PMID- 30412360
OWN - NLM
STAT- MEDLINE
DCOM- 20200728
LR  - 20211204
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 8
IP  - 4
DP  - 2019 May
TI  - Bioequivalence of the Once-Daily Single-Tablet Regimen of Darunavir, Cobicistat, 
      Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the 
      Separate Agents and the Effect of Food on Bioavailability.
PG  - 480-491
LID - 10.1002/cpdd.628 [doi]
AB  - The effect of food on the bioavailability of the components of the once-daily, 
      single-tablet human immunodeficiency virus (HIV) type 1 regimen containing 
      darunavir (DRV 800 mg), cobicistat (COBI 150 mg), emtricitabine (FTC 200 mg), and 
      tenofovir alafenamide (TAF 10 mg) (D/C/F/TAF) (NCT02475135) and the 
      bioequivalence of D/C/F/TAF versus combined intake of the separate agents 
      (NCT02578550) were evaluated. These were 2 phase 1, open-label, randomized, 
      2-period crossover studies (7-day washout between treatments) in HIV-negative 
      healthy volunteers. Twenty-four participants each received a single dose of 
      D/C/F/TAF in fasted conditions (test) or after a standardized high-fat breakfast 
      (reference). Ninety-six participants each received a single dose of D/C/F/TAF 
      (test) or combined intake of a single DRV 800-mg tablet, a COBI 150-mg tablet, 
      and an FTC/TAF 200/10-mg tablet (reference), both after a standardized 
      regular-calorie, regular-fat breakfast. Pharmacokinetic profiles for all 
      D/C/F/TAF components, safety, and tolerability were assessed. Following D/C/F/TAF 
      in fasted conditions, DRV peak concentration, area under the concentration-time 
      curve from time of administration until the last time point with a measurable 
      concentration (AUC)(last) , and extrapolated to infinity (AUC(inf) ) were lower 
      by 45%, 34%, and 30%, respectively, compared with fed conditions, with no 
      clinically relevant differences in COBI, FTC, or TAF exposures between fed and 
      fasted conditions. In the bioequivalence study 90% confidence intervals of the 
      geometric mean ratios of all main pharmacokinetic parameters were within the 
      80.00% to 125.00% bioequivalence limits for DRV, COBI, FTC, and TAF. No grade 3/4 
      adverse events (AEs), serious AEs, deaths, or discontinuations due to AEs 
      occurred. D/C/F/TAF is bioequivalent to combined administration of the separate 
      agents. Consistent with other (co)formulations of DRV, DRV exposure was lower in 
      fasted than in fed conditions as evaluated when taken with food, so D/C/F/TAF 
      should be taken with food.
CI  - (c) 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley 
      Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.
FAU - Crauwels, Herta M
AU  - Crauwels HM
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Baugh, Bryan
AU  - Baugh B
AD  - Janssen Research & Development LLC, Raritan, NJ, USA.
FAU - Van Landuyt, Erika
AU  - Van Landuyt E
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Vanveggel, Simon
AU  - Vanveggel S
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Hijzen, Anja
AU  - Hijzen A
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Opsomer, Magda
AU  - Opsomer M
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
LA  - eng
SI  - ClinicalTrials.gov/NCT02475135
SI  - ClinicalTrials.gov/NCT02578550
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20181109
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Drug Combinations)
RN  - 0 (Tablets)
RN  - 99YXE507IL (Tenofovir)
RN  - EL9943AG5J (tenofovir alafenamide)
RN  - JAC85A2161 (Adenine)
RN  - LW2E03M5PG (Cobicistat)
RN  - OF5P57N2ZX (Alanine)
RN  - YO603Y8113 (Darunavir)
SB  - IM
MH  - Adenine/administration & dosage/*analogs & derivatives/pharmacokinetics
MH  - Adult
MH  - Alanine
MH  - Area Under Curve
MH  - Biological Availability
MH  - Cobicistat/administration & dosage/*pharmacokinetics
MH  - Cross-Over Studies
MH  - Darunavir/administration & dosage/*pharmacokinetics
MH  - Drug Combinations
MH  - Fasting/*blood
MH  - Female
MH  - Food
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Tablets
MH  - Tenofovir/analogs & derivatives
MH  - Therapeutic Equivalency
MH  - Young Adult
OTO - NOTNLM
OT  - bioavailability
OT  - bioequivalence
OT  - cobicistat
OT  - darunavir
OT  - emtricitabine
OT  - tenofovir alafenamide
EDAT- 2018/11/10 06:00
MHDA- 2020/07/29 06:00
CRDT- 2018/11/10 06:00
PHST- 2018/03/16 00:00 [received]
PHST- 2018/10/08 00:00 [accepted]
PHST- 2018/11/10 06:00 [pubmed]
PHST- 2020/07/29 06:00 [medline]
PHST- 2018/11/10 06:00 [entrez]
AID - 10.1002/cpdd.628 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2019 May;8(4):480-491. doi: 10.1002/cpdd.628. Epub 2018 
      Nov 9.