Thomas Barrett1, Kenneth Kostenbader2, Srinivas Nalamachu3, Michael Giuliani4, Jim L Young5. 1. Clinical Research, Mallinckrodt Pharmaceuticals, Hazelwood, Missouri, U.S.A. 2. Mallinckrodt Pharmaceuticals, Hazelwood, Missouri, U.S.A. 3. International Clinical Research Institute, Overland Park, Kansas, U.S.A. 4. Research and Development, Mallinckrodt Pharmaceuticals, Hazelwood, Missouri, U.S.A. 5. Clinical Affairs & Program Management, Research and Development, Mallinckrodt Pharmaceuticals, Hazelwood, Missouri, U.S.A.
Abstract
OBJECTIVES: To characterize the safety of immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP). METHODS: Data were assessed from 9 phase 1 trials in healthy volunteers and recreational users of prescription opioids (N = 405), including 5 single-dose and 3 multidose open-label pharmacokinetic studies of IR/ER OC/APAP and active comparators; and 1 randomized, controlled, single-dose human abuse potential (HAP) study comparingIR/ER OC/APAP, IR OC/APAP, and placebo in recreational users of opioids; and 2 phase 3 trials (N = 701) including a 48-hour placebo-controlled safety and efficacy study in patients with moderate to severe postbunionectomy pain with a 14-day open-label safety extension and a long-term (≤ 35 days) open-label safety study in patients with chronic osteoarthritis pain or chronic low back pain. RESULTS: Adverse events (AEs) experienced by ≥ 10% of participants receiving IR/ER OC/APAP in all trials were pruritus, nausea, vomiting, dizziness, headache, and somnolence; these AEs occurred with similar frequency for equianalgesic doses of IR OC/APAP and IR OC but less frequently for IR tramadol HCl/APAP. In the HAP study, crushing IR/ER or IR OC/APAP tablets did not increase frequency of AEs. Constipation was experienced by < 10% of participants receiving IR/ER OC/APAP. No serious (SAE) or severe AEs were reported in phase 1 trials. In phase 3 trials of 8 reported SAEs, only 1 treatment-related SAE (hypersensitivity to placebo) required treatment discontinuation. No clinically meaningful changes in vital signs, oxygen saturation, electrocardiograms, or laboratory values were reported. CONCLUSIONS:Safety and tolerability of IR/ER OC/APAP are similar to other low-dose opioid/APAP analgesics.
RCT Entities:
OBJECTIVES: To characterize the safety of immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP). METHODS: Data were assessed from 9 phase 1 trials in healthy volunteers and recreational users of prescription opioids (N = 405), including 5 single-dose and 3 multidose open-label pharmacokinetic studies of IR/ER OC/APAP and active comparators; and 1 randomized, controlled, single-dose human abuse potential (HAP) study comparing IR/ER OC/APAP, IR OC/APAP, and placebo in recreational users of opioids; and 2 phase 3 trials (N = 701) including a 48-hour placebo-controlled safety and efficacy study in patients with moderate to severe postbunionectomy pain with a 14-day open-label safety extension and a long-term (≤ 35 days) open-label safety study in patients with chronic osteoarthritis pain or chronic low back pain. RESULTS: Adverse events (AEs) experienced by ≥ 10% of participants receiving IR/ER OC/APAP in all trials were pruritus, nausea, vomiting, dizziness, headache, and somnolence; these AEs occurred with similar frequency for equianalgesic doses of IR OC/APAP and IR OC but less frequently for IR tramadolHCl/APAP. In the HAP study, crushing IR/ER or IR OC/APAP tablets did not increase frequency of AEs. Constipation was experienced by < 10% of participants receiving IR/ER OC/APAP. No serious (SAE) or severe AEs were reported in phase 1 trials. In phase 3 trials of 8 reported SAEs, only 1 treatment-related SAE (hypersensitivity to placebo) required treatment discontinuation. No clinically meaningful changes in vital signs, oxygen saturation, electrocardiograms, or laboratory values were reported. CONCLUSIONS: Safety and tolerability of IR/ER OC/APAP are similar to other low-dose opioid/APAP analgesics.