# P-359. Evaluation of Relative Bioavailability and Food Effect of a Fixed-Dose Combination Tablet of Islatravir and Lenacapavir

## TL;DR

This study evaluated how well a combined HIV drug tablet works in the body and how food affects it, supporting its potential as a once-weekly treatment.

## Contribution

The study provides new pharmacokinetic data for a fixed-dose combination of islatravir and lenacapavir under different conditions.

## Key findings

- The fixed-dose combination tablet showed comparable drug exposure to single-agent co-administration under fasted conditions.
- Food had minimal clinically meaningful impact on drug absorption for the fixed-dose combination.
- No new safety concerns were observed in the study.

## Abstract

Combination treatment with islatravir (ISL), a nucleoside reverse transcriptase translocation inhibitor, and lenacapavir (LEN), an HIV-1 capsid inhibitor, has the potential to provide a complete, once-weekly (QW) oral regimen for HIV-1 treatment. In an ongoing Phase 2 study, 94% of participants receiving QW ISL and LEN co-administration maintained virologic suppression at Week 48. Phase 3 studies are evaluating a fixed-dose combination (FDC) tablet of ISL/LEN. To inform development of the FDC for the Phase 3 studies, a Phase 1 study was conducted to examine the pharmacokinetics (PK) of ISL/LEN FDC vs ISL and LEN single-agent co-administration, and the effect of food on ISL/LEN FDC PK.Figure 1.Study DesignSafety was assessed at each visit and AEs were recorded through the Day 61 follow-up phone call. PK sampling occurred through Day 14 for ISL and Day 43 for LEN and samples were analyzed by high-performance liquid chromatography–tandem mass spectrometry.AE, adverse event; FDC, fixed-dose combination; ISL, islatravir; LEN, lenacapavir; PK, pharmacokinetics.Figure 2.Arithmetic Mean (SD) Plasma Concentration-Time Profiles of (A) ISL and (B) LEN After a Single Dose of ISL and LEN Single-Agent Co-Administration Under Fasted Conditions, and ISL/LEN FDC Under Fasted or Fed Conditions**First 24 hours shown in insets.The LLOQ for ISL and LEN was 0.02 ng/mL and 0.1 ng/mL, respectively.FDC, fixed-dose combination; ISL, islatravir; LEN, lenacapavir; LLOQ, lower limit of quantitation.

Study Design

Safety was assessed at each visit and AEs were recorded through the Day 61 follow-up phone call. PK sampling occurred through Day 14 for ISL and Day 43 for LEN and samples were analyzed by high-performance liquid chromatography–tandem mass spectrometry.

AE, adverse event; FDC, fixed-dose combination; ISL, islatravir; LEN, lenacapavir; PK, pharmacokinetics.

Arithmetic Mean (SD) Plasma Concentration-Time Profiles of (A) ISL and (B) LEN After a Single Dose of ISL and LEN Single-Agent Co-Administration Under Fasted Conditions, and ISL/LEN FDC Under Fasted or Fed Conditions*

*First 24 hours shown in insets.

The LLOQ for ISL and LEN was 0.02 ng/mL and 0.1 ng/mL, respectively.

FDC, fixed-dose combination; ISL, islatravir; LEN, lenacapavir; LLOQ, lower limit of quantitation.

In this Phase 1, open-label, parallel-design study, participants without HIV-1 received single oral doses of ISL 2 mg and LEN 300 mg single agents simultaneously under fasted conditions (n=31) or ISL/LEN FDC 2/300 mg under fasted (n=31) or fed conditions (n=31) (Figure 1). Plasma PK samples were analyzed using validated methods. PK parameters were determined by standard non-compartmental analysis; geometric least-squares mean ratios were calculated for test vs reference treatment. Safety was monitored by physical examinations, clinical laboratory tests, and adverse event reporting.Table 1.PK Parameter Estimates and Comparisons

PK Parameter Estimates and Comparisons

ISL and LEN PK parameters were comparable (e.g., extrapolated areas under the concentration-time curves [AUCinf] % geometric least squares mean ratios [90% CI]: 107 [97.8; 116] and 90.2 [72.1; 113], respectively) for ISL/LEN FDC vs single-agent co-administration under fasted conditions (Figure 2; Table 1), with the exception of a lower ISL maximum concentration for the FDC. However, this finding is not considered clinically meaningful, as AUCinf indicates a similar extent of ISL absorption with a slower absorption rate. Similar exposures for ISL and elevated exposures for LEN were observed under fed vs fasted conditions for the ISL/LEN FDC (Table 1) that were considered not clinically meaningful. There were no new safety concerns.

The PK results from this relative bioavailability and food-effect characterization of ISL/LEN 2/300 mg FDC support continued clinical development of an ISL/LEN QW oral FDC dosing regimen without regard to food for the treatment of HIV-1 infection.

Jing Niu, MD, MS, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Haeyoung Zhang, PharmD, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) John Ling, n/a, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Sharline Madera, MD, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Nerissa Kwok, PharmD, Gilead Sciences, Inc.: Employee Steve West, MSPH, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Diane Longo, PhD, Merck & Co., Inc.: Employee|Merck & Co., Inc.: Stocks/Bonds (Public Company) Gillian Gillespie, MB, Bchir, Dohme: employee|Dohme: Stocks/Bonds (Public Company)|Merck & Co., Inc.: Employee|Merck & Co., Inc.: Stocks/Bonds (Public Company) Cyril Llamoso, MD, Merck & Co., Inc.: Employee Dhananjay Marathe, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company)