Pharmacodynamics Studies providing pharmacodynamic data Table 5 shows the studies relating to each PD topic. Table 5: Submitted pharmacodynamic studies. PD Subtopic ID Primary Pharmacology Effect on Act-1 and MAdCAM Study C13009 C13001 Study L297-007 Study L297-005 Study L297-006 Study M200-021 C13002 Study CPH-001 Study L299-016 Study M200-022 Secondary Pharmacology Effect on CSF CD4+/CD8+ Study C13012 Effect on immunogenicity Study C13013 Population PD and PK-PD analyses Target population Projections Research Population PKPD Report Metrum Research Group Population PK-PD Report None of the PD studies had deficiencies that excluded their results from consideration. Evaluator’s summary and conclusions on pharmacodynamics The PD characteristics of vedolizumab have been adequately characterised. Vedolizumab given using the proposed dose regimen inhibited the PD endpoints Act-1 and MAdCAM nearly maximally at all time points where vedolizumab was measurable and the time of maximal effect was generally the first sample time. At both the 300 mg and 600 mg dose levels, maximal inhibition of Act-1 and MAdCAM-1-Fc was achieved within 24 h (time of the first sample). Maximal or near maximal inhibition of Act-1 and MAdCAM persisted to Day 113 for the 2.0 and 6.0 mg/kg doses and to Day 169 for the 10.0 mg/kg dose. The duration of effect for the 300 mg dose level was up to 155 days.
patients from Studies C13004, C13006, C13007, and C13011 Important potential risks Infections: Gastrointestinal infections and systemic infections against which the gut constitute a defensive barrier Routine Pharmacovigilance: signal detection, AE surveillance and reporting, literature surveillance Additional Pharmacovigilance: MLN-0002_401: A postmarketing, prospective, observational, cohort safety study of vedolizumab versus other biologic agents for inflammatory bowel disease. C13008: Ongoing long-term safety extension study of patients from Studies C13004, C13006, C13007, and C13011 Other serious infections, including opportunistic infections such as progressive multifocal leukoencephalopathy (PML) Routine Pharmacovigilance: signal detection, PSURs, AE surveillance and reporting, literature surveillance follow-up form for cases of suspected neurologic symptoms/PML (annex 7) Additional Pharmacovigilance: MLN-0002_401: A postmarketing, prospective, observational, cohort safety study of vedolizumab versus other biologic agents for inflammatory bowel disease C13008: Ongoing long-term safety extension study of patients from Studies C13004, C13006, C13007, and C13011 Malignancies Routine Pharmacovigilance: signal detection, PSURs, AE surveillance and reporting, literature surveillance Additional Pharmacovigilance: MLN-0002_401: A postmarketing, prospective, observational, cohort safety study of vedolizumab versus other biologic agents for inflammatory bowel disease C13008: Ongoing long-term safety extension study of patients from Studies C13004, C13006, C13007, and C13011 Missing information Pregnancy and lactation Paediatric Elderly Use in patients with hepatic impairment Use in patients with impairment Routine Pharmacovigilance: signal detection, AE surveillance and reporting, literature surveillance Additional Pharmacovigilance: MLN-0002_401: A postmarketing, prospective, observational, cohort safety study of vedolizumab versus other biologic agents for inflammatory bowel disease