Long-Term Safety and Tolerability Study of NKTR-181 in Subjects With Chronic Low Back Pain or Chronic Non-Cancer Pain

Study Overview
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Brief Summary
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The purpose of this 52-week open label study is to determine the long-term safety of a new opioid molecule, NKTR-181, in patients with moderate to severe chronic low back pain or chronic non-cancer pain.

Detailed Description
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This is an open-label safety and tolerability study in which approximately 600 subjects will receive NKTR-181 for up to 52 weeks. Subjects may include newly enrolled subjects and subjects who have recently completed SUMMIT-07 study. This study will also investigate the pharmacokinetics of NKTR-181 in patients with chronic low back pain or chronic non-cancer pain.

Official Title
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A Phase 3 Multicenter, Open-Label, 52-Week Study To Evaluate the Long-Term Safety and Tolerability of NKTR-181 in Subjects With Moderate to Severe Chronic Low Back Pain or Chronic Non-Cancer Pain

Conditions
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Low Back Pain, Chronic Pain

Intervention / Treatment
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* Drug: NKTR-181 BID tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant, non-nursing female aged 18 to 75 years old Clinical diagnosis of moderate to severe, chronic low back or non-cancer pain for at least three months Not experiencing adequate pain relief or have failed previous treatment with non-opioid analgesics Opioid analgesia is necessary Currently taking no less than 10 mg but no more than 60 mg of morphine sulfate equivalents (MSE) per day of opioid analgesics for at least 7 days prior to entry Females of child bearing potential must be using a highly effective form of birth control. All subjects must agree to use double-barrier contraception during participation in this study and for at least 2 months after the last dose of the study drug. Willing and able to provide informed consent Exclusion Criteria: History of hypersensitivity, intolerance, or allergy to opioids Surgical procedures in the last 4 weeks or plans to undergo surgical procedures during the study period Untreated moderate to severe sleep apnea Chronic migraines as the primary pain condition Cancer related pain

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NKTR-181<br>NKTR-181 twice daily (BID) tablets | Drug: NKTR-181 BID tablets<br>* NKTR-181 tablets 100-600 mg twice daily (BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Adverse Events | Count of subjects reporting treatment emergent adverse events | Screening baseline through end of study, an average of 57 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Brief Pain Inventory (BPI) Pain Intensity Item to Week 52 | A self-reported scale measuring severity of pain on function. The mean of the 4 intensity items (3-6) is calculated and used as a measure of pain severity. If there were missing items when the pain severity score was calculated, the mean of the completed items in one dimension (dimensions include pain severity and pain interference) were imputed to substitute the missing item, provided that more than 50% of the items in one dimension were completed (Halling, 1999). The range of pain intensity and interference for each question is from 0 to 10. The range of possible scores is from 0 to 70. Higher score indicates relatively worse pain severity and greater interference that pain causes in day to day activities. | Baseline, monthly change from baseline till the end of study | 
| Change From Baseline in Brief Pain Inventory (BPI) Pain Interference Item to Week 52 | A self-reported scale measuring interference of pain on function. The mean of the 7 interference items was calculated and used as a measure of Pain interference. If there were missing items when the pain interference score was calculated, the mean of the completed items in one dimension (dimensions include pain severity and pain interference) were imputed to substitute the missing item, provided that more than 50% of the items in one dimension were completed (Halling, 1999). The range of pain interference is from 0 to 10. Higher score indicates relatively worse pain problem. | Baseline, monthly change from baseline till the end of study |