Safety and efficacy of oxycodone/naloxone vs. oxycodone vs. morphine in the treatment of chronic low back pain - a 12-week prospective (optionally randomized) open-label blinded endpoint streamlinded study with prolonged-release preparations (PROBE)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  MORPHINE

  OXYCODONE

  NALOXONE HYDROCHLORIDE DIHYDRATE
• Medical condition to be studied:
  Back pain

Population studied

• Short description of the study population:
  Males and nonpregnant, nonlactating females who were at least 18 years, with a documented history of moderate to severe, nonmalignant chronic lower back pain, previously treated with WHO step I or II analgesics with or without adjuvant treatments, who experienced either insufficient pain relief and/or unacceptable side effects and who required an around-the-clock therapy with any of the three mentioned WHO step III opioids.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)
• Special population of interest:
  Other
• Special population of interest, other:
  Patients with chronic low back pain
• Estimated number of subjects:
  900

Study design details

• Main study objective:
  To demonstrate (a) the superiority of OXN vs. OXY vs. MOR with respect to OIC, and (b) the non-inferiority of OXN vs. OXY vs. MOR with respect to its analgesic efficacy under real-life conditions.
• Outcomes:
  Percentage of patients, who (a) completed the whole 12-week treatment period without any treatment emergent adverse event related premature study discontinuation, who in addition showed (b) at least a 50% relief with respect to each: pain intensity, functionality and quality-of-life, as well as (c) a maximum BFI worsening of 50% vs. baseline. Efficacy: absolute and relative (percent vs. baseline) change in (a) LBP intensity, (b) pain-related disabilities in daily life, and (c) quality-of-life impairments by pain.Tolerability: percentages of patients with (a) normal BFI scores (≤28.8), (b) a ≥1 decline in the number of CSBMs per week, and (c) ≥4 CSBMs per week, each at the end of the 12-week observation period.
• Data analysis plan:
  Data analyses will be performed for the intent-to-treat (ITT) population, which consists of all enrolled patients, who took at least one dose of study medication and who had at least one post-baseline/post-dose measure. Sample size estimations, performed prior to this study resulted in a required number of 133 valid patients in each treatment group, providing a 90% power to conclude the superiority of OXN vs OXY vs. MOR with respect to the combined endpoint, assuming an anticipated responder rate of 25% for OXN, a treatment difference of 15%, and a two-sided Type I error of 5%. Assuming a dropout rate after randomization of ~10%, and a ~50% rejection of the randomized treatment recommendation, a total of 300 subjects per treatment group have to be enrolled to ensure a patient number of ~130 evaluable patients per ITT group.