纳地美定治疗接受阿片类药物治疗的慢性非癌性疼痛患者阿片类药物引起的便秘的安全性和有效性的肾功能损害亚组分析。
A Renal Impairment Subgroup Analysis of the Safety and Efficacy of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain Receiving Opioid Therapy.
作者信息
Webster Lynn R, Hale Martin E, Yamada Tadaaki, Wild James E
机构信息
PRA Health Sciences, Salt Lake City, UT, USA.
Gold Coast Research LLC, Plantation, FL, USA.
出版信息
J Pain Res. 2020 Mar 24;13:605-612. doi: 10.2147/JPR.S237833. eCollection 2020.
PURPOSE
Naldemedine, an oral, peripherally acting μ-opioid receptor antagonist approved for the treatment of opioid-induced constipation (OIC), is renally excreted. This subgroup analysis integrated data from 3 Phase 3 trials (COMPOSE-1, COMPOSE-2, COMPOSE-3) to evaluate the safety and efficacy of naldemedine in patients with renal impairment (RI).
PATIENTS AND METHODS
Patients age 18-80 years with chronic non-cancer pain (CNCP) and OIC received oral naldemedine 0.2 mg or placebo once daily. RI subgroups consisted of patients with normal function (baseline glomerular filtration rate ≥90 mL/min/1.73 m), mild (≥60 to <90 mL/min/1.73 m), and moderate (≥30 to <60 mL/min/1.73 m) RI. Safety assessments based on ≤12 weeks of treatment from all 3 studies included incidence of treatment-emergent adverse events (TEAEs). Efficacy was based on the proportion of responders in COMPOSE-1 and COMPOSE-2 only, defined as ≥3 spontaneous bowel movements (SBMs)/week and a ≥1-SBM/week increase from baseline for ≥9 of 12 weeks and ≥3 of the last 4 weeks.
RESULTS
In total, 2328 patients were included in this analysis. The incidence of TEAEs was similar in the naldemedine and placebo groups (overall, 47.1% vs 45.6%; normal, 44.6% vs 43.6%; mild RI, 49.0% vs 44.7%; moderate RI, 46.6% vs 55.9%). GI-related TEAEs occurred more frequently in the naldemedine group versus placebo (overall, 21.8% vs 13.8%; normal, 21.6% vs 12.5%; mild RI, 22.6% vs 14.7%; moderate RI, 18.0% vs 14.2%). A significantly greater proportion of patients in the naldemedine 0.2 mg group were responders versus the placebo group (overall, 50.1% vs 34.1%, <0.0001; normal, 52.0% vs 39.3%; mild RI, 48.3% vs 30.3%; moderate RI, 52.5% vs 31.7%).
CONCLUSION
This integrated analysis confirmed that OIC treatment with naldemedine 0.2 mg was generally well tolerated and effective in patients with CNCP and mild or moderate RI. Safety and efficacy results were consistent with the overall population.
CLINICALTRIALSGOV REGISTRATION
COMPOSE-1: NCT01965158; COMPOSE-2: NCT01993940; COMPOSE-3: NCT01965652.
目的
纳洛酮是一种口服的外周作用μ-阿片受体拮抗剂，已被批准用于治疗阿片类药物引起的便秘（OIC），经肾脏排泄。该亚组分析整合了3项3期试验（COMPOSE - 1、COMPOSE - 2、COMPOSE - 3）的数据，以评估纳洛酮在肾功能损害（RI）患者中的安全性和有效性。
患者和方法
年龄在18 - 80岁、患有慢性非癌性疼痛（CNCP）和OIC的患者每天口服0.2 mg纳洛酮或安慰剂一次。RI亚组包括功能正常（基线肾小球滤过率≥90 mL/min/1.73 m²）、轻度（≥60至<90 mL/min/1.73 m²）和中度（≥30至<60 mL/min/1.73 m²）RI的患者。基于所有3项研究≤12周治疗期的安全性评估包括治疗中出现的不良事件（TEAE）发生率。疗效仅基于COMPOSE - 1和COMPOSE - 2中反应者的比例，定义为每周≥3次自主排便（SBM），且在12周中的≥9周以及最后4周中的≥3周内较基线每周增加≥1次SBM。
结果
本分析共纳入2328例患者。纳洛酮组和安慰剂组的TEAE发生率相似（总体，47.1%对45.6%；正常，44.6%对43.6%；轻度RI，49.0%对44.7%；中度RI，46.6%对55.9%）。与安慰剂相比，纳洛酮组胃肠道相关TEAE的发生频率更高（总体，21.8%对13.8%；正常，21.6%对12.5%；轻度RI，22.6%对14.7%；中度RI，18.0%对14.2%）。0.2 mg纳洛酮组中反应者的比例显著高于安慰剂组（总体，50.1%对34.1%，P<0.0001；正常，52.0%对39.3%；轻度RI，48.3%对30.3%；中度RI，52.5%对31.7%）。
结论
该综合分析证实，0.2 mg纳洛酮治疗OIC在患有CNCP以及轻度或中度RI的患者中总体耐受性良好且有效。安全性和有效性结果与总体人群一致。
临床试验注册
COMPOSE - 1：NCT01965158；COMPOSE - 2：NCT01993940；COMPOSE - 3：NCT01965652。
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