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

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.