Methods: Fourteen Phase I/IIa studies were pooled across studies. Adverse events were described and summarized separately as injection site reaction (ISR) or non-ISR events. Lab data was summarized by the toxicity grade.
Results: CAB was administered to 423 subjects, including 408 healthy subjects and 15 HIV-infected subjects, in 14 Phase I/IIa studies. Oral CAB was given to 365 subjects, while LA CAB was administered to 136 subjects. Four non-drug related SAEs (osteomyelitis, uterine fibroids, appendicitis, seizure) were reported, all occurring in the LA studies. Nine subjects withdrew due to non-drug related AEs. The most frequent (>=4%) non–ISR AEs were headache (16%), upper respiratory tract infection (6%), and nausea (4%). Six Grade 3 AEs (elevated creatine kinase [CK], hyperbilirubinemia, joint dislocation) and four Grade 4 AEs (elevated CK, hyperbilirubinemia, osteomyelitis) were reported in LA dosing studies, and were assessed by investigators as unrelated to CAB. ISR AEs (n=458) related to CAB LA injection were ≤ Grade 2 and were largely mild (93%). The most frequent ISR AEs for IM and SC dosing, respectively, were pain (67% and 24%), erythema (7% and 23%), and nodules (10% and 22%). For pain and erythema, median ISR AE durations for IM and SC dosing were no more than 5 days and 7 days, respectively; for nodule, the respective medians were 19 and 53 days. Overall treatment-emergent ≥ Grade 2 laboratory abnormalities were infrequent and included elevations in total cholesterol (7%), lipase (4%), bilirubin (2%), and CK (2%). QTc study demonstrated no QT prolongation.
Conclusion: CAB given orally, intramuscularly or subcutaneously was well tolerated, and supports continued development of both oral and parenteral CAB formulations.
C. Fu, PAREXEL International: Employee , Salary
A. Tenorio, ViiV Healthcare: Employee , Salary
W. Spreen, ViiV Healthcare: Employee , Salary
P. Patel, ViiV Healthcare: Employee , Salary
D. Margolis, ViiV Healthcare: Employee , Salary