%PDF-1.3
%
6 0 obj
<>>>/BBox[0 0 612 792]/Length 53>>stream
xs
w3T0WI2P0T5T R
Ɩf
!\!Y\ !p
o
endstream
endobj
9 0 obj
<>>>/BBox[0 0 612 792]/Length 53>>stream
xs
w3T0WI2P0T5T R
Ɩf
!\!Y\ !p
o
endstream
endobj
5 0 obj
<>>>/BBox[0 0 612 792]/Length 53>>stream
xs
w3T0WI2P0T5T R
Ɩf
!\!Y\ !p
o
endstream
endobj
10 0 obj
<>>>/BBox[0 0 612 792]/Length 53>>stream
xs
w3T0WI2P0T5T R
Ɩf
!\!Y\ !p
o
endstream
endobj
8 0 obj
<>>>/BBox[0 0 612 792]/Length 53>>stream
xs
w3T0WI2P0T5T R
Ɩf
!\!Y\ !p
o
endstream
endobj
3 0 obj
<>>>/BBox[0 0 612 792]/Length 53>>stream
xs
w3T0WI2P0T5T R
Ɩf
!\!Y\ !p
o
endstream
endobj
4 0 obj
<>>>/BBox[0 0 612 792]/Length 53>>stream
xs
w3T0WI2P0T5T R
Ɩf
!\!Y\ !p
o
endstream
endobj
7 0 obj
<>>>/BBox[0 0 612 792]/Length 53>>stream
xs
w3T0WI2P0T5T R
Ɩf
!\!Y\ !p
o
endstream
endobj
1 0 obj
<>>>/BBox[0 0 612 792]/Length 53>>stream
xs
w3T0WI2P0T5T R
Ɩf
!\!Y\ !p
o
endstream
endobj
12 0 obj
<>stream
Acrobat Distiller 8.1.0 (Windows); modified using iText 4.2.0 by 1T3XT
Arbortext Advanced Print Publisher 9.0.114/W
2023-05-25T13:50:49-07:00
2023-05-15T23:45:55+05:30
application/pdf
CAP-2023-0012-ver9-Childress_2P 134..142
uuid:60e918a3-1dc7-449f-807e-054c1d52a97c
uuid:8db42de1-33a3-491b-999a-031c156bf453
endstream
endobj
13 0 obj
<>stream
x+ |
endstream
endobj
14 0 obj
<>stream
xS**T0T0 Bi y+
endstream
endobj
15 0 obj
<>stream
x+ |
endstream
endobj
16 0 obj
<>stream
xS**T0T0 Bi yw*
endstream
endobj
17 0 obj
<>stream
x+ |
endstream
endobj
18 0 obj
<>stream
xS**T0T0 Bi yS&
endstream
endobj
19 0 obj
<>stream
x+ |
endstream
endobj
20 0 obj
<>stream
xS**T0T0 Bi y\'
endstream
endobj
21 0 obj
<>stream
x+ |
endstream
endobj
22 0 obj
<>stream
xS**T0T0 Bi ye(
endstream
endobj
23 0 obj
<>stream
x+ |
endstream
endobj
24 0 obj
<>stream
xS**T0T0 Bi yn)
endstream
endobj
25 0 obj
<>stream
x+ |
endstream
endobj
26 0 obj
<>stream
xS**T0T0 Bi y8#
endstream
endobj
27 0 obj
<>stream
x+ |
endstream
endobj
28 0 obj
<>stream
xS**T0T0 Bi yJ%
endstream
endobj
29 0 obj
<>stream
x+ |
endstream
endobj
30 0 obj
<>stream
xS**T0T0 Bi yA$
endstream
endobj
32 0 obj
<>stream
/GS1 gs
BT
/F6 1 Tf
8.9663 0 0 8.9663 69.7323 725.7825 Tm
0 0 0 rg
0 Tc
0 Tw
[(In)-298.8(a)-292.8(pivotal,)-298.5(randomized,)-300(placebo-controlled,)-305.7(double-blind)-295.8(lab-)]TJ
-1.1128 -1.2203 TD
[(oratory)-469.8(classroom)-468.2(study)-464.3(of)-463.2(children)-466.8(with)-464.6(ADHD,)-469.4(SDX/d-MPH)]TJ
0 -1.2266 TD
[(treatment)-381.5(was)-378.5(shown)-381.4(to)-376.1(signicantly)-381.6(improve)-375.9(ADHD)-378(symptoms)]TJ
0 -1.2203 TD
[(compared)-363.6(with)-357.2(placebo)-361.9(\(Kollins)-356.7(et)-359.5(al.)-356.1(2021\).)-357.2(SDX/d-MPH)-364.1(onset)]TJ
T*
[(began)-223.7(by)-226.6(30)-220.3(minutes)-226.7(postdose,)-222.8(and)-222.3(the)-226.3(treatment)-229.7(effect)-222.2(lasted)-226.1(up)-220.3(to)]TJ
0 -1.2266 TD
[(13)-359.4(hours.)-358.4(Adverse)-356.3(events)-361.2(\(AEs\))-361.2(were)-356.5(similar)-359.8(to)-357.1(other)-360.7(stimulants)]TJ
0 -1.2203 TD
[(used)-286.2(for)-275.6(the)-283.2(treatment)-280.3(of)-286.2(patients)-279.7(with)-281.3(ADHD.)]TJ
1.1128 -1.2203 TD
[(A)-205.1(subsequent,)-211.6(1-year,)-206(open-label)-215.4(safety)-205.7(study)-205.1(of)-210.3(SDX/d-MPH)-206(in)]TJ
-1.1128 -1.2266 TD
[(children)-264.5(with)-268.6(ADHD)-264.2(showed)-263.2(that)-261.4(SDX/d-MPH)-262.9(was)-264.7(well)-264.7(tolerated)]TJ
0 -1.2203 TD
[(and)-513.1(had)-513.1(sustained)-516.7(efcacy)-513.3(during)-515.9(the)-510.8(1-year)-512.9(treatment)-520.6(period)]TJ
T*
[(\(Childress)-302.4(et)-302.6(al.)-299.2(2023\).)-300.3(Of)-302.1(the)-302.1(238)-295.7(subjects)-302.2(assessed)-305.3(in)-300.2(the)-302.1(1-year)]TJ
T*
[(study,)-296.5(the)-295.8(most)-297.6(common)-297.4(treatment-emergent)-302.2(AEs)-293.7(were)-299.6(decreased)]TJ
0 -1.2266 TD
[(appetite)-407.4(\(18.5%\),)-408.6(upper)-400.9(respiratory)-408.5(tract)-405.1(infection)-407.1(\(9.7%\),)-402.7(naso-)]TJ
0 -1.2203 TD
[(pharyngitis)-664.2(\(8.0%\),)-655.7(decreased)-662.7(weight)-655.8(\(7.6%\),)-655.7(and)-658.5(irritability)]TJ
T*
(\(6.7%\).)Tj
1.1128 -1.2266 TD
[(Long-term)-276.2(treatment)-280.3(with)-275(stimulants,)-275.4(such)-273.5(as)-280.8(MPH)-273(for)-275.6(ADHD,)]TJ
-1.1128 -1.2203 TD
[(in)-420.4(children)-416.2(has)-413.1(been)-413.9(associated)-419.9(with)-420.4(modest)-412.9(slowing)-413.8(of)-418.9(growth)]TJ
T*
[(velocity)-265.9(and)-266.5(prescribing)-260.5(information)-264.4(for)-263(these)-266.8(treatments)-262(warns)-266.3(of)]TJ
0 -1.2266 TD
[(long-term)-293(growth)-291.5(suppression,)-288.4(which)-291.8(can)-287.9(cause)-290.5(concern)-291(and)-285.5(limit)]TJ
0 -1.2203 TD
[(their)-213(use)-204.5(\(Spencer)-215.8(et)-207.8(al.)-210.7(2006;)-203.9(Faraone)-213.7(and)-203.3(Giefer)-210.4(2007;)-210.2(Krinzinger)]TJ
T*
[(et)-473.4(al.)-470(2019\).)-471(The)-475(objective)-470.2(of)-469.5(the)-472.9(current)-472.2(investigation)-475(was)-467(to)]TJ
T*
[(characterize)-245.6(the)-232.6(effects)-241.9(of)-235.6(SDX/d-MPH)-237.6(on)-233(growth)-240.9(in)-237(children)-232.9(with)]TJ
0 -1.2266 TD
[(ADHD)-485.5(treated)-488.7(with)-483.6(SDX/d-MPH)-490.6(from)-481(the)-485.5(1)-480.1(year,)-488.9(open-label,)]TJ
0 -1.2203 TD
[(safety)-287.9(study)-274.7(\(Childress)-283.4(et)-283.7(al.)-280.3(2023\).)]TJ
/F4 1 Tf
0 -2.6493 TD
(Methods)Tj
/F6 1 Tf
1.1128 -1.8336 TD
[(Thi)16.6(s)]TJ
/F8 1 Tf
2.0613 0 TD
[(pos)12.9(t)-300.7(h)0(o)13.6(c)]TJ
/F6 1 Tf
3.6863 0 TD
[(ana)15.6(lys)15.2(is)-295.1(of)-292.5(a)-299.1(d)0(o)13.6(se-)14.2(opt)16.4(im)12.4(ize)11.6(d,)-293.3(op)13.6(en-)15.4(lab)14(el,)-286.6(phas)17.3(e)-299.1(3)]TJ
-6.8604 -1.2203 TD
[(saf)14.2(ety)-479.2(st)14.7(udy)-472.8(of)-482.2(SDX)15.2(/d-)13.8(MP)14.3(H)-489.7(i)0(n)-477.3(chi)14(ld)15.9(ren)-477.8(age)15.6(d)-486.4(6)0()13.6(1)0(2)-479.6(yea)15.6(rs)-483.4(wi)12.6(th)]TJ
0 -1.2267 TD
[(ADH)10.5(D)-350.6(\()0(N)14(CT0)15.9(346)14.1(06)13.6(52\))-342.6(\(C)12.6(hil)18.7(dre)15.4(ss)-349.2(et)-346.9(al)13.5(.)-350.7(2)0(0)13.6(23\))-342.6(was)-340.6(con)18(duc)18(ted)-340.1(at)]TJ
0 -1.2203 TD
[(18)-504.9(sit)17.5(es)-508.5(in)-502.6(the)-498.2(Uni)19.4(ted)-498.2(Sta)15.4(tes)12.8(.)-508.7(T)0(h)13.8(e)-514.1(ori)20.1(gin)16.4(al)-505(stu)15.2(dy)-504.9(pro)17.8(toc)14(ol)-502.6(and)]TJ
T*
[(ame)12.1(nd)13.6(men)14.5(ts)-225.5(wer)12.1(e)-235.9(app)18(rov)17.8(ed)-229.1(by)-226.6(an)-229.1(in)15.9(stit)20.3(uti)12.4(on)13.6(al)-226.8(rev)15.4(iew)-223.2(boa)18(rd)-229.3(bef)15.4(ore)]TJ
T*
[(eac)13.2(h)-378.9(c)0(e)15.1(nte)14(r)-375.2(ini)12.4(tia)16.3(te)13.5(d)-378.9(t)0(h)15.9(e)-381.3(st)14.7(udy)14.1(.)-376(T)0(h)13.8(e)-375(r)12.4(st)-371(pat)14(ien)14(t)-370.3(was)-365.8(scr)14.2(een)15.6(ed)-374.5(on)]TJ
0 -1.2266 TD
[(Feb)13.1(rua)15.4(ry)-172.3(21,)-172.7(20)13.6(18,)-172.7(and)-165.3(the)-175.7(la)13.5(st)-174.9(fol)13.8(low)19.4(-up)-171.9(vis)15.2(it)-171.5(was)-176.2(on)-169.7(Jun)12.9(e)-179(27,)-172.7(20)13.6(19)13.6(.)]TJ
/F11 1 Tf
0 -2.6493 TD
(Subjects)Tj
/F6 1 Tf
1.1128 -1.8336 TD
[(The)-291.6(subjects)-295.9(were)-293.3(children)-289.8(aged)-293.7(612)-288.9(years)-290.7(with)-293.9(ADHD)-289.5(at)-290(the)]TJ
-1.1128 -1.2203 TD
[(start)-378.5(of)-374.7(the)-378(dose-optimization)-374.1(\(DO\))-376.6(phase)-376.6(of)-374.7(the)-378(study.)-372.4(Subjects)]TJ
T*
[(included)-571.7(those)-567.9(rolled)-566.5(over)-572.1(from)-563.2(the)-567.7(antecedent)-571.7(pivotal)-567.5(study)]TJ
0 -1.2266 TD
[(\(Kollins)-344(et)-346.9(al.)-343.5(2021\))-341.6(within)-341.2(45)-346.8(days)-343.1(of)-343.1(their)-339.4(last)-344.8(dose)-343.1(of)-343.1(SDX/d-)]TJ
0 -1.2203 TD
[(MPH,)-225.3(and)-215.9(new)-225.6(subjects)-220(who)-223.1(did)-217.5(not)-223.9(participate)-225.3(in)-218(the)-219.9(pivotal)-219.7(study)]TJ
T*
[(or)-197.6(who)-197.9(entered)-200.1(the)-201(trial)-198(more)-196.3(than)-194.2(45)-201.4(days)-197.7(after)-195(their)-200.3(last)-199.4(dose)-197.7(in)-199.1(the)]TJ
T*
[(pivotal)-308.2(study)-299.9(\(Childress)-308.7(et)-302.6(al.)-305.6(2023\).)-306.6(Subjects)-305.9(had)-304.5(to)-300.2(have)-306.4(a)-305.4(body)]TJ
0 -1.2266 TD
[(weight)-187.9(of)-185(at)-188.8(least)-182.3(21)-169.7(kg)-182.4(at)-188.8(the)-182(screening)-187.7(phase)-186.9(and)-184.3(be)-184.8(in)-186.4(good)-187.7(health.)]TJ
0 -1.2203 TD
[(At)-183.4(least)-182.3(one)-184.3(parent)-179.2(or)-178.7(legal)-187.5(guardian)-178.3(was)-182.5(required)-180.9(to)-180.1(provide)-182.7(written)]TJ
T*
[(permission,)-415.4(and)-418.3(each)-410(subject)-415.3(had)-418.3(to)-414(give)-409.1(written)-415.3(or)-412.6(verbal)-419.5(per-)]TJ
0 -1.2266 TD
[(mission)-282.4(for)-282(study)-281(participation.)]TJ
/F11 1 Tf
0 -2.6493 TD
[(Study)-338.6(design)]TJ
/F6 1 Tf
1.1128 -1.8336 TD
[(The)-310.6(study)-306.3(design)-308.2(included)-306.1(a)-305.4(30-day)-305.6(screening)-314.2(phase,)-303.7(a)-311.8(3-week)]TJ
-1.1128 -1.2203 TD
[(DO)-283.8(phase,)-284.7(a)-280.1(360-day)-286.1(treatment)-286.6(phase,)-278.4(and)-285.5(a)-280.1(follow-up)-284(visit.)-285.6(Only)]TJ
T*
[(new)-282.5(subjects)-289.6(underwent)-282.3(screening)-282.6(and)-285.5(DO.)-280.4(During)-285.2(the)-283.2(DO)-283.8(phase,)]TJ
T*
[(new)-219.2(subjects)-220(were)-217.4(titrated)-215.6(to)-218(their)-213(optimized)-218.4(dose)-216.6(based)-218.6(on)-214(the)-220(best)]TJ
0 -1.2266 TD
[(dose)-185(response)-189.3(and)-184.3(individual)-184.3(tolerability)-190.1(to)-180.1(the)-188.3(treatment)-185.5(\(Childress)]TJ
0 -1.2203 TD
[(et)-283.7(al.)-280.3(2023\).)]TJ
1.1128 -1.2203 TD
[(New)-450.2(subjects)-447.6(started)-443.2(treatment)-451(with)-445.7(the)-447.6(39.2/7.8)-165(mg)-445.2(dose)-444.3(of)]TJ
-1.1128 -1.2266 TD
[(SDX/d-MPH)-395.7(daily,)-384(which)-393(is)-389.9(a)-387.6(molar)-389.5(equivalent)-387.5(to)-388.7(30)-169.7(mg)-381.9(of)-393.6(to-)]TJ
0 -1.2203 TD
[(tal)-470.6(d-MPH)-470.6(HCl,)-468.7(for)-465.3(7)-467.4(days.)-466.1(If)-465.8(needed,)-475.1(dose)-463.2(adjustments)-472.7(were)]TJ
T*
[(performed)-403.8(based)-395.6(on)-397.4(the)-397(investigators)-401(assessment)-400.4(of)-393.7(the)-397(subject)]TJ
0 -1.2266 TD
[(at)-467(weekly)-464.5(intervals.)-468.1(The)-468.7(SDX/d-MPH)-465.3(dose)-463.2(could)-465.6(be)-463(increased)]TJ
0 -1.2203 TD
[(to)-439.3(52.3/10.4)-164.5(mg)-438.8(\(40)-165.5(mg)-432.5(molar)-440.1(equivalent)-438.1(of)-431.6(total)-442(d-MPH)-432.7(HCl\),)]TJ
28.0042 74.5598 TD
[(decreased)-289.7(to)-281.3(26.1/5.2)-165(mg)-287.1(\(20)-165.5(mg)-287.1(molar)-282(equivalent)-286.3(of)-286.2(total)-290.2(d-MPH)]TJ
0 -1.2203 TD
[(HCl\),)-274.9(or)-273.5(maintained)-270.9(at)-277.3(the)-270.5(same)-279.5(dose)-273.5(for)-269.3(the)-276.9(next)-276.4(week)-271.7(of)-273.5(dosing.)]TJ
1.1128 -1.2266 TD
[(T)13.3(h)0(e)-304.9(d)0(o)19.9(s)0(e)-306.1(a)0(t)-302.6(t)0(h)15.9(e)-311.8(en)17.5(d)-315.7(o)13.1(f)-318.3(t)0(h)22.3(e)-318.1(th)22.2(ir)19.6(d)-315.7(w)0(e)20.5(e)0(k)-304.9(w)0(a)20.5(s)-316.8(as)16.3(si)21.1(g)13.1(n)0(e)17.5(d)-315.7(as)-306.1(th)22.3(e)-318.1(o)13.1(pt)15.9(i-)]TJ
-1.1128 -1.2203 TD
[(mi)18.7(ze)21.4(d)-404.2(d)0(o)19.9(s)0(e)16.3(.)-407.6(S)14.5(u)0(b)19.9(j)0(e)13.5(c)0(t)19.8(s)-405.4(wh)23(o)-410.5(r)0(o)23.7(l)0(l)18.2(e)0(d)-399.8(o)13.1(v)13.1(e)0(r)-402.4(f)0(r)21.1(o)13.1(m)-407.7(t)0(h)22.2(e)-412.9(p)13.1(i)0(v)22.2(o)0(t)15.9(a)0(l)-397.5(s)0(t)21.1(u)13.1(dy)-397.4(re)14.9(-)]TJ
T*
[(ma)20.3(in)22.3(ed)-165.8(on)-163.4(th)22.2(ei)13.5(r)-172.8(o)13.1(pt)15.9(im)18.7(i)15.4(z)0(e)15.1(d)-170.2(do)20(se)-167(fr)21.1(om)-167(th)22.3(at)-163.5(st)14.7(u)13.1(d)0(y)20(.)-173.6(Th)20.1(e)-172.6(o)0(p)20(t)0(i)18.2(m)0(i)18.7(z)0(e)21.4(d)-176.5(SD)18.1(X/)]TJ
0 -1.2266 TD
[(d)13.1(-)0(M)16.6(P)0(H)-215.9(d)0(o)19.9(s)0(e)-217.6(w)0(a)20.5(s)-228.3(us)18.8(ed)-216.4(du)19.9(ri)19.6(ng)-220.3(th)22.3(e)-229.6(t)0(r)19.6(e)0(a)21.4(t)0(m)18.7(e)0(n)17.5(t)-224.8(ph)19.9(as)16.3(e.)-213.5(Al)18.9(l)-231.2(s)0(u)25.1(b)0(j)15.9(e)0(c)21.4(t)0(s)-219.2(w)0(e)20.5(r)0(e)]TJ
0 -1.2203 TD
[(ad)17.5(m)15.9(i)0(n)15.9(i)0(s)21.1(t)0(e)19.8(r)0(e)14.9(d)-170.2(1)-170.2(c)0(a)15.1(p)13.1(su)18.8(le)-163.5(da)17.5(il)18.2(y)-170.2(o)0(f)-166(t)0(h)22.3(e)0(i)19.8(r)-179.2(o)13.1(p)0(t)22.2(i)0(m)18.7(i)0(z)19.8(e)0(d)-165.8(d)0(o)19.9(s)0(e)-167(o)13.1(f)-172.8(S)0(D)18.1(X)0(/)18.9(d)13.1(-M)16.6(PH)18.1(.)]TJ
T*
[(We)21.9(ig)15.9(h)13.1(t)-294.4(an)17.5(d)-290.4(h)0(e)17.5(i)0(g)22.2(h)0(t)-287.6(a)0(n)17.5(a)0(l)19.8(y)13.1(se)16.3(s)-291.5(w)0(e)20.5(r)0(e)-288.6(c)0(o)17.5(n)13.1(du)19.9(ct)19.8(ed)-286(in)-281.3(th)15.9(e)-292.8(t)0(r)19.6(e)0(a)21.4(t)0(m)18.7(e)0(n)17.5(t)-294.4(p)13.1(h)0(a)17.5(s)0(e)]TJ
0 -1.2266 TD
[(sa)22.7(fe)14.9(ty)-464.6(po)19.9(pu)19.9(la)19.8(ti)18.2(o)13.1(n)-480(o)13.1(f)-482.7(en)23.9(ro)17.3(ll)18.2(ed)-463(su)18.8(bj)15.9(ec)21.4(ts)21.1(.)-477.1(T)0(h)20.1(i)0(s)-472.1(p)13.1(op)19.9(ul)22.3(at)13.5(io)22.3(n)-473.7(i)0(n)15.9(c)0(l)19.8(u)13.1(de)17.5(d)]TJ
0 -1.2203 TD
[(th)22.3(os)18.8(e)-318.1(w)0(h)16.6(o)-315.7(re)14.9(ce)21.4(iv)15.9(ed)-304.9(at)-315.3(le)19.8(as)22.7(t)-319.7(1)-322(d)13.1(o)0(s)18.8(e)-324.4(o)13.1(f)-318.3(st)14.7(u)13.1(d)0(y)-308.8(m)0(e)20.3(d)0(i)15.9(c)0(a)21.4(t)0(i)18.2(o)13.1(n)-322(a)0(n)17.5(d)-315.7(ha)17.5(d)-322(a)0(t)]TJ
T*
[(le)19.8(as)16.3(t)-420.8(1)-423.1(p)13.1(o)0(s)18.8(t)0(d)22.3(o)0(s)18.8(e)-425.6(sa)22.7(fe)14.9(ty)-407.7(as)16.3(se)16.3(ss)23.9(me)14(n)13.1(t)-420.8(in)-414(th)22.3(e)-425.6(t)0(r)19.6(e)0(a)21.4(t)0(m)18.7(e)0(n)17.5(t)-420.8(ph)20(as)16.3(e.)-409.5(Co)15.2(m-)]TJ
T*
[(p)13.1(l)0(e)19.8(t)0(e)13.5(r)0(s)-255.7(a)0(r)14.9(e)-267.5(th)15.9(o)13.1(s)0(e)-261.9(s)0(u)18.8(b)13.1(je)19.8(ct)13.5(s)-266.3(t)0(h)15.9(a)0(t)-258.4(c)0(o)17.5(m)0(p)22.7(l)0(e)19.8(t)0(e)19.8(d)-271.4(12)-258.3(mo)16.4(n)13.1(t)0(h)15.9(s)-266.3(of)-260.9(tr)19.6(ea)15.1(tm)18.7(en)23.8(t.)]TJ
/F11 1 Tf
0 -2.5355 TD
[(Weight)-331.4(and)-335.7(height)-334.3(measurements)]TJ
/F6 1 Tf
1.1128 -1.8336 TD
[(Body)-287.3(weight)-295.4(\(in)-296(kg\))-292(and)-291.8(height)-292.1(\(in)-296(cm\))-291.6(were)-293.3(measured)-295.2(at)-296.3(each)]TJ
-1.1128 -1.2203 TD
[(monthly)-273.7(visit.)-273(Body)-274.7(weight)-276.4(was)-271(measured)-282.6(using)-268.3(a)-280.1(calibrated)-272.4(scale)]TJ
T*
[(while)-333.8(subjects)-340.1(remained)-336(in)-338.2(their)-333.1(normal)-338.4(clothing,)-336(with)-331.9(shoes)-337.5(and)]TJ
0 -1.2266 TD
[(jacket)-202(\(and/or)-210.6(outer)-202.6(clothing\))-202.4(removed.)-206.5(Height)-206.8(was)-207.8(measured)-206.7(using)]TJ
0 -1.2203 TD
[(a)-280.1(stadiometer)-280.5(with)-281.3(the)-283.2(subjects)-285.3(shoes)-280.6(removed.)]TJ
/F11 1 Tf
0 -2.5292 TD
(Assessments)Tj
/F6 1 Tf
1.1128 -1.8336 TD
[(The)-260(predicted)-260.1(weight)-257.4(and)-260.2(height)-260.4(for)-263(each)-258.2(subject)-263.6(and)-260.2(visit)-257.4(were)]TJ
-1.1128 -1.2266 TD
[(calculated)-405(based)-401.9(on)-403.7(the)-397(United)-402.9(States)-408.1(2000)-396.4(Centers)-406(for)-402.1(Disease)]TJ
0 -1.2203 TD
[(Control)-296.5(\(CDC\))-293.7(Growth)-294.8(Charts)-296.6(\(ages)-297(2)-296.7(t)0(o)]TJ
/F7 1 Tf
16.9011 0 TD
(<)Tj
/F6 1 Tf
.5501 0 TD
[(20)-296.2(years\))-299.2(\(Kuczmarski)]TJ
-17.4512 -1.2203 TD
[(et)-479.7(al.)-482.6(2002\),)-483.6(using)-483.3(each)-485.8(subjects)-481.4(observed)-485.3(baseline)-486.8(weight)-478.7(or)]TJ
0 -1.2266 TD
[(height.)-320.3(The)-316.9(predicted)-323.3(weight)-320.7(and)-323.4(height)-317.4(assumed)-323.5(maintenance)-321.8(of)]TJ
0 -1.2203 TD
[(baseline)-385.6(weight)-383.9(and)-380.3(height)-386.9(percentile)-386.2(for)-383.1(each)-384.7(subject.)-380.3(The)-386.5(pre-)]TJ
T*
[(dicted)-180.7(weight)-181.6(and)-184.3(height)-184.6(over)-180.1(time)-182.8(were)-185.8(used)-178.7(as)-186(references)-186.9(to)-180.1(assess)]TJ
0 -1.2266 TD
[(the)-276.9(trajectory)-285.2(of)-279.8(the)-283.2(observed)-282.9(weight)-282.7(and)-279.2(height)-279.4(over)-281.3(time.)]TJ
/F8 1 Tf
1.1128 -1.2203 TD
(Z)Tj
/F6 1 Tf
.5501 0 TD
[(-score,)-207.2(which)-203.3(expresses)-211.4(an)-203.8(anthropometric)-210.9(value)-208.7(as)-205(the)-207.3(number)]TJ
-1.6629 -1.2203 TD
[(of)-305.1(standard)-312.2(deviations)-310.4(\(SDs\))-315.7(below)-310.8(or)-305.1(above)-312.2(the)-308.5(mean)-309.9(of)-311.5(a)-311.8(refer-)]TJ
T*
[(ence)-270.9(population,)-265.4(was)-271(calculated)-272.2(for)-269.3(each)-270.9(subject)-269.9(at)-271(each)-270.9(visit.)-266.6(The)]TJ
0 -1.2266 TD
[(reference)-382.2(population)-376.3(was)-378.5(based)-383(on)-378.4(the)-378(United)-377.6(States)-382.8(2000)-377.4(CDC)]TJ
0 -1.2203 TD
[(Growth)-415(Charts)-416.7(\(ages)-417.2(2)-410.5(t)0(o)]TJ
/F7 1 Tf
11.1283 0 TD
(<)Tj
/F6 1 Tf
.5501 0 TD
[(20)-416.3(years\))-419.3(\(Kuczmarski)-417.5(et)-410.1(al.)-419.4(2002\).)]TJ
/F8 1 Tf
-11.6784 -1.2203 TD
(Z)Tj
/F6 1 Tf
.5501 0 TD
[(-scores)-363.1(were)-369.2(assessed)-362.2(against)-364.7(the)-365.4(reference)-369.6(population)-363.7(for)-364.1(both)]TJ
-.5501 -1.2266 TD
[(weight)-282.7(and)-279.2(height)-279.4(\(Kuczmarski)-284.7(et)-283.7(al.)-280.3(2002\),)-275(as)-287.2(follows:)]TJ
/F8 1 Tf
.3983 -2.9654 TD
(Z)Tj
/F12 1 Tf
.7777 0 TD
()Tj
/F6 1 Tf
.9358 0 TD
(score)Tj
/F12 1 Tf
2.2826 0 TD
()Tj
ET
360.17 305.121 186.18 .39685 re
f
BT
/F8 1 Tf
8.9663 0 0 8.9663 360.17 309.2031 Tm
[(observed)-309.2(value)]TJ
/F12 1 Tf
6.266 0 TD
()Tj
/F8 1 Tf
.9358 0 TD
[(mean)-275.7(of)-426.7(the)-276.9(reference)-286(population)]TJ
-3.1298 -1.3657 TD
[(SD)-280.5(of)-420.4(the)-283.2(reference)-279.7(population)]TJ
/F6 1 Tf
-8.4601 -2.2004 TD
(A)Tj
/F8 1 Tf
1.0559 0 TD
(Z)Tj
/F6 1 Tf
.5501 0 TD
[(-score)-343.4(change)]TJ
/F7 1 Tf
5.9688 0 TD
(<)Tj
/F6 1 Tf
.5501 0 TD
[(0.5)-343.4(SD)-336(is)-339.3(considered)-339(not)-344(clinically)-338.6(signi-)]TJ
-9.2378 -1.2203 TD
(cant.)Tj
/F8 1 Tf
2.3142 0 TD
(Z)Tj
/F6 1 Tf
.5564 0 TD
[(-score)-387.7(change)-396.3(from)-392.5(baseline)-392(was)-391.1(calculated)-398.6(based)-389.3(on)-391(the)]TJ
-2.8706 -1.2266 TD
[(baseline)-335(values)-329.6(for)-332.5(the)-333.8(subjects)-333.8(remaining)-337.1(in)-331.8(the)-333.8(study)-331.6(at)-334.2(the)-327.4(ob-)]TJ
0 -1.2203 TD
[(servation)-214.6(time)-208(point.)-210.9(Percentiles)-221.1(were)-211.1(assessed)-216.8(as)-211.3(the)-213.6(percentage)-216.2(of)]TJ
T*
-.0135 Tc
[(obs)-13.5(e)9.2(r)-13.5(v)10.2(a)-13.5(t)6.3(i)1.9(on)-13.5(s)-304.6(t)-13.5(h)8.8(a)-13.5(t)-309.8(f)3.4(e)-13.5(l)6.3(l)-314.2(b)-13.5(elow)-319.8(a)-318.9(c)-13.5(e)7.9(r)-13.5(t)12.5(a)-13.5(i)6.3(n)-316.5(va)-13.5(l)12.7(u)-13.5(e)-305.8(f)-13.5(o)10.2(r)-319.1(t)-13.5(h)8.7(e)-318.9(r)-13.5(e)14.1(f)-13.5(e)7.8(r)-13.5(e)7.8(n)-.4(c)-13.5(e)-308.2(popu)-13.5(-)]TJ
0 -1.2266 TD
0 Tc
[(l)15.4(a)0(t)19.8(i)15.4(on)19.9(.)]TJ
/F8 1 Tf
2.9085 0 TD
(Z)Tj
/F6 1 Tf
.5374 0 TD
[(-s)22.5(co)23.9(re)-427.7(b)13.1(y)-442.1(b)13.1(a)0(s)22.7(e)0(l)26.2(i)0(n)22.2(e)-438.2(b)13.1(o)0(d)19.9(y)-435.8(ma)20.3(ss)-425(in)22.3(d)13.1(e)0(x)-425.1(\()0(B)18.9(M)12.4(I\))-427.9(q)13.1(u)13.1(a)0(r)21.2(t)15.4(il)24.6(e)-444.5(w)16.2(as)]TJ
-3.446 -1.2203 TD
[(ca)21.4(l)15.4(c)0(u)23.9(l)0(a)19.8(t)15.4(ed)-216.4(b)13.1(a)0(s)22.7(e)0(d)-216.4(o)13.1(n)-227.1(t)0(h)22.2(e)-229.6(fo)23.7(l)15.4(l)0(o)22.3(w)0(i)18.9(n)13.1(g)-227.1(b)13.1(as)22.7(el)26.1(in)22.3(e)-229.6(B)14.7(M)12.4(I)-229.7(q)13.1(u)13.1(a)0(r)21.3(t)0(i)24.5(l)0(e)19.8(s)0(:)-212.9(q)13.1(u)13.1(a)0(r)21.3(t)0(i)24.5(l)0(e)-220.4(1)13.1(,)]TJ
T*
(BMI)Tj
/F7 1 Tf
2.1371 0 TD
()Tj
/F6 1 Tf
.5564 0 TD
[(16.1;)-251.6(quartile)-262.2(2,)-255.3(BMI)]TJ
/F7 1 Tf
8.7636 0 TD
(>)Tj
/F6 1 Tf
.5501 0 TD
[(16.1)-254.4(to)]TJ
/F7 1 Tf
3.0413 0 TD
()Tj
/F6 1 Tf
.5501 0 TD
[(17.8;)-257.9(quartile)-262.2(3,)-255.3(BMI)]TJ
/F7 1 Tf
8.7636 0 TD
(>)Tj
/F6 1 Tf
.5564 0 TD
(17.8)Tj
-24.9186 -1.2203 TD
(to)Tj
/F7 1 Tf
1.0622 0 TD
()Tj
/F6 1 Tf
.5501 0 TD
[(21.6;)-276.9(quartile)-287.5(4,)-274.3(BMI)]TJ
/F7 1 Tf
8.8584 0 TD
(>)Tj
/F6 1 Tf
.5501 0 TD
(21.6.)Tj
-9.908 -1.2266 TD
[(The)-209.4(descriptive)-220.1(statistics)-213.3(included)-217.6(number)-214.3(of)-210.3(subjects)-220(\()]TJ
/F8 1 Tf
21.8267 0 TD
(n)Tj
/F6 1 Tf
.5058 0 TD
[(\),)-213.7(mean,)]TJ
-23.4454 -1.2203 TD
[(SD,)-193.5(standard)-192.1(error,)-194.1(and)]TJ
/F8 1 Tf
9.3326 0 TD
(Z)Tj
/F6 1 Tf
.5501 0 TD
[(-score.)-194.6(No)-192(statistical)-199.1(tests)-193.8(were)-198.5(conducted.)]TJ
/F4 1 Tf
-9.8827 -2.5292 TD
(Results)Tj
/F11 1 Tf
0 -1.8336 TD
[(Subject)-333.7(disposition)]TJ
/F6 1 Tf
1.1128 -1.8336 TD
[(Subject)-457(disposition)-455.7(has)-457.4(been)-458.1(previously)-458.3(described)-459.6(\(Childress)]TJ
-1.1128 -1.2266 TD
[(et)-220.4(al.)-217(2023\).)-218.1(Briey,)-221(323)-213.5(subjects)-226.3(were)-217.4(screened,)-221.1(among)-218.5(whom)-219.9(282)]TJ
0 -1.2203 TD
[(were)-179.5(enrolled)-188.6(in)-180.1(the)-182(study.)-182.7(Of)-182(the)-182(282)-181.9(enrolled)-182.3(subjects,)-185(254)-181.9(entered)]TJ
T*
[(the)-529.8(treatment)-539.5(phase)-534.7(\(which)-534.2(included)-533.8(70)-536.5(rollover)-530.2(subjects)-536.1(and)]TJ
0 -1.2266 TD
[(184)-422.2(new)-421.6(subjects\),)-421(of)-425.3(whom)-422.2(238)-415.8(subjects)-428.7(were)-419.8(included)-426.3(in)-420.4(the)]TJ
0 -1.2203 TD
[(treatment)-280.3(phase)-281.8(safety)-281.6(population)-281.5(\(Fig.)-284.4(1\).)]TJ
/F4 1 Tf
-28.0042 77.228 TD
[(GROWTH)-341.3(VELOCITY)-336.9(IN)-328.8(CHILDREN)-337.3(TREATED)-338(WITH)-335.9(SDX/)]TJ
6.4556 0 0 6.4556 304.8944 749.7069 Tm
(D)Tj
8.9663 0 0 8.9663 309.5432 749.7069 Tm
[(-MPH)-22602.6(135)]TJ
ET
endstream
endobj
43 0 obj
<>stream
hbd`ab`ddrvL)0q6q57+iWo<>G I102clg`VѿWwE'NZ6wf+o"5}RCAofKVUL{.yIgo/\[8y
ϩlt/_*sOEg?Vkڊyݳ&:"S#%[
Df&HwcZKKwOm| 3 zo
endstream
endobj
45 0 obj
<>stream
hTP1n0
2lxu]hW@M <'E#wll N`dFpew<(%蠮%:Gg6Ȗ&8\w$_4`p}WC2ܗ3xM; bbq,qwg*LW._#$sK|w>y7 di
endstream
endobj
48 0 obj
<>stream
/GS1 gs
BT
/F11 1 Tf
8.9663 0 0 8.9663 62.022 554.9668 Tm
0 0 0 rg
0 Tc
0 Tw
[(Subject)-333.7(demographics)-334.2(and)-335.7(baseline)-331.7(characteristics)]TJ
/F6 1 Tf
1.1128 -1.8336 TD
[(The)-196.8(mean)-196.1(\(SD\))-194.8(age)-193.1(for)-193.4(the)-194.7(subjects)-201(was)-195.1(9.1)-191.6(\(1.9\))-195.9(years;)-199.4(60.9%)-192.8(of)]TJ
-1.1128 -1.2266 TD
[(the)-346.4(subjects)-352.8(were)-343.9(male,)-348.5(and)-348.7(39.1%)-344.5(were)-350.2(female.)-352.5(The)-342.2(mean)-347.9(\(SD;)]TJ
0 -1.2203 TD
[(minimum,)-359.6(maximum\))-357.2(for)-357.8(weight)-358.6(was)-359.5(38.6)-355.5(\(13.9;)-354.9(21.0,)-358.5(97.0\))-357.7(kg,)]TJ
T*
[(BMI)-246.8(was)-252(19.2)-248(\(4.6;)-247.9(13.1,)-244.6(37.5\))-250.2(kg/m)]TJ
6.7246 0 0 5.9768 193.6629 509.6125 Tm
(2)Tj
8.9663 0 0 8.9663 197.0078 505.644 Tm
[(,)-249.5(and)-247.5(height)-247.8(was)-252(139.6)-247.6(\(11.9;)]TJ
-15.0549 -1.2203 TD
[(113.5,)-231.5(171.2\))-237(cm)-232.6(\(Table)-236(1\).)-232.2(Additional)-238.2(subject)-238.3(characteristics)-239.5(have)]TJ
0 -1.2266 TD
[(been)-281.1(previously)-281.3(reported)-282(\(Childress)-283.4(et)-283.7(al.)-280.3(2023\).)]TJ
/F11 1 Tf
0 -2.4533 TD
[(Growth)-336.5(velocity)]TJ
/F2 1 Tf
1.1128 -1.6123 TD
(Weight.)Tj
/F6 1 Tf
4.4956 0 TD
.0188 Tc
[(The)-640.7(m)3.1(ean)-638.3(\(SD\))-640.9(body)-638.3(weight)-636(at)-642.3(baseline)-640.7(w)-3(as)]TJ
-5.6084 -1.2203 TD
0 Tc
[(38.6)-260.7(\(13.9\))-258.6(kg)-258.3(with)-256(a)]TJ
/F8 1 Tf
8.6877 0 TD
(Z)Tj
/F6 1 Tf
.5501 0 TD
[(-score)-261.2(of)-260.9(0.74)-254.4(\(1.13\))-258.6(\(Table)-261.3(2\),)-257.5(indicating)-262.6(a)]TJ
-9.2378 -1.2266 TD
[(baseline)-227.6(weight)-225.8(higher)-227.4(than)-225.8(the)-226.3(mean)-227.7(expected)-231.1(body)-225.7(weight)-225.8(for)-225(the)]TJ
0 -1.2203 TD
[(reference)-319(population.)-309.7(In)-311.5(the)-308.5(rst)-314.3(30)-308.8(days)-311.5(after)-315.1(initiating)-312.5(the)-314.8(treat-)]TJ
T*
[(ment)-216.7(phase,)-221.5(mean)-215.1(observed)-219.7(weight)-213.2(decreased)-220.1(slightly,)-218.6(and)-215.9(this)-215.9(was)]TJ
T*
[(followed)-543.6(by)-542.8(2)-537(months)-543.3(of)-539.1(slowdown)-545.4(in)-540.5(observed)-542.2(weight)-542(gain)]TJ
0 -1.2267 TD
[(\(Fig.)-233.8(2A\).)-235(After)-233.8(this)-234.9(slowdown,)-238.5(a)-235.9(steady)-234.7(increase)-234.9(in)-237(observed)-232.3(body)]TJ
0 -1.2203 TD
[(weight)-206.8(paralleled)-209.1(the)-207.3(predicted)-203.2(weight)-206.8(curve,)-210.3(but)-204.9(at)-201.5(a)-204.3(lower)-212.2(starting)]TJ
T*
[(point)-264.8(because)-273(of)-267.2(the)-264.2(weight)-270.1(decits)-268.5(in)-262.3(the)-270.5(study)-262(population)-268.8(during)]TJ
0 -1.2266 TD
[(the)-283.2(rst)-276.3(3)-284(months.)]TJ
1.1128 -1.2203 TD
[(At)-183.4(90)-188.7(days,)-187.9(the)-188.3(mean)-183.5(observed)-188.1(weight)-187.9(and)-190.6(predicted)-190.5(weight)-187.9(were)]TJ
-1.1128 -1.2203 TD
[(38.5)-197.5(and)-197(40.2)-165.8(kg,)-198(respectively,)-199.6(with)-192.8(a)-197.9(difference)-200(between)-200.8(the)-194.7(means)]TJ
0 -1.2266 TD
[(of)-336.7(1.7)-166.3(kg.)-330.7(At)-335.1(the)-333.8(end)-329.7(of)-336.7(the)-333.8(study)-331.6(\(360)-329.4(days\),)-335.5(the)-333.8(mean)-335.2(observed)]TJ
0 -1.2203 TD
[(weight)-327(and)-329.7(predicted)-329.6(weight)-327(were)-324.9(41.1)-330.2(and)-323.4(42.8)-165.8(kg,)-324.4(respectively,)]TJ
27.9978 29.7556 TD
[(with)-452(the)-447.6(same)-443.9(difference)-452.9(between)-447.4(the)-447.6(means)-449.7(of)-444.2(1.7)-166.3(kg)-448(as)-445.2(after)]TJ
0 -1.2203 TD
[(3)-284(months)-277.7(of)-279.8(treatment.)]TJ
1.1128 -1.2267 TD
[(The)-190.5(mean)-189.8(\(SD\))-188.5(weight)]TJ
/F8 1 Tf
9.1619 0 TD
(Z)Tj
/F6 1 Tf
.5501 0 TD
[(-score)-191.7(at)-188.8(baseline)-189.6(was)-188.8(0.74)-191.1(\(1.13\).)-185.6(Mean)]TJ
-10.8248 -1.2203 TD
(weight)Tj
/F8 1 Tf
3.0856 0 TD
(Z-)Tj
/F6 1 Tf
.8915 0 TD
[(score)-353.9(decreased)-365.6(during)-357.8(the)-352.7(rst)-358.5(month)-359.2(in)-357.1(the)-359.1(treatment)]TJ
-3.9771 -1.2203 TD
[(phase,)-215.2(as)-217.6(evidenced)-211.6(by)-214(the)-213.6(decline)-214.2(at)-207.8(30)-214(days)-216.6(\(Fig.)-208.5(2B\).)-211.1(Most)-212.6(of)-216.6(the)]TJ
0 -1.2267 TD
[(mean)-449(weight)-447.1(Z-score)-443.9(decline)-448.2(occurred)-444.8(in)-445.6(the)-447.6(rst)-440.7(4)-448.4(months)-442.1(of)]TJ
0 -1.2203 TD
[(treatment)-242.4(and)-234.9(remained)-241.1(stable)-238.8(thereafter,)-244.9(near)-239.4(0.5.)-232.5(For)-240(all)-236.6(subjects,)]TJ
T*
[(the)-523.5(mean)-524.9(\(SD\))-517.3(weight)]TJ
/F8 1 Tf
10.1546 0 TD
(Z)Tj
/F6 1 Tf
.5501 0 TD
[(-score)-526.8(during)-515.9(the)-523.4(rst)-522.9(3)-518(months)-524.3(was)]TJ
-10.7047 -1.2203 TD
[(0.53)-342.9(\(1.17\),)-343.7(and)-342.4(at)-346.9(12)-340.5(months,)-343.8(it)-342.2(was)-340.6(0.51)-342.9(\(1.08\),)-343.7(a)-343.4(change)-345.8(from)]TJ
0 -1.2267 TD
[(baseline)-240.2(of)]TJ
/F7 1 Tf
4.5968 0 TD
(-)Tj
/F6 1 Tf
.5501 0 TD
[(0.22)-235.4(\(0.31\))-233.3(at)-233.1(3)-233.5(months)-233.4(and)]TJ
/F7 1 Tf
11.1916 0 TD
(-)Tj
/F6 1 Tf
.5564 0 TD
[(0.20)-229.1(\(0.50\))-233.3(at)-239.4(12)-233(months)]TJ
-16.8948 -1.2203 TD
[(based)-383(on)-378.4(the)-378(baseline)-379.3(scores)-379.9(for)-376.8(those)-378.2(subjects)-384.4(remaining)-375(in)-382.4(the)]TJ
T*
[(study)-281(at)-283.7(3)-277.7(and)-285.5(12)-277.2(months,)-280.6(respectively.)]TJ
1.1128 -1.2266 TD
[(For)-473.9(subjects)-466.6(who)-476.1(completed)-469.7(the)-472.9(study,)-467.3(smaller)-472(decreases)-474.2(or)]TJ
-1.1128 -1.2203 TD
[(lower-than-expected)-433.1(increases)-431.6(were)-432.4(observed)-428.4(during)-421(the)-428.6(second)]TJ
T*
[(and)-443.6(third)-431.8(months,)-438.7(after)-441.6(which)-437.3(the)-434.9(weight)-440.8(velocity)-436.6(resumed,)-441.6(al-)]TJ
0 -1.2266 TD
[(though)-317.2(at)-315.3(a)-318.1(lower)-313.4(starting)-317.9(weight)-314.3(at)-321.6(90)-308.8(days.)-320.7(The)-316.9(average)-312.4(weight)]TJ
0 -1.2203 TD
[(decreased)-365.6(from)-367.2(the)-359.1(68.4)-361.9(\(27.4\))-359.8(percentile)-367.2(to)-357.1(the)-365.4(64.3)-355.5(\(28.8\))-366.1(per-)]TJ
T*
[(centile)-338.4(during)-332.5(the)-340.1(rst)-333.2(month)-333.9(in)-331.8(the)-333.8(treatment)-337.2(phase,)-335.3(with)-338.2(an)-330.2(ad-)]TJ
0 -1.2266 TD
[(ditional)-292.8(small)-284.6(decrease)-296.5(to)-287.6(the)-283.2(62.8)-286(\(27.7\))-290.2(percentile)-291.3(by)-283.6(12)-289.9(months)]TJ
0 -1.2203 TD
[(\(Fig.)-284.4(2C\).)]TJ
1.1128 -1.2203 TD
[(Approximately)-190.7(the)-188.3(same)-184.6(mean)-189.8(weight)-187.9(percentile)-190.2(was)-182.5(maintained)]TJ
-1.1128 -1.2203 TD
[(for)-402.1(the)-397(remainder)-395(of)-400(the)-397(study.)-397.7(The)-392.8(percentage)-405.8(of)-393.7(subjects)-397(with)]TJ
0 -1.2266 TD
[(clinically)-344.9(notable)-344.6(weight)-339.6(loss,)-342.5(dened)-341.9(as)-344.1(a)-343.4(weight)-339.6(decrease)-347.1(from)]TJ
0 -1.2203 TD
(baseline)Tj
/F7 1 Tf
3.4776 0 TD
(>)Tj
/F6 1 Tf
.5564 0 TD
[(7%,)-181.1(was)-188.8(8.7%)-186.9(at)-182.5(30)-188.7(days.)-181.6(The)-190.5(percentage)-184.6(of)-185(subjects)-188.4(with)]TJ
-4.034 -1.2203 TD
[(weight)-352.3(loss)-352.2(increased)-354.5(over)-350.8(time,)-350.1(peaking)-346.9(at)-353.2(14.5%)-350.8(of)-349.4(subjects)-352.8(at)]TJ
0 -1.2266 TD
[(4)-303(months)-303(and)-298.1(then)-301.7(declining)-303.4(to)-300.2(5.2%)-300.7(of)-305.1(subjects)-302.2(at)-302.6(the)-302.2(end)-298.1(of)-305.1(the)]TJ
0 -1.2203 TD
[(study)-502.3(\(360)-500.2(days\).)-493.6(This)-502.6(time)-498.9(course)-498.9(is)-497.4(consistent)-501.3(with)-502.6(average)]TJ
T*
[(weight)-314.3(loss)-307.9(observed)-308.2(during)-313.5(the)-308.5(beginning)-309.6(of)-305.1(the)-308.5(treatment)-311.9(phase)]TJ
0 -1.2266 TD
[(followed)-284.3(by)-283.6(weight)-276.4(gains)-283.4(later)-284.9(in)-274.9(the)-283.2(study.)]TJ
1.1128 -1.2203 TD
[(The)-279(mean)-278.3(weight)]TJ
/F8 1 Tf
7.303 0 TD
(Z)Tj
/F6 1 Tf
.5501 0 TD
[(-scores)-280.9(over)-281.3(time)-277.6(by)-277.2(baseline)-278.1(BMI)-278.5(quartiles)]TJ
-8.9659 -1.2203 TD
[(are)-379(shown)-368.8(in)-369.8(Figure)-371.4(3.)-375.5(The)-373.8(mean)-373.1(baseline)-373(Z-scores)-375.1(were)]TJ
/F7 1 Tf
24.1156 0 TD
(-)Tj
/F6 1 Tf
.5564 0 TD
(0.40,)Tj
-24.672 -1.2266 TD
[(0.32,)-415.4(0.92,)-415.4(and)-418.3(2.16,)-409(for)-414.7(baseline)-417.2(BMI)-417.5(quartiles)-414.6(1,)-419.7(2,)-413.4(3,)-413.4(and)-411.9(4,)]TJ
0 -1.2203 TD
[(respectively.)-471.5(At)-467.9(the)-472.9(end)-462.5(of)-469.5(treatment,)-472.9(the)-466.5(mean)-468(Z-scores)-469.9(were)]TJ
/F7 1 Tf
T*
(-)Tj
/F6 1 Tf
.5564 0 TD
[(0.46,)-200.4(0.12,)-200.4(0.55,)-200.4(and)-197(1.95,)-200.4(a)-204.3(change)-200.3(from)-202.8(baseline)-202.3(of)]TJ
/F7 1 Tf
20.8087 0 TD
(-)Tj
/F6 1 Tf
.5564 0 TD
(0.07,)Tj
/F7 1 Tf
2.194 0 TD
(-)Tj
/F6 1 Tf
.5564 0 TD
(0.13,)Tj
/F7 1 Tf
-24.672 -1.2203 TD
(-)Tj
/F6 1 Tf
.5564 0 TD
[(0.33,)-415.4(and)]TJ
/F7 1 Tf
4.2806 0 TD
(-)Tj
/F6 1 Tf
.5501 0 TD
[(0.25)-418.8(for)-414.7(baseline)-423.6(BMI)-417.5(quartiles)-421(1,)-413.4(2,)-419.7(3,)-413.4(and)-418.3(4,)-419.7(re-)]TJ
-5.3871 -1.2266 TD
(spectively.)Tj
1.1128 -1.2203 TD
[(The)-285.3(Z-scores)-286.5(for)-288.3(subjects)-283.2(with)-287.6(a)-286.5(baseline)-284.5(BMI)]TJ
/F7 1 Tf
19.0825 0 TD
(<)Tj
/F6 1 Tf
.5564 0 TD
[(16.1)-165.9(kg/m)]TJ
6.7246 0 0 5.9768 534.7841 181.0204 Tm
(2)Tj
8.9663 0 0 8.9663 540.6802 177.0519 Tm
(ap-)Tj
-25.3865 -1.2203 TD
[(proached)-341.1(the)-333.8(baseline)]TJ
/F8 1 Tf
9.1998 0 TD
(Z)Tj
/F6 1 Tf
.5501 0 TD
[(-score)-337.1(by)-327.8(the)-333.8(end)-336.1(of)-330.4(the)-333.8(study)-337.9(after)-334.1(a)-330.7(de-)]TJ
-9.7499 -1.2266 TD
[(crease)-320.4(in)-312.9(weight)]TJ
/F8 1 Tf
6.9615 0 TD
(Z)Tj
/F6 1 Tf
.5501 0 TD
[(-score)-311.8(during)-313.5(the)-314.8(initial)-310(3)-315.7(months)-309.3(of)-311.4(treatment.)]TJ
-7.5116 -1.2203 TD
[(The)-430.7(weight)]TJ
/F8 1 Tf
5.1469 0 TD
(Z)Tj
/F6 1 Tf
.5501 0 TD
[(-score)-431.9(of)-425.3(subjects)-428.7(with)-426.7(mean)-430(BMI)]TJ
/F7 1 Tf
14.9094 0 TD
(>)Tj
/F6 1 Tf
.5564 0 TD
[(21.6)-165.8(kg/m)]TJ
6.7246 0 0 5.9768 538.4691 148.1385 Tm
(2)Tj
8.9663 0 0 8.9663 545.6691 144.17 Tm
(at)Tj
-25.9429 -1.2203 TD
[(baseline)-417.2(decreased)-416.1(during)-408.4(the)-409.6(initial)-411.1(2)-410.5(months)-410.5(of)-412.6(treatment)-413.1(and)]TJ
0 -1.2266 TD
[(remained)-285.4(approximately)-284.7(constant)-282(thereafter.)]TJ
/F2 1 Tf
1.1128 -3.5535 TD
(Height.)Tj
/F6 1 Tf
4.268 0 TD
[(The)-184.1(mean)-183.5(\(SD\))-182.2(height)-184.6(at)-182.5(baseline)-183.3(was)-182.5(139.6)-184.3(\(11.9\))-182.7(cm)]TJ
-5.3808 -1.2203 TD
[(with)-249.7(a)]TJ
/F8 1 Tf
2.7189 0 TD
(Z)Tj
/F6 1 Tf
.5501 0 TD
[(-score)-248.6(of)-241.9(0.54)-248(\(0.98\))-239.6(\(Table)-248.6(2\),)-244.8(indicating)-243.7(that)-248.8(the)-245.2(baseline)]TJ
-3.2689 -1.2266 TD
[(height)-450.1(was)-441.7(higher)-442.4(than)-447.1(the)-441.3(mean)-449(expected)-446.1(body)-440.7(height)-443.8(for)-446.4(the)]TJ
0 -1.2203 TD
[(reference)-382.2(population)-370(\(i.e.,)-376.7(the)-371.7(subjects)-371.8(in)-376.1(the)-371.7(present)-376(study)-369.5(were)]TJ
ET
q
1 i
81.354 732.245 m
281.82 732.245 l
281.82 603.099 l
81.354 603.099 l
W n
q
200.706 0 0 129.146 81.354 603.099 cm
/Im2 Do
Q
Q
BT
/F9 1 Tf
8.9663 0 0 8.9663 127.3322 586.318 Tm
[(FIG.)-334.8(1.)]TJ
/F6 1 Tf
4.1099 0 TD
[(Subject)-336.8(disposition.)]TJ
ET
62.022 258.009 239.131 .22675 re
f
62.022 69.109 239.131 .22675 re
f
62.022 239.301 239.131 .22682 re
f
BT
/F10 1 Tf
8.9663 0 0 8.9663 76.0819 273.5999 Tm
(Table)Tj
/F6 1 Tf
2.9971 0 TD
(1.)Tj
/F10 1 Tf
1.2519 0 TD
[(Subjects)-329.2(Demographics.)-337.1(Treatment)-333.7(Phase)]TJ
3.2184 -1.1065 TD
[(Safety)-330.4(Population)]TJ
/F8 1 Tf
-9.0354 -2.0233 TD
[(Parameter)-16171.3(Total)-333(\()]TJ
/F6 1 Tf
23.2304 0 TD
(N)Tj
/F7 1 Tf
.8852 0 TD
(=)Tj
/F8 1 Tf
.7208 0 TD
(238\))Tj
/F6 1 Tf
-24.8364 -2.0866 TD
[(Age,)-336(years)]TJ
.999 -1.1065 TD
[(Mean)-338.7(\(SD\))-16255(9.1)-337.1(\(1.87\))]TJ
0 -1.1128 TD
[(Minimum,)-337.8(maximum)-12849.1(6,)-337.5(12)]TJ
-.999 -1.4479 TD
(Sex,)Tj
/F13 1 Tf
2.0866 0 TD
(n)Tj
/F6 1 Tf
.8283 0 TD
(\(%\))Tj
-1.9158 -1.1065 TD
[(Male)-18502.1(145)-333.7(\(60.92\))]TJ
0 -1.1128 TD
[(Female)-18106.6(93)-334.1(\(39.08\))]TJ
-.999 -1.4416 TD
[(Weight,)-334.8(kg)]TJ
.999 -1.1128 TD
[(Mean)-338.7(\(SD\))-15755.5(38.6)-336.6(\(13.9\))]TJ
T*
[(Minimum,)-337.8(maximum)-11850.1(21.0,)-333.2(97.0)]TJ
-.999 -1.4416 TD
[(Height,)-336.2(cm)]TJ
.999 -1.1128 TD
[(Mean)-338.7(\(SD\))-15256(139.6)-336.1(\(11.92\))]TJ
T*
[(Minimum,)-337.8(maximum)-11350.6(113.5,)-332.7(171.2)]TJ
-.999 -1.4416 TD
[(Body)-331.6(mass)-335.2(index,)-335.7(kg/m)]TJ
6.7246 0 0 5.9768 149.0456 99.326 Tm
(2)Tj
8.9663 0 0 8.9663 70.9795 85.3795 Tm
[(Mean)-338.7(\(SD\))-15755.5(19.2)-336.6(\(4.6\))]TJ
0 -1.1128 TD
[(Minimum,)-337.8(maximum)-11850.1(13.1,)-333.2(37.5)]TJ
7.9702 0 0 7.9702 70.0157 57.2598 Tm
[(SD,)-329.4(standard)-327.2(deviation.)]TJ
ET
313.058 690.236 239.131 .22668 re
f
313.058 612.907 239.131 .22675 re
f
313.058 661.549 239.131 .28345 re
f
BT
/F10 1 Tf
8.9663 0 0 8.9663 333.7511 725.7825 Tm
(Table)Tj
/F6 1 Tf
2.9971 0 TD
(2.)Tj
/F10 1 Tf
1.2519 0 TD
[(Baseline)-333.2(Observed)-332.9(Mean)-338.6(Body)-333.6(Weight)]TJ
-4.9698 -1.1128 TD
[(and)-336.9(Height,)-334.5(Predicted)-330.5(Weight)-336.5(and)-330.6(Height,)-334.5(Weight)]TJ
1.41 -1.1128 TD
[(and)-330.6(Height)-337.9(Z-Score,)-327.9(and)-337(Weight)-336.5(and)-330.6(Height)]TJ
-1.0433 -1.1065 TD
[(Percentiles:)-330.6(Treatment)-340(Phase)-330.8(Safety)-336.7(Population)]TJ
/F8 1 Tf
-1.9538 -3.1362 TD
[(Parameter,)-341.7(mean)-332.6(\(SD\))]TJ
12.8671 1.1128 TD
[(Weight)-332.1(\(kg\),)]TJ
/F6 1 Tf
1.0812 -1.1128 TD
(n)Tj
/F7 1 Tf
.6639 0 TD
(=)Tj
/F8 1 Tf
.7208 0 TD
(238)Tj
6.1901 1.1128 TD
[(Height)-339.6(\(cm\),)]TJ
/F6 1 Tf
1.1318 -1.1128 TD
(n)Tj
/F7 1 Tf
.6639 0 TD
(=)Tj
/F8 1 Tf
.7208 0 TD
(238)Tj
/F6 1 Tf
-24.0397 -2.0802 TD
[(Observed)-9309(38.6)-330.2(\(13.9\))-3963.8(139.6)-329.8(\(11.9\))]TJ
0 -1.1128 TD
[(Predicted)-9351(38.6)-330.2(\(13.9\))-3963.8(139.6)-329.8(\(11.9\))]TJ
T*
[(Z-score)-10080(0.74)-330.2(\(1.13\))-4463.3(0.54)-330.2(\(0.98\))]TJ
T*
[(Percentile)-9123(68.4)-330.2(\(27.4\))-4463.3(64.9)-330.2(\(26.6\))]TJ
7.9702 0 0 7.9702 321.0519 601.1148 Tm
[(SD,)-329.4(standard)-327.2(deviation.)]TJ
/F4 1 Tf
8.9663 0 0 8.9663 62.022 749.6502 Tm
(136)Tj
45.3353 0 TD
[(CHILDRESS)-336.6(ET)-338.7(AL.)]TJ
ET
endstream
endobj
50 0 obj
<>stream
Adobe d
s !1AQa"q2B#R3b$r%C4Scs5D'6Tdt&
EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz m !1AQa"q2#BRbr3$4CS%cs5DT
&6E'dtU7()euFVfvGWgw8HXhx9IYiy*:JZjz ? $Ծ{UHҴ8I$:э\
|~<O䈜/>N\xn.ԫTT;u} +{KSH(k%ޝ V>o~iתT'>A|Iw-7 +{KW $i?/. V>o~iתT'>A|Iw-7 +{KS $i?Ko- նo[ߚ_6j/#I|Iw-7 +{KS $i?Ko- նo[ߚ_5/#I|Iw-7 +{KS $i?Ko- նo[ߚ_6j/#I_] yo}s T ?O8Ko- նo[ߚ_6j/#I_] yo}s T ?O8|w[moVM%KqH(_] yo}s T ?O8|w[moVMz%KqH(_] yo}s T ?O8|w[moVMz%KqHė{[ ls\4l?*_FNBw[moVMz%KqHC(_] yo}s T ?O8|w[moVMz%KqH(_] yo}s T ?O8|w[moVM%KqHė{[ ls\~[gc_yy]Fx~#zr\HQJsKMxb!?"(A#U11