Study Procedures

Subjects underwent examinations at the study center during the screening visit (days −6 to −3), at the beginning of each treatment episode (days 1, 15, 29, and 43), at the end of the last treatment episode (day 57), and at the follow-up visit (days 60 to 68).

Baseline neuropathic pain intensity was assessed using an 11-point NRS during the screening visit, at day −2, day −1, day 0, and during hospital visit at day 1 (prior to the first IMP intake), and was defined as the median of these five values. After the first IMP intake, a daily assessment of neuropathic pain using the 11-point NRS, of adverse events, and of analgesic co-medication were conducted by the patients and documented in a diary. A clinically relevant analgesic effect was defined for a particular treatment episode if pain was reduced by at least 30% or two scale units comparing baseline neuropathic pain intensity and the median NRS values of the last 5 days of the respective treatment episode (Frampton and Hughes-Webb, 2011; Haanpää et al., 2011).

Additional procedures in the study center included assessment of the painDETECT questionnaire (Freynhagen et al., 2006a), a patient-reported classification instrument to identify the neuropathic component of pain without clinical examination. The questionnaire includes seven items on sensory symptoms, one item about pain course pattern and one item about the presence of radiating pain. The total score ranges from −1 to 38 points, whereby scores of <13 were considered to indicate unlikely, 13–18 uncertain, and >18 likely presence of neuropathic pain (Baron et al., 2017). Furthermore, we assessed quality of life (QOL) using the 12-item Short Form Health Survey [SF-12v2 (Morfeld et al., 2011)] and anxiety and depression using the Hospital Anxiety and Depression Scale - German version (HADS-D) scale (Hermann-Lingen et al., 2011). These procedures were performed at screening visit, day 1, day 15, day 29, day 43, day 57, and follow-up visit. ECG, safety lab, and vital signs were analyzed at screening visit, day 1, day 15, day 29, day 43, and follow-up visit. Physical examinations were conducted at screening visit and follow-up visit.