Safety and efficacy of once-daily hydromorphone extended-release versus twice-daily oxycodone hydrochloride controlled-release in chinese patients with cancer pain: a phase 3, randomized, double-blind, multicenter study.
Noninferiority of the efficacy of once-daily hydromorphone hydrochloride extended-release (hydromorphone ER) compared with twice-daily oxycodone hydrochloride controlled-release (oxycodone CR) was investigated in this randomized, double-blind study in Chinese patients with moderate to severe cancer pain requiring strong oral opioid analgesics. Randomization (1:1) to hydromorphone ER (8-32 mg) or oxycodone CR (10-40 mg) was followed by dose titration (up to 8 days) and dose maintenance (28 days, weekly visits). Primary endpoint was change from baseline to end of study in "worst pain in the past 24 hours" of Brief Pain Inventory (Short Form) score on last observation carried forward (per protocol set). A total of 137 of 260 randomized patients completed maintenance phase (hydromorphone ER: n = 70; oxycodone CR: n = 67); per protocol set: 81 patients. Mean age was 53.1 years (range: 18-70 years; males: 65.3%); most common Eastern Cooperative Oncology Group performance status = 2. Least square mean difference between 2 treatment groups for primary endpoint using analysis of covariance (baseline score, covariate) was -.1 (95% confidence interval: -1.3, 1.1), with upper bound of 95% confidence interval <1.5 (predefined noninferiority margin). Most common reason for deaths was disease progression (hydromorphone ER: 6.3%; oxycodone CR: 12.7%). Treatment-emergent adverse events were comparable between treatment groups. Hydromorphone ER was noninferior to oxycodone CR in alleviating cancer pain and was well tolerated.


CONCLUSIONS
This article demonstrates clinical noninferiority of the efficacy of once-daily hydromorphone ER compared with twice-daily oxycodone CR in alleviating cancer pain in Chinese patients, with comparable safety profiles between the 2 treatment groups. Thus, a treatment option with the potential for a reduced dosing frequency exists for health care providers and patients.
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, China.
Shiying
S
Yu
Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wei
W
Shen
Xi'an Janssen Pharmaceutical Company, Beijing, China. Electronic address: lyu13@its.jnj.com.
Lu
L
Yu
Xi'an Janssen Pharmaceutical Company, Beijing, China.
Yanyan
Y
Hou
Janssen Research & Development, LLC, Raritan, New Jersey.
John
J
Han
Janssen Research & Development, LLC, Raritan, New Jersey.
Henry M
HM
Richards
D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D002681:China; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D010098:Oxycodone / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D018401:Sample Size; D016896:Treatment Outcome; D055815:Young Adult
D000701:Analgesics, Opioid; D010098:Oxycodone; D004091:Hydromorphone
Brief Pain Inventory; cancer pain; hydromorphone extended-release; oxycodone; strong opioids