controlled, multicentre, dose finding study. 92 female 45.7 years gel Single dose. effect was superior to vehicle gel and consistently dose dependent with the highest concentration (0.5%) being the most effective. Safety and tolerability were good and comparable between the groups treated the brimonidine tartrate gel and vehicle gel. 18161 Randomised, double blind, parallel group, vehicle controlled, multicentre, efficacy and safety study. 269 subjects 52 male, 217 female 44.3 Brimonidine tartrate (0.5% q.d., 0.18% q.d. or b.i.d.) gel or vehicle gel (q.d. or b.i.d.). Brimonidine tartrate 0.5% gel was statistically superior to vehicle gel for the primary endpoint. No evidence of tachyphylaxis was observed. All brimonidine tartrate gel concentrations/regimens were well-tolerated with an acceptable safety profile during the treatment and follow up phases. ROSE-201 Outpatient, randomised, double blind, vehicle controlled, parallel group, multicentre study. 110 subjects 27 male 83 female 47.6 years Brimonidine tartrate 0.2%, 0.07%, 0.02% or vehicle gel Applied each morning and as needed thereafter but no more than once every 4 hours and no more than 3 times per day for 28 days. This previous study provided supportive data on the efficacy of brimonidine tartrate gel in the treatment of erythema of rosacea. However the interpretation was limited as brimonidine tartrate 0.5% gel was not used and the endpoints evaluated were different to those used in the pivotal studies. Based on the Phase IIb study results and additional data from previous studies, brimonidine tartrate 0.5% gel applied once daily was an appropriate concentration and dose regimen selected for the Phase III program. Efficacy Studies providing efficacy data Pivotal efficacy studies Study 18140, was, a Phase III multicentre, randomised, double blind, parallel group, vehicle controlled pivotal study. The main objective of the study was to demonstrate the efficacy of brimonidine tartrate 0.5% gel, applied topically q.d. for 4 weeks versus
Ethnicity other than white Caucasian European patient experience Lactating women Pregnancy Patients with and/or hepatic impairment Concurrent significant disease including depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, thrombangiitis obliterans, scleroderma, or Sjögren’s syndrome. OPR reviewer comment Notwithstanding the evaluation of the non clinical and clinical aspects of the safety specifications, the listed ongoing safety concerns are considered acceptable. Pharmacovigilance plan The sponsor proposes routine and additional pharmacovigilance activities (a patient reported outcome study; and a 4 week vehicle controlled study) for important identified and potential risks and missing information. Risk minimisation activities The sponsor’s conclusion in regard to the need for additional risk minimisation activities is: ‘No risk management activities than labelling through the Summary of Product Characteristics (SmPC) and Patient Information Leaflet are proposed for identified risks or for missing information.’ OPR reviewer comment: The sponsor’s conclusion is acceptable. Risk minimisation plan No additional risk minimisation activities are proposed for brimonidine tartrate. Reconciliation of issues outlined in the RMP report Table 7 summarises the OPR’s first round evaluation of the RMP, the sponsor’s responses to issues raised by the OPR and the OPR’s evaluation of the sponsor’s responses. Table 7. Reconciliation of issues outlined in the RMP report. Recommendation in RMP evaluation report Sponsor’s response (or summary of the response) OPR evaluator’s comment Safety considerations may be raised by the nonclinical and clinical evaluators through the TGA consolidated request for further information and/or the nonclinical and clinical evaluation report (CER) ‘No safety considerations were raised by nonclinical and clinical evaluators via the TGA consolidated request for further information or the nonclinical or CER reports that impact the RMP. Should such considerations arise, the This is considered acceptable.