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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 296
- 试验地点
- 32
- 主要终点
- The Mean Change From Baseline Pain Score to Pain Score at the End of the Double-blind Randomized Treatment Period.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
100 mg NKTR-181
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.
干预措施: NKTR-181 (Drug)
200 mg NKTR-181
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.
干预措施: NKTR-181 (Drug)
300 mg NKTR-181
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
干预措施: NKTR-181 (Drug)
400 mg NKTR-181
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
干预措施: NKTR-181 (Drug)
Placebo
Placebo dosing will be only in the double-blind randomization arm and will be identical in form to the Experimental NKTR-181.
干预措施: Placebo (Drug)
结局指标
主要结局
The Mean Change From Baseline Pain Score to Pain Score at the End of the Double-blind Randomized Treatment Period.
时间窗: Baseline and Visit 10 (day 69)
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).
次要结局
- Time to Discontinuation During the Double-blind Randomized Treatment Period for Any Reason(Randomization Treatment period is 24 days)