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Key findings from these early studies included: Long half-life (~200300 hours): Tesofensine has an exceptionally long elimination half-life, allowing for once-daily oral dosing and stable plasma concentrations Dose-proportional pharmacokinetics: Blood levels increased predictably with dose across the 0.125 mg to 1.0 mg range Acceptable tolerability: The most common side effects were dry mouth, insomnia, nausea, and constipation consistent with its monoaminergic mechanism Cardiovascular signal: Dose-dependent increases in heart rate (typically 510 bpm) were observed, along with modest blood pressure changes at higher doses The Parkinson's disease Phase I/II trials were particularly informative

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doi: 10.1016/S2468-1253(21)00261-2 113 ArmstrongMJGauntPAithalGPBartonDHullDParkerRet al