergent Adverse Event | Number of subjects that reported nausea as a treatment-emergent adverse event during the study. | Day 0 and Day 10/last visit | 
| Summary of Subjects Having Vomiting as a Treatment-Emergent Adverse Event | Number of subjects that reported vomiting as a treatment emergent adverse event during the study. | Day 0 and Day 10/last visit | 
| Summary of Subjects Having Constipation as a Treatment-Emergent Adverse Event | Number of subjects that reported constipation as a treatment emergent adverse event during the study. | Day 0 and Day 10/last visit | 
| Summary of Subjects Having Pruritus as a Treatment-Emergent Adverse Event | Number of subjects that reported pruritus as a treatment emergent adverse event during the study. | Day 0 and Day 10/last visit | 
| Kaplan-Meier First Time to 30% Response From Baseline for Low Back Pain | 30% response means >= 30% reduction from baseline in low back pain intensity score. | Day 0 and Day 10/last visit | 
| Kaplan-Meier First Time to 50% Response From Baseline for Low Back Pain | 50% response means >= 50% reduction from baseline in low back pain intensity score. | Day 0 and Day 10/last visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Low Back Pain, Low Back Pain With Leg Pain Below The Knee, Radiculopathy, Oxycodone, Tapentadol, NUCYNTA