Common abbreviations Abbreviation Meaning 3TC Lamivudine ABC Abacavir ADME Absorption, distribution, metabolism, and elimination ADR Adverse drug reaction AE Adverse event aGFR Actual glomerular filtration rate AIDS Acquired immunodeficiency syndrome ANCOVA Analysis of covariance ANOVA Analysis of variance ART Antiretroviral therapy ARV Antiretroviral ATR Efavirenz/emtricitabine/tenofovir disoproxil fumarate (coformulated; Atripla ) ATV/co Cobicistat-boosted atazanavir ATV/r Ritonavir-boosted atazanavir BHIVA British HIV association BLQ Below the limit of quantitation BMD Bone mineral density BMI Body mass index
Table 4: Tenofovir alafenamide fumarate (Table sourced from Genvoya; Submission) Species Study duration drug Sex Study dose TFV AUCss 0–24h ng∙h/mL TAF AUCss ng∙h/mL TFV/TAF exposure Mouse (CD1) 13 (TAF) Combined 10 213 NC 0.72/NC 30 1507 NC 5.14/NC 100 7397 NC 25.24/NC 2 years (TDF) Males 600 44,300 NA 151.19/NA Females 50,900 NA 173.72/NA Rat (SD) 6 months (TAF) Males 5 740 NA 2.52 25 3530 NA 12.05 100 15,930 NA 54.37 Females 5 600 NA 2.05 25 4000 NA 13.65 100 15,140 NA 51.67 2 (TDF) Males 10/ 300 16,690 NA 56.96/NA 30 2700 NA 9.22/NA 100 6600 NA 22.53/NA Females 10/ 300 15,720 NA 53.65/NA 30 3060 NA 10.44/NA 100 7460 NA 25.46/NA Dog (Beagle) 9 months (TAF) Males 2 1300 90 4.44/0.44 6 3890 1290 6.25/6.26 18/12 14,900 2160 13.28/10.48 Females 2 1070 60 3.65/0.29 6 5010 780 17.10/3.79
information provided in response to these includes a consideration of the relevance for the Risk Management Plan, and any specific information needed to address this issue in the RMP. For any safety considerations so raised, the sponsor should provide information that is relevant and necessary to address the issue in the RMP. nonclinical and clinical evaluators’. Study will be included in the when this document is next updated. The sponsor should systematically identify and justify any differences between the summaries of the safety concerns and missing information for the similar products, Descovy and Genvoya. Any subsequent changes to the summary of the safety concerns and missing information for Descovy as specified in the ASA must be entirely captured in a revised ASA to be provided to the TGA for review. In addition consideration must be given to proposing appropriate pharmacovigilance and risk minimisation activities for any new ongoing safety concerns, to be reflected accordingly in the revised ASA. The sponsor has prepared a summary of the differences between the safety concerns and missing information for these similar products and concluded that no changes to the summary of the safety concerns or missing information are required, apart from the addition of safety in patients with severe renal impairment as missing information. This is acceptable. The sponsor should provide an assurance that the draft protocol for the planned clinical study of E/C/F/TAF in ARV HIV-1 infected patients from 6 to < 18 years of age (GS-US-292-0113) will be attached to the ASA once it becomes available. The sponsor states Study was planned to study E/C/F/TAF in ARV HIV-1 infected patients from 6 to < 18 years of age. Virologically suppressed, HIV-infected children 6 to < 12 years of age are now being enrolled into Cohort 2 of the ongoing, pediatric Study rather than Study Study has been renumbered as Study GS-US-292-1515 for administrative reasons. As younger children 6 to < 12 years of age are now being enrolled in Cohort 2 of Study Study GS-US-292-1515 is This is acceptable.