ProSpective, MultI-Center, Observational PrograM to Assess the Effectiveness of Dual TheraPy (Lopinavir/Ritonavir + LamivudinE) in Treatment-Experienced HIV Infected Patients in the Routine Clinical Settings of the Russian Federation (SIMPLE)
Conditions: HIV-1 Infection
Sponsor: AbbVie

 
 
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ion 01, dated 1
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17 August 201
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Mar
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MA
 
 
ion 01, dated 1
rketing A
arketing Auth
AH Contact P
Lopinavir/rito
P15-452 Prot
17 August 201
Authorisa
horisation Hol
Person 
onavir and Lam
tocol 
15 
ation Ho
lder(s)
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mivudine 
lder(s) 
AbbVie Deutsc
Ludwigshafen, 
Not applicable
chland GmbH 
 Germany 
& Co. KG, Knollstrasse 67
2 
7061 

 
 
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ion 01, dated 1
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Lopinavir/rito
P15-452 Prot
17 August 201
Table 
Table of 
Abbrevia
Responsi
Abstract
Amendm
Mileston
Rational
Backgroun
Rationale .
Research
Primary Ob
Secondary
Research
Study Desi
Product Su
Setting .....
Program D
Investigato
Inclusion C
Exclusion 
Description
Terminatio
Endpoints 
Primary En
Secondary
Data Sourc
Study Size
Data Mana
Data Analy
Quality Co
Limitation
onavir and Lam
tocol 
15 
of Conte
Contents
ations .....
ible Parti
t ..............
ments and
nes ...........
le and Bac
nd ...............
..................
h Question
bjective .....
 Objectives 
h Method
ign .............
upply ..........
..................
Duration ......
or selection 
Criteria ......
Criteria .....
n of Activit
on of the Pro
..................
ndpoint ......
 Endpoints
ces .............
e .................
agement .....
ysis ............
ontrol .........
ns of the Res
mivudine 
ents
s ...............
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ies ............
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ckground
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n and Ob
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criteria ......
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ion 01, dated 1
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Lopinavir/rito
P15-452 Prot
17 August 201
Other Aspe
Protectio
Managem
Medical C
Adverse Ev
Severity ...
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Serious Ad
Serious Ad
Pregnancy
Product Co
Definition 
Reporting .
Plans for
Results ..
Referenc
onavir and Lam
tocol 
15 
ects ............
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ment and 
omplaints ..
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Versi
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3TC
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ART
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CRO
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Lopinavir/rito
P15-452 Prot
17 August 201
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3.0
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ion 01, dated 1
Vie 
tract Resear
Lopinavir/rito
P15-452 Prot
17 August 201
Respo
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onavir and Lam
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onsible P
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mivudine 
Parties
O) 
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Versi
4.0
Title
(Lopi
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exam
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Lopinavir/rito
P15-452 Prot
17 August 201
Abstra
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f the Russian F
Background: 
he use of a
ogues (NRTIs
RTIs can caus
idney dysfunc
ohort studies 
ely used as a f
of LPV/r (lop
er of different 
therapy has b
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py in virologic
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a triple antire
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first line drug 
pinavir/ritonav
clinical trials,
been studied 
pectively (1-3)
to LPV/r + 2
cally suppresse
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fected patients
mivudine 
nal Program to
ent-Experienc
of care treatm
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dovudine), neu
ir).  Cardiovas
vudine (3TC) 
for the treatm
vir) has been 
, for periods o
in HIV-1-naï
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2 NRTIs, as f
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ata from treatm
no data exists
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rapy (ART) 
ays well tolera
urotoxicity an
scular disease
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ment of HIV in
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of up to seven y
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eeks, LPV/r + 
first line regim
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ment-experien
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inical settings 
ffectiveness o
ected Patients 
-1-infected pa
with regimen
ated (short an
nd lipodystroph
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nfected adults 
nstrated in a 
years (13-14).
-1 experience
3TC demonst
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-3). 
nced HIV-1 po
tiveness of LP
of the Russian
of Dual Therap
in the Routine
atients is usu
ns including 
nd long term).
hy (stavudine
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good safety pr
and children. 
wide spectrum
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n Federation.  
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ually 
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ion 01, dated 1
arch Question
ary Objective 
ssess the virolo
lation of treat
(for at least 6
ian Federation
ndary Objectiv
1.
To evalua
2.
To evalua
3.
To assess 
4.
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5.
To evalua
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ol group.  
ulation:  HIV-
ma HIV-1 RNA
edically appro
points   
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1.
Proportion
level at we
ndary endpoin
1.
Proportion
week 24 o
2.
Absolute v
the baselin
3.
Absolute v
baseline. 
4.
Proportion
5.
Absolute v
waist circu
Lopinavir/rito
P15-452 Prot
17 August 201
n and Object
ogic effectiven
tment-experien
6 months) at th
n.  
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ate virologic ef
ate immune rec
the developm
ate metabolic 
ate the safety a
is is a non-inte
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A level for at l
priate to LPV
n of patients o
eek 48 of the o
nts 
n of patients o
of the observat
values of HIV
ne (untransfor
values of CD4
n of patients w
values at week
umference in 
onavir and Lam
tocol 
15 
tives:   
ness of dual th
nced HIV-1 in
he 48 week ti
ffectiveness of
constitution on
ment level of dr
and anthropom
and tolerability
erventional, pr
tients aged 18 
least 6 months
V/r + 3TC in th
on dual therap
observational 
on dual therap
tional period.
V-1- RNA vira
rmed and base
4+ T-cell coun
who develop re
ks 24 and 48 a
cm) as compa
mivudine 
herapy (lopina
nfected patien
imepoint of tr
f dual therapy
n the dual ther
rug resistance 
metric parame
y of dual thera
roduct-focused
years and old
s (two consequ
he routine clini
py (LPV/r + 3
period. 
py (LPV/r + 3
al loader at we
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and changes of
ared to the base
avir/ ritonavir 
nts with an un
eatment in the
y at week 24. 
rapy at weeks 
over 48 week
eters change ov
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ical settings. 
3TC) with un
3TC) with und
eeks 24 and 48
m transformed d
24 and 48 and
ach drug in the
f anthropomet
eline. 
(LPV/r) + lam
ndetectable pla
e routine clini
24 and 48. 
ks of treatment
ver 48 weeks o
3TC) 
l and multi-ce
le HAART  w
HIV-1 RNA 
ndetectable pla
detectable HIV
8 and the chan
data).   
d the change a
e study regime
tric measurem
mivudine (3TC
asma HIV-1 R
ical settings o
t. 
of treatment. 
enter study wit
with undetectab
levels) transfe
asma HIV-1 R
V-1- RNA lev
nge as compare
as compared to
en.  
ments (arm, hip
8 
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RNA 
f the 
th no 
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erred 
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vel at 
ed to 
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6
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ion 01, dated 1
6.
Absolute 
total chol
baseline. 
7.
Proportion
causing tr
period.  
Sources: Dat
ce documents a
include hospit
ensing and oth
y Size: The O
ted patients re
at 48 weeks,
rvational prog
undetectable 
opout is 196, a
mal distribution
ortion for an 
ber of enrolled
Analysis:  Si
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itative variable
ion, two-sided
rated for visua
stones:   
of Data Colle
of Data Collec
im Report:   
Report of Stu
Lopinavir/rito
P15-452 Prot
17 August 201
values at wee
lesterol, LDL-
n of patients 
reatment disco
ta for the study
at the center. S
tal records, cli
er records, rec
OLE study (1
emained suppr
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ram, it is estim
plasma HIV-1
a Simple Asym
n will extend 
expected prop
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ince this is an 
riptive summa
ndard deviatio
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ction:        1
ction: 
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udy Results: 1
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eks 24 and 48
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ressed (undete
feriority to th
mated that a s
1 RNA level a
mptotic two-s
5% (i.e. half 
portion of 85%
constitute 216
open-label, no
ary statistics. Q
on, median, 1s
mmarized with
ence intervals w
on of the result
6 October 201
4 April 2017
15 November 2
10 December 2
mivudine 
8 and change
holesterol, tri
non-serious A
SAEs, [includ
ected from clin
ments will be o
ce charts, labo
om automated
at 87.8% of p
ectable plasma
he LPV/r plu
similar percent
at week 48. W
sided 95% con
width of the 
%. Considerin
6.  
on-randomized
Quantitative va
t quartile, 3rd 
h the number a
will be genera
ts, as appropri
15 
2016 
2017 
es of metaboli
igclycerides, c
AEs spontane
ding SAEs tha
nical interview
riginal docum
oratory data/in
d instruments, 
pre-suppressed
a HIV-1 RNA
us 2 NRTi co
tage of the pa
When the samp
nfidence interv
95% confiden
ng an approxi
d trial, the ana
ariables will b
quartile, mini
and proportion
ated for param
iate. 
ic parameters 
creatinine) as 
eously reporte
at cause deaths
w with the pare
ments, data and
nformation, ph
etc. 
d treatment-ex
A level) on the
ontrol arm. T
atients among 
ple size witho
val for a single
nce interval) f
imate dropout
alyses will prim
be summarized
imum and max
n of patients in
meter estimates
(glucose, ins
compared to
ed [including 
s] ) over the s
ent and from 
d records. This
harmacy 
xperienced HI
e LPV/r plus 
Therefore, for 
study sample 
out a considera
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ximum values
n each category
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9 
ulin, 
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will 
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erved 
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be 

 
 
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5.0
Not 
 
6.0
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7.0
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a trip
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ion 01, dated 1
applicable b
or study mil
rt of Data Coll
d of Data Colle
dy Progress R
erim Report: 
gistration in th
al Report of S
ndard of care
ple antiretro
RTIs) (4). N
e NRTIs ca
didanosine
ciated with 
addition, the
ractions wit
hepatitis C
 be ineffect
in some cas
Lopinavir/rito
P15-452 Prot
17 August 201
Amend
by now. 
Milest
lestones and
lection: 
ection: 
Report: 
he EU PAS reg
Study Results: 
Ration
Backgr
e treatment 
oviral therap
NRTIs are n
an cause ane
e) and kidn
abacavir in 
e selection 
th drugs for
. Excluding
tive. And fin
ses may not 
onavir and Lam
tocol 
15 
dments a
ones 
d their plann
gister 
nale and 
round  
of HIV-1 in
py (ART) w
not always w
emia (zidov
ney dysfun
some cohor
of drugs in
r the treatm
g these inter
nally, the d
be available
mivudine 
and Upda
ned dates ar
16 October 
14 April 20
N/A 
15 Novemb
N/A 
10 Decembe
Backgro
nfected pati
with regimen
well tolerat
vudine), neu
nction (teno
rt studies (5
n the regim
ment of com
ractions as 
drugs includ
e for use for
ates
e as follows
2015 
17 
ber 2016 
er 2017 
ound
ents is usua
ns including
ed (short an
urotoxicity a
ofovir), car
5 - 7). 
mens of AR
morbidities d
treatment f
ded in the st
r different re
s: 
ally associat
g two nucleo
nd long ter
and lipodys
rdiovascular
RT should t
diseases suc
for HIV and
tandard tripl
easons. 
ted with the 
os(t)ide ana
rm). For ex
strophy (stav
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take into a
ch as tuberc
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le ART reg
10 
use of 
alogues 
ample, 
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is also 
ccount 
culosis 
iseases 
gimens, 

 
 
Versi
NRT
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studi
supp
load
Main
limit
first 
susc
rend
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for t
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ion 01, dated 1
TI-sparing s
boosted wi
ies reportin
pression, the
d is usually
ntaining or 
tation. 3TC 
line drug 
eptible to a
ders lamivud
viral potenc
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rs (13-14). 
V/r+3TC dua
GARDEL 
monstrated n
regimen in 
ents in OLE
cost of anti
the health sy
C may signif
eric ARV. 
 
 
 
Lopinavir/rito
P15-452 Prot
17 August 201
studies have
ith ritonavir
ng non-infer
e proportion
y higher in
adding lam
is an effect
for the tre
a single poi
dine inactiv
cy of LPV/r
tients in a n
al therapy w
and OLE 
on-inferior 
GARDEL 
E study (1-3)
iretroviral th
ystems (12)
ficantly red
onavir and Lam
tocol 
15 
e historically
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n of patients
n the grou
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ive drug wi
atment of 
int mutation
ve but also
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number of 
was studied
studies res
efficacy an
study and a
). 
herapy and 
). As an add
duce the cos
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y focused o
r or darunav
his strategy 
s showing o
ups treated
or 3TC) to 
th good safe
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n in the HI
o impacts t
/ritonavir) h
different cl
d in HIV-1-
spectively (
nd comparab
as maintena
its cost imp
ded value, s
st of treatm
n monother
vir) (8, 9). 
when used 
one or more
d with boo
this strateg
ety profile t
ected adults
IV-1 genom
he viral re
has been cle
linical trials
naïve and H
(1-3). Over
ble safety t
ance therapy
plications ar
simplifying 
ment, especia
rapy with a 
However, a
following 
e episodes o
osted PI m
gy could he
that has been
s and childr
me (M184V
plicative ca
early demon
s, for period
HIV-1 expe
r 48 week
to LPV/r + 
y in virolog
re also incre
 triple thera
ally as 3TC
protease in
although the
HAART-led
of detectabl
monotherapy
elp overcom
n widely use
ren. This d
V mutation) 
apacity (11
nstrated in a
ds of up to 
erience patie
s, LPV/r +
2 NRTIs, a
gically supp
easingly imp
apy to LPV
C is an estab
11 
nhibitor 
ere are 
d viral 
le viral 
y (10). 
me this 
ed as a 
drug is 
which 
). The 
a wide 
 seven 
ents in 
+ 3TC 
as first 
pressed 
portant 
V/r plus 
blished 

 
 
Versi
7.2
Effic
popu
worl
the r
Expe
settin
the a
 
8.0
8.1
To a
lami
an un
of tr
8.2
1
2
3
4
5
 
ion 01, dated 1
cacy data 
ulations are 
ld effectiven
routine clini
erience of u
ngs could le
additional an
assess the 
ivudine (3T
ndetectable 
eatment in t
1. To evalu
2. To evalu
3. To asses
4.  To eval
of treatm
5.  To eval
Lopinavir/rito
P15-452 Prot
17 August 201
Rationa
for LPV/r+
overwhelm
ness of LPV
ical settings 
using the dua
ead to its ad
nd less expe
Resea
Primary
virologic e
TC)) in popu
 plasma HIV
the routine c
Second
uate the viro
uate the imm
ss the develo
uate the me
ment. 
uate the saf
onavir and Lam
tocol 
15 
ale 
+3TC dual 
mingly from
V/r + 3TC i
of the Russ
al therapy (L
ddition to th
ensive regim
arch Que
y Objectiv
effectivenes
ulation of tr
V-1 RNA le
clinical setti
dary Objec
ologic effect
mune recons
opment leve
etabolic and 
fety and tole
mivudine 
therapy da
m OLE study
in treatment
sian Federat
LPV/r+3TC
he National 
men of choic
stion and
ve
s of dual
reatment-ex
evel (for at l
ings of the R
ctives 
tiveness of d
stitution on 
el of drug re
anthropome
erability of d
ata from tr
y (1) where
t-experience
tion.  
C) regimen i
guidelines 
ce for stakeh
d Object
therapy (lo
xperienced H
least 6 mon
Russian Fed
dual therapy
the dual the
esistance ov
etric parame
dual therapy
reatment-ex
as no data e
ed HIV-1 in
in the Russi
and provide
holders. 
tives
opinavir/ rito
HIV-1 infec
nths) at the 4
deration.  
y at week 24
erapy at wee
ver 48 weeks
eters change
y (LPV/r + 3
xperienced 
exists on th
nfected patie
an routine c
e the advant
onavir (LPV
cted patient
48 week tim
4. 
eks 24 and 4
s of treatme
e over 48 w
3TC) 
12 
HIV-1 
hat real 
ents in 
clinical 
tage of 
V/r) + 
ts with 
mepoint 
48. 
nt. 
weeks 

 
 
Versi
9.0
9.1
This
cont
This
3TC
plasm
the r
9.2
As t
supp
presc
9.3
For p
15 n
9.4
Enro
LPV
label
telep
will 
 
 
ion 01, dated 1
s is a non-in
trol group.  
s study desi
C) in populat
ma HIV-1 R
routine clini
this is a pos
ply since the
cribed by th
purpose of 
national and 
ollment wil
V/r + 3TC w
l to all enr
phone conta
be organize
Lopinavir/rito
P15-452 Prot
17 August 201
Resea
Study D
nterventiona
gn will be 
tion of treat
RNA level (
ical settings 
Produc
st-marketing
e drug is be
he physician
Setting
this program
regional AI
Program
l start from
will be adm
rolled subje
act at 30 da
ed according
onavir and Lam
tocol 
15 
arch Meth
Design
al, product-f
used to acc
ment-exper
(for at least 
of the Russ
ct Supply
g observatio
eing used a
n under usua
g
m participan
IDS centers
m Duratio
m 16 Octob
ministrated a
ects. All en
ays after the
g to routine 
mivudine 
hods
focused, lon
cess the effe
rienced HIV
6 months) a
sian Federat
onal study, A
ccording to
al and custom
nts will be r
. 
n
ber 2015 an
according to
nrolled patie
eir last dose
clinical pra
ngitudinal an
ectiveness o
V-1 infected 
at the 48 we
tion.  
AbbVie is N
o the approv
mary practi
recruited an
nd continue
o physician
ents will be
e in the stud
actice (appro
nd multi-cen
of the dual 
patients wit
eek time poi
NOT involv
ved market 
ce of physic
nd observed
e approxim
n’s prescript
e followed 
dy. All visi
oximately ev
nter study w
therapy (LP
th an undete
int of treatm
ved in the p
label and is
cian prescrip
d in approxim
mately 6-8 m
tion and the
by a perso
its of the pr
very 3 mont
13 
with no 
PV/r + 
ectable 
ment in 
product 
s to be 
ption. 
mately 
months 
e local 
onal or 
rogram 
ths).     

 
 
Versi
9.5
In or
durin
x
x
x
x
9.6
ART
Patie
+ 3T
inter
wish
the f
1. A
2. H
copi
as m
clini
(LPV
3. Cu
4. A
 
 
ion 01, dated 1
rder to assur
ng the recru
x
Physicia
x
Physicia
x
Availabi
x
Ability t
 
T therapy w
ent can be in
TC) due to 
ractions, sid
h to simplify
following cr
ge 18 years
HIV-1 infect
es/mL for a
medically ap
ical settings
V/r + 3TC) n
umulative H
uthorization
Lopinavir/rito
P15-452 Prot
17 August 201
Investig
re credibilit
uitment proc
an licensed i
an is workin
ility of patie
to appropria
Inclusio
will be presc
ncluded in t
any reason
de effects, p
y regimen, a
riteria: 
 and older (
ted patients
at least 6 mo
ppropriate t
s. OR HIV
no more tha
HAART exp
n (Consent) 
onavir and Lam
tocol 
15 
gator sele
ty of the fina
cess of phys
in infection 
ng at a nation
ent populati
ately conduc
on Criteria
cribed by p
the study, if
n such as do
prevention o
actual regim
(male and fe
s on any tr
onths (two c
to LPV/r +
-1 infected 
an 60 days a
perience at l
for Use/Dis
mivudine 
ction crite
al results th
sician/invest
diseases; 
nal or region
on fulfilling
ct the observ
a
physician ac
f he/she will
ocumented 
of long-term
men no long
emale). 
riple HAAR
consequently
+ 3TC as d
patients w
ago.   
least 6 mont
sclosure of D
eria 
he below list
tigators: 
nal AIDS ce
g the inclusi
vational pro
ccording to 
l be switche
toxicity, m
m toxicity (
er recomme
RT with pla
y plasma HI
decided by 
who were sw
ths.  
Data signed
ted criteria w
enter; 
ion/exclusio
ogram. 
the routine
ed on the du
management 
(pre-emptiv
ended, etc, a
asma HIV-1
IV-1 RNA l
the physici
witched on 
d by the pati
will be cons
on criteria; 
e clinical pr
ual therapy (
of potentia
ve switch), p
and will be 
1 RNA leve
levels) trans
ian in the r
the dual th
ient. 
14 
sidered 
ractice. 
(LPV/r 
al drug 
patient 
satisfy 
el <50 
sferred 
routine 
herapy 

 
 
Versi
9.7
A pa
1
2
 
9.8
The 
cons
mon
follo
inter
 
ion 01, dated 1
atient will n
1. Has con
(please s
2. Previous
patient visi
sulting phys
nths) when d
ow-up visit/
rvals of pati
Lopinavir/rito
P15-452 Prot
17 August 201
Exclusi
ot be eligibl
ntraindicatio
see the lates
s participati
Descrip
its will be s
sician. How
dual therapy
/termination
ent visits w
onavir and Lam
tocol 
15 
ion Criteri
le for this P
ons for the 
st versions o
on in this pr
ption of Ac
cheduled ba
wever, it w
y (LPV/r + 
n contact. 
will not const
mivudine 
ia
MOS if he/
treatment w
of the locally
rogram. 
ctivities  
ased on rou
would be 5
3TC) will 
Failure to 
titute a brea
she fulfils th
with lopina
y approved 
utine clinica
 observatio
be adminis
observe th
ach or violat
he following
avir/ritonavi
labels). 
al practice an
onal visits 
strated to th
hese 3-mon
tion of the p
g criterion: 
ir and lamiv
nd prescript
(approx. ev
he patient an
nth usual p
protocol. 
15 
 
vudine 
tion of 
very 3 
nd one 
ractice 

 
 
Versi
x
x
x
x
x
x
x
x
x
x
Obs
x
x
x
x
 
ion 01, dated 1
Assignm
digit pat
Inclusion
Last ava
Last ava
Collectio
Last ava
Registra
Collectio
circumfe
Collectio
choleste
(mmol/L
SAEs m
 
ervational
Last ava
Last ava
was don
Last ava
level is d
was und
after 1 m
HIV-1 d
designat
Registra
Lopinavir/rito
P15-452 Prot
17 August 201
ment of pati
tient individ
n/exclusion
ailable CD4+
ailable HIV-
on of releva
ailable resist
ation of start
on of anth
erence in cm
on of labor
rol (mmol
L), creatinin
monitoring 
visits 2 and
ailable CD4+
ailable HIV-
ne or planned
ailable resis
detectable a
detectable, d
month. If the
drug resistan
ted these tes
ation of pres
onavir and Lam
tocol 
15 
ient’s identi
dual enrollm
n criteria ver
+ T-cell cou
-1- RNA tes
ant medical 
tance test re
t date and do
hropometric
m).    
ratory tests 
/L), LDL-
ne(μmol/L), 
d 4 
+ T-cell cou
-1- RNA tes
d both test a
stance test r
at a given vi
data of conf
e confirmat
nce genotyp
sts and the s
scribed med
mivudine 
ification num
ment number
rification 
unt test resu
st result 
history 
esult for LPV
oses of pres
c parameter
results (glu
and HDL
ALT (u/l), 
unt test resu
st result. If 
and re-test r
result for L
isit and at th
firmatory pl
ory plasma 
ing test will
such informa
ications 
mber (two-
r) 
ult 
V/r and 3TC
scribed LPV
rs measure
ucose (mmo
L-cholestero
AST (u/l)).
ult 
last test res
results will b
LPV/r and 3
he previous 
lasma HIV-
HIV-1 RNA
l be collecte
ation is avai
digit center
C, if any 
V/r and 3TC 
ement (arm
ol/L), insuli
ol (mmol/L
ult was dete
be collected
3TC (if pla
visit the pla
1 RNA test
A is >400 c
ed, if the con
ilable) 
r number + 
m, hip and 
in (μEq/ml)
L), trigclyc
ectable and 
d  
asma HIV-1
asma HIV-1
t will be co
copies/mL, d
nsulting phy
17 
three-
waist 
), total 
cerides 
re-test 
1 RNA 
1 RNA 
llected 
data of 
ysician 

 
 
Versi
Obs
x
x
x
x
x
x
x
Follo
cont
x
9.9
Deci
parti
treat
 
ion 01, dated 1
Monitor
causing 
ervational
Last ava
Last ava
was don
Last ava
Registra
Collectio
circumfe
Collectio
choleste
(mmol/L
Monitor
causing 
ow-up Visi
tact
x
Monitor
causing 
Complet
patient p
will be c
ision regard
icipant will 
tment discon
Lopinavir/rito
P15-452 Prot
17 August 201
ring of AE
treatment d
visits 3 and
ailable CD4+
ailable HIV-
ne or planned
ailable resist
ation of pres
on of anth
erence in cm
on of labor
rol (mmol
L), creatinin
ring of AE
treatment d
it/Terminat
ring of AE
treatment d
tion form of
prematurely
collected     
Termin
ding the di
be ultimate
ntinuation w
onavir and Lam
tocol 
15 
Es (non-seri
discontinuati
d 5  
+ T-cell cou
-1- RNA tes
d both test a
tance test re
scribed med
hropometric
m)    
ratory tests 
/L), LDL-
ne(μmol/L), 
Es (non-seri
discontinuati
tion or Ear
Es (non-seri
discontinua
f eCRF has 
y discontinu
       
ation of th
iscontinuatio
ely based on
will be colle
mivudine 
ious AEs s
ions], SAEs
unt test resu
st result. If 
and re-test r
esult for LPV
ications 
c parameter
results (glu
and HDL
ALT (u/l), 
ious AEs s
ions], SAEs
rly Termin
ious AEs s
ations], SAE
to be comp
ued the study
he Program
on of the 
n the treatin
cted and sum
spontaneous
s, [including
ult 
last test res
results will b
V/r and 3TC
rs measure
ucose (mm
L-cholestero
AST (u/l))
spontaneous
s, [including
ation Cont
spontaneous
Es, [includi
leted at the 
y. Reason f
m
dual therap
ng physician
mmarized in
sly reported
g SAEs that 
ult was dete
be collected
C 
ement (arm
ol/L), insul
ol (mmol/L
sly reported
g SAEs that 
tact - Perso
sly reported
ng SAEs th
end of the s
for prematur
py (LPV/r 
n’s judgmen
n the study 
d) [includin
cause death
ectable and 
d 
m, hip and 
lin (μEq/ml
L), trigclyc
d) [includin
cause death
onal or tele
d) [includin
hat cause d
study and al
re discontin
+ 3TC) for
nt. The reas
report. 
18 
ng AE  
hs] 
re-test 
waist 
l), otal 
cerides 
ng AE  
hs]  
ephone 
ng AE  
deaths] 
lso if a 
nuation 
r each 
son for 

 
 
Versi
Abb
done
 
9.10
9.10
1
9.10
1
2
3
4
5
6
7
 
ion 01, dated 1
Vie may sto
e to particip
0
0.1
1. Proporti
RNA lev
0.2
1. Proporti
RNA lev
2. Absolute
change 
transform
3. Absolute
compare
4. Proporti
regimen
5. Absolute
measure
baseline
6. Absolute
(glucose
creatinin
7.  Proport
[includin
Lopinavir/rito
P15-452 Prot
17 August 201
op the prog
ants if they 
Endpoi
Primary
on of patien
vel at week 
Second
on of patie
vel at week 
e values of
as compar
med data).  
e values of 
ed to the bas
on of patien
n.  
e values a
ements (arm
. 
e values at 
e, insulin, 
ne, ALT, AS
ion of pat
ng AE  cau
onavir and Lam
tocol 
15 
gram in case
continue to
ints
y Endpoin
nts on dual
48 of the ob
dary Endp
ents on dual
24 of the ob
f HIV-1- R
red to the 
 
CD4+ T-ce
seline. 
nts who dev
at the wee
m, hip and 
the weeks
total chole
ST) as comp
tients with 
using treatm
mivudine 
e there is ev
o participate
nt
l therapy (L
bservational
oints 
l therapy (L
bservational
RNA viral lo
baseline (
ell counts at
velop resist
eks 24 and
waist circu
 24 and 48
sterol, LDL
pared to the 
AEs (non
ment discont
vidence of h
. 
LPV/r + 3TC
l period. 
LPV/r + 3T
l period. 
oader at th
(untransform
t the weeks 
ance to eac
d 48 and 
umference 
8 and chang
L- and HD
baseline. 
n-serious A
tinuations], 
harm that is
C) with und
TC) with un
he weeks 24
med and b
24 and 48 
ch class of d
changes o
in cm) as 
ges of meta
DL-choleste
AEs spontan
SAEs, [inc
 done or co
detectable H
ndetectable 
4 and 48 a
base-10 log
and the cha
drugs in the
of anthropo
compared 
abolic para
rol, triglyc
neously rep
cluding SAE
19 
ould be 
HIV-1- 
HIV1- 
nd the 
garithm 
ange as 
e study 
ometric 
to the 
meters 
cerides, 
ported) 
Es that 

 
 
Versi
 
9.11
Data
docu
This
phar
9.12
The 
infec
LPV
arm.
the p
Whe
two-
exten
for a
num
9.13
For 
eCR
and 
subje
prog
 
ion 01, dated 1
cause d
(SOCs) 
1
a for the stu
ument at the
s may includ
rmacy dispe
2
OLE study
cted patient
V/r plus 3TC
. Therefore,
patients amo
en the samp
-sided 95% 
nd 5% (i.e. 
an expected
mber of enrol
3
this progra
RF data man
reviewed/ap
ect enrolled
gram data fo
Lopinavir/rito
P15-452 Prot
17 August 201
eaths], with
and by frequ
Data So
udy will be 
e center. So
de hospital 
ensing and o
Study S
y (1) reporte
ts remained 
C arm at 48
 for this obs
ong study sa
ple size wit
confidence
half width 
d proportion 
lled patients
Data Ma
m electroni
nagement pla
pproved by
d in this pr
or AbbVie (
onavir and Lam
tocol 
15 
h AEs orga
uency 
ources
collected w
ource docum
records, clin
other records
Size 
ed that 87.8
suppressed
 weeks, wit
servational 
ample will h
thout a cons
 interval fo
of the 95%
of 85%. Co
s will consti
anagemen
ic Case rep
an and data
y AbbVie re
rogram. The
(or a CRO f
mivudine 
anized acco
within clinic
ments will b
nical and of
s, recorded 
8% of pre-s
d  (undetect
th non-infer
program, it 
have undete
sideration o
r a single p
% confidence
onsidering a
itute 216. 
nt
port forms (
a validation 
epresentativ
ese forms w
for data man
ording to S
cal interview
be original d
ffice charts,
data from au
suppressed t
table plasma
riority to the
is estimate
ctable plasm
of dropout i
proportion u
e interval) f
an approxim
(eCRF) will
specificatio
ve(s). eCRF
will be used
nagement) 
System Org
w with the p
documents, 
, laboratory
utomated in
treatment-ex
a HIV-1 RN
e LPV/r plu
d that a sim
ma HIV-1 R
is 196, a Si
using norma
from the ob
mate dropou
l be used. P
on will be d
F will be co
d to transm
and regulato
gan Classifi
patient and 
data and re
 data/inform
nstruments, 
xperienced 
NA level)) 
us 2 NRTi c
milar percent
RNA at week
imple Asym
al distributio
bserved prop
ut rate abou
Prior to set
eveloped by
ompleted fo
mit and colle
ory authorit
20 
fication 
source 
ecords. 
mation, 
etc. 
HIV-1 
on the 
control 
tage of 
k 48.  
mptotic 
on will 
portion 
t 10%, 
t-up of 
y CRO 
or each 
ect the 
ties, as 

 
 
Versi
appl
must
for 
auto
infor
The 
his/h
princ
subje
revie
   
9.14
The 
Sinc
gene
with
mini
Qual
each
appr
Data
The 
 
ion 01, dated 1
icable. Elec
t be entered
site staff 
matically. D
rmation ente
investigato
her routine p
cipal investi
ect’s set of
ewed period
4
principal fe
ce this is an
eration of d
h number o
imum and 
litative vari
h category. 
ropriate. 
a Analysis S
following a
Lopinavir/rito
P15-452 Prot
17 August 201
ctronic CRF
d by trained
during site
Data discrep
ered in the e
or will store
practice. Th
igator will r
f eCRFs b
dically for c
Data An
eatures of th
n open-label
descriptive s
f patients, 
maximum 
iables will b
Graphs m
Set 
analysis pop
onavir and Lam
tocol 
15 
Fs will be se
d and author
e initiation.
pancies dete
eCRFs must
e subject d
hese subject 
review the e
y electronic
ompletenes
nalysis 
he statistica
, non-rando
summary st
mean, stan
values, and
be summari
may be gene
pulations wil
mivudine 
et by CRO d
rized person
. eCRF tra
ected by eCR
t also be ref
data in his/h
files will se
eCRFs for c
c signature
s, legibility 
al analysis o
omized trial
tatistics. Qu
ndard deviat
d 95% CI 
ized with th
erated for 
ll be defined
designee as 
n only. eCR
acks all ch
RF will be a
flected in th
her source 
erve as sour
completenes
e where ind
and accepta
of the data 
, the analys
uantitative v
tion, media
for mean
he number a
visual inter
d: 
web based s
RF training w
hanges to 
addressed to
e patient so
documents 
rce data for 
ss and accur
dicated. Th
ability by A
are describe
ses will prim
variables wi
an, 1st quar
or median 
and proport
rpretation o
site. In eCR
will be perf
the entered
o investigat
urce docum
in accorda
the program
racy and sig
e eCRFs w
AbbVie/CRO
ed in this s
marily invol
ill be summ
rtile, 3rd qu
(as approp
tion of patie
of the resu
21 
RF data 
formed 
d data 
tor. All 
ments. 
ance to 
m. The 
gn each 
will be 
O. 
ection. 
lve the 
marized 
uartile, 
priate). 
ents in 
ults, as 

 
 
Versi
All 
Use/
Enro
The 
No i
 
Base
Base
statis
Ana
Num
HIV
asym
Ana
1. N
HIV
asym
2. A
chan
data)
gene
untra
 
ion 01, dated 1
Enrolled S
/Disclosure 
olled Set be 
primary and
imputations 
eline Demo
eline demog
stics mentio
alysis of prim
mber and pro
V-1- RNA le
mptotic two-
alysis of seco
Number and 
V-1- RNA le
mptotic two-
Absolute val
nge as comp
) will be s
erated for 
ansformed d
Lopinavir/rito
P15-452 Prot
17 August 201
Set will inc
of Data for
used for all
d secondary
for missing
ographic an
graphic and
oned above. 
mary endp
oportion of p
vel at week
-sided 95% 
ondary end
proportion 
evel at wee
-sided 95% 
lues of HIV
pared to the
summarized
transforme
data.   
onavir and Lam
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15 
clude all p
rm to partic
l study analy
y effectivene
g data will b
nd Clinical C
d clinical ch
point 
patients on 
k 48 of the o
confidence 
dpoints 
of patients
ek 24 of the
confidence 
V-1- RNA v
e baseline (
d with desc
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mivudine 
patients wh
cipate in the
yses.    
ess analyses
be performed
Characteri
haracteristic
dual therapy
bservationa
interval for
 on dual th
e observatio
interval for
viral load a
(untransform
cribed abov
nd 95% CI
ho signed A
e study and 
s will be per
d.    
istics 
cs will be s
y (LPV/r + 
al period wil
r a single pro
herapy (LPV
onal period 
r a single pro
at baseline, 
med and ba
ve statistics.
I for med
Authorizatio
have any c
rformed on t
summarized
3TC) with u
ll be present
oportion wi
V/r + 3TC) 
will be pre
oportion wi
at weeks 2
ase-10 logar
. 95% CI f
dian will b
on (Consen
collected da
the observe
d with desc
undetectable
ted. A simp
ill be genera
with undete
esented. A 
ill be genera
4 and 48 a
rithm transf
for mean w
be generate
22 
nt) for 
ata. All 
d data. 
criptive 
e 
le 
ated. 
ectable 
simple 
ated. 
and the 
formed 
will be 
ed for 

 
 
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3. A
chan
abov
4. N
prese
deve
num
enro
will 
5. A
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with
6. A
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ion 01, dated 1
Absolute val
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Number and
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be generate
Absolute val
m, hip and w
h described w
Absolute val
mol/L), insu
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mpared to th
stics. 95% C
Number and
orted) [inclu
se deaths]wi
portion will 
h non-seriou
tment disco
ed by Prefer
Lopinavir/rito
P15-452 Prot
17 August 201
lues of CD4
mpared to 
d statistics. 
d proportion
rately. The t
esistance div
ent who dev
study.  An e
ed.  
lues at wee
waist circum
with abovem
lues at wee
ulin (μEq/m
clycerides 
he baseline
CIs for mean
d proportion
uding AE  ca
ill be presen
be generate
us AEs, SA
ntinuations 
rred Terms 
onavir and Lam
tocol 
15 
4+ T-cell c
the basel
95% CIs for
n of patien
two proport
vided on nu
velops the r
exact two-si
eks 24 and 
mference in c
mentioned s
eks 24 and 
ml), total ch
(mmol/L), 
e will be s
ns will be g
n of patien
ausing treatm
nted. An ex
ed. The com
AEs, SAE in
will be pre
(PTs) cons
mivudine 
ounts at the
line will b
r means wil
nts who de
tions will b
umber of p
resistance d
ided 95% co
48 and ch
cm) as comp
tatistics. 95
48 and cha
holesterol (
creatinine
summarized
generated.  
nts with all
ment discon
xact two-sid
mmon table 
ncluding SA
esented. Th
istent with
e baseline, 
be summa
ll be generat
evelop resis
be presented
patients who
divided on n
onfidence in
hanges of an
pared to the
% CIs for m
anges of m
(mmol/L), 
(μmol/L), 
d with desc
l AEs (non
ntinuations]
ded 95% con
with all AE
AEs that cau
he tables of 
the latest ve
at weeks 2
arized with
ted. 
stance to ea
d: (1) numb
o had the re
number of p
nterval for a
nthropomet
 baseline w
means will b
etabolic par
LDL- and 
ALT (u/l)
cribed with
n-serious A
, SAEs, [inc
nfidence int
Es as well a
use deaths, 
f AEs will b
ersion of M
24 and 48 a
h described
ach drug w
ber of patien
esistance te
patients who
a single prop
ric measure
will be summ
be generated
rameters (g
HDL-chol
, AST (u/
h abovemen
Es spontan
cluding SAE
terval for a 
as separated
and AEs c
be generate
MedDRA (M
23 
and the 
d with 
will be 
nt who 
est; (2) 
o were 
portion 
ements 
marized 
d. 
glucose 
esterol 
/l)) as 
ntioned 
neously 
Es that 
single 
d tables 
causing 
d with 
Medical 

 
 
Versi
Dict
(incl
acco
com
inclu
frequ
9.15
The 
assu
docu
appl
Stud
and 
The 
discr
will 
Data
appr
data 
Stud
in ac
 
ion 01, dated 1
tionary for 
luding death
ording to PT
mmon AEs, 
uded in the
uencies may
5
AbbVie rep
urance system
umented, an
icable local
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guidelines. 
AbbVie re
repancies w
be made to 
a Manageme
roved by Ab
process wit
dy report wi
ccordance w
Lopinavir/rito
P15-452 Prot
17 August 201
Regulatory
hs), non-seri
T frequencie
SAEs, and 
e body of t
y be append
Quality
presentative
m is in plac
nd reported 
l laws and re
is developed
epresentative
will be comm
the databas
ent Plan and
bbVie repre
thin the stud
ill be develo
with internal
onavir and Lam
tocol 
15 
y Activities
ious AEs, an
es and by S
AEs causin
the report. 
ded to the re
y Control 
es are respon
ce to ensure
in complia
egulations. 
d by AbbVi
e can moni
municated 
se per applic
d Data Vali
esentative b
dy and respo
oped by CR
l templates a
mivudine 
s) . Tables 
nd AEs cau
OC, Severit
ng treatmen
A complete
port. 
nsible for en
e that the pr
ance with th
ie Study Tea
itor the elec
to site for 
cable EDC p
dation Spec
efore eCRF
onsible pers
RO and revi
and guidelin
will prese
using treatme
ty and Caus
nt discontinu
e tabulated 
nsuring that
rogram is co
he protocol,
am in accor
ctronic case
clarification
procedures. 
cification wi
F launch. Th
sonal.  
iewed/appro
nes. 
ent informa
ent disconti
sality. Summ
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list of the
t a quality c
onducted an
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rdance with 
e report for
n. Any nece
 
ill be develo
hese docum
oved by Abb
ation about 
inuation org
mary tables 
be generate
se AEs and
control and q
nd data gen
standards an
internal tem
rms in EDC
essary corre
oped by CR
ments will de
bVie Study
24 
SAEs 
ganized 
 of the 
ed and 
d their 
quality 
erated, 
nd any 
mplates 
C. Any 
ections 
RO and 
escribe 
y Team 

 
 
Versi
9.16
The 
cente
dual
patie
week
Ther
natu
thera
9.17
Not 
10.0
This
(15) 
Writ
prior
writt
will 
All 
indiv
The 
of C
enro
 
ion 01, dated 1
6
study is pl
ers study w
 therapy (L
ents with an
ks in the rou
refore, the l
ure and resul
apy (LPV/r 
7
applicable. 
0
s observation
and with Fe
tten authoriz
r to enrollin
ten authoriz
be made in 
data will b
vidual patien
protocol an
Central and/o
ollment will 
Lopinavir/rito
P15-452 Prot
17 August 201
Limitat
lanned as a
with no contr
LPV/r + 3T
n undetectab
utine clinica
limitations 
lts of the stu
+ 3TC) in r
Other A
Protec
nal program
ederal Law 
zation to us
ng each pat
zation will n
order to av
be captured 
nts and hen
nd relevant p
or local (if a
start only a
onavir and Lam
tocol 
15 
ions of the
a non-interv
rol group. T
TC) in pop
ble plasma 
al settings o
of the stud
udy are valid
routine clini
Aspects
ction of H
m will be co
of 27 July 2
se and/or dis
tient in the
not be inclu
oid subject 
and handl
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program do
applicable) 
after obtainin
mivudine 
e Researc
ventional, p
The study is 
pulation of 
HIV-1 RN
f the Russia
dy based on
d only for u
ical settings 
Human S
onducted in 
2006 N 152-
sclose perso
 program a
ded in the p
identifying 
ed in such 
onfidentiali
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ch Methods
product-focu
 aimed to a
f treatment-
NA level (fo
an Federatio
n its observ
understandin
in Russia.  
Subjects
accordance 
-FZ “On pe
onal and/or 
and parents 
program. Ho
information
a way so 
ity will be m
ill be submi
nt Ethics Co
approval fro
s
used, longit
ccess the ef
-experienced
or at least 6
on.  
vational and
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with Decla
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health data 
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n (such as n
as to not r
maintained a
itted for rev
ommittee(s) 
m the IEC. 
udinal and 
ffectiveness
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6 months) o
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veness of th
aration of H
” (18). 
must be ob
g to provid
reasonable 
name, addres
reveal iden
at all times. 
view and ap
(IEC) and p
25 
multi-
 of the 
nfected 
ver 48 
arative 
he dual 
elsinki 
btained 
e such 
efforts 
ss, etc). 
ntity of 
pproval 
patient 

 
 
Versi
11.0
A Co
relat
relia
distr
Com
repo
Sect
11.1
11.1
An a
does
there
findi
whet
Such
accid
pre-e
If an
even
De
Lif
 
ion 01, dated 1
0
omplaint is 
ted to the ph
ability, safet
ribution. 
mplaints asso
orted to the S
tions 11.1.1 
1
1.1
adverse even
s not necessa
efore be any
ing), sympto
ther or not t
h an event 
dental or int
existing con
n adverse ev
nt (SAE): 
ath of Patie
fe-Threaten
Lopinavir/rito
P15-452 Prot
17 August 201
Manag
any written
hysical chara
ty, effectiven
ociated with
Sponsor (Se
through 11
Medica
Advers
Catego
nt (AE) is d
arily have a
y unfavorab
om, or disea
the event is 
can result fro
tentional ov
ndition or ill
vent meets a
ent:
ning: 
onavir and Lam
tocol 
15 
gement a
n, electronic
acteristics, i
ness, or per
h any compo
ection 11.2.2
.1.6.  For pr
al Complai
se Event D
ories 
defined as an
a causal rela
le and unint
ase tempora
considered 
om use of th
verdose, dru
lness is cons
any of the fo
An e
An e
wou
inter
inclu
occu
mivudine 
and Repo
, or oral com
identity, qua
formance of
onent of this
2). For adve
roduct comp
nts
Definition a
ny untoward
ationship wit
tended sign 
ally associat
causally rel
he drug as st
g abuse, or 
sidered an a
ollowing crit
event that re
event that, i
uld have resu
rvention had
ude an even
urred in a m
orting of 
mmunication
ality, purity
f a product/
s investigati
erse events, 
plaints, plea
and Seriou
d medical oc
th their treat
(including a
ed with the 
lated to the 
tipulated in 
drug withdr
adverse even
teria, it is co
esults in the
in the opinio
ulted in imm
d not been t
nt that would
more severe f
Complai
n that allege
y, potency, d
/device after
ional produc
please refer
ase refer to S
us Advers
ccurrence in
tment.  An a
an abnorma
use of a me
use of the p
the labeling
rawal.  Any
nt. 
onsidered a 
e death of a p
on of the inv
mediate fata
taken.  This 
d have been
form. 
ints 
es deficienc
durability, 
r it is release
ct must be 
r to 
Section 11.2
e Event 
n a patient, w
adverse eve
al laboratory
edicinal prod
product. 
g, as well as
 worsening 
serious adv
patient. 
vestigator, 
ality if medi
does not 
n fatal if it h
26 
cies 
ed for 
2. 
which 
ent can 
y 
duct, 
s from 
of a 
verse 
cal 
had 

 
 
Versi
Ho
Pro
Ho
Co
Per
Dis
Im
Re
Sur
Pre
 
11.1
The 
colle
 
ion 01, dated 1
ospitalizatio
olongation 
ospitalizatio
ongenital An
rsistent or 
sability/Inc
mportant Me
quiring Me
rgical Inter
event Serio
1.2
following d
ected as an e
Lopinavir/rito
P15-452 Prot
17 August 201
on:
of
on:
nomaly: 
Significant
capacity: 
edical Even
edical or 
rvention to 
ous Outcom
Severit
definitions w
endpoint/da
onavir and Lam
tocol 
15 
An e
for a
eme
facil
An e
hosp
An a
that 
t
An e
inter
patie
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such
influ
ankl
nt
me:
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imm
hosp
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surg
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hosp
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disa
spon
imp
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dysc
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depe
ty
will be used 
ata point in t
mivudine 
event that re
any length o
ergency room
lity. 
event that o
pitalized and
anomaly det
results in fe
event that re
rferes with t
ent.  Disabil
eriences of r
h as headach
uenza, and a
le). 
important m
mediately lif
pitalization,
pardize the p
gical interve
ed above (i.e
pitalization,
genital anom
ability/incap
ntaneous ab
ortant medi
ude allergic
tment in an 
crasias or co
atient hospit
endency or 
to rate the s
the study an
esults in an 
of time.  Thi
m visit or ad
ccurs while
d prolongs t
tected at or 
etal loss. 
esults in a c
the activitie
lity is not in
relatively m
he, nausea, v
accidental tr
medical even
fe-threatenin
 but based o
patient and m
ention to pre
e., death of p
 prolongatio
maly, or per
pacity).  Add
ortion or sti
cal event.  E
c bronchospa
emergency 
onvulsions t
talization, or
drug abuse.
severity for 
nd for all ser
admission t
is does not i
dmission to 
e the study p
the patient's
after birth, 
ondition tha
es of daily li
ntended to in
minor medica
vomiting, d
rauma (e.g.,
nt that may n
ng or result 
on medical j
may require
event any of
patient, life 
on of hospit
rsistent or si
ditionally, an
illbirth is co
Examples of
asm requirin
room or at 
that do not r
r the develo
 
any adverse
rious advers
to the hospit
include an 
an outpatie
patient is 
s hospital sta
or any anom
at substantia
iving of a stu
nclude 
al significan
diarrhea, 
, sprained 
not be 
in death or 
judgment m
e medical or
f the outcom
threatening
talization, 
ignificant 
ny elective 
onsidered an
f such event
ng intensive
home, bloo
result in 
opment of dr
e event bein
se events. 
27 
tal 
ent 
ay. 
maly 
ally 
udy 
nce 
may 
r 
mes 
g, 
or 
n 
ts 
e 
d 
rug 
ng 

 
 
Versi
Mi
Mo
Sev
 
11.1
The 
the u
Re
No
 
If no
be pr
11.1
Serio
patie
until
11.1
In th
 
ion 01, dated 1
ild: 
oderate:
vere:
1.3
following d
use of produ
asonable P
o Reasonabl
o reasonable
rovided for 
1.4
ous adverse
ent's authori
l 30 days fo
1.5
he event of a
Ɣ
For e
conta
awar
Lopinavir/rito
P15-452 Prot
17 August 201
The a
The a
patie
The a
patie
threa
Relatio
definitions w
uct: 
Possibility 
le Possibilit
e possibility
the adverse
Serious
e events will
ization to us
llowing the 
Serious
a serious adv
events from
act person i
re of the eve
onavir and Lam
tocol 
15 
adverse eve
adverse eve
nt's usual ac
adverse eve
nt's usual ac
atening. 
nship to P
will be used 
An adv
causal 
event.
ty
An adv
causal 
event.
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e event. 
s Adverse
l be reported
se and disclo
intake of th
s Adverse
verse event,
m patients us
dentified be
ent. 
mivudine 
nt is transie
nt causes th
ctivities. 
nt causes co
ctivities and
Pharmaceu
to assess th
verse event 
relationship
verse event 
relationship
elated to pro
 Event Co
d to AbbVie
ose informa
he last dose 
 Event Re
, the physici
ing and Abb
elow within 
ent and easil
he patient di
onsiderable 
d may be inc
utical Prod
he relationsh
where there
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where there
p between th
oduct is give
ollection P
e from the ti
ation (or the 
of physician
porting 
ian will: 
bVie produc
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ly tolerated 
scomfort an
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capacitating
duct
hip of the ad
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he product a
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he product a
en, an altern
eriod
ime the phy
patient's in
n-prescribed
ct - notify th
f the physic
by the patie
nd interrupts
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g or life 
dverse event
e to suggest
and the adve
ence to sugg
and the adve
nate etiology
ysician obtai
formed con
d treatment.
he AbbVie 
ian becomin
28 
ent. 
s the 
t to 
t a 
erse 
gest a 
erse 
y must 
ins the 
nsent) 
. 
ng 

 
 
Versi
Con
Back
11.1
In th
cont
awar
11.2
11.2
A Pr
drug
For 
pack
discr
miss
 
ion 01, dated 1
ntact for SA
k-up contact
1.6
he event of 
tact person 
re of the pre
2
2.1
roduct Com
g component
a product 
kaging, prod
repancies/in
sing compon
Lopinavir/rito
P15-452 Prot
17 August 201
AEs reportin
t for SAEs r
Pregna
a pregnanc
identified i
egnancy. 
Produc
Definiti
mplaint is an
t of the prod
this may 
duct appeara
nadequacies
nents/produ
onavir and Lam
tocol 
15 
ng: 
reporting: 
ancy Repo
cy occurrenc
in Section 1
ct Complai
ion 
ny Complain
duct.  
include, bu
ance whose
 in the lab
ct, or packa
mivudine 
rting
ce in the pa
11.1.5 with
int 
nt (see Secti
ut is not li
 color/mark
beling/instru
aging issues
atient, the p
in 24 hours
ion 11.0 for
imited to, 
kings do not
ructions (ex
. 
physician w
s of the ph
r the definit
damaged/br
t match the 
xample:  p
will notify A
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ion) related
roken prod
labeling, la
printing ille
29 
AbbVie 
coming 
d to the 
duct or 
abeling 
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Versi
11.2
Prod
Spon
Com
follo
the S
Spon
summ
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the i
Prod
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The 
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2.2
duct Compl
nsor within
mplaint repo
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Sponsor (or 
nsor.  Produ
mary.  All o
duct compla
identified co
duct Compl
dition. In in
stigator to 
hin 30 days, 
description
stigate and 
mary contac
Lopinavir/rito
P15-452 Prot
17 August 201
Reporti
laints conce
n 24 hours 
orting practi
a satisfacto
an authoriz
uct Complai
other compl
aints involvi
ontact or ma
laints may 
nstances wh
return the p
the site will
n of the com
determine i
ct for Prod
onavir and Lam
tocol 
15 
ing
erning the 
of the stud
ices.  Produ
ory conclusi
zed represen
ints associat
aints will be
ing a non-Sp
anufacturer, 
require re
here a return
product wit
l need to pro
mplaint is im
f any correc
duct Compl
mivudine 
investigatio
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uct Compla
ion.  All fol
ntative) and 
ted with adv
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ponsor inve
as necessar
eturn of the
n is request
thin 30 day
ovide justifi
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aint report
onal produ
owledge of 
aints occurri
llow-up info
documented
verse events
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e product 
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fication and 
or AbbVie i
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product sho
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with the a
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ns cannot b
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the study w
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ported in the
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to the 
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Back
12.0
At th
repo
meth
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with
The 
publ
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13.0
1.
2.
 
ion 01, dated 1
k-up contac
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he end of th
ort author. T
hodology o
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study will 
lished at th
OS will be p
r prior writ
ntific confer
0
Gatell JM
Lamivud
Maintena
AIDS 20
M.J. Rolo
GARDEL
Lopinavir/rito
P15-452 Prot
17 August 201
ct for Prod
Plans
Result
he study, a 
This report 
f the study
study repor
eased to un
s written app
be registere
his web-bas
published b
tten agreem
rences.  
Refere
M et al. Non
dine vs. Trip
ance of HIV
14, Poster #
on et al. Du
L study. AID
onavir and Lam
tocol 
15 
duct Compl
for Disse
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study repo
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rt must be t
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3.
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6.
7.
8.
9.
10.
11.
 
ion 01, dated 1
Cahn et a
therapy w
inhibitors
results of
Dis. 2014
Thompso
Internatio
Gallant J
associate
reverse-tr
D:A:D St
transcript
enrolled i
(9622): 1
Brinkman
nucleosid
pathogen
354:1112
Arribas J
lopinavir
analysis. 
Arribas J
or withou
AIDS, 20
Paton et a
2014 Abs
Pery CM
pharmaco
infection
Lopinavir/rito
P15-452 Prot
17 August 201
al Dual thera
with lopinav
s in antiretro
f the random
4 Jul;14(7):5
on MA, Abe
onal AIDS S
JE, Parish M
ed with teno
ranscriptase
tudy Group
tase inhibito
in the D:A:D
1417-26 
n K, Smeitin
de-analogue
nesis of antir
2-1115. 
JR, Delgado
r-ritonavir an
J Acquir Im
JR, Horban A
ut nucleosid
010; 24: 223
al RCT of P
stract 550LB
M and Faulds
okinetic pro
". Drugs, 19
onavir and Lam
tocol 
15 
apy with lop
vir and riton
oviral-therap
mised, open 
572-80 
erg JA, Cahn
Society_US
MA, Keruly J
fovir disopr
e inhibitor tr
, Sabin CA,
ors and risk 
D study: a m
nk JA, Rom
e reverse-tra
retroviral-th
o R, Arranz A
nd 2 nucleo
mmune Defi
A, Gerstoft 
de analogues
3-30. 
PI monother
B 
s D. "Lamiv
operties and 
997, vol. 53
mivudine 
pinavir and 
navir plus tw
py-naive ad
label, non-i
n P, et al. A
SA Panel. 20
JC, Moore R
roxil fumara
reatment". C
, Worm SW
of myocard
multi-cohort
mijn JA, Rei
anscriptase i
herapy-relate
A et al. Lop
osides for ma
ic Syndr, 20
J, et al."The
s, for patien
rapy switch 
vudine: A re
therapeutic
, no4, pp. 6
ritonavir pl
wo nucleosid
dults with H
inferiority G
Antiretrovira
010;304:321
RD. "Chang
ate treatmen
Clin Infect D
W, et al. "Use
dial infarctio
t collaborati
ss P. Mitoch
inhibitors is 
ed lipodystr
pinavir-riton
aintenance t
009; 51: 147
e MONET t
nts with HIV
for long ter
view of its a
c efficacy in
57-80 
lus lamivudi
de reverse tr
HIV-1 infecti
GARDEL tri
al Recomme
1-333 JAMA
ges in renal 
nt, compared
Dis, 2005; 4
e of nucleos
on in HIV-in
ion". Lancet
hondrial tox
a key facto
rophy. Lanc
navir monot
therapy of H
7-52. 
trial: daruna
V RNA belo
rm HIV man
antiviral act
n the manage
ine versus tr
ranscriptase
ion: 48 wee
ial. Lancet I
endations of
A. 
function 
d with nucle
40(8): 1194-
side reverse 
nfected pati
t, 2008. 371
xicity induce
or in the 
cet. 1999; 
therapy vers
HIV: 96-we
avir/ritonavi
w 50 copies
nagement. C
tivity, 
ement of HI
32 
riple 
e 
k 
Infect 
f the 
eoside 
8 
ients 
1 
ed by 
sus 
ek 
ir with 
s/mL" 
CROI 
IV 

 
 
Versi
12.
13.
14.
15.
16.
 
 
 
 
 
 
 
 
 
 
 
ion 01, dated 1
Cleary S,
priority s
Benson C
lopinavir
in human
patients. 
Murphy R
lopinavir
HIV Clin
WMA De
Human S
17. Feder
Lopinavir/rito
P15-452 Prot
17 August 201
, McIntyre D
setting". Hea
CA, Deeks S
r/ritonavir pl
n immunode
J Infect Dis
RL, da Silva
r/ritonavir-b
n Trials 200
eclaration o
Subjects, 20
ral Law of 2
onavir and Lam
tocol 
15 
DE. "Afford
alth Econ, 2
SG, Brun SC
lus nevirapi
eficiency vir
s 2002;185:5
a BA, Hicks
based regime
8;9:1-10 
of Helsinki -
13. 
27 July 2006
mivudine 
dability: The
2009;18:373
C, et al. Safe
ine and 2 nu
rus type 1-in
599-607  
s CB, et al. 
en in antiret
- Ethical Pri
6 N 152-FZ
e forgotten c
3-75 
fety and anti
ucleoside rev
nfected prot
Seven-year 
troviral-naiv
inciples for 
Z “ON PERS
criterion in 
iviral activit
verse-transc
tease inhibit
efficacy of 
ve HIV-1-in
Medical Re
SONAL DA
health-care 
ty at 48 wee
criptase inhi
tor-experien
f a 
nfected patie
esearch Invo
ATA”. 
33 
eks of 
ibitors 
nced 
ents. 
olving