Jou nal o Pa kinson’s Disease 13 (2023) 769–783
DOI 10.3233/JPD-225105
IOS P ess
769
Clinical Resea ch
Le odopa Ca bidopa In es inal Gel in
Ad anced Pa kinson’s Disease:
DUOGLOBE Final 3-Yea Resul s
K. Ray Chaudhu ia,∗, No be Ko ´
acsb, F ancesco E. Pon ie ic,d, Jason Ald ede, Paul Bou geois ,
Thomas L. Da isg, Es he Cuboh, Ma ie a Anca-He schko i schi, Robe Iansekj, Mus a a S.
Siddiquik, Mihaela Simul, La s Be gmannm, May a Ballinam, Pa ni Kuk ejam, Oma Ladhanim, Jia
Jiamand Da id G. S andae n
aPa kinson’s Founda ion In e na ional Cen e o Excellence, King’s College Hospi al, and King’s College
Ins i u e o Psychia y, Biomedical Resea ch Cen e, Psychology & Neu oscience, London, Uni ed Kingdom
bDepa men o Neu ology, Uni e si y o P´ecs, P´ecs, Hunga y
cDepa men o Neu oscience, Men al Heal h and Senso y O gans, Sapienza Uni e si y o Rome, Rome, I aly
dSan a Lucia Founda ion, IRCCS, Rome, I aly
eSelki k Neu ology, Spokane, WA, USA
Depa men o Neu ology AZ G oeninge, Ko ijk, Belgium
gDepa men o Neu ology, Vande bil Uni e si y Medical Cen e , Nash ille, TN, USA
hNeu ology Depa men , Hospi al Uni e si a io Bu gos, Bu gos, Spain
iDepa men o Neu ology, Edi h Wol son Medical Cen e , Holon, Is ael
jKings on Cen e, Monash Heal h, Melbou ne, Vic o ia, Aus alia
kDepa men o Neu ology, Wake Fo es School o Medicine, Wins on Salem, NC, USA
lDepa men o Neu ology, Vic o Babes Uni e si y o Medicine and Pha macy, Timisoa a, Romania
mAbbVie Inc., No h Chicago, IL, USA
nDepa men o Neu ology, Uni e si y o Alabama a Bi mingham, Bi mingham, AL, USA
Accep ed 14 May 2023
P e-p ess 5 June 2023
Published 25 July 2023
Abs ac .
Backg ound: Le odopa-ca bidopa in es inal gel (LCIG) imp o es mo o and non-mo o symp oms in pa ien s wi h ad anced
Pa kinson’s disease (aPD).
Objec i e: To p esen he inal 36-mon h e icacy and sa e y esul s om DUOGLOBE (DUOdopa/Duopa in Pa ien s wi h
Ad anced Pa kinson’s Disease – a GLobal OBse a ional S udy E alua ing Long-Te m E ec i eness; NCT02611713).
Me hods: DUOGLOBE was an in e na ional, p ospec i e, long- e m, eal-wo ld, obse a ional s udy o pa ien s wi h aPD
ini ia ing LCIG in ou ine clinical ca e. The p ima y endpoin was change in pa ien - epo ed “O ” ime o Mon h 36. Sa e y
was assessed by moni o ing se ious ad e se e en s (SAEs).
∗Co espondence o: D . K. Ray Chaudhu i, Depa men o
Basic and Clinical Neu oscience, The Mau ice Wohl Clinical
Neu oscience Ins i u e, King’s College London, 5 Cu combe
Road, London SE5 9RT, UK. Tel.: +44 203 299 7154; E-mail:
Ray[email p o ec ed].; ORCiD: 0000-0003-2815-0505.
ISSN 1877-7171 © 2023 – The au ho s. Published by IOS P ess. This is an Open Access a icle dis ibu ed unde he e ms
o he C ea i e Commons A ibu ion License (CC BY 4.0).
770 K.R. Chaudhu i e al. / Final 3-yea Resul s om he DUOGLOBE S udy
Resul s: Signi ican imp o emen s in “O ” ime we e main ained o e 3 yea s (mean [SD]: –3.3 hou s [3.7]; p< 0.001).
The e we e signi ican imp o emen s o Mon h 36 in o al sco es o he Uni ied Dyskinesia Ra ing Scale (–5.9 [23.7];
p= 0.044), Non-Mo o Symp oms Scale (–14.3 [40.5]; p= 0.002), Pa kinson’s Disease Sleep Scale-2 (–5.8 [12.9]; p< 0.001),
and Epwo h Sleepiness Scale (–1.8 [6.0]; p= 0.008). Heal h- ela ed quali y o li e and ca egi e bu den signi ican ly imp o ed
h ough Mon hs 24 and 30, espec i ely (Mon h 24, 8-i em Pa kinson’s Disease Ques ionnai e Summa y Index, –6.0 [22.5];
p= 0.006; Mon h 30, Modi ied Ca egi e S ain Index, –2.3 [7.6]; p= 0.026). Sa e y was consis en wi h he well-es ablished
LCIG p o ile (SAEs: 54.9% o pa ien s; discon inua ions: 54.4%; discon inua ions due o an ad e se e en : 27.2%). O 106
s udy discon inua ions, 32 pa ien s (30.2%) con inued LCIG ou side he s udy.
Conclusion: DUOGLOBE demons a es eal-wo ld, long- e m, educ ions in mo o and non-mo o symp oms in pa ien s
wi h aPD ea ed wi h LCIG.
Keywo ds: DUOGLOBE, Pa kinson’s disease, le odopa-ca bidopa in es inal gel, dyskinesia, eal-wo ld da a
INTRODUCTION
Le odopa is conside ed he “gold s anda d” o
he ea men o Pa kinson’s disease (PD) [1]. Wi h
disease p og ession, he bene i o o al le odopa
diminishes as he he apeu ic window na ows due
o he sho hal -li e o le odopa and p og essi e
dene a ion o he s ia um and subsequen pos -
synap ic plas ici y [2]. In addi ion, e a ic gas ic
emp ying (a common symp om wi h ad ancing PD)
leads o i egula gas oin es inal abso p ion o o al
le odopa and uns able plasma le odopa concen a-
ions, collec i ely esul ing in pulsa ile s imula ion
[2, 3]. Thus, mo o and non-mo o symp oms become
inc easingly di icul o manage wi h o al le odopa,
which can cause pa ien s o expe ience p edic able
and unp edic able luc ua ions be ween “On” pe i-
ods wi h po en ially disabling dyskinesias and “O ”
pe iods when he pa ien expe iences a e u n o hei
pa kinsonian symp oms and may e en be “ ozen”
and akine ic [2, 4, 5]. These symp oms p og es-
si ely wo sen o e ime and g ea ly impac pa ien s’
unc ional capaci y and heal h- ela ed quali y o li e
(HRQoL) [6, 7].
Le odopa ca bidopa in es inal gel (LCIG; also
known as ca bidopa-le odopa en e al suspension
[CLES]) is a s able gel suspension o le odopa-
ca bidopa (20 mg/mL and 5 mg/mL, espec i ely)
o con inuous day ime in usion in pa ien s wi h
ad anced PD (aPD) [8, 9]. Con inuous in usion
enables le odopa concen a ions o be kep a a con-
s an le el wi hin he indi idual’s op imal he apeu ic
window, making LCIG a meaning ul op ion o man-
aging aPD [3, 10]. Resul s om con olled clinical
ials ha e demons a ed bene icial e ec s o LCIG
he apy on mo o symp oms, including educ ions in
“O ” ime, inc eases in “On” ime wi hou ouble-
some dyskinesia, and imp o emen s in HRQoL and
ac i i ies o daily li ing [11–14]. No ably, esul s
om a ecen andomized clinical ial demons a ed
an imp o ed educ ion in dyskinesia as measu ed by
he Uni ied Dyskinesia Ra ing Scale (UDysRS) ol-
lowing ea men wi h LCIG s. op imized medical
ea men [15]. LCIG has also demons a ed bene-
icial e ec s on mo o and non-mo o symp oms in
obse a ional s udies [16–21], and sys ema ic li e a-
u e e iews and me a-analyses [22, 23].
DUOdopa/Duopa in Pa ien s wi h Ad anced
Pa kinson’s Disease, a GLobal OBse a ional
S udy E alua ing Long-Te m E ec i eness
(DUOGLOBE), was he i s in e na ional, ully
p ospec i e, long- e m, non-in e en ional, pos -
ma ke ing, obse a ional s udy o pa ien s wi h
aPD ea ed wi h LCIG in a ou ine clinical se -
ing. One-yea in e im esul s indica ed signi ican
imp o emen s in mo o symp oms (including “O ”
ime and dyskinesia), non-mo o symp oms (includ-
ing sleep), HRQoL, and ca egi e bu den, wi h
sa e y e en s consis en wi h hose no ed in p e ious
con olled clinical ials and obse a ional s udies
[24]. This epo p esen s he inal 36-mon h esul s
om he DUOGLOBE s udy.
METHODS
S udy design and ea men
DUOGLOBE was a global mul icen e , single-
a m, non-in e en ional, pos -ma ke ing, obse a-
ional s udy (NCT02611713) conduc ed in 55 si es
ac oss 10 coun ies (Aus alia, Belgium, Hunga y,
Is ael, I aly, Romania, Slo enia, Spain, Uni ed King-
dom, and he Uni ed S a es) [24].
De ailed me hods o his s udy ha e been pub-
lished [24]. In b ie , pa ien s en olled in his 36-mon h
eal-wo ld s udy had aPD o whom hei physi-
K.R. Chaudhu i e al. / Final 3-yea Resul s om he DUOGLOBE S udy 771
cians decided o s a LCIG ea men acco ding o
he local p oduc label and speci ic eimbu semen
c i e ia. LCIG dosage was indi idually op imized
o clinical esponse and concomi an PD med-
ica ions we e pe mi ed a he disc e ion o he
ea ing physician. Na ional and/o local indepen-
den e hics commi ees, ins i u ional e iew boa ds,
and/o heal h au ho i ies in all coun ies app o ed he
p o ocol, pa ien in o ma ion, and in o med consen
equi emen s acco ding o he applicable na ional
egula o y equi emen s.
Pa ien s
In addi ion o pa ien inclusion being based on
local LCIG label and eimbu semen c i e ia, key
eligibili y c i e ia included pa ien s ha ing no p io
exposu e o LCIG; a Mini-Men al S a e Examina-
ion sco e ≥24; no p io su ge y o PD including,
bu no limi ed o, deep b ain s imula ion o cell
ansplan a ion ( o non-US cen e s); and no cu -
en subcu aneous apomo phine in usion (wi h ≥4
weeks equi ed be ween d ug discon inua ion and
s udy inclusion). All pa ien s and ca egi e s p o ided
in o med consen .
Assessmen s
Assessmen occu ed be o e s a ing LCIG (base-
line) he apy; a Day 1 (s a o LCIG ea men ia
pe cu aneous endoscopic gas os omy wi h jejunal
ex ension o hose pa ien s who pa icipa ed in he
p eceding nasojejunal es phase only); and a ou-
inely scheduled isi s, which we e closes o Mon hs
3, 6, 12, 18, 24, 30, and 36 (±14 days each), o a he
ime o p ema u e discon inua ion.
The p ima y endpoin was he change in he num-
be o hou s o “O ” ime as epo ed by he pa ien
o he day be o e he clinical isi (baseline) com-
pa ed wi h he same measu e a Mon h 36. Seconda y
endpoin s included mean change om baseline o
he end o he s udy in he Uni ied Pa kinson’s Dis-
ease Ra ing Scale (UPDRS) Pa II (ac i i ies o
daily li ing); Pa III (mo o examina ion pe o med
in he “On” s a e); and he ollowing i ems in Pa
IV: i em 33 (dyskinesia- ela ed disabili y), i em 34
(dyskinesia- ela ed pain), and i em 35 (ea ly mo n-
ing dys onia). Seconda y endpoin s also included
he UDysRS o al sco e (signs/symp oms o dyski-
nesia) and subdomain sco es, Non-mo o Symp om
Scale (NMSS) o al and subdomain sco es, Pa kin-
son’s Disease Sleep Scale-2 (PDSS-2) o al sco e
(sleep quali y), Epwo h Sleepiness Scale (ESS)
o al sco e (day ime somnolence), 8-i em PD Ques-
ionnai e (PDQ-8) summa y index (HRQoL), and
ca egi e bu den (Modi ied Ca egi e S ain Index).
Only se ious ad e se e en s (SAEs) and ad e se
e en s (AEs) leading o p ema u e discon inua ion
we e epo ed as pa o his obse a ional s udy om
ini ia ion o LCIG ea men o 30 days a e he las
s udy isi .
S a is ical analysis
Planned en ollmen was app oxima ely 200
pa ien s. I was assumed ha 60% o pa ien s would
comple e he 36-mon h ollow-up pe iod and ha he
mean (SD) dec ease om baseline o Mon h 36 in
he numbe o hou s in “O ” ime would be 4 hou s.
The e o e, he dis ance om he lowe limi o he
95% con idence in e al (CI) o he mean dec ease
would be 0.72 hou s (i.e., he lowe limi o he 95%
CI o he mean dec ease om baseline o Mon h
36 would be 3.28 hou s). Signi icance o all e i-
cacy measu es was de e mined using a one-sample
es compa ed wi h baseline e icacy assessmen s.
Sa e y assessmen s we e pe o med wi h he sa e y
popula ion, which included all pa ien s who had
nasojejunal and/o pe cu aneous endoscopic gas os-
omy wi h jejunal ex ension placemen , i espec i e
o whe he pa ien s wi hd ew p ema u ely o no .
E icacy assessmen s we e pe o med wi h he ull
analysis popula ion, which included all pa ien s in he
sa e y popula ion who had a leas one pos -baseline
e ec i eness assessmen a e unde going pe cu a-
neous endoscopic gas os omy wi h jejunal ex ension
placemen .
Da a sha ing
Clinical ial da a can be eques ed by any
quali ied esea che s who engage in igo ous, inde-
penden scien i ic esea ch, and will be p o ided
ollowing e iew and app o al o a esea ch p o-
posal and s a is ical analysis plan and execu ion
o a da a sha ing ag eemen . Da a eques s can
be submi ed a any ime and he da a will be
accessible o 12 mon hs, wi h possible ex en-
sions conside ed. Fo mo e in o ma ion on he
p ocess, o o submi a eques , isi he ollowing
link: h ps://www.abb ieclinical ials.com/hcp/da a-
sha ing/.
772 K.R. Chaudhu i e al. / Final 3-yea Resul s om he DUOGLOBE S udy
RESULTS
Pa ien s
Pa ien demog aphics and baseline cha ac e is ics
o he 195 pa ien s included in he analysis ha e been
epo ed p e iously [24]. Mos pa ien s we e male
(61.5%), mean (SD) age was 70.2 (8.2) yea s, and
mean du a ion o PD was 11.2 (4.8) yea s (Table 1).
Two pa ien s p e iously unde wen deep b ain s im-
ula ion. Mean (SD) LCIG ea men du a ion was
923.5 (367.2) days, wi h a median daily du a ion o
LCIG in usion o 16 hou s om Day 1 h ough Mon h
36. A each imepoin , be ween nine and 12 pa ien s
we e ecei ing 24-hou LCIG he apy.
O no e, mean (SD) daily dose o LCIG
emained ai ly s able om Day 1 (1241.2 [501.6]
mg/day) h ough Mon h 36 (1365.4 [499.1] mg/day)
(Fig. 1A). Wi hin he i s 6 mon hs o LCIG
use, he e we e dec eases in concomi an use
o o al le odopa de i a i es; monoamine oxidase
B inhibi o s; and, mos p ominen ly, ca echol-O-
me hyl ans e ase inhibi o s ha emained s eady
h oughou he nex 2.5 yea s (Fig. 1B). A Mon h 3,
18.1% o pa ien s we e ecei ing LCIG mono he apy
and 13.3% we e ecei ing LCIG in combina ion wi h
o al le odopa only (“le odopa mono he apy”); hese
pe cen ages emained ela i ely s able h oughou
he s udy (Mon h 36 : 15.5% and 17.9%, espec-
i ely) (Fig. 1C). To al le odopa equi alen dose also
emained s able h oughou he s udy, ega dless o
whe he pa ien s we e ecei ing LCIG as a mono he -
apy o in combina ion wi h o he PD medica ions
(Fig. 1D).
O 195 en olled pa ien s, 106 (54.4%) discon in-
ued he s udy p ema u ely wi h AEs being he p ima y
eason (pa ien s could ha e mul iple easons o dis-
con inua ion) in 48 o hese pa ien s (Supplemen a y
Figu es 1 and 2). Impo an ly, o he 106 pa ien s who
discon inued he s udy, 32 (30.2%) con inued ea -
men wi h LCIG ou side he s udy (Supplemen a y
Figu e 2).
Mo o complica ions
Mean (SD) daily hou s spen in he “O ” s a e
signi ican ly dec eased om baseline o Day 1 and
emained dec eased h ough Mon h 36 (Mon h 36
[p ima y endpoin ]: –3.3 [3.7]; p< 0.001) (Fig. 2A).
Changes om baseline a Mon h 36 we e s a is ically
signi ican in all age g oups (Fig. 2B).
Table 1
Baseline demog aphics and clinical cha ac e is ics
Cha ac e is ic To al
N= 195
Sex, n(%)
Male 120 (61.5)
Female 75 (38.5)
Age (y); mean ±SD 70.2 ±8.2
<65 y, n(%) 44 (22.6)
65–75 y, n(%) 95 (48.7)
>75 y, n(%) 56 (28.7)
BMI; mean ±SD BMI, kg/m225.9 ±4.1a
PD du a ion, y: mean ±SD 11.2 ±4.8
<10 y, n(%) 94 (48.5)
≥10 y, n(%) 100 (51.5)
Time o LCIG ini ia ion, y; mean ±SD om:
PD symp oms 12.2 ±5.0
S a o mo o luc ua ions 5.6 ±4.7
MMSE o al sco eb; mean ±SD 27.7 ±2.2
Hoehn and Yah s age; n(%)
Du ing “On”
1 4 (2.1)
1.5 0
2 33 (17.6)
2.5 21 (11.2)
3 80 (42.6)
4 43 (22.9)
5 7 (3.7)
Missing 7
Du ing “O ”
10
1.5 2 (1.1)
2 6 (3.2)
2.5 15 (8.1)
3 59 (31.7)
4 82 (44.1)
5 22 (11.8)
Missing 9
Daily “O ” ime (h); mean ±SD 6.0 ±3.4
UPDRS Pa II (ADL); mean ±SD 14.8 ±7.8
UPDRS Pa III (mo o unc ion); mean ±SD 27.6 ±13.2
UDysRS o al sco e; mean ±SD 33.7 ±21.1
NMSS o al sco e; mean ±SD 88.2 ±51.1
PDSS-2 o al sco e (sleep quali y); mean ±SD 26.6 ±11.7
ESS o al sco e (day ime sleepiness); mean ±SD 9.8 ±5.3
PDQ-8 summa y index (HRQoL); mean ±SD 45.1 ±18.1
MCSI o al sco e (ca egi e bu den); mean ±SD 10.9 ±6.4
an=182. bPa ien MMSE o al sco e a baseline mus be ≥24
o inclusion. ADL, ac i i ies o daily li ing; BMI, body mass
index; ESS, Epwo h Sleepiness Scale; HRQoL, heal h- ela ed
quali y o li e; LCIG, le odopa-ca bidopa in es inal gel; MCSI,
Modi ied Ca egi e S ain Index; MMSE, Mini-Men al S a e
Examina ion; NMSS, Non-Mo o Symp oms Scale; PD, Pa kin-
son’s disease; PDSS-2, Pa kinson’s Disease Sleep Scale-2; PDQ-8,
8-i em Pa kinson’s Disease Ques ionnai e; SD, s anda d de ia-
ion; UDysRS, Uni ied Dyskinesia Ra ing Scale, UPDRS, Uni ied
Pa kinson’s Disease Ra ing Scale.
Fo UDysRS o al sco es, signi ican educ ions
om baseline we e obse ed a all ime poin s
h ough Mon h 36 (Mon h 36 mean [SD]: –5.9
[23.7]; p= 0.044) (Fig. 2C). Explo a o y analysis
K.R. Chaudhu i e al. / Final 3-yea Resul s om he DUOGLOBE S udy 773
Fig. 1. S abili y o he apy o e ime. (A) LCIG dose, (B) an i-PD comedica ions, (C) mono he apy s. combina ion he apy, and (D)
o al le odopa equi alen dose. aOnly pa ien s who pa icipa ed in he p eceding nasojejunal es phase we e assessed a D1. BL, baseline;
COMT, ca echol-O-me hyl ans e ase; D, day; LCIG, le odopa-ca bidopa in es inal gel; LED, le odopa equi alen dose; M, mon h; MAO-B,
monoamine oxidase-B; PD, Pa kinson’s disease; SD, s anda d de ia ion.
was conduc ed o e alua e he e ec o LCIG on
UDysRS a Mon h 36 based on age; he e was no
signi ican di e ence a any o he ages e alua ed
(Fig. 2D). The composi e his o ical sco e was sig-
ni ican ly educed om baseline h ough Mon h 36
(Mon h 36 p= 0.012). The subdomain o “On” dyski-
nesia (Pa I) was signi ican ly educed om baseline
un il Mon h 24 (Mon h 24 p= 0.001), wi h “O ” dys-
onia (Pa II) signi ican ly educed h ough Mon h
36 (Mon h 36 p< 0.001); bo h hese imp o emen s
exceeded he le el o clinical ele ance [25]. Signi -
ican educ ions om baseline du ing he s udy we e
seen o o he componen s o he UDysRS, includ-
ing he objec i e sco e h ough Mon h 18 (Mon h
18 p= 0.045), he impai men subdomain (Pa III)
h ough Mon h 6 (Mon h 6 p< 0.001), and he disabil-
i y subdomain (Pa IV) h ough Mon h 24 (Mon h
24 p= 0.033) (Supplemen a y Figu e 3). Addi ional
suppo o he educ ion o he p esence and symp-
oms o dyskinesia and dys onia h ough Mon h 36
was seen in he UPDRS scale, including dyskinesia-
ela ed disabili y (mean [SD], –0.4 [1.3]; p= 0.016),
dyskinesia- ela ed pain (–0.4 [1.0]; p< 0.001), and
ea ly mo ning dys onia (–0.2 [0.6]; p< 0.001) (Sup-
plemen a y Figu e 4).
UPDRS Pa II and III sco es, a e ini ial imp o e-
men s (signi ican o UPDRS III un il Mon h 3),
demons a ed signi ican wo sening om baseline o
Mon h 36 in he o e all g oup (Supplemen a y Fig-
u e 4). Pa ien s aged ≥65 yea s showed signi ican
wo sening in UPDRS Pa II and III sco es a Mon h
36, while pa ien s aged younge han 65 yea s had
nominal, bu no s a is ically signi ican , imp o e-
men s in UPDRS Pa III sco es h oughou he s udy
(Supplemen a y Figu e 4).
A summa y o baseline and change- om-baseline
alues o pa ien s wi h Mon h 36 da a can be ound
in Table 2.

774 K.R. Chaudhu i e al. / Final 3-yea Resul s om he DUOGLOBE S udy
Fig. 2. Change om baseline o Mon h 36 in (A) pa ien epo ed “O ” ime, (B) “O ” ime by age subg oups, (C) dyskinesia as measu ed
by UDysRS o al sco e, and (D) UDysRS o al sco e by age subg oups. Signi icance le el o change om baseline was de e mined using he
one-sample es . *p<0.05; **p<0.01; ***p<0.001. aOnly pa ien s who pa icipa ed in he p eceding nasojejunal es phase we e assessed a
D1. bAs epo ed in Hause e al [26]. BL, baseline; D, day; LCIG, le odopa-ca bidopa in es inal gel; M, mon h; MCID, minimal clinically
impo an di e ence; SD, s anda d de ia ion; UDysRS, Uni ied Dyskinesia Ra ing Scale.
Table 2
Change om baseline o mon h 36 in mo o and non-mo o endpoin s among pa ien s wi h 36-mon h da a
Endpoin s nBaseline Change om baseline
Daily “O ” ime (h) 80 5.8 (3.1) –3.3 (3.7)***
UDysRS o al sco e 67 35.2 (21.4) –5.9 (23.7)*
UPDRS Pa II (ADL) 85 13.4 (8.5) 4.3 (8.3)***a
UPDRS Pa III (mo o unc ion) 83 24.9 (13.6) 5.8 (13.9)***a
NMSS o al sco e 79 83.7 (46.5) –14.3 (40.5)**
PDSS-2 o al sco e (sleep quali y) 85 27.7 (12.3) –5.8 (12.9)***
ESS o al sco e (day ime sleepiness) 84 9.6 (5.3) –1.8 (6.0)**
PDQ-8 summa y index (HRQoL) 84 45.2 (18.6) –2.5 (19.6)
MCSI o al sco e (ca egi e bu den) 52 12.3 (6.8) –1.3 (7.8)
Table includes pa ien s wi h Mon h 36 da a only. All da a a e p esen ed as mean ±SD. aRe lec s wo sening
om baseline. *p<0.05; **p<0.01; ***p<0.001. ADL, ac i i ies o daily li ing; ESS, Epwo h Sleepiness Scale;
HRQoL, heal h- ela ed quali y o li e; MCSI, Modi ied Ca egi e S ain Index; NMSS, Non-Mo o Symp oms
Scale; PDSS-2, Pa kinson’s Disease Sleep Scale-2; PDQ-8, 8-i em Pa kinson’s Disease Ques ionnai e; SD,
s anda d de ia ion; UDysRS, Uni ied Dyskinesia Ra ing Scale, UPDRS, Uni ied Pa kinson’s Disease Ra ing
Scale.
K.R. Chaudhu i e al. / Final 3-yea Resul s om he DUOGLOBE S udy 775
Fig. 3. Change om baseline in (A) NMSS o al sco e and (B) NMSS o al sco e by age subg oups. Signi icance le el o change om
baseline was de e mined using he one-sample es . *p<0.05; **p<0.01; ***p<0.001. aOnly pa ien s who pa icipa ed in he p eceding
nasojejunal es phase we e assessed a D1. bAs epo ed in Ma inez-Ma in e al [31]. BL, baseline; D, day; M, mon h; MCID, minimal
clinically impo an di e ence; NMSS, Non-Mo o Symp om Scale; SD, s anda d de ia ion.
Non-mo o symp oms
NMSS o al sco es demons a ed signi ican and
sus ained imp o emen om baseline a Mon h
36 (mean [SD], –14.3 [40.5]; p= 0.002) and all
ime poin s (Fig. 3A,B). In addi ion, h ee o nine
NMSS subdomains we e signi ican ly imp o ed
h ough Mon h 36: sleep/ a igue (mean [SD],
–3.7 [12.3]; p= 0.007), gas oin es inal ac (–2.5
[6.1]; p< 0.001), and miscellaneous (–3.9 [10.3];
p< 0.001) (Supplemen a y Figu e 5). O no e, he
las s a is ically signi ican imp o emen was mea-
su ed a Mon h 12 o one domain (ca dio ascula ,
including alls), and Mon h 24 o h ee domains
(mood/cogni ion, a en ion/memo y, and sexual unc-
ion) (Supplemen a y Figu e 5).
In addi ion o imp o emen in he NMSS
sleep/ a igue subdomain, s able and signi ican
imp o emen in sleep quali y (Fig. 4A,B) and day-
ime sleepiness (Fig. 4C) was seen wi h LCIG.
Signi ican imp o emen om baseline a Mon h 36
was obse ed o PDSS-2 o al sco es (mean [SD],
–5.8 [12.9]; p< 0.001) and ESS o al sco es (mean
[SD], –1.8 [6.0]; p= 0.008). Signi ican imp o emen
was seen om Day 1 (PDSS-2) and Mon h 3 (ESS)
onwa d.
Pa ien HRQoL and ca egi e bu den
Pa ien HRQoL and ca egi e bu den imp o ed
om baseline, wi h signi ican and consis en
imp o emen in PDQ-8 h ough Mon h 24 (mean
[SD]: –6.0 [22.5]; p= 0.006) (Fig. 5A,B) and Modi-
ied Ca egi e S ain Index h ough Mon h 30 (–2.3
[7.6]; p= 0.026) (Fig. 5C,D). Bo h scales con inued
o show nume ical, bu no s a is ically signi ican ,
imp o emen s a Mon h 36.
Sa e y
A o al o 107 (54.9%) pa ien s expe ienced SAEs
(Table 3), wi h 31 SAEs conside ed as ha ing a
easonable possibili y o being ela ed o LCIG ea -
men . The mos common SAEs we e all (n= 8),
(wo sening o ) PD (n= 8), and u ina y ac in ec-
ion (n= 7) (Table 3). One pa ien expe ienced an
SAE o polyneu opa hy, and one expe ienced an SAE
o ch onic in lamma o y demyelina ing poly adicu-
loneu opa hy; bo h SAEs we e adjudica ed by he
in es iga o as ha ing no easonable possibili y o
ela ionship o s udy d ug. A o al o 53 (27.2%)
pa ien s discon inued he s udy owing o an SAE.
Howe e , his includes 34/195 (17.4%) a al AEs,
wi h all epo ed as ha ing no easonable possi-
bili y o ela ionship o s udy ea men wi h he
excep ion o one pa ien wi h an in es inal obs uc-
ion and a medical his o y o di e iculi is ha
was adjudica ed as possibly ela ed o ea men
(Supplemen a y Table 1). Mos a al AEs we e
ela ed o complica ions o aPD, ca dio ascula dis-
ease, and complica ions om non- ea men - ela ed
in ec ions.
A o al o six pa ien s (3.1%) discon inued he
s udy due o COVID- ela ed in ec ions, es ic ions,
o ea s o in ec ion. These discon inua ions included
wo pa ien s (1.0%) who had an SAE o COVID-
776 K.R. Chaudhu i e al. / Final 3-yea Resul s om he DUOGLOBE S udy
Fig. 4. Change om baseline in (A) PDSS-2 o al sco e, (B) PDSS-2 o al sco e by age subg oups, and (C) ESS o al sco e. Signi icance le el
o change om baseline was de e mined using he one-sample es . *p<0.05; **p<0.01; ***p<0.001. aOnly pa ien s who pa icipa ed in
he p eceding nasojejunal es phase we e assessed a D1. bAs epo ed in Ho a h e al [32]. BL, baseline; D, day; ESS, Epwo h Sleepiness
Scale; M, mon h; MCID, minimal clinically impo an di e ence; PDSS-2, Pa kinson’s Disease Sleep Scale-2; SD, s anda d de ia ion.
19 and/o COVID- ela ed pneumonia, bo h o which
esul ed in dea h.
In gene al, body weigh and body mass index
(BMI) emained ela i ely s able h oughou he
s udy. A baseline, mean body weigh was 73.2 kg
and mean BMI was 25.7 kg/m2; a Mon h 36, mean
weigh and BMI we e 71.2 kg and 24.9 kg/m2, espec-
i ely, wi h bo h dec easing h oughou he s udy
(Supplemen a y Figu e 6A). Mean (SD) dec ease
om baseline o Mon h 36 was –3.1 (8.0) kg o
weigh and –1.2 (2.8) kg/m2 o BMI. A las isi ,
8.2% o pa ien s demons a ed an inc ease in base-
line weigh ≥7%, while 22.1% demons a ed ≥7%
dec ease. Mos pa ien s emained wi hin he same
BMI ca ego y a he end o he s udy ha hey we e
in a baseline (Supplemen a y Figu e 6B).
Looking a sa e y indings ac oss age, pa ien s in
he 65- o 75-yea age g oup expe ienced highe a es
o SAEs han did hose in he younge han 65-yea
age g oup and olde han 75-yea age g oups (whose
a es we e simila o each o he ), wi h a es o se e e
AEs lowes in he younge han 65-yea age g oup
and simila in he 65 o 75 yea and olde han 75-
yea age g oups (Table 3). Ra es o se e e AEs we e
lowes in pa ien s aged younge han 65 yea s and
we e simila in pa ien s aged 65 o 75 yea s and olde
han 75 yea s.
DISCUSSION
We epo he inal esul s o DUOGLOBE, a 3-
yea , ully p ospec i e s udy designed o e alua e
LCIG use in ou ine clinical p ac ice in a la ge eal-
wo ld popula ion wi h aPD. T ea men wi h LCIG
demons a ed “O ” ime imp o emen s ha we e
main ained o e 3 yea s and emained abo e he min-
K.R. Chaudhu i e al. / Final 3-yea Resul s om he DUOGLOBE S udy 777
Fig. 5. Change om baseline in (A) PDQ-8 summa y index, (B) PDQ-8 summa y index by age subg oups, (C) MCSI o al sco e, and
(D) MCSI o al sco e by age subg oups. Signi icance le el o change om baseline was de e mined using he one-sample es . *p<0.05;
**p<0.01; ***p<0.001. aOnly pa ien s who pa icipa ed in he p eceding nasojejunal es phase we e assessed a D1. bAs epo ed in Ho a h
e al [36]. BL, baseline; D, day; MCID, minimal clinically impo an di e ence; MCSI, Modi ied Ca egi e S ain Index; PDQ-8, 8-i em
Pa kinson’s Disease Ques ionnai e; SD, s anda d de ia ion.
imal clinically impo an di e ence (MCID) o 1 hou
in his popula ion, despi e he p og essi e na u e o
PD [26].
The bene icial e ec s o LCIG use we e also
e lec ed in imp o emen s in UDysRS sco es and
subsco es. Imp o emen s in “On” dyskinesia (Pa
I) we e abo e he MCID o –2.1 h ough Mon h 24
and imp o emen s in “O ” dys onia (Pa II) we e
abo e he MCID o –1.8 h ough Mon h 36 [25].
Reduc ions in UDysRS sco es a e pa icula ly no e-
wo hy, as his scale (which includes bo h pa ien
subjec i e and clinician objec i e dyskinesia a ings)
has demons a ed a high sensi i i y o de ec ing
ea men - ela ed changes [27]. The cu en indings
o signi ican dec eases in “O ” ime coupled wi h
signi ican imp o emen s in “On” dyskinesia wi h
LCIG ea men a e consis en wi h hose epo ed in
p e ious s udies [15, 28, 29]. Pa allel imp o emen s
in “O ” ime and “On” ime wi h dyskinesia a e pos-
sible wi h LCIG, likely due o con inuous deli e y o
s able plasma le odopa le els ha can emain in he
he apeu ic window [10, 15, 28].
Non-mo o symp oms o PD a e o en un ecog-
nized and un ea ed [30]. Signi ican imp o emen s
we e obse ed in he NMSS o al sco es, which
emained abo e he 13.9-poin MCID h oughou
he 3 yea s [31]. Imp o emen s in sleep and day-
ime sleepiness (as measu ed by he PDSS-2 and
ESS, espec i ely) we e also obse ed h oughou he
s udy, wi h PDSS-2 changes exceeding he –3.4 poin
MCID h eshold a all imepoin s [32]. These indings
a e pa icula ly ele an , as non-mo o symp oms and
sleep dis u bances ha e been di ec ly linked o de e-
io a ion o HRQoL [33–35]. This s udy suppo s
his ela ionship, wi h bo h non-mo o symp oms and
HRQoL imp o ing a e LCIG ea men . Signi i-