Björn Boße - Academia.edu (original) (raw)
Papers by Björn Boße
Movement Disorders, 2021
Background: Excessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's... more Background: Excessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's disease (PD) without approved treatment. THN102 is a novel combination drug of modafinil and low-dose flecainide. Objectives: To evaluate the safety and efficacy of THN102 in PD patients with EDS. Methods: Randomized, double-blind, placebo-controlled, cross-over trial testing two doses of THN102 (200mg/d modafinil with 2mg/d (200/2) or 18mg/d flecainide (200/18)) versus placebo; 75 patients were exposed to treatment. The primary endpoint was safety. The primary efficacy outcome was the change in Epworth Sleepiness Scale (ESS) score. Results: Both doses of THN102 were well tolerated. ESS significantly improved with THN102 200/2 (Least Square means versus placebo [95% CI]:-1.4 [-2.49;-0.31], p = 0.012) but did not change significantly with the 200/18 dosage. Conclusions: THN102 was well tolerated and showed a signal of efficacy at the 200/2 dose supporting further development for the treatment of EDS in PD.
Sleep Medicine, 2013
Introduction In severe cases of restless legs syndrome (RLS), symptoms result in bothersome impac... more Introduction In severe cases of restless legs syndrome (RLS), symptoms result in bothersome impact on sleep and impairment of daytime function. This study showed superior efficacy of oxycodone/naloxone prolonged-release fixed-combination (OXNPR) vs. placebo for the primary endpoint (International Restless Legs Syndrome Study Group Rating Scale (IRLS) total score) in severely affected RLS patients. The impact of RLS on sleep quality was assessed as a secondary endpoint. Materials and methods After screening and a 7-day washout, 304 patients (age 62iA11.2 years) with failed prior RLS therapy and an IRLS score iÝ21 were randomized to double- blind OXNPR bid (mean oxycodone dose 21.9iA15.0 mg/day) or placebo for 12 weeks. 197 patients participated in a 40-week open-label extension (mean oxycodone dose 18.1iA10.5 mg/day). Sleep was subjectively assessed by the Medical Outcomes Study (MOS) sleep scale, by item 4 of the IRLS (sleep disturbance due to RLS symptoms) and 4 questions of the RLS-6: Q1 (sleep satisfaction), Q2/3 (RLS symptom severity at falling asleep/during the night), and Q6 (daytime tiredness). Results MOS sleep scale results showed greater improvement in sleep quality for OXNPR vs. placebo; OXNPR-treated patients fell asleep more quickly, slept for longer, experienced less sleep disturbance and greater sleep adequacy than placebo- treated patients ( p 0.001). The IRLS¨C item 4 showed that sleep disturbance was ’very severe’ at baseline (median = 4 on a scale of 0–4) but had improved to ’mild’ (median = 1) in the OXNPR group and severe (median = 3) in the placebo group at Week 12. These results support results for IRLS total score. The RLS-6 was scored on a 0–10 scale; higher values represent more severe symptoms. Patients were highly dissatisfied with sleep at baseline (score of 8.2iA2.0 for Q1), but improved with a score of 3.8iA3.1 for OXNPR at Week 12. Similarly, results for Q2 improved from 7.2iA2.6 to 2.7iA2.9, results for Q3 improved from 7.5iA2.4 to 2.8iA3.0 and results for Q6 improved from 6.4iA2.8 to 3.7iA3.0. The improvement was significantly larger for OXNPR than placebo ( p 0.001). Conclusion In this analysis of an important secondary outcome measure, we demonstrated that treatment with OXNPR improves sleep quality in the context of an overall favorable treatment effect in severely affected RLS patients who failed on previous RLS medications. Acknowledgements Karen Paine provided medical writing services on behalf of Mundipharma Research. (Funded by Mundipharma Research; ClinicalTrials.gov number, NCT01112644).
The Lancet Neurology, 2013
Journal of International Medical Research, 2011
Opioid-induced constipation (OIC) is a severe, persisting side-effect of opioid therapy. The Bowe... more Opioid-induced constipation (OIC) is a severe, persisting side-effect of opioid therapy. The Bowel Function Index (BFIa, numerical analogue scale 0 − 100), calculated as the mean of three variables (ease of defaecation, feeling of incomplete bowel evacuation, and personal judgement of constipation) was developed to evaluate bowel function in opioid-treated patients with pain. This clinician-administered tool allows easy measurement of OIC from the patient's perspective. The purpose of this investigation was to define a reference range reflecting BFI values in non-constipated chronic pain patients who were recruited into a cross-sectional survey and asked for their perceptions of constipation. The BFI scores were assessed and compared with those of patients with confirmed OIC obtained from two previously published trials. Results were analysed and a reference range of BFI values of 0 − 28.8, into which 95% of non-constipated chronic pain patients fell, was defined. This permits d...
CNS Drugs, Jul 11, 2016
Objective The aim was to assess the effects of prolonged release oxycodone/naloxone (OXN PR) on s... more Objective The aim was to assess the effects of prolonged release oxycodone/naloxone (OXN PR) on sleep and quality of life (QoL) in patients with severe restless legs syndrome (RLS) refractory to first-line dopaminergic RLS treatment. Methods Sleep and QoL data from a 12-week, randomized, double-blind, placebo-controlled study with subsequent 40-week, open-label extension were analyzed. Instruments included the Medical Outcomes Study (MOS) sleep scale, RLS-6 rating scale, and RLS-QoL questionnaire. Results The full analysis population included 132 OXN PR and 144 placebo patients. After 12 treatment weeks, improvements in the MOS domains 'sleep disturbance' [-18.6; 95 % confidence interval (CI)-24.4 to-12.9; p \ 0.0001], 'sleep adequacy' (14.9; 95 % CI 7.9-21.9; p \ 0.0001), and 'sleep quantity' (0.77 h; 95 % CI 0.43-1.11; p \ 0.0001) were significantly greater under OXN PR than under placebo. OXN PR also reduced symptom severity (when falling asleep and during the night) and daytime tiredness, and increased sleep satisfaction to a significantly greater extent than placebo (all p \ 0.001; RLS-6). QoL improved in both treatment arms, with a significant difference of-9.02 (95 % CI-12.85 to-5.19; p \ 0.001) in the mean sum score in favor of OXN PR. All sleep and QoL aspects also improved under 40 weeks of open-label OXN PR treatment. Conclusions OXN PR improved RLS symptom severity and sleep quantity and adequacy, resulting in greater sleep satisfaction, less daytime tiredness, and improved QoL. In appropriate patients, OXN PR should be considered as an alternative treatment option for severe RLS that cannot be controlled by first-line dopaminergic medications. Trial Registration ClinicalTrials.gov (NCT01112644) and EudraCT (2009-011107-23).
Journal of Opioid Management
Opioids are the mainstay of management for patients with cancer-related pain. Although the analge... more Opioids are the mainstay of management for patients with cancer-related pain. Although the analgesic efficacy of opioid therapy is well documented, the recent European Pain in Cancer survey demonstrated that the management of moderate-to-severe pain in patients with cancer is far from optimal. Bowel dysfunction, and importantly constipation, is a common side effect and has a significant impact on the patient's morbidity and quality of life. Nonpharmacological strategies and laxatives are often not effective in the management of opioid-induced constipation (OIC), making it necessary to search for new strategies for the treatment of opioid-induced bowel dysfunction. One promising strategy is the prevention of OIC with peripherally acting opioid antagonists that specifically target the underlying cause of this condition, without affecting centrally mediated analgesia. In recent studies, the novel combination of prolonged-release oral oxycodone and prolonged-release oral naloxone pr...
Efficacy and safety of combined prolongedrelease oxycodone and naloxone in the management of mode... more Efficacy and safety of combined prolongedrelease oxycodone and naloxone in the management of moderate/severe chronic non-malignant pain: results of a prospectively designed pooled analysis of two randomised, double-blind clinical trials
Opioids are the mainstay of management for patients with cancer-related pain. Although the analge... more Opioids are the mainstay of management for patients with cancer-related pain. Although the analgesic efficacy of opioid therapy is well documented, the recent European Pain in Cancer survey demonstrated that the management of moderate-to-severe pain in patients with cancer is far from optimal. Bowel dysfunction, and importantly constipation, is a common side effect and has a significant impact on the patient's morbidity and quality of life. Nonpharmacological strategies and laxatives are often not effective in the management of opioid-induced constipation (OIC), making it necessary to search for new strategies for the treatment of opioid-induced bowel dysfunction. One promising strategy is the prevention of OIC with peripherally acting opioid antagonists that specifically target the underlying cause of this condition, without affecting centrally mediated analgesia. In recent studies, the novel combination of prolonged-release oral oxycodone and prolonged-release oral naloxone pr...
Addiction (Abingdon, England), Jan 16, 2017
Take-home naloxone can prevent death from heroin/opioid overdose, but pre-provision is difficult ... more Take-home naloxone can prevent death from heroin/opioid overdose, but pre-provision is difficult because naloxone is usually given by injection. Non-injectable alternatives, including naloxone nasal sprays, are currently being developed. To be effective, the intranasal (i.n.) spray dose must be adequate but not excessive, and early absorption must be comparable to intramuscular (i.m.) injection. We report on the pharmacokinetics (PK) of a specially produced concentrated novel nasal spray. The specific aims were to: (1) estimate PK profiles of i.n. naloxone, (2) compare early systemic exposure with i.n. versus i.m. naloxone and (3) estimate i.n. bioavailability. Open-label, randomized, five-way cross-over PK study. Clinical trials facility (Croydon, UK). Thirty-eight healthy volunteers (age 20-54 years; 11 female). Three doses of i.n. (1 mg/0.1 ml, 2 mg/0.1 ml, 4 mg/0.2 ml) versus 0.4 mg i.m. (reference) and 0.4 mg intravenous (i.v.) naloxone. Regular blood samples were taken, with h...
The Lancet Neurology, 2013
Opioids are a potential new treatment for severe restless legs syndrome. We investigated the effi... more Opioids are a potential new treatment for severe restless legs syndrome. We investigated the efficacy and safety of a fixed-dose combination of prolonged release oxycodone-naloxone for patients with severe restless legs syndrome inadequately controlled by previous, mainly dopaminergic, treatment. This multicentre study consisted of a 12-week randomised, double-blind, placebo-controlled trial and 40-week open-label extension phase done at 55 sites in Austria, Germany, Spain, and Sweden. Patients had symptoms for at least 6 months and an International RLS Study Group severity rating scale sum score of at least 15; patients with severe chronic obstructive pulmonary disease or a history of sleep apnoea syndrome were excluded. Patients were randomly assigned (1:1) to either study drug or matched placebo with a validated interactive response technology system in block sizes of four. Study drug was oxycodone 5·0 mg, naloxone 2·5 mg, twice per day, which was up-titrated according to investi...
Objective: An examination of whether oxycodone/naloxone prolonged-release tablets (OXN PR) can im... more Objective: An examination of whether oxycodone/naloxone prolonged-release tablets (OXN PR) can improve constipation and maintain analgesia, compared with oxycodone prolonged-release tablets (OxyPR) in patients with moderate/severe cancer pain. Methods: Randomized, double-blind, active-controlled, double-dummy, parallel-group study in which 185 patients were randomized to receive up to 120 mg/day of OXN PR or OxyPR over 4 weeks. Efficacy assessments included Bowel Function Index (BFI), Brief Pain Inventory Short-Form (BPI-SF), laxative and rescue medication use. Quality of life (QoL) and safety assessments were conducted. Results: After 4 weeks, mean BFI score was significantly lower with OXN PR; mean total laxative intake was 20% lower with OXN PR. Mean BPI-SF scores were similar for both treatments and the average rate of analgesic rescue medication use was low and comparable. QoL assessments were stable and comparable with greater improvements in constipation-specific QoL assessme...
Movement Disorders, 2021
Background: Excessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's... more Background: Excessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's disease (PD) without approved treatment. THN102 is a novel combination drug of modafinil and low-dose flecainide. Objectives: To evaluate the safety and efficacy of THN102 in PD patients with EDS. Methods: Randomized, double-blind, placebo-controlled, cross-over trial testing two doses of THN102 (200mg/d modafinil with 2mg/d (200/2) or 18mg/d flecainide (200/18)) versus placebo; 75 patients were exposed to treatment. The primary endpoint was safety. The primary efficacy outcome was the change in Epworth Sleepiness Scale (ESS) score. Results: Both doses of THN102 were well tolerated. ESS significantly improved with THN102 200/2 (Least Square means versus placebo [95% CI]:-1.4 [-2.49;-0.31], p = 0.012) but did not change significantly with the 200/18 dosage. Conclusions: THN102 was well tolerated and showed a signal of efficacy at the 200/2 dose supporting further development for the treatment of EDS in PD.
Sleep Medicine, 2013
Introduction In severe cases of restless legs syndrome (RLS), symptoms result in bothersome impac... more Introduction In severe cases of restless legs syndrome (RLS), symptoms result in bothersome impact on sleep and impairment of daytime function. This study showed superior efficacy of oxycodone/naloxone prolonged-release fixed-combination (OXNPR) vs. placebo for the primary endpoint (International Restless Legs Syndrome Study Group Rating Scale (IRLS) total score) in severely affected RLS patients. The impact of RLS on sleep quality was assessed as a secondary endpoint. Materials and methods After screening and a 7-day washout, 304 patients (age 62iA11.2 years) with failed prior RLS therapy and an IRLS score iÝ21 were randomized to double- blind OXNPR bid (mean oxycodone dose 21.9iA15.0 mg/day) or placebo for 12 weeks. 197 patients participated in a 40-week open-label extension (mean oxycodone dose 18.1iA10.5 mg/day). Sleep was subjectively assessed by the Medical Outcomes Study (MOS) sleep scale, by item 4 of the IRLS (sleep disturbance due to RLS symptoms) and 4 questions of the RLS-6: Q1 (sleep satisfaction), Q2/3 (RLS symptom severity at falling asleep/during the night), and Q6 (daytime tiredness). Results MOS sleep scale results showed greater improvement in sleep quality for OXNPR vs. placebo; OXNPR-treated patients fell asleep more quickly, slept for longer, experienced less sleep disturbance and greater sleep adequacy than placebo- treated patients ( p 0.001). The IRLS¨C item 4 showed that sleep disturbance was ’very severe’ at baseline (median = 4 on a scale of 0–4) but had improved to ’mild’ (median = 1) in the OXNPR group and severe (median = 3) in the placebo group at Week 12. These results support results for IRLS total score. The RLS-6 was scored on a 0–10 scale; higher values represent more severe symptoms. Patients were highly dissatisfied with sleep at baseline (score of 8.2iA2.0 for Q1), but improved with a score of 3.8iA3.1 for OXNPR at Week 12. Similarly, results for Q2 improved from 7.2iA2.6 to 2.7iA2.9, results for Q3 improved from 7.5iA2.4 to 2.8iA3.0 and results for Q6 improved from 6.4iA2.8 to 3.7iA3.0. The improvement was significantly larger for OXNPR than placebo ( p 0.001). Conclusion In this analysis of an important secondary outcome measure, we demonstrated that treatment with OXNPR improves sleep quality in the context of an overall favorable treatment effect in severely affected RLS patients who failed on previous RLS medications. Acknowledgements Karen Paine provided medical writing services on behalf of Mundipharma Research. (Funded by Mundipharma Research; ClinicalTrials.gov number, NCT01112644).
The Lancet Neurology, 2013
Journal of International Medical Research, 2011
Opioid-induced constipation (OIC) is a severe, persisting side-effect of opioid therapy. The Bowe... more Opioid-induced constipation (OIC) is a severe, persisting side-effect of opioid therapy. The Bowel Function Index (BFIa, numerical analogue scale 0 − 100), calculated as the mean of three variables (ease of defaecation, feeling of incomplete bowel evacuation, and personal judgement of constipation) was developed to evaluate bowel function in opioid-treated patients with pain. This clinician-administered tool allows easy measurement of OIC from the patient's perspective. The purpose of this investigation was to define a reference range reflecting BFI values in non-constipated chronic pain patients who were recruited into a cross-sectional survey and asked for their perceptions of constipation. The BFI scores were assessed and compared with those of patients with confirmed OIC obtained from two previously published trials. Results were analysed and a reference range of BFI values of 0 − 28.8, into which 95% of non-constipated chronic pain patients fell, was defined. This permits d...
CNS Drugs, Jul 11, 2016
Objective The aim was to assess the effects of prolonged release oxycodone/naloxone (OXN PR) on s... more Objective The aim was to assess the effects of prolonged release oxycodone/naloxone (OXN PR) on sleep and quality of life (QoL) in patients with severe restless legs syndrome (RLS) refractory to first-line dopaminergic RLS treatment. Methods Sleep and QoL data from a 12-week, randomized, double-blind, placebo-controlled study with subsequent 40-week, open-label extension were analyzed. Instruments included the Medical Outcomes Study (MOS) sleep scale, RLS-6 rating scale, and RLS-QoL questionnaire. Results The full analysis population included 132 OXN PR and 144 placebo patients. After 12 treatment weeks, improvements in the MOS domains 'sleep disturbance' [-18.6; 95 % confidence interval (CI)-24.4 to-12.9; p \ 0.0001], 'sleep adequacy' (14.9; 95 % CI 7.9-21.9; p \ 0.0001), and 'sleep quantity' (0.77 h; 95 % CI 0.43-1.11; p \ 0.0001) were significantly greater under OXN PR than under placebo. OXN PR also reduced symptom severity (when falling asleep and during the night) and daytime tiredness, and increased sleep satisfaction to a significantly greater extent than placebo (all p \ 0.001; RLS-6). QoL improved in both treatment arms, with a significant difference of-9.02 (95 % CI-12.85 to-5.19; p \ 0.001) in the mean sum score in favor of OXN PR. All sleep and QoL aspects also improved under 40 weeks of open-label OXN PR treatment. Conclusions OXN PR improved RLS symptom severity and sleep quantity and adequacy, resulting in greater sleep satisfaction, less daytime tiredness, and improved QoL. In appropriate patients, OXN PR should be considered as an alternative treatment option for severe RLS that cannot be controlled by first-line dopaminergic medications. Trial Registration ClinicalTrials.gov (NCT01112644) and EudraCT (2009-011107-23).
Journal of Opioid Management
Opioids are the mainstay of management for patients with cancer-related pain. Although the analge... more Opioids are the mainstay of management for patients with cancer-related pain. Although the analgesic efficacy of opioid therapy is well documented, the recent European Pain in Cancer survey demonstrated that the management of moderate-to-severe pain in patients with cancer is far from optimal. Bowel dysfunction, and importantly constipation, is a common side effect and has a significant impact on the patient's morbidity and quality of life. Nonpharmacological strategies and laxatives are often not effective in the management of opioid-induced constipation (OIC), making it necessary to search for new strategies for the treatment of opioid-induced bowel dysfunction. One promising strategy is the prevention of OIC with peripherally acting opioid antagonists that specifically target the underlying cause of this condition, without affecting centrally mediated analgesia. In recent studies, the novel combination of prolonged-release oral oxycodone and prolonged-release oral naloxone pr...
Efficacy and safety of combined prolongedrelease oxycodone and naloxone in the management of mode... more Efficacy and safety of combined prolongedrelease oxycodone and naloxone in the management of moderate/severe chronic non-malignant pain: results of a prospectively designed pooled analysis of two randomised, double-blind clinical trials
Opioids are the mainstay of management for patients with cancer-related pain. Although the analge... more Opioids are the mainstay of management for patients with cancer-related pain. Although the analgesic efficacy of opioid therapy is well documented, the recent European Pain in Cancer survey demonstrated that the management of moderate-to-severe pain in patients with cancer is far from optimal. Bowel dysfunction, and importantly constipation, is a common side effect and has a significant impact on the patient's morbidity and quality of life. Nonpharmacological strategies and laxatives are often not effective in the management of opioid-induced constipation (OIC), making it necessary to search for new strategies for the treatment of opioid-induced bowel dysfunction. One promising strategy is the prevention of OIC with peripherally acting opioid antagonists that specifically target the underlying cause of this condition, without affecting centrally mediated analgesia. In recent studies, the novel combination of prolonged-release oral oxycodone and prolonged-release oral naloxone pr...
Addiction (Abingdon, England), Jan 16, 2017
Take-home naloxone can prevent death from heroin/opioid overdose, but pre-provision is difficult ... more Take-home naloxone can prevent death from heroin/opioid overdose, but pre-provision is difficult because naloxone is usually given by injection. Non-injectable alternatives, including naloxone nasal sprays, are currently being developed. To be effective, the intranasal (i.n.) spray dose must be adequate but not excessive, and early absorption must be comparable to intramuscular (i.m.) injection. We report on the pharmacokinetics (PK) of a specially produced concentrated novel nasal spray. The specific aims were to: (1) estimate PK profiles of i.n. naloxone, (2) compare early systemic exposure with i.n. versus i.m. naloxone and (3) estimate i.n. bioavailability. Open-label, randomized, five-way cross-over PK study. Clinical trials facility (Croydon, UK). Thirty-eight healthy volunteers (age 20-54 years; 11 female). Three doses of i.n. (1 mg/0.1 ml, 2 mg/0.1 ml, 4 mg/0.2 ml) versus 0.4 mg i.m. (reference) and 0.4 mg intravenous (i.v.) naloxone. Regular blood samples were taken, with h...
The Lancet Neurology, 2013
Opioids are a potential new treatment for severe restless legs syndrome. We investigated the effi... more Opioids are a potential new treatment for severe restless legs syndrome. We investigated the efficacy and safety of a fixed-dose combination of prolonged release oxycodone-naloxone for patients with severe restless legs syndrome inadequately controlled by previous, mainly dopaminergic, treatment. This multicentre study consisted of a 12-week randomised, double-blind, placebo-controlled trial and 40-week open-label extension phase done at 55 sites in Austria, Germany, Spain, and Sweden. Patients had symptoms for at least 6 months and an International RLS Study Group severity rating scale sum score of at least 15; patients with severe chronic obstructive pulmonary disease or a history of sleep apnoea syndrome were excluded. Patients were randomly assigned (1:1) to either study drug or matched placebo with a validated interactive response technology system in block sizes of four. Study drug was oxycodone 5·0 mg, naloxone 2·5 mg, twice per day, which was up-titrated according to investi...
Objective: An examination of whether oxycodone/naloxone prolonged-release tablets (OXN PR) can im... more Objective: An examination of whether oxycodone/naloxone prolonged-release tablets (OXN PR) can improve constipation and maintain analgesia, compared with oxycodone prolonged-release tablets (OxyPR) in patients with moderate/severe cancer pain. Methods: Randomized, double-blind, active-controlled, double-dummy, parallel-group study in which 185 patients were randomized to receive up to 120 mg/day of OXN PR or OxyPR over 4 weeks. Efficacy assessments included Bowel Function Index (BFI), Brief Pain Inventory Short-Form (BPI-SF), laxative and rescue medication use. Quality of life (QoL) and safety assessments were conducted. Results: After 4 weeks, mean BFI score was significantly lower with OXN PR; mean total laxative intake was 20% lower with OXN PR. Mean BPI-SF scores were similar for both treatments and the average rate of analgesic rescue medication use was low and comparable. QoL assessments were stable and comparable with greater improvements in constipation-specific QoL assessme...