Rabbit Embryofetal 2 89.9 0.1 (NZW); development 6 377 0.3 Adderall (GD 19) 16 1464 1.0 20 2578 1.8 Rat Pre-/postnatal Amphetamine (SD); development 2 674 0.5 Adderall (mean GD 6 and PPD 20) 6 2173 1.5 10 4247 2.9 Human$ d-amphetamine^^ steady [70 mg] 1453** NA LDX@ steady state [70 mg] 61.1 NA # = animal:human plasma AUC0–24 h; * doses of LDX refer to the salt, doses of Adderall refer to total damphetamine base; ^ males/females; ^^ study NRP104.104 conducted in healthy adults aged 18-55 years; $ day 7 data; ** AUC0-∞; NA = not applicable Impurities Related substances do not exceed the ICH thresholds, and two impurities with genotoxic potential have been controlled in the drug substance to levels below the Threshold of Toxicological Concern. Nonclinical summary and conclusions Shire Australia Pty Ltd has applied to register a new chemical entity, LDX (Vyvanse) which is a prodrug of d-amphetamine covalently linked to llysine by an amide bond. Vyvanse is proposed for the treatment of ADHD in adults, adolescents and children. The maximum recommended dose is 70 mg/day. amphetamine is a well-characterised medicine, an abridged program of nonclinical studies was conducted focusing on identifying any characteristics of the prodrug that are not related to d-amphetamine. This is appropriate and an adequate set of studies was submitted, with all pivotal studies being GLP compliant. LDX appears to be pharmacologically inactive and lacks affinity for the dopamine and noradrenaline transporters that mediate the actions of d-amphetamine, as well as for a range of other receptors, transporters and ion channels. The active moiety, amphetamine, is a well-known sympathomimetic psychostimulant, and its primary
Rabbit (NZW); Adderall Embryofetal development (GD 19) 2 89.9 0.1 6 377 0.3 16 1464 1.0 20 2578 1.8 Rat (SD); Adderall Pre-/postnatal development (mean GD 6 and PPD 20) Amphetamine 2 674 0.5 6 2173 1.5 10 4247 2.9 Human$ d-amphetamine^^ steady [70 mg] 1453** NA LDX@ steady state [70 mg] 61.1 NA # = animal:human plasma AUC0–24 h; * doses of LDX refer to the salt, doses of Adderall refer to total damphetamine base; ^ males/females; ^^ study NRP104.104 conducted in healthy adults aged 18-55 years; $ day 7 data; ** AUC0-∞; NA = not applicable Impurities Related substances do not exceed the ICH thresholds, and two impurities with genotoxic potential have been controlled in the drug substance to levels below the Threshold of Toxicological Concern. Nonclinical summary and conclusions Shire Australia Pty Ltd has applied to register a new chemical entity, LDX (Vyvanse) which is a prodrug of d-amphetamine covalently linked to llysine by an amide bond. Vyvanse is proposed for the treatment of ADHD in adults, adolescents and children. The maximum recommended dose is 70 mg/day. amphetamine is a well-characterised medicine, an abridged program of nonclinical studies was conducted focusing on identifying any characteristics of the prodrug that are not related to d-amphetamine. This is appropriate and an adequate set of studies was submitted, with all pivotal studies being GLP compliant. LDX appears to be pharmacologically inactive and lacks affinity for the dopamine and noradrenaline transporters that mediate the actions of d-amphetamine, as well as for a range of other receptors, transporters and ion channels. The active moiety, is a well-known sympathomimetic psychostimulant, and its primary amphetamine,
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