TRIUMEQ ®* (DTG/ABC/3TC): BIOEQUIVALENCE DATA UK/TRIM/0048/14(2) Date of preparation: March2017 Prescribing information is available at the end of this presentation *In studies supporting TRIUMEQ, DTG 50 mg + ABC 600 mg/3TC 300 mg were used. Bioequivalence has been demonstrated. DTG, dolutegravir; ABC, abacavir; 3TC, lamivudine
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TRIUMEQ®* (DTG/ABC/3TC):
BIOEQUIVALENCE DATA
UK/TRIM/0048/14(2)
Date of preparation: March2017
Prescribing information is available at the end of this presentation
In studies supporting TRIUMEQ, DTG 50 mg + ABC 600 mg/3TC 300 mg were used
Bioequivalence was demonstrated between the TRIUMEQ as a single-pill and the
separate co-administered tablet formulations of DTG + ABC/3TC
INTRODUCTION: TRIUMEQ AND DTG + ABC/3TC –
BIOEQUIVALENCE
TRIUMEQ Summary of Product Characteristics, January 2017; Weller S et al. JAIDS 2014;66:393-8
KEY STUDIES
† DTG 50mg + ABC 600mg/3TC 300mg were
used. Bioequivalence has been
demonstrated.13
* BR - background regimen
** OBR - optimised background regimen
1. Clotet B et al. Lancet. 2014;383(9936):2222-2231. 2. Orrell C et al. Presented at 21st International AIDS Conference, 18th-22nd July, 2016; Durban, South Africa.
Abstract THAB0205LB. 3. Walmsley S et al. N Engl J Med. 2013;369(19):1807-1818. 4. Walmsley S et al. J Acquir Immune Defic Syndr. 2015;70:515-519. 5. Molina
J-M et al. Lancet HIV.2015;2(4):e127-e136. January 2017. 6. Raffi F et al. Lancet Infect Dis. 2013;13:927–935 7. Raffi F et al. Lancet. 2013; 381: 735–743. 8. Cahn P
et al. Lancet. 2013; 382: 700–708. 9. Trottier B et al. Presented at 55th Interscience Conference on Antimicrobial Agents and Chemotherapy, 17th-21st September,
2015; San Diego, CA. LB3271. 10 Lake JE et al. Presented at 21st International AIDS Conference, 18th-22nd July, 2016; Durban, South Africa. Abstract THAB0203.
11. Castagna A et al. J Infect Dis. 2014; 210:354-362.
AT
RIP
LA
®
SINGLE Treatment-naïve patients
TRIUMEQ® † QD vs Atripla® QD (N=833)
SUPERIOR EFFICACY
vs Atripla®
at weeks 48 (primary endpoint),
96 and 144
BO
OS
TE
D P
ls
FLAMINGO Treatment-naïve patients
DTG + 2 NRTIs QD vs DRV/r + 2 NRTIs QD (N=484)
SUPERIOR EFFICACY
vs darunavir/r
at weeks 48 (primary endpoint)
and 96
ARIA Treatment-naïve women
TRIUMEQ QD vs ATV/r + TDF/FTC QD (N=495)
SUPERIOR EFFICACY
vs atazanavir/r
at week 48 (primary endpoint)
INIs
SPRING-2 Treatment-naïve patients
DTG + 2 NRTIs QD vs RAL + 2 NRTIs BID (N=822)
NON-INFERIOR EFFICACY
vs raltegravir
at weeks 48 (primary endpoint) and 96
SAILING Treatment-experienced,
INI-naïve patients
DTG QD + BR* vs RAL BID + BR* (N=719)
SUPERIOR EFFICACY
vs raltegravir
at week 48 (primary endpoint)
Co
nti
nu
ing
AR
T
STRIIVING Treatment-experienced,
stable-switch patients
TRIUMEQ QD vs continuing ARV regimen (N=551)
NON-INFERIOR EFFICACY
up to weeks 24 (primary endpoint)
and 48
Hea
vily
Trea
tmen
t-
Exp
erie
nce
d
VIKING-3
Heavily treatment experienced
patients with RAL and/or EVG
resistant HIV-1
DTG 50mg BD + OBR** (N=183)-single-arm study
SUSTAINED EFFICACY
up to weeks 24 (primary endpoint)
and 48
BIOEQUIVALENCE
FDCs have greatly simplified the treatment of patients with HIV
DTG is a booster-free INI approved for treatment of HIV-1 infection in combination
with other antiretroviral agents
ABC and 3TC are NRTIs available as a single pill (Kivexa®)
The combination of DTG, ABC and 3TC as a single pill would have several potential
advantages over other FDCs, including fewer drug interactions, once daily dosing,
no need for boosting and no time-of-day or food restrictions
DTG, ABC and 3TC as a single pill is suitable for HLA-B*5701-negative patients
TRIUMEQ (DTG/ABC/3TC) SINGLE PILL
REGIMEN BIOEQUIVALENCE: INTRODUCTION
TRIUMEQ Summary of Product Characteristics, January 2017; Kivexa Summary of Product Characteristics, October 2016; Ramjan R et al. Trop Med Int Health
2014;19:501-13; Weller S et al. JAIDS 2014;66:393-8
Primary objective
Evaluate single-dose bioequivalence in the fasted state between the TRIUMEQ
(DTG/ABC/3TC; 50/600/300 mg) single-pill and DTG 50 mg given with separate
ABC/3TC (600/300 mg) to healthy volunteers (Part A)
Secondary objectives
Evaluate the effect of food on the bioavailability of single-dose TRIUMEQ (Part B)
Assess the safety and tolerability of single-dose administration of DTG, ABC and 3TC
in healthy volunteers either fasted or with food
TRIUMEQ SINGLE PILL REGIMEN
BIOEQUIVALENCE: OBJECTIVES
Weller S et al. JAIDS 2014;66:393-8
Single-dose, open-label, randomised, two-period crossover study
Part A: Bioequivalence
Part B: Food effect
TRIUMEQ SINGLE PILL REGIMEN
BIOEQUIVALENCE: STUDY DESIGN
Pharmacokinetic study of TRIUMEQ vs component exposures and TRIUMEQ food effect
Randomisation
(N=65)
Single-dose
TRIUMEQ FDC
(fasted)
Single-dose
DTG + ABC/3TC
(fasted)
Washout
(≥7 days)
Washout
(≥7 days)
Single-dose
DTG + ABC/3TC
(fasted)
Single-dose
TRIUMEQ FDC
(fasted)
48-hour serial PK sampling 48-hour serial PK sampling
12 patients from
Part A
Single-dose TRIUMEQ
FDC + high-fat meal
Washout
(≥7 days)
48-hour serial PK sampling
Adapted from Weller S et al. JAIDS 2014;66:393-8
7 and 14 day
follow up
7 and 14 day
follow up
TRIUMEQ SINGLE PILL REGIMEN
BIOEQUIVALENCE: STUDY DESIGN
Point estimates and their associated 90% confidence intervals (CIs) were constructed for the
differences, test treatment (A) – reference treatment (B), for bioequivalence assessment Adapted from Weller S et al. JAIDS 2014;66:393-8
• Serial blood samples were collected up to 48 hours after each treatment for determination of AUC and Cmax
for each of DTG, ABC and 3TC
Plasma parameters such as AUC and Cmax are used to determine the pharmacokinetics (PK) of a drug
There was a ≥7-day washout
period between the second dose
in part A and the dose in part B
TRIUMEQ SINGLE PILL REGIMEN
BIOEQUIVALENCE: STUDY PROCEDURE
Adapted from Weller S et al. JAIDS 2014;66:393-8
65 subjects randomised to either Group 1 or Group 2
Group 1 received a single dose of Triumeq FDC followed by DTG +
ABC/3TC
Group 2 received DTG + ABC/3TC followed by a single dose of TRIUMEQ
FDC
62 subjects completed the study
TRIUMEQ SINGLE PILL REGIMEN
BIOEQUIVALENCE: STUDY POPULATION
TRIUMEQ SINGLE PILL REGIMEN
BIOEQUIVALENCE: PATIENT DEMOGRAPHICS
Demographics
TRIUMEQ
fasted
(n=65)
DTG + ABC/3TC
fasted
(n=65)
TRIUMEQ
fed
(n=12)
Age, mean (SD), years 29.3 (9.59) 29.3 (9.55) 33.8 (11.06)
Sex, n (%)
Female 22 (34%) 22 (34%) 4 (33%)
Male 43 (66%) 43 (66%) 8 (67%)
BMI, mean (SD), kg/m2 25.03 (3.72) 25.16 (3.71) 26.48 (3.09)
Height, mean (SD), cm 172.55 (10.01) 172.58 (9.97) 175.86 (11.64)
Weight, mean (SD), kg 74.69 (13.72) 75.05 (13.48) 82.29 (14.75)