A Phase IIb/III, Double-Blind, Placebo-Controlled, Randomized Study Investigating the Safety, Tolerability and Efficacy of Flupirtine as Adjunct to Opioids When Administered to Cancer Subjects Who Are Experiencing Pain With Neuropathic Features

INTERVENTION: Trade Name: Katadolon 100mg, Hartkapsel Pharmaceutical Form: Capsule, hard INN or Proposed INN: FLUPIRTINE MALEATE CAS Number: 75507‐68‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Pain with neuropathic features in cancer subjects which is inadequately controlled despite optimized opioid treatment ; MedDRA version: 14.0 Level: LLT Classification code 10045158 Term: Tumor pain System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Symptoms and general pathology [C23] PRIMARY OUTCOME: Main Objective: The primary objective of this study is to explore the overall analgesic efficacy of flupirtine administered in combination with opioids for a period of 5 weeks. Primary end point(s): Change in the 11‐point Likert scale for average daily pain from the baseline mean pain score (the mean of non‐missing daily diary entries for average pain during the 7 days before randomization) to the final mean pain score (the mean of last 7 daily diary entries for average pain during the Treatment Period) Secondary Objective: Secondary objectives of this study are to:; ‐ Investigate the safety and tolerability of flupirtine administered in combination with opioids; ; ‐ Investigate the efficacy of flupirtine using various secondary measures of efficacy. ; Timepoint(s) of evaluation of this end point: Day 36 visit SECONDARY OUTCOME: Secondary end point(s): ‐ Percentage of subjects achieving at least 30% improvement from baseline based on the primary efficacy endpoint;; ‐ Physician and Subject Global Assessment of study drug;; ‐ Change in the 11‐point Likert scale from the baseline mean pain score to the mean pain score during each week of the Treatment Period; ; ‐ Percentage of subjects achieving pre‐specified pain reduction thresholds (e.g., 20% to 100%); and; ‐ Opioid consumption, BPI (short‐form), average pain the past 24 hours, least pain in past 24 hours, and worst pain in past 24 hours.; Timepoint(s) of evaluation of this end point: Day 36 visit INCLUSION CRITERIA: 1. Presence of a solid neoplasm and between the ages of 18 and 65 years, inclusive 2. Able to understand written and verbal communication in the primary language of the country in which the study is being undertaken 3. Life expectancy a minimum of 3 months with Karnofsky score =50 at the Screening Visit (Day ‐7) 4. History of daily pain attributable to cancer and requiring treatment with strong opioids for at least 3 months duration 5. Pain with neuropathic characteristics that include one or more of the following: throbbing, shooting, stabbing, sharp, cramping, gnawing, hot‐burning, aching, heavy, tender, splitting, tiring‐exhausting, sickening, fearful, punishing‐cruel, electric‐shock, cold‐freezing, piercing, caused by light touch, itching, tingling or ‘pins and needles’, or numbness. 6. Pain inadequately relieved despite active management including strong opioids 7. Currently taking morphine, oxycodone, hydromorphone, buprenorphine, or tra