A multicenter, 12-month, open-label, single-arm safety study of oxycodone-hydrochloride/naltrexone-hydrochloride extended-release capsules (ALO-02) in patients with moderate-to-severe chronic noncancer pain

Samir Arora, MD; Beatrice Setnik, PhD; Michael Drass, MD; John D. Hudson, MD; Ray Clemmer, MS; Paul Meisner, PharmD; Glenn C. Pixton, MS; Veeraindar Goli, MD; Kenneth W. Sommerville, MD

doi:10.5055/jom.2014.0239

Authors

Samir Arora, MD
Beatrice Setnik, PhD
Michael Drass, MD
John D. Hudson, MD
Ray Clemmer, MS
Paul Meisner, PharmD
Glenn C. Pixton, MS
Veeraindar Goli, MD
Kenneth W. Sommerville, MD

DOI:

https://doi.org/10.5055/jom.2014.0239

Keywords:

opioids, oxycodone, naltrexone, safety, withdrawal, abuse-deterrent

Abstract

Objective: To evaluate the long-term safety of oxycodone-hydrochloride and sequestered naltrexone-hydrochloride (ALO-02) administered for up to 12 months.

Design: Open-label, single-arm safety study.

Setting: Thirty-two US research centers (ClinicalTrials.gov identifier NCT01428583).

Patients: Three hundred ninety-five adults (opioid experienced and opioid naïve) with moderate-to-severe chronic noncancer pain (CNCP).

Interventions: Open-label, oral ALO-02 capsules, daily dose ranging from 20 to 160 mg oxycodone for up to 12 months.

Main outcome measures: Number and type of adverse events (AEs) and drug-related AEs, including assessments of withdrawal (Clinical Opiate Withdrawal Scale; COWS), pharmacokinetics, efficacy, and aberrant behaviors (Current Opioid Misuse Measure).

Results: A total of 193 (48.9 percent) patients received ALO-02 for ≥181 days and 105 (26.6 percent) patients for ≥361 days. The most common treatment-emergent AEs were nausea (25.3 percent), constipation (21.3 percent), vomiting (13.9 percent), and headache (11.6 percent). The most common drug-related AEs were constipation (18.0 percent), nausea (14.9 percent), somnolence (8.4 percent), fatigue (6.8 percent), dizziness (5.6 percent), and vomiting (5.1 percent). A majority of patients (86.6 percent) had a maximum COWS total score below the level for mild withdrawal symptoms at every visit throughout the study. Pain severity scores as measured by the short Form of the Brief Pain Inventory (BPI-SF) decreased over time.

Conclusions: Repeat dosing of ALO-02 for up to 12 months is safe and well tolerated in a CNCP population of both opioid-experienced and opioid-naïve patients. ALO-02 demonstrated a safety profile consistent with extended-release opioids and the expected analgesic efficacy. The addition of sequestered naltrexone had no significant clinical effect on patients when taken as directed.

Author Biographies

Samir Arora, MD

Columbus Clinical Research, Columbus, Ohio.

Beatrice Setnik, PhD

Pfizer Inc., Durham, North Carolina.

Michael Drass, MD

Allegheny Pain Management, Altoona, Pennsylvania.

John D. Hudson, MD

Future Search Trials of Neurology, Austin, Texas.

Ray Clemmer, MS

Pfizer Inc., Groton, Connecticut.

Paul Meisner, PharmD

Pfizer Inc., Durham, North Carolina.

Glenn C. Pixton, MS

Pfizer Inc., Durham, North Carolina.

Veeraindar Goli, MD

Pfizer Inc., Durham, North Carolina; Duke University Medical Center, Durham, North Carolina.

Kenneth W. Sommerville, MD

Pfizer Inc., Durham, North Carolina; Duke University Medical Center, Durham, North Carolina.

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