Flora M Hammond1, William Sauve2, Fred Ledon3, Charles Davis4, Andrea E Formella3. 1. Indiana University School of Medicine, Rehabilitation Hospital of Indiana, 4141 Shore Drive, Indianapolis, IN 46254. 2. TMS NeuroHealth Centers, Richmond, VA. 3. Avanir Pharmaceuticals, Inc, Aliso Viejo, CA. 4. CSD Biostatistics, Inc, Tucson, AZ.
Abstract
BACKGROUND: Dextromethorphan 20 mg / quinidine 10 mg (DM/Q) was approved to treat pseudobulbar affect (PBA) based on phase 3 trials conducted in participants with amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness, safety, and tolerability for PBA following stroke, dementia, or traumatic brain injury (TBI). OBJECTIVE: To report results from the TBI cohort of PRISM II, including a TBI-specific functional scale. DESIGN: Open-label trial evaluating twice-daily DM/Q over 90 days. STUDY PARTICIPANTS: Adults (n = 120) with a clinical diagnosis of PBA secondary to nonpenetrating TBI; stable psychiatric medications were allowed. METHODS: PRISM II was an open-label, 12-week trial enrolling adults with PBA secondary to dementia, stroke, or TBI (NCT01799941). All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at day 30 and day 90. SETTING: 150 U.S. centers. MAIN OUTCOME MEASUREMENTS: Primary endpoint was change in Center for Neurologic Study-Lability Scale (CNS-LS) score from baseline to day 90. Secondary outcomes included PBA episode count, Clinical and Patient Global Impression of Change (CGI-C; PGI-C), Quality of Life-Visual Analog Scale (QOL-VAS), treatment satisfaction, Neurobehavioral Functioning Inventory (NFI), Patient Health Questionnaire (PHQ-9), and Mini Mental State Examination (MMSE). RESULTS: DM/Q-treated participants showed significant mean (SD) reductions in CNS-LS from baseline (day 30, -5.6 [5.2]; day 90, -8.5 [5.2]; both, P<.001). Compared with baseline, PBA episodes were reduced by 61.3% and 78.5% at days 30 and 90 (both, P<.001). At day 90, 78% and 73% of study participants had "much improved" or "very much improved" on the CGI-C and PGI-C. QOL-VAS scores were significantly reduced from baseline (-3.7 [3.3], P<.001). Mean (SD) PHQ-9 scores improved compared to baseline at day 30 (-3.2 [5.3], P<.001) and 90 (-5.2 [6.4], P<.001). NFI T scores were significantly improved (P<.001), whereas MMSE scores were unchanged. Adverse events (AEs) were consistent with the known DM/Q safety profile; the most common AE was diarrhea (8.3%). CONCLUSIONS: DM/Q was well tolerated, and it significantly reduced PBA episodes in study participants with TBI. Changes in CNS-LS and PBA episode count were similar to changes with DM/Q in phase 3 trials. LEVEL OF EVIDENCE: II.
BACKGROUND:Dextromethorphan 20 mg / quinidine 10 mg (DM/Q) was approved to treat pseudobulbar affect (PBA) based on phase 3 trials conducted in participants with amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness, safety, and tolerability for PBA following stroke, dementia, or traumatic brain injury (TBI). OBJECTIVE: To report results from the TBI cohort of PRISM II, including a TBI-specific functional scale. DESIGN: Open-label trial evaluating twice-daily DM/Q over 90 days. STUDY PARTICIPANTS: Adults (n = 120) with a clinical diagnosis of PBA secondary to nonpenetrating TBI; stable psychiatric medications were allowed. METHODS: PRISM II was an open-label, 12-week trial enrolling adults with PBA secondary to dementia, stroke, or TBI (NCT01799941). All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at day 30 and day 90. SETTING: 150 U.S. centers. MAIN OUTCOME MEASUREMENTS: Primary endpoint was change in Center for Neurologic Study-Lability Scale (CNS-LS) score from baseline to day 90. Secondary outcomes included PBA episode count, Clinical and Patient Global Impression of Change (CGI-C; PGI-C), Quality of Life-Visual Analog Scale (QOL-VAS), treatment satisfaction, Neurobehavioral Functioning Inventory (NFI), Patient Health Questionnaire (PHQ-9), and Mini Mental State Examination (MMSE). RESULTS:DM/Q-treated participants showed significant mean (SD) reductions in CNS-LS from baseline (day 30, -5.6 [5.2]; day 90, -8.5 [5.2]; both, P<.001). Compared with baseline, PBA episodes were reduced by 61.3% and 78.5% at days 30 and 90 (both, P<.001). At day 90, 78% and 73% of study participants had "much improved" or "very much improved" on the CGI-C and PGI-C. QOL-VAS scores were significantly reduced from baseline (-3.7 [3.3], P<.001). Mean (SD) PHQ-9 scores improved compared to baseline at day 30 (-3.2 [5.3], P<.001) and 90 (-5.2 [6.4], P<.001). NFI T scores were significantly improved (P<.001), whereas MMSE scores were unchanged. Adverse events (AEs) were consistent with the known DM/Q safety profile; the most common AE was diarrhea (8.3%). CONCLUSIONS:DM/Q was well tolerated, and it significantly reduced PBA episodes in study participants with TBI. Changes in CNS-LS and PBA episode count were similar to changes with DM/Q in phase 3 trials. LEVEL OF EVIDENCE: II.
Authors: Daniela Baracaldo-Santamaría; Daniel Felipe Ariza-Salamanca; María Gabriela Corrales-Hernández; Maria José Pachón-Londoño; Isabella Hernandez-Duarte; Carlos-Alberto Calderon-Ospina Journal: Pharmaceutics Date: 2022-01-08 Impact factor: 6.321