Pharmacokinetics of SYMTUZA - Food Effect

SUMMARY

• A study conducted in healthy subjects which assessed the impact of food on the single-dose pharmacokinetics (PK) of the components of SYMTUZA found a food effect for darunavir (DRV), whereas differences in exposure to cobicistat (COBI), emtricitabine (FTC), and tenofovir alafenamide (TAF) in fasted versus fed conditions were not considered to be clinically relevant.¹
• A study conducted in healthy subjects found that the SYMTUZA tablet was bioequivalent to the combined administration of the separate agents DRV 800 mg, FTC/TAF 200/10 mg fixed-dose combination (FDC), and COBI 150 mg.¹

CLINICAL STUDIES

Phase 1 Study-Impact of Food

Crauwels et al (2019)¹ assessed the impact of food on the single-dose PK of the components of SYMTUZA in healthy subjects (N=24).

Study Design/Methods

• Phase 1, single-dose, open-label, randomized, 2-period, single center, crossover study.
• In 2 treatment sessions, subjects received a single oral dose of SYMTUZA under fasted conditions or 30 minutes after a standard high-fat breakfast with a washout period of ≥7 days between each treatment session.
• The standard high-fat breakfast (928 kCal; 56 g fat) consisted of 2 eggs fried in butter, 2 strips of bacon, 2 slices of white bread with butter, 1 croissant with 1 slice of cheese, and 240 mL (8 oz) of whole milk (or its equivalent).
• PK profiles of the component drugs were determined up to 72 hours for DRV and COBI, 48 hours for FTC, and 12 hours for TAF.

Results

Patient Characteristics

• Twenty-four subjects completed the study; 12 males and 12 females; median (range) age 35 (18-54) years.

PK

• Effects of food on the bioavailability of the components of SYMTUZA are summarized in Table: DRV, COBI, FTC, and TAF PK Parameters and Statistical Analyses Following Administration of a Single Dose of D/C/F/TAF Under Fed (Standard High-Fat Breakfast) and Fasted Conditions.

Safety

• Adverse events (AEs) were observed in 9 (38%) and 10 (42%) subjects under fasted and fed conditions, respectively, following a single-dose administration of SYMTUZA.
• All AEs were grade 1 or 2.
• The most common AEs were headache (13% fasted versus 21% fed) and nausea (17% fasted versus 8% fed).
• Grade 2 AEs included irritable bowel syndrome (fasted), and nausea and headache (fed).
• One grade 3 laboratory abnormality (transient increase in LDL) was reported.

Phase 1 Study - Bioequivalence

In a separate study, Crauwels et al (2019)¹ assessed the bioequivalence of the SYMTUZA tablet compared to combined intake of the separate agents in healthy subjects (N=96).

Study Design/Methods

• Phase 1, open-label, randomized, 2-period, crossover study.
• In 2 treatment sessions, subjects received a single oral dose of the SYMTUZA tablet (test) or a single oral dose of DRV as one 800 mg tablet, FTC/TAF as one 200/10 mg FDC tablet, and COBI as one 150 mg tablet (as combined intake, reference), with a washout period of ≥7 days between each treatment session.
• Bioequivalence was assessed under fed conditions. Doses were administered within 5 minutes after standard regular breakfast.
  • The standard regular breakfast (533 kCal; 21 g fat) consisted of 4 slices of bread, 2 slices of ham and/or cheese, butter, fruit preserve, and 2 cups (up to 480 mL) of decaffeinated coffee or tea with milk and/or sugar (or its equivalent).
• PK profiles of the component drugs were determined over 72 hours for DRV, COBI, and FTC, and over 8 hours for TAF.

Results

Patient Characteristics

• Ninety-six subjects completed the study; 52 males and 44 females; median (range) age 26.0 (18-55) years.
• PK data for DRV, COBI, and FTC (test treatment only) were excluded from the PK analysis of one subject who vomited on Day 1 of both treatment sessions (within 2 times the median t_max for DRV, COBI, and FTC in one or both treatments).

PK

• Component drug PK parameters and statistical analysis are summarized in Table: PK Parameters and Statistical Analysis of DRV, COBI, FTC, and TAF Following Administration of a Single Oral Dose of SYMTUZA or a Single Oral Dose of the Separate Agents Under Fed Conditions (Standard Regular Breakfast).

Safety

• All AEs were grade 1.
• AEs were observed in 52/94 (55%) and 46/96 (48%) subjects following single-dose administration of SYMTUZA or the separate agents, respectively.
• The most common AEs were headache (14/94 [15%] with SYMTUZA versus 15/96 [16%] with separate agents) and nausea (17/94 [18%] versus 14/96 [15%], respectively).
• A total of 28 subjects (30%) experienced ≥1 AE that was considered possibly related to SYMTUZA by the investigator, most commonly nausea, headache, vomiting, abdominal pain, dizziness, somnolence, and diarrhea.
• Laboratory abnormalities were mostly grade 1 and not reported as AEs.
  • One patient had a transient grade 3 increase in lipase plus grade 2 increases in total amylase and pancreatic amylase following treatment with the separate agents on day 4, but values were within normal limits at all other time points.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 11 August 2025.