Aron H Lichtman1, Eberhard Albert Lux2, Robert McQuade3, Sandro Rossetti3, Raymond Sanchez3, Wei Sun3, Stephen Wright4, Elena Kornyeyeva3, Marie T Fallon5. 1. Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA; Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia, USA. Electronic address: aron.lichtman@vcuhealth.org. 2. Faculty of Medicine, Witten/Herdecke University, Witten, Germany; Clinic for Pain and Palliative Care Medicine, St.-Marien-Hospital, Luenen, Germany. 3. Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA. 4. GW Pharmaceuticals Ltd, Cambridge, UK. 5. Edinburgh Cancer Research Centre, The University of Edinburgh, Edinburgh, UK.
Abstract
CONTEXT: Prior Phase 2/3 studies found that cannabinoids might provide adjunctive analgesia in advanced cancer patients with uncontrolled pain. OBJECTIVES: To assess adjunctive nabiximols (Sativex®), an extract of Cannabis sativa containing two potentially therapeutic cannabinoids (Δ9-tetrahydrocannabinol [27 mg/mL] and cannabidiol [25 mg/mL]), in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy. METHODS: Phase 3, double-blind, randomized, placebo-controlled trial in patients with advanced cancer and average painNumerical Rating Scale scores ≥4 and ≤8 despite optimized opioid therapy. Patients randomized to nabiximols (n = 199) or placebo (n = 198) self-titrated study medications over a two-week period, followed by a three-week treatment period at the titrated dose. RESULTS: Median percent improvements in average pain Numerical Rating Scale score from baseline to end of treatment in the nabiximols and placebo groups were 10.7% vs. 4.5% (P = 0.0854) in the intention-to-treat population (primary variable) and 15.5% vs. 6.3% (P = 0.0378) in the per-protocol population. Nabiximols was statistically superior to placebo on two of three quality-of-life instruments at Week 3 and on all three at Week 5. In exploratory post hoc analyses, U.S. patients, but not patients from the rest of the world, experienced significant benefits from nabiximols on multiple secondary endpoints. Possible contributing factors to differences in nabiximols efficacy include: 1) the U.S. participants received lower doses of opioids at baseline than the rest of the world and 2) the subgroups had different distribution of cancer pain types, which may have been related to differences in pathophysiology of pain. The safety profile of nabiximols was consistent with earlier studies. CONCLUSIONS: Although not superior to placebo on the primary efficacy endpoint, nabiximols had benefits on multiple secondary endpoints, particularly in the U.S. PATIENTS: Nabiximols might have utility in patients with advanced cancer who receive a lower opioid dose, such as individuals with early intolerance to opioid therapy.
RCT Entities:
CONTEXT: Prior Phase 2/3 studies found that cannabinoids might provide adjunctive analgesia in advanced cancerpatients with uncontrolled pain. OBJECTIVES: To assess adjunctive nabiximols (Sativex®), an extract of Cannabis sativa containing two potentially therapeutic cannabinoids (Δ9-tetrahydrocannabinol [27 mg/mL] and cannabidiol [25 mg/mL]), in advanced cancerpatients with chronic pain unalleviated by optimized opioid therapy. METHODS: Phase 3, double-blind, randomized, placebo-controlled trial in patients with advanced cancer and average pain Numerical Rating Scale scores ≥4 and ≤8 despite optimized opioid therapy. Patients randomized to nabiximols (n = 199) or placebo (n = 198) self-titrated study medications over a two-week period, followed by a three-week treatment period at the titrated dose. RESULTS: Median percent improvements in average pain Numerical Rating Scale score from baseline to end of treatment in the nabiximols and placebo groups were 10.7% vs. 4.5% (P = 0.0854) in the intention-to-treat population (primary variable) and 15.5% vs. 6.3% (P = 0.0378) in the per-protocol population. Nabiximols was statistically superior to placebo on two of three quality-of-life instruments at Week 3 and on all three at Week 5. In exploratory post hoc analyses, U.S. patients, but not patients from the rest of the world, experienced significant benefits from nabiximols on multiple secondary endpoints. Possible contributing factors to differences in nabiximols efficacy include: 1) the U.S. participants received lower doses of opioids at baseline than the rest of the world and 2) the subgroups had different distribution of cancer pain types, which may have been related to differences in pathophysiology of pain. The safety profile of nabiximols was consistent with earlier studies. CONCLUSIONS: Although not superior to placebo on the primary efficacy endpoint, nabiximols had benefits on multiple secondary endpoints, particularly in the U.S. PATIENTS: Nabiximols might have utility in patients with advanced cancer who receive a lower opioid dose, such as individuals with early intolerance to opioid therapy.
Authors: Julio A Yanes; Zach E McKinnell; Meredith A Reid; Jessica N Busler; Jesse S Michel; Melissa M Pangelinan; Matthew T Sutherland; Jarred W Younger; Raul Gonzalez; Jennifer L Robinson Journal: Exp Clin Psychopharmacol Date: 2019-05-23 Impact factor: 3.157