22nd International AIDS Conference (AIDS 2018) Single-Dose Fed Bioequivalence Study of Lamivudine, Tenofovir Disoproxil Fumarate and Dolutegravir Tablets (300mg/300mg/50mg) versus EPIVIR® (300mg; ViiV Healthcare), VIREAD® (300mg; Gilead Sciences) and TIVICAY® (50mg; ViiV Healthcare) Tablets in Healthy Adult Volunteers D. Abhijit1, C Santanu1, R. Chetan1, S. Gahoi1, R. Bangaru2, A. K. Datla2, P. Deshpande3, A. Kanda3, E. Patras3 1 Mylan Laboratories Limited, R&D, Hyderabad, India, 2 Mylan Laboratories Limited, Clinical Research Center, Hyderabad, India, 3 Mylan Laboratories Limited, Business Development, Hyderabad, India 22nd International AIDS Conference (AIDS 2018) Amsterdam, Netherlands, 23-27 July 2018

300 mg Epivir, 300 mg Viread, 50 mg Tivicay (R) Objective and Design Primary Objective: Compare the relative bioequivalence and safety profile of Mylan’s lamivudine, tenofovir disoproxil fumarate and dolutegravir tablet, 300 mg/300 mg/50 mg FDC tablets (T) with the reference combination (R) of EPIVIR® (300 mg, ViiV Healthcare), VIREAD® (300 mg, Gilead Sciences) and TIVICAY® (50 mg, ViiV Healthcare) Design: Open label, randomized, two-period, two-treatment, cross-over, single dose evaluation in 36 healthy adult human subjects under fed conditions In each period, each subject received a single, oral dose of T (Mylan’s 3TC/TDF/DTG tablet, “TLD”) or R (300 mg 3TC [Epivir®], 300 mg TDF [Viread®] and 50 mg [Tivicay®]) Serial blood samples (1 x 6 mL) were collected at pre-dose (within 120 minutes prior to dosing), 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 3.5, 4, 5, 6, 8, 10,12, 24, 36, 48 and 72 hours post-dose High fat FDA standardized breakfast TLD Mylan (300/300/50 mg) (T) 300 mg Epivir, 300 mg Viread, 50 mg Tivicay (R) 30 min 10 h Fasting Sampling pre-dose 0 – post-dose 72 h Wash-Out Period 7 days Abhijit D et al., 22nd IAC (AIDS 2018) Amsterdam 2018; #WEPDB0204

Methods Analytical Methods: Drug concentrations in plasma were quantified by using a validated method for the test product (T) and reference combination (R) All analyses were performed using 96-well liquid-liquid extraction and high performance liquid chromatography with tandem mass spectroscopy Limits of quantification were 40 ng/mL for DTG, 25 ng/mL for 3TC and 3 ng/mL for tenofovir Criteria for Bioequivalence Evaluation: The 90% confidence interval for the LSMeans ratio of CPEAK, AUCL, and AUCINF for the T and R products should be between 80% and 125%. Statistical Methods: Single-dose pharmacokinetic parameters for 3TC/TDF/DTG were calculated using non-compartmental techniques. Statistical analyses were performed on the pharmacokinetic parameters using the General Linear Models Procedure (PROC GLM) of SAS Software (SAS Institute, Cary, NC). Abhijit D et al., 22nd IAC (AIDS 2018) Amsterdam 2018; #WEPDB0204

Pharmacokinetic Results (n=34) Tenofovir Lamivudine Dolutegravir All statistical analyses of these data reveal that the 90% confidence intervals are within the acceptable bioequivalent range of 80% and 125% for the natural log transformed parameters AUCL, AUCINF, and CPEAK. Abhijit D et al., 22nd IAC (AIDS 2018) Amsterdam 2018; #WEPDB0204

Conclusions This study demonstrates that Mylan’s 3TC/TDF/DTG 300 mg/300 mg/50 mg tablet is bioequivalent to a combination of EPIVIR® (300 mg), VIREAD® (300 mg) and TIVICAY® (50 mg) as separate tablets following administration of a single, oral dose administered under fed conditions. Abhijit D et al., 22nd IAC (AIDS 2018) Amsterdam 2018; #WEPDB0204

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Results: Safety 34 subjects completed the study, one subject withdrew consent due to personal reasons; one discontinued due to an adverse event (loose stool) 25 post-dose adverse events (AEs) were experienced by 15 subjects over the course of this study. Mylan product (TLD): 9 AEs were considered probably related: diarrhea (n=2), dizziness, feeling hot, nausea (n=2) somnolence (n=3) 3 AEs were considered possibly related: dizziness, somnolence (n=2) Reference combination (Viread ®, Epivir® and Tivicay ®): 1 definitely related AE (upper abdominal pain) 7 AEs were considered probably related: upper abdominal pain, diarrhea, headache, nausea (n=2), somnolence (n=2) 4 AEs were considered possibly related: fatigue, headache, nausea, somnolence 1 AE was considered unrelated: catheter site hematoma All AEs were mild in severity. No deaths, serious adverse events (SAE) or other significant AEs were reported. Abhijit D et al., 22nd IAC (AIDS 2018) Amsterdam 2018; #WEPDB0204