A Phase 2 Study To Assess The Efficacy, Tolerability, And Safety OF NKTR-181 In Subjects With Chronic OA Knee Pain

Study Overview
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Brief Summary
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NKTR-181 is being developed as an analgesic compound for the treatment of moderate to severe chronic pain - active as a mu agonist, but with inherent molecular properties designed to provide a unique clinical profile, including most notably, reduced CNS side effects and an attenuated attractiveness as a target of abuse.

Official Title
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A Phase 2, Enriched-Enrollment, Randomized-Withdrawal, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy, Tolerability, and Safety of NKTR-181 in Opioid-Naïve Subjects With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee

Conditions
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Osteoarthritis of the Knee

Intervention / Treatment
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* Drug: NKTR-181
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to give written informed consent; Willing and able to understand the study procedures, and comply with all study procedures; Females or males, age ≥ 18 years old; Body mass index 18-39, inclusive; In good general health; Clinical diagnosis of OA in one or both knees; Have been on a stable regimen of pain medication for the management of OA knee pain; Not experiencing adequate pain relief with their current dosing regimen; Women of childbearing potential (WCBP) must agree to use highly effective methods of birth control. Male subjects must agree to use contraception. Exclusion Criteria: Females who are pregnant or lactating; Known history of hypersensitivity, intolerance, or allergy to opioids; Diagnosed as having any chronic pain symptom that in the Investigator's opinion would interfere with the assessment of pain and other symptoms of OA; Presence of any medical condition that would preclude study participation in the opinion of the investigator; Clinically significant abnormalities of vital signs or clinical laboratory results; Clinically significant electrocardiographic abnormalities; Received systemic corticosteroids within 30 days prior to signing the consent form; Subjects who are known or suspected to be currently abusing alcohol or drugs; Positive urine drug screen, or alcohol breath test during Screening Period testing; Positive serology for the surface antigen of Hepatitis B (HBsAg) or Hepatitis C (anti-HCV) during Screening Period testing; Known to be human immunodeficiency virus (HIV) positive; Donation of blood or plasma within 30 days prior to signing the consent form; Participation in another drug or biologic study within 30 days prior to signing the consent form; Any other reason that, in the opinion of the Investigator or Medical Monitor, would render the subject unsuitable for participation in the study.

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: 100 mg NKTR-181<br>100 mg of NKTR-181 in tablet form, BID. Dosing to occur at Titration period up to 30 days and at Randomization period up to 24 days. | Drug: NKTR-181<br> <br> |
| Experimental: 200 mg NKTR-181<br>200 mg of NKTR-181 in tablet form, BID. Dosing to occur at Titration period up to 30 days and at Randomization period up to 24 days. | Drug: NKTR-181<br> <br> |
| Experimental: 300 mg NKTR-181<br>300 mg of NKTR-181 in tablet form, BID. Dosing to occur at Titration period up to 30 days and at Randomization period up to 24 days | Drug: NKTR-181<br> <br> |
| Experimental: 400 mg NKTR-181<br>400 mg of NKTR-181 in tablet form, BID. Dosing to occur at Titration period up to 30 days and at Randomization period up to 24 days | Drug: NKTR-181<br> <br> |
| Placebo Comparator: Placebo<br>Placebo dosing will be only in the double-blind randomization arm and will be identical in form to the Experimental NKTR-181. | Drug: Placebo<br>* Placebo dosing will be only in the double-blind randomization arm and will be identical in form to the Experimental NKTR-181<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Mean Change From Baseline Pain Score to Pain Score at the End of the Double-blind Randomized Treatment Period. | The first phase of this trial involved an open-label titration period where patients were given NKTR-181 at increasing doses up to a maximum of 400 mg twice daily until adequate pain control was achieved. Patients achieving adequate pain control were then progressed to the second phase of the trial where patients were randomized in a 1:1 ratio to receive either placebo or their tolerable dose level of NKTR-181. All efficacy data for NKTR-181 patients was combined into one group regardless of tolerable dose level. For this outcome, the subjects had to rate their worst pain intensity during the past 4 hours from 0 to 10 on an 11-point scale, where 0 represented one end of the continuum (i.e., no pain) and 10 represented the other extreme of pain intensity (i.e., worst pain imaginable). | Baseline and Visit 10 (day 69) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Discontinuation During the Double-blind Randomized Treatment Period for Any Reason | The first phase of this trial involved an open-label titration period where patients were given NKTR-181 at increasing doses up to a maximum of 400 mg twice daily until adequate pain control was achieved. Patients achieving adequate pain control were then progressed to the second phase of the trial where patients were randomized in a 1:1 ratio to receive either placebo or their tolerable dose level of NKTR-181. All efficacy data for NKTR-181 patients was combined into one group regardless of tolerable dose level. | Randomization Treatment period is 24 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nektar, NKTR-181