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A 2-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase III trial comparing the efficacy of oxymorphone extended release and placebo in adults with pain associated with osteoarthritis of the hip or knee.
Clin Ther 2006; 28(3):352-64CT

Abstract

BACKGROUND

Oxymorphone extended release (ER) is a tablet formulation of the mu-opioid agonist oxymorphone designed to achieve a low peak-to-trough fluctuation in plasma concentrations over a 12-hour dosing period.

OBJECTIVE

This study compared the analgesic efficacy, dose response, and tolerability of 3 doses of oxymorphone ER given every 12 hours with those of placebo in patients with pain related to osteoarthritis (OA) of the hip or knee.

METHODS

This was a 2-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, Phase III trial. Patients with OA of the hip or knee who were receiving an opioid medication for chronic, moderate to severe pain or who were judged by the investigator to have received suboptimal analgesia with nonopioid analgesics entered a 2- to 7-day washout of analgesic medication. When pain in the index joint was >40 mm on a 100-mm visual analog scale (VAS), patients were randomized to receive 1 of 4 regimens: oxymorphone ER 10 mg q12h during weeks 1 and 2; oxymorphone ER 20 mg q12h in week 1 and 40 mg q12h in week 2; oxymorphone ER 20 mg q12h in week 1 and 50 mg q12h in week 2; or placebo q12h during weeks 1 and 2. The primary end point was the change in VAS score for arthritis pain intensity. Other assessments included the Western Ontario and McMaster Universities (WOMAC) OA Index subscales for pain, stiffness, and physical function and the composite index; the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) physical health component summary (PCS) score; the Chronic Pain Sleep Inventory (CPSI) score; vital signs; clinical laboratory parameters; and adverse events (AEs). AEs were recorded at each clinic visit.

RESULTS

Three hundred seventy patients were randomized to treatment (95 oxymorphone ER 10 mg, 93 oxymorphone ER 40 mg, 91 oxymorphone ER 50 mg, and 91 placebo), and 198 completed the study. Least squares mean changes from baseline in the VAS arthritis pain intensity score were -21, -28, -29, and -17 mm in the oxymorphone ER 10, 40, and 50 mg and placebo groups, respectively (P = 0.002, modified Tukey linear trend test). Oxymorphone ER 40 and 50 mg produced significant improvements from baseline compared with placebo in the WOMAC subscale scores for pain (least squares mean change: -85.1, -108.0, and -42.5, respectively; P < or = 0.025 for 40 mg, P < or = 0.001 for 50 mg), stiffness (-40.5, -48.1, and -17.0; both, P < or = 0.001), and physical function (-256.8, -310.8, and -116.5; P < or = 0.01 and P < or = 0.001, respectively); the SF-36 PCS score (4.6, 3.6, and -0.1; P < 0.001); and the CPSI score (-21.2, -22.2, and -10.7; P < 0.05). The 10-mg dose also was associated with significant improvements compared with placebo in the WOMAC pain (-83.6; P < or = 0.025) and physical function subscales (-232.9; P < or = 0.025) and the SF-36 PCS score (3.9; P < 0.001). The most frequently reported AEs (> or =5% of patients) in the oxymorphone ER groups were nausea (39.4%), vomiting (23.7%), dizziness (22.6%), constipation (22.2%), somnolence (17.6%), pruritus (16.5%), and headache (15.0%). The majority of AEs with oxymorphone ER were mild or moderate in intensity. Three serious AEs (urinary retention, central nervous system depression, and pancreatitis) were considered possibly or probably related to study medication.

CONCLUSION

In these patients with chronic, moderate to severe pain related to OA of the hip or knee, oxymorphone ER administered twice daily for 2 weeks produced dose-related reductions in arthritis pain intensity and improvements in physical function.

Authors+Show Affiliations

Altoona Center for Clinical Research, Duncansville, Pennsylvania, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16750450

Citation

Kivitz, Alan, et al. "A 2-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging, Phase III Trial Comparing the Efficacy of Oxymorphone Extended Release and Placebo in Adults With Pain Associated With Osteoarthritis of the Hip or Knee." Clinical Therapeutics, vol. 28, no. 3, 2006, pp. 352-64.
Kivitz A, Ma C, Ahdieh H, et al. A 2-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase III trial comparing the efficacy of oxymorphone extended release and placebo in adults with pain associated with osteoarthritis of the hip or knee. Clin Ther. 2006;28(3):352-64.
Kivitz, A., Ma, C., Ahdieh, H., & Galer, B. S. (2006). A 2-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase III trial comparing the efficacy of oxymorphone extended release and placebo in adults with pain associated with osteoarthritis of the hip or knee. Clinical Therapeutics, 28(3), pp. 352-64.
Kivitz A, et al. A 2-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging, Phase III Trial Comparing the Efficacy of Oxymorphone Extended Release and Placebo in Adults With Pain Associated With Osteoarthritis of the Hip or Knee. Clin Ther. 2006;28(3):352-64. PubMed PMID: 16750450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A 2-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase III trial comparing the efficacy of oxymorphone extended release and placebo in adults with pain associated with osteoarthritis of the hip or knee. AU - Kivitz,Alan, AU - Ma,Carl, AU - Ahdieh,Harry, AU - Galer,Bradley S, PY - 2006/01/23/accepted PY - 2006/6/6/pubmed PY - 2006/7/11/medline PY - 2006/6/6/entrez SP - 352 EP - 64 JF - Clinical therapeutics JO - Clin Ther VL - 28 IS - 3 N2 - BACKGROUND: Oxymorphone extended release (ER) is a tablet formulation of the mu-opioid agonist oxymorphone designed to achieve a low peak-to-trough fluctuation in plasma concentrations over a 12-hour dosing period. OBJECTIVE: This study compared the analgesic efficacy, dose response, and tolerability of 3 doses of oxymorphone ER given every 12 hours with those of placebo in patients with pain related to osteoarthritis (OA) of the hip or knee. METHODS: This was a 2-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, Phase III trial. Patients with OA of the hip or knee who were receiving an opioid medication for chronic, moderate to severe pain or who were judged by the investigator to have received suboptimal analgesia with nonopioid analgesics entered a 2- to 7-day washout of analgesic medication. When pain in the index joint was >40 mm on a 100-mm visual analog scale (VAS), patients were randomized to receive 1 of 4 regimens: oxymorphone ER 10 mg q12h during weeks 1 and 2; oxymorphone ER 20 mg q12h in week 1 and 40 mg q12h in week 2; oxymorphone ER 20 mg q12h in week 1 and 50 mg q12h in week 2; or placebo q12h during weeks 1 and 2. The primary end point was the change in VAS score for arthritis pain intensity. Other assessments included the Western Ontario and McMaster Universities (WOMAC) OA Index subscales for pain, stiffness, and physical function and the composite index; the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) physical health component summary (PCS) score; the Chronic Pain Sleep Inventory (CPSI) score; vital signs; clinical laboratory parameters; and adverse events (AEs). AEs were recorded at each clinic visit. RESULTS: Three hundred seventy patients were randomized to treatment (95 oxymorphone ER 10 mg, 93 oxymorphone ER 40 mg, 91 oxymorphone ER 50 mg, and 91 placebo), and 198 completed the study. Least squares mean changes from baseline in the VAS arthritis pain intensity score were -21, -28, -29, and -17 mm in the oxymorphone ER 10, 40, and 50 mg and placebo groups, respectively (P = 0.002, modified Tukey linear trend test). Oxymorphone ER 40 and 50 mg produced significant improvements from baseline compared with placebo in the WOMAC subscale scores for pain (least squares mean change: -85.1, -108.0, and -42.5, respectively; P < or = 0.025 for 40 mg, P < or = 0.001 for 50 mg), stiffness (-40.5, -48.1, and -17.0; both, P < or = 0.001), and physical function (-256.8, -310.8, and -116.5; P < or = 0.01 and P < or = 0.001, respectively); the SF-36 PCS score (4.6, 3.6, and -0.1; P < 0.001); and the CPSI score (-21.2, -22.2, and -10.7; P < 0.05). The 10-mg dose also was associated with significant improvements compared with placebo in the WOMAC pain (-83.6; P < or = 0.025) and physical function subscales (-232.9; P < or = 0.025) and the SF-36 PCS score (3.9; P < 0.001). The most frequently reported AEs (> or =5% of patients) in the oxymorphone ER groups were nausea (39.4%), vomiting (23.7%), dizziness (22.6%), constipation (22.2%), somnolence (17.6%), pruritus (16.5%), and headache (15.0%). The majority of AEs with oxymorphone ER were mild or moderate in intensity. Three serious AEs (urinary retention, central nervous system depression, and pancreatitis) were considered possibly or probably related to study medication. CONCLUSION: In these patients with chronic, moderate to severe pain related to OA of the hip or knee, oxymorphone ER administered twice daily for 2 weeks produced dose-related reductions in arthritis pain intensity and improvements in physical function. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/16750450/A_2_week_multicenter_randomized_double_blind_placebo_controlled_dose_ranging_phase_III_trial_comparing_the_efficacy_of_oxymorphone_extended_release_and_placebo_in_adults_with_pain_associated_with_osteoarthritis_of_the_hip_or_knee_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(06)00073-7 DB - PRIME DP - Unbound Medicine ER -