Pharmacokinetics Studies providing pharmacokinetic data The submitted pharmacokinetic (PK) studies are summarised in Table 3. There were no studies excluded from consideration. 3: Submitted pharmacokinetic studies PK topic Subtopic Study ID * PK in healthy General PK; Single dose Study R668-AS-0907 * adults Study R668-HV-1108 * TDU12265 * Bioequivalence; Single dose Study PKM12350 * Study PKM14161 * Study PKM14271 * PK in special Target population; dose Study R668-AD-0914 * populations Study R668-AD-1026 * Population PK Target population Study analyses * Indicates the primary PK aim of the study. Evaluator’s conclusions on pharmacokinetics The basic pharmacokinetics of dupilumab has been adequately described by the sponsor in the draft PI and have been adequately characterised. However, the sponsor has made the assumption that the elimination of dupilumab will be identical to that for other monoclonal antibody drugs. The sponsor has not confirmed this in mass balance studies. The sponsor has studied the effect of ADA on the PK. The effect of ADA on elimination was clinically significant and resulted in an increase of 17.8% in elimination rate constant. Greater disease severity, as measured by Eczema Area and Severity (EASI) score, also contributed to an increase in clearance. Interactions between dupilumab and other immunomodulatory drugs have not been studied. Hence, combinations of these drugs should be contraindicated. Dupilumab has the potential to be used extensively in the paediatric population. The PK in this population will need to be carefully characterised. Effects on vaccines will need further investigation. There were few older patients in the PK studies. The effects of aging on the PK of dupilumab have not been adequately characterised.
Pharmacokinetics Studies providing pharmacokinetic data The submitted pharmacokinetic (PK) studies are summarised in Table 3. There were no studies excluded from consideration. 3: Submitted pharmacokinetic studies PK topic Subtopic Study ID * PK in healthy adults General PK; Single dose Study R668-AS-0907 * Study R668-HV-1108 * TDU12265 * Bioequivalence; Single dose Study PKM12350 * Study PKM14161 * Study PKM14271 * PK in special populations Target population; dose Study R668-AD-0914 * Study R668-AD-1026 * Population PK analyses Target population Study * Indicates the primary PK aim of the study. Evaluator’s conclusions on pharmacokinetics The basic pharmacokinetics of dupilumab has been adequately described by the sponsor in the draft PI and have been adequately characterised. However, the sponsor has made the assumption that the elimination of dupilumab will be identical to that for other monoclonal antibody drugs. The sponsor has not confirmed this in mass balance studies. The sponsor has studied the effect of ADA on the PK. The effect of ADA on elimination was clinically significant and resulted in an increase of 17.8% in elimination rate constant. Greater disease severity, as measured by Eczema Area and Severity (EASI) score, also contributed to an increase in clearance. Interactions between dupilumab and other immunomodulatory drugs have not been studied. Hence, combinations of these drugs should be contraindicated. Dupilumab has the potential to be used extensively in the paediatric population. The PK in this population will need to be carefully characterised. Effects on vaccines will need further investigation. There were few older patients in the PK studies. The effects of aging on the PK of dupilumab have not been adequately characterised.
auspar-dupilumab-180612.docx