Impact of a Nutritional Supplement on Bone Turnover Markers in Indian Healthy Premenopausal Women (25-45 Yrs; Inclusive) After 6 Months of Intervention: a Randomised Double Blind Controlled Trial
Phase: NA
Conditions: Growth and Development
Sponsor: GlaxoSmithKline

Cli nic al Pr ot oc ol
2 0 7 1 9 2
C O N FI D E N TI A L
S U M M A R Y I N F O R M A TI O N
Title:
I mpact of a N utri tio n al  s u p ple me nt o n B o ne t ur n o ver 
mar kers i n I n dia n healt h y pre me n o pa usal w o me n ( 2 5-
4 5 yr s; i ncl usi ve) after 6 m o nt hs of i nter ve nt i on: a 
ra n d omise d d o u ble bli n d c o ntr olle d trial.
Pr ot oc ol N u m ber:
2 0 7 1 9 2
S p o ns or:
Gl a x o S mit hKli ne C o ns u mer Healt hcare ( G S K C H)
R & D, Pl ot N o. 6 7, Sect or 3 2, G ur ga o n 1 2 2 0 0 1 I n dia
Pr o d uct N a me:
F ortifie d H F D
De vel o p me nt P h ase:
N A
E x pert A d vice O utsi de of 
N or m al W or ki n g H o urs:
Tel: 
Ke y Pr ot oc ol A ut h ors:
P RI M A R Y C O N T A C T
M Sc.   
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 1 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 2 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
P P D
C CI
C CI
C CI

Cli nic al St u d y M a n a ger:
, M S c .
T el :
T E L:
Fa x:
Bi ost atistici a n:
Me dic al Le a d:
Dr. 
, M S
Ot her Pr ot oc ol A ut h ors:
Cli nic al S u p plies:
D at a M a n a ger:
 B. Sc
Me dic al E x pert:
Dr. 
, M S
Pri nci p al I n vesti g at or:
D R. P R A M O D B. U M A R JI                
D R. 
St u d y Site N a me & A d dress:
S ass o n H os pit al, P u ne B. J. 
M E DI C A L C O L L E G E A N D 
S A S S O O N H O S PI T A L,
J AI P R A K A S H N A R A Y A N 
R O A D, N E A R P U N E 
R AI L W A Y S T A TI O N, P U N E, 
M A H A R A S H T R A 4 1 1 0 0 1, 
I N DI A
St u d y Site Tele p h o ne N u m ber:
St u d y E x a mi ner :
D R. 
 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 2 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 3 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
C CI
C CI
C CI

Cli nic al L a b or at or y:
Q 2 S O L U TI O N S T B D
Q S Q U A R E D S O L U TI O N S ( Q U E S T) 
L L C, 2 7 0 2 7 T O U R N E Y R O A D, 
S UI T E 2 E, V A L E N CI A, C A 9 1 3 5 5, 
U S A
Q S Q U A R E D S O L U TI O N S ( Q U E S T) 
L L C, A T T N: BI O M A R K E R L A B, 
2 7 0 2 7 T O U R N E Y R O A D, S UI T E 2 E, 
V A L E N CI A, C A
9 1 3 5 5, U S A
Q S Q U A R E D S O L U TI O N S
LI MI T E D, T H E A L B A C A M P U S 
( R O S E B A N K), LI VI N G S T O N, W E S T 
L O T HI A N E H 5 4 7 E G, S C O T L A N D, 
U NI T E D KI N G D O M
Q U E S T DI A G N O S TI C S NI C H O L S 
I N S TI T U T E, 3 3 6 0 8 O R T E G A 
HI G H W A Y, S A N J U A N 
C A PI S T R A N O, C A
9 2 6 7 5- 2 0 4 2, U S A
S P E CI A L T Y L A B O R A T O RI E S, 
I N C. ( D/ B/ A Q U E S T DI A G N O S TI C S 
NI C H O L S I N S TI T U T E O F 
V A L E N CI A, I N C.), 2 7 0 2 7 T O U R N E Y 
R O A D, S UI T E 2 E, V A L E N CI A, C A
9 1 3 5 5, U S A
A n al ytic al L a b or at or y:
Q 2 S O L U TI O N S
A D D R E S S: S A M E A S A B O V E T B D
Re g ul at or y A ge nc y I de ntifier N u m ber 
(if a p plic a ble):
N A
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 3 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 4 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

P RI N CI P A L I N V E S TI G A T O R P R O T O C O L A G R E E M E N T 
P A G E
I c o nfir m a gree me nt t o c o n d uct t he st u d y in c o m p lia nce with t he pr ot oc ol a n d a n y 
a me n d me nts a n d acc or di n g t o t he c urre nt I C H G C P g ui deli nes.
I ac k n o wle d ge t hat I a m res p o nsi ble f or o verall st u d y  c o n d uct. I a gree t o pers o nall y 
c o n d uct or s u per vise t he descri be d st u d y.
I a gree t o e ns ure t hat all ass ociates, c ollea g ues a n d e m pl oyees assist i n g i n t he c o n d uct 
of  t he st u d y are i nf or me d a b o ut t heir o bli gati ons. Mec ha nis ms are i n place t o e ns ure 
site staff recei ves all a p pr o priate i nf or mati on t hr o u g h o ut t he st u d y .
I a gree t o c o n d uct t his st u d y  in f ull c o nf or ma nce with t he l a ws a n d re g ulati o ns of t he 
c o u ntr y in w hic h t he researc h is c o n d ucte d a n d t he Declarat i on of Helsi n ki.
I n vesti gat or Na me:
D R. P R A M O D B U M A R JI 
I n vesti gat or Q ualificati ons:
M B B S, M D
I n vesti gat or Si g nat ure:
Date of Si g nat ure/ A gree me nt:
D D/ M M M/ Y Y Y Y
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 4 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 5 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI
C CI

T a ble of C o nte nt :
P RI N CI P A L I N V E S TI G A T O R P R O T O C O L A G R E E M E N T 
P A G E ..............................................................................4
T a ble of C o nte nt: ....................................................................5
P R O C E S S F O R A M E N DI N G T H E P R O T O C O L ...............9
P R O T O C O L A M E N D M E N T P A G E ....................................1 0
S C H E D U L E O F E V E N T S .....................................................2 0
P R O T O C O L S Y N O P SI S F O R S T U D Y 2 0 7 1 9 2 ...................2 1
Brief S u m m ar y ..........................................................................2 1
O bjecti ves a n d E n d p oi nts .........................................................2 3
St u d y Desi g n ..............................................................................2 4
St atistic al Met h o ds ....................................................................2 5
1. I N T R O D U C TI O N ...............................................................2 5
2. O B J E C TI V E S A N D E N D P OI N T S ....................................2 7
3. S T U D Y P L A N .....................................................................2 9
3. 1. St u d y Desi g n .......................................................................2 9
3. 2. S u bject Restricti o ns ...........................................................3 3
3. 3. T y pe a n d Pl a n ne d N u m ber of S u bjects ............................3 4
3. 4. St u d y Desi g n a n d D ose J ustific ati o n .................................3 4
4. S E L E C TI O N O F S T U D Y P O P U L A TI O N A N D 
WI T H D R A W A L C RI T E RI A ........................................3 4
4. 1. I ncl usi o n Criteri a ...............................................................3 4
4. 2. E xcl usi o n Criteri a ..............................................................3 5
4. 3. Scree ni n g/ B aseli ne F ail ures ..............................................3 8
4. 4. Wit h dr a w al/ St o p pi n g Criteri a .........................................3 8
4. 5. S u bject Re pl ace me nt ..........................................................3 9
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 5 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 6 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

4. 6. S u bject a n d St u d y C o m pleti o n ..........................................3 9
5. P R O D U C T I N F O R M A TI O N .............................................3 9
5. 1. St u d y Pr o d uct .....................................................................3 9
5. 2. D ose Sc he d ule .....................................................................4 0
5. 3. D ose A d mi nistr ati o n ..........................................................4 0
5. 4. D ose M o dific ati o n ..............................................................4 1
5. 5. Pr o d uct C o m pli a nce ..........................................................4 1
5. 6. Pre c a uti o ns .........................................................................4 1
5. 7. O ver d ose .............................................................................4 1
5. 8. Resc ue T her a p y ..................................................................4 1
5. 9. Pr o d uct Assi g n me nt ...........................................................4 1
5. 9. 1 R a n d o miz ati o n ........................................................................4 2
5. 9. 2 Bli n di n g ....................................................................................4 2
5. 9. 3 C o de Bre a ks .............................................................................4 2
5. 1 0. P ac k a gi n g a n d L a belli n g .................................................4 2
5. 1 0. 1. Acc o u nt a bilit y of Pr o d uct ....................................................4 3
5. 1 0. 2. St or a ge of Pr o d uct ................................................................4 3
6. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S ..............4 3
6. 1. Tele p h o ne Scree ni n g ..........................................................4 3
6. 2. I nf or me d C o nse nt ..............................................................4 4
6. 3. De m o gr a p hics .....................................................................4 4
6. 4. Me dic al Hist or y a n d C o nc o mit a nt Me dic ati o n ................4 4
6. 5. Ge ner al P h ysic al E x a mi n ati o n ..........................................4 4
6. 6. Vit al Si g ns ...........................................................................4 5
6. 7. A nt hr o p o metric Me as ure me nts ( Hei g ht, Wei g ht, a n d B MI)
..........................................................................................4 5
6. 8. H b Assess me nt ....................................................................4 5
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 6 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 7 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

6. 9. L a b or at or y assess me nt ......................................................4 6
6. 1 0. Diet ar y assess me nt ( 7 d a y f o o d di ar y) .............................4 7
6. 1 1. St u d y C o ncl usi o n ..............................................................4 8
6. 1 2. Cli n ic al S afet y L a b or at or y Assess me nts.........................4 8
7. S A F E T Y A S S E S S M E N T S ..................................................4 8
7. 1. Defi niti o ns of a n A d verse E ve nt a n d Seri o us A d verse 
E ve nt .................................................................................4 8
7. 1. 1. A d verse E ve nts .......................................................................4 8
7. 1. 2. Seri o us A d verse E ve nts ..........................................................5 0
7. 2. Rec or di n g A d verse E ve nts a n d Seri o us A d verse E ve nts .5 1
7. 3. E v al u ati n g A d verse E ve n ts a n d Seri o us A d verse E ve nts 5 2
7. 4. Re p orti n g A d verse E ve nts a n d Seri o us A d verse E ve nts ..5 3
7. 5. F oll o w -u p of A d verse E ve nts a n d Seri o us A d verse E ve nts
..........................................................................................5 5
7. 7. C ollecti o n of Pre g n a nc y I nf or m ati o n ................................5 6
7. 7. 1. Ti me Peri o d f or C ollecti n g of Pre g n a nc y I nf or m ati o n ........5 6
7. 7. 2. Acti o n t o be T a ke n if Pre g n a nc y Occ urs ..............................5 6
8. D A T A M A N A G E M E N T ....................................................5 7
8. 1. S o urce D oc u me nts/ D at a ....................................................5 7
8. 2. Electr o nic C ase Re p ort F or m ............................................5 7
8. 3. D at a H a n dli n g ....................................................................5 8
8. 3. 1. D at a Q ueries ...........................................................................5 8
8. 4. Pr ocessi n g P atie nt Re p orte d O utc o mes ............................5 9
8. 5. E xter n al D at a .....................................................................5 9
9. S T A TI S TI C A L C O N SI D E R A TI O N S A N D D A T A 
A N A L Y S E S ....................................................................5 9
9. 1 S a m ple Size Deter mi n ati o n .................................................5 9
9. 2. Ge ner al C o nsi der ati o ns .....................................................6 2
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 7 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 8 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

9. 2. 1. Defi niti o n of A n al ysis P o p ul ati o ns ........................................6 2
9. 2. 4. Criteri a f or Assessi n g Effic ac y ..............................................6 2
9. 2. 5. Criteri a f or Assessi n g T oler a bilit y ........................................6 2
9. 3. St atistic al Met h o ds a n d A n al ytic al Pl a n ...........................6 3
9. 3. 1. De m o gr a p hic a n d B aseli ne C h ar acteristics ..........................6 3
9. 3. 2. Pri m ar y A n al ysis ....................................................................6 3
9. 3. 3. Sec o n d ar y A n al ysis ................................................................6 3
9. 3. 3. E x pl or at or y A n al ysis .............................................................6 4
9. 3. 4. S afet y A n al ysis .......................................................................6 4
1 0. S T U D Y G O V E R N A N C E C O N SI D E R A TI O N S .............6 5
1 0. 1. P osti n g of I nf or m ati o n o n P u blicl y A v ail a ble Cli nic al 
Tri als Re g isters................................................................6 5
1 0. 2. Re g ul at or y a n d Et hic al C o nsi der ati o ns, I ncl u di n g t he 
I nf or me d C o nse nt ............................................................6 5
1 0. 3. Q u alit y C o ntr ol ( St u d y M o nit ori n g) ...............................6 5
1 0. 4. Q u alit y Ass ur a nce ............................................................6 6
1 0. 5. C o n diti o ns f or Ter mi n ati n g t he St u d y ............................6 6
1 0. 6. Rec or ds Rete nti o n ............................................................6 7
1 0. 7. Pr o visi o n of St u d y Res ul ts t o I n vesti g at ors, p osti n g of 
I nf or m ati o n o n P u blicl y A v ail a ble Cli nic al Tri als 
Re gisters a n d P u blic ati o n ................................................6 8
1 1. R E F E R E N C E S ..................................................................6 9
1 2. A P P E N DI C E S ...................................................................7 8
1 2. 1. A p pe n di x 1 – Pr o d uct N utriti o n al Pr ofile .......................7 8
1 2. 2. A p pe n di x II - A b bre vi ati o ns ............................................7 9
1 2. 3. A p pe n di x III - 7 d a y f o o d di ar y te m pl ate ........................8 1
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 8 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 9 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

C o p y rig ht:  Gl a x o S mit h Kli ne.  A n u n p u blis he d w or k s u bject t o tra de secret 
pr otecti o n.  T hi s w or k c o ntai ns c o nfi de ntial a n d pr o prietar y inf or mat i on of 
Gl a x o S mit hKli ne a n d s h o ul d n ot be c o pie d, circ ulate d , or distri b ute d t o pers o ns n ot 
e mpl o y e d b y Gla x o S mit hKli ne u nless s pecificall y a ut h orize d.  U na ut h orize d 
di s clos ure of t his w or k is e x pressl y  pr o hi bite d.
P R O C E S S F O R A M E N DI N G T H E P R O T O C O L
Pr ot oc ol  mo dificati o ns t o o n g oi n g st u dies w hic h c o ul d p ote nti all y a d versel y affect t he 
safety of  s u bjects or w hic h alter t he sc o pe of t he i n vesti gati o n, t he scie ntific q uality of  
t he st u d y, t he e x peri me ntal desi g n, d osa ges, d urati o n of t hera p y, assess me nt 
varia bles, t he n u m ber of s u bjects treate d, or s u bject select i on cri t eria are c o nsi dere d 
maj or/s u bsta nt ial a me n d me nts a n d m ust be ma de o nl y after a p pr o priate c o ns ult atio n 
bet wee n a n a p pr o priate re prese ntati ve of G S K C H a n d t he i n vest i gat or.
Details o f a me n d me nts t o t he pr ot oc ols s h o ul d be rec or de d o n t he f o ll owi n g pa ge. 
Pr ot oc ol  mo dificati o ns m ust be pre pare d b y  a re prese ntati ve of G S K C H.  All c ha n ges 
m ust be j ust ifie d i n t he Reas o n f or A me n d me nt secti o n of t he f oll owi n g Pr ot oc ol  
A me n d me nt Pa ge. A p pr o val of a me n d me nts will be ma de b y t he ori gi nal pr o t oc ol 
sig nat ori es or t heir a p pr o priate desig nees.
All maj or/s u bsta nt ial pr ot oc ol  mo dificat i ons m ust be re vie we d a n d a p pr o ve d b y t he 
a p pr o priate I R B/I E C i n acc or da nce wit h l ocal re q uire me nts, bef ore t he re vise d 
e ditio n ca n be i m ple me nte d. 
All n o n-s u bsta ntial/ mi n or/ a d mi nistrati ve a me n d me nts s h o ul d be s u b mitte d t o t he 
I R B/ I E C as per c o u ntr y s pecific re q uire me nts. I n s o me c o u ntries pre -a p pr o val of a 
mi n or a m e n d me nt is n ot re q uire d a n d will j ust be hel d o n file b y t he s p o ns or a n d 
i n vesti gat or.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 9 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 1 0 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

P R O T O C O L A M E N D M E N T P A G E
Details o f all a me n d me nts s h o ul d be rec or de d i n t he ta ble bel o w. Affecte d secti o ns s h o ul d be liste d i n t he ta ble; t he act ual 
a me n d me nt/ c ha n ge s h o ul d be ma de i n t he rele va nt secti o n of t he mai n pr ot oc ol. 
T o hi g hli g ht t he c ha n ge, t he f o ll owi n g feat ures wil l be use d: 
T o a d d te xt: Use of C A PI T A L L E T T E R S, B O L D A N D U N D E R LI N E
T o delete te xt: Use of Striket hr o u g h e. g. stri ket hr o u g h
A me n d me nt 
N o. & Ne w 
Pr ot oc ol 
Versi o n N o.
T y pe of A me n d me nt
Re as o n f or A me n d me nt
Ot her 
D oc u me nts 
Re q uiri n g 
A me n d me nt
Secti o n(s) A me n de d 
PI A me n d me nt 
A gree me nt
Si g n at ure & 
D ate
A me n d me nt 
N o.:
0 1
N o n -S u bsta nt ial/ Mi n or    Si te a n d PI a n d la b orat or y 
detail was n ot fi nalize d 
earlier 
I nf or me d 
C o nse nt   
Ye s 
N o
S u m mar y  
i nf or mat i on , PI, Sit e 
a n d la b details a d de d
Si g nat ure:
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 1 0 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 1 1 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI
C CI

Pr ot oc ol 
Versi o n 
N o.:
0 2
S u bsta nt ial/ Maj or           
S af et y 
State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
Date:
A me n d me nt 
N o.:
0 1
N o n -S u bsta nt ial/ Mi n or    S a m ple life c ycle details 
were n ot a vaila ble earlier, 
n o w la b pr o vi de d t his
I nf or me d 
C o nse nt   
Ye s 
N o
S af et y 
State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
S T U D Y 
A S S E S S M E N T S 
A N D 
P R O C E D U R E S , 
La b assess me nt
pr oce d ure detail 
a d de d a b o ut 
c ollect i on, st ora ge, 
tra ns p ort a n d 
a nal ysis of H B S
Si g nat ure:
Pr ot oc ol 
Versi o n 
N o.:
0 2
S u bsta nt ial/ Maj or           
Date:
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 1 1 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 1 2 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
P P D
P P D
C CI
C CI
C CI

A me n d me nt 
N o. & Ne w 
Pr ot oc ol 
Versi o n N o.
T y pe of A me n d me nt
Re as o n f or A me n d me nt
Ot her D oc u me nts 
Re q uiri n g A me n d me nt
Secti o n(s) A me n de d 
PI 
A me n d me nt 
A gree me nt
Si g n at ure & 
D ate
A me n d me nt 
N o.:
0 1
N o n -S u bsta nt ial/ Mi n or    S of t ware u p dates n ot 
a vaila ble earlier
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
S T U D Y 
A S S E S S M E N T S 
A N D 
P R O C E D U R E S , 
Di et ar y assess me nt
detail re gar di n g 
s oft ware t o be use d 
f or diet ar y data 
a nalys is a d de d
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
0 2
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o.:
0 1
N o n -S u bsta nt ial/ Mi n or    Ne w pr o d uct c o de pr o vi de d 
b y N P D
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
Pr o d uct 
i nf or mat i on, M F C, 
ne w pr o d uct a d de d
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
0 2
S u bsta nt ial/ Maj or           
Date:
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 1 2 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 1 3 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
P P D
P P D
P P D
C CI
C CI
C CI

A me n d me nt 
N o.:
0 1
N o n -S u bsta nt ial/ Mi n or    U p date d i nf or mat i on fr om 
N P D recei ve d a n d 
s u g gesti on recei ve d fr o m 
re vie wers t o a d d s o me 
i nf or mat i on 
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
A p pe n di x, Pr o d uct 
n utri tio nal pr ofile
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
0 2
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o.:
0 1
N o n -S u bsta nt ial/ Mi n or    D ue t o a me n d me nts 
c ha n ge d re q uire d i n 
sc he d ule
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
St u d y  sc he d ule 
u p date d as per 
a me n d me nts 
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
0 2
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o. & Ne w 
Pr ot oc ol 
Versi o n N o.
T y pe of A me n d me nt
Re as o n f or A me n d me nt
Ot her D oc u me nts 
Re q uiri n g A me n d me nt
Secti o n(s) A me n de d 
PI 
A me n d me nt 
A gree me nt
Si g n at ure & 
D ate
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 1 3 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 1 4 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
P P D
P P D
P P D
C CI
C CI
C CI

A me n d me nt 
N o.:
0 2
N o n -S u bsta nt ial/ Mi n or    D ue t o re g ulat or y  
re q uire me nt N F T re vise d, 
K ( P otassi u m a d de d t o 
N F T) w hic h was n ot 
me nt i one d.
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
Secti o n 1 2. 1 
A p pe n di x 1 
Pr o d uct Pr ofile
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
0 3
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o.:
0 2
N o n -S u bsta nt ial/ Mi n or    M o del  of Weig hi n g 
mac hi ne is c ha n ge d b y  
ma n ufact urer, ne w na me is 
use d 
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
6. 7 
A nt hr o p o m etric 
meas ure me nt 
hei g ht a n d wei g ht
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
0 3
0 3
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o.:
0 2
N o n -S u bsta nt ial/ Mi n or    La b m a n ual u p date d wit h 
ne w met h o d w hic h is 
c o n ve nie nt a n d acc urate , 2 4 
h o ur uri ne c ollecti o n n ot 
re q uire d, s p ot test f or C T X-
1, Calci u m a n d Creat i ni ne 
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
6. 9 La b assess me nt
Si g nat ure:
Pr ot oc ol 
S u bsta nt ial/ Maj or           
Date:
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 1 4 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 1 5 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
P P D
P P D
P P D
P P D
C CI
C CI
C CI

Versi o n N o.:
0 3
0 3
will w or k.
C R F                       
Ye s 
N o
A me n d me nt 
N o.:
0 2
N o n -S u bsta nt ial/ Mi n or    F or di et ar y assess me nt 
P orti o n size is n ot acc urate 
meas ure a n d s u bject i ve, use 
of  w eig hi n g scale gi ves 
acc urate a m o u nt c o ns u me . 
P orti o n size is re place d  b y 
meas ure d a m o u nt
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
6. 1 0 Di et ar y 
assess me nt. 
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
0 3
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o.:
0 2
N o n -S u bsta nt ial/ Mi n or    Acc or di n g t o latest la b 
ma n ual Z n a n d Vit B 6 is 
meas ure d i n plas ma n ot i n 
ser u m
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
Secti o n - 2 
O bjecti ves a n d 
E n d p oi nts
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
0 3
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o.:
N o n -S u bsta nt ial/ Mi n or    Acc or di n g t o latest la b 
ma n ual o nl y  test r u n 
I nf or me d C o nse nt   
Ye s 
N o
Secti o n -6. 9 La b 
assess me nt 
Si g nat ure:
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 1 5 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 1 6 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
P P D
P P D
P P D
P P D
P P D
C CI
C CI
C CI

0 2
bi o mar ker l a b will be r u n 
batc hes n ot all beca use kit 
ca n a nal yze 3 6 test i n o ne 
batc h. 
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
Pr ot oc ol 
Versi o n N o.:
0 3
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o.:
0 3
N o n -S u bsta nt ial/ Mi n or    O n few pl aces re place me nt 
of  ser u m b y plas ma f or 
testi n g Vita mi n B 6 a n d Z n 
was misse d i n pre vi o us 
a me n d me nt d ue t o t yp o 
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
1.
I ntr o d ucti o n, 
o bj ect i ves a n d 
e n d p o i nts
2. 9. 3. 3 
sec o n dar y 
a nal ysis 
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
0 4
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o.:
0 3
N o n -S u bsta nt ial/ Mi n or    He m o gl o bi n meas ure me nt 
was misse d fr o m 
me nt i oni n g i n sc he d ule of  
e ve nts o n visit 2 w hile it is 
i n pr oce d ure 
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
Sc he d ule of e ve nts
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
S u bsta nt ial/ Maj or           
Date:
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 1 6 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 1 7 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
P P D
P P D
P P D
P P D
C CI
C CI
C CI

0 4
A me n d me nt 
N o.:
0 3
N o n -S u bsta nt ial/ Mi n or    C ha n ge of st u d y  ma na ger 
a n d c o ntact n u m ber 
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
S u m mar y  details
Si g nat u re:
Pr ot oc ol 
Versi o n N o.:
4
0 4
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o.:
0 3
N o n -S u bsta nt ial/ Mi n or    St ora ge te m perat ure f or 
H B S i s u p date d as per 
re vise d sta bility data s hare d 
b y la b.
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
6. 9 La b assess me nt 
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
0 4
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o.:
0 3
N o n -S u bsta nt ial/ Mi n or    Ti me d urat i on of S A Es
c ollect i on was n o t matc hi n g 
bet wee n A Es rec or di n g a n d 
S A Es rec or di n g secti on 
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
7. 2 Rec or di n g of  
A Es a n d S A Es
Si g nat ure:
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 1 7 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 1 8 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
P P D
P P D
P P D
P P D
C CI
C CI
C CI

Pr ot oc ol 
Versi o n N o.:
0 4
S u bsta nt ial/ Maj or           w hic h is u p date d n o w 
Ye s 
N o
C R F                       
Ye s 
N o
Date:
A me n d me nt 
N o.:
0 3
N o n -S u bsta nt ial/ Mi n or    Ti me o f sa m ple st ora ge 
c ha n ge d fr o m 1 4 da ys after 
last sa m ple a nal ysis t o 1 4 
da ys after eac h sa m ple 
a nal ysis t o ali g n wit h la b 
c o ntract 
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
6. 9 La b assess me nt
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
0 4
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o.:
0 3
N o n -S u bsta nt ial/ Mi n or    Cl arificat i on re gar di n g 
pr o d uct a d mi nistrati o n u pt o
visit 6 was misse d 
I nf or me d C o nse nt   
Ye s 
N o
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
Sc he d ule of e ve nt 
St u d y  desi g n ( visit 
6)
Si g nat ure:
Pr ot oc ol 
Versi o n N o.:
0 4
S u bsta nt ial/ Maj or           
Date:
A me n d me nt 
N o.:
N o n -S u bsta nt ial/ Mi n or    Ter mi n o l og y ‘ Pr o d uct 
c o mplia nce re p ort’ re place d 
wi t h ‘S u bject diar y  car d f or 
I nf or me d C o nse nt   
Ye s 
N o
Secti o n 5. 5 
Pr o d uct 
Si g nat ure:
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 1 8 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 1 9 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
P P D
P P D
P P D
P P D
P P D
C CI
C CI
C CI

0 3
d ose c o m plia nce’
S af et y State m e nt     
Ye s 
N o
C R F                       
Ye s 
N o
c o mplia nce 
Pr ot oc ol 
Versi o n N o.:
0 4
S u bsta nt ial/ Maj or           
Date:
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 1 9 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 2 0 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI
C CI

S C H E D U L E O F E V E N T S
Pr oce d ure/ Assess me nt
Visit 1  
Visit 2
Visit 3  
Visit 4
Visit 5
Visit 6
Scree ni n g
Baseli ne Visit ( + 7ᵞ
t o 1 0 da ys p ost 
scree ni n g)
F oll o w u p visit 
( 4 5 da ys +/ - 7 
da ys fr o m visit 2)
Mi dli ne Visit ( 9 0 
da ys fr o m baseli ne 
+/ - u p t o 7 3 da ys)
F oll o w u p visit 
( 1 3 5 d a ys +/ - 7 
da ys fr o m baseli ne 
)
E n d of st u d y visit ( 1 8 0 da ys fr o m 
baseli ne +/ - u p t o 7 3 da ys)
I nf or me d c o nse nt
X
De m o gra p hics
X
Me dical Hist or y
X
C urre nt / C o nc o mita nt me dicati o n
X  
X
X
X
X
X
Ge neral p h ysical e xa mi nati o n
X
X
X
X
X
X
Vital si g ns
X
X
X
X
X
X
He m o gl o bi n ( H b) assess me nt usi n g Pr o nt o
X
X
X
X
X
X
A nt hr o p o metric meas ure me nts ( hei g ht, wei g ht a n d 
B MI)
X
I ncl usi o n / E xcl usi o n criteria e val uati o n
X
S u bject Eli gi bilit y
X
Ra n d o mizati o n
X
X
C o nti n ue d Eli gi bilit y
X
X
X
X
X
7- da y diar y f or assess me nt 
of dietar y i nta ke
Diar y a n d we i ghi n g sc ale
distri b uti o n
X
X @
Diar y a n d we i ghi n g sc ale
c ollecti o n
X
X
Pre g na nc y Test
X  
X
X
X
X
X
Bl o o d Sa m ple c ollecti o n f or a nal ysis of ser u m C T X -1, 
N T X -1, P 1 N P, B S A P, t otal O C, c O C, u O C, P T H, 2 5 
( O H) D, Ca, P, t otal A L P, I G F-1, Z n, Se, B 6, B 1 2 a n d 
F olic aci d
X
X
X
U RI N E Sa m ple c ollecti o n f or a nal ysis of uri nar y 
calci u m, creati ni ne a n d C T X- 1
X
X
X
Pr o d uct A d mi nistrati o n a n d dis pe nsi n g
X
X
X
X
X $
C ollecti o n of ret ur ne d pac ks
X
X
X
X
A d verse E ve nts m o nit ori n g
X
X
X
X
X
St u d y C o ncl usi o n/ Me dical Si g n -off
X
(* Diar y will be c ollecte d o n first m o nit ori n g S U B S E Q U E N T visit after distri b uti o n , # pr o d uct c o m plia nce assess me nt will be d o ne o n visits E V E R Y VI SI T
m o nit ori n g A F T E R VI SI T 2 , @ Tele p ho nic f oll o w u p will be d o ne 8 -1 0 da ys pri or t o visit -6 t o re mi n d filli n g of f o o d diar y f or last  se ve n da ys of i nter ve nti o n/ 7 da ys 
pri or t o visit - 6, $ T o be c o ns u me d u ntil last e ve ni n g bef ore visit -6 n ot act uall y o n t he da y beca use we are dra wi n g last bl o o d sa m ple fasti n g a n d after t hat it is n ot 
nee de d )
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 2 0 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 2 1 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

P R O T O C O L S Y N O P SI S F O R S T U D Y 2 0 7 1 9 2
Brief S u m m ar y
C ha n ge i n lifest yle, dietar y ha bits a n d e n vir o n me nt is k n o w n t o ha ve si g nifica nt effect o n 
w o m e n’s p h ysi o l og y  a nd b o nes are n ot s pare d fr o m t he i m pact.  I n p ost me n o pa usal w o me n, t he 
pre vale nce o f l ow b o ne mi neral de nsit y ( B M D), its ass ociat i on t o fract ure ris k a n d t he efficac y of 
p har mac o l ogi c t hera p y t o re d uce t he ris k of fract ures are well esta blis he d. T he W orl d Health 
Or ga nisat i on cri t eria for dia g n osi n g oste o pe nia ( B M D sc ore bet wee n 1 a n d 2. 5 Sta n dar d 
De viat i on ( S D) bel o w t he y o u n g a d ul t mea n i.e. bet wee n −1 t o −2. 5 S D) a n d oste o p o r osis ( B M D 
sc ore of 2. 5 S D or m ore bel o w t he yo u n g a d ul t mea n i.e. -2. 5 S D or l o wer) are als o base d o n 
e pide mi ol o gical data o btai ne d i n p ost - me n o pa usal w o m e n a n d t he treat me nt g ui deli nes are als o 
tar gete d f or p ost me n o pa usal w ome n. T his is mai nl y beca use b o ne mass a n d b o ne t ur n o ver are 
ge nerall y t h o u g ht t o re mai n sta ble fr o m t he e n d of p u bert y t o me n o pa use. H o we ver, se veral 
cr oss-secti o nal & l on git u di nal  st u dies ha ve re p orte d t hat b o ne mi neral de nsit y ( B M D) a n d b o ne 
t ur n o ver mar kers c ha n ge bet wee n t he 2 n d t o t he 4t h deca de of life. I n I n dia n fe males, b o ne 
mi neral de nsit y reac hes a pea k at a ge 2 8 years f or fe m ur, at 2 9 years f or f orear m a n d at t he a ge 
of  2 0 years f or lu m bar s pi ne. F urt her, it is re p orte d t hat I n dia ns ha ve si g nifica ntl y l o wer B M D & 
attai n l o wer Pea k B o ne mass ( P B M) t ha n t heir N ort h A merica n c o u nter parts ( M u k herjee et al., 
2 0 1 0). P ost attai n me nt of P B M, si g nifica nt l oss i n b o ne mass occ urs as e vi de nce d b y ver y hi g h 
pre vale nce o f os te o pe nia a n d oste o p or osis i n pre me n o pa usal i n dia n w o me n ( Mit hal et al., 2 0 0 9, 
Mi t hal et al., 2 0 1 4, A gar wal & Ver ma 2 0 1 3, Sil va n us et al., 2 0 1 2, Ka da m et al., 2 0 1 0 Desai et 
al., 2 0 0 7). 
I n t he 2 0 0 9 I nter nati o nal Oste o p or osis F o u n dati o n (I O F) Asia n A u dit, e x pert gr o u ps esti mate d 
t hat t he n u m ber of oste o p or osis pat ient s in I n dia was a p pr o xi matel y  2 6 millio n  in 2 0 0 3, wi t h 
pr oj ect i ons i n dicati n g t hat t his w o ul d rise t o 3 6 milli on patie nts b y 2 0 1 3( Mit hal et al., 2 0 0 9) . I n 
2 0 1 3, s o urces esti mate t hat 5 0 milli o n pe o ple i n I n dia are eit her oste o p or otic or ha ve l o w b o ne 
mass ( Mit h al  et al., 2 0 1 4)
A gar wal a n d Ver ma ( 2 0 1 3) re p orte d 4 8 % pre vale nce of oste o pe nia & 1 3 % of oste o p or osis 
a mo n g ur ba n I n dia ns w o m e n a b o ve t he a ge of 3 5 years. A cr oss secti o nal st u d y  c o mpari n g B M D 
a n d its varia bles i n pre me n o pa usal (a ge: 3 2. 4 6 ± 7. 8 years) a n d p ost m e n o pa usal w o me n (a ge : 
5 1. 7 4 ± 7. 1 y ears) s h o we d t hat sig nifica nt n u m ber of w o me n ( 4 3. 5 4 %)  ha d oste o pe nia d uri n g 
pr e m e n o pa usal p erio d w hile 9. 6 % of t he pre me n o pa usal w o me n als o ha d oste o p or osis ( Mittal et 
al., 2 0 1 1).
Reas o ns ascri be d f or l o wer P B M a n d B M D i n I n dia ns ot her t ha n ge net ic differe nces is pri maril y 
n utri tio nal deficie ncies , i n partic ular Calci u m a n d Vita mi n D deficie nc y d uri n g gr o wt h years, 
a d ult h o o d a n d old er y ears. F or e. g. t he re p orte d me dia n dietar y calciu m i nta kes f or I n dia n a d ults 
is b et wee n 3 0 0-3 5 0 m g/ da y ( Mi t hal et al., 2 0 0 9; Hari nara ya n et al., 2 0 0 7). C o nsi deri n g t hat A d ult 
R D A of Calci u m f or I n dia n’s is 6 0 0 m g, t here e xists a deficit of 2 5 0 -3 0 0 m g/ d a y .  Si milarl y, 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 2 1 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 2 2 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

Vi ta mi n D deficie nc y has bee n s h o w n u ne q ui v ocall y acr oss all a ges t hr o u gh o ut I n dia, des pite 
a b u n da nt s u ns hi ne. Vita mi n D deficie nc y d uri n g c hil d h o o d a n d a d olesce nce decreases pea k b o ne 
mass i n a d ults a n d ma y  increase t he ris k of de vel o pi n g oste o p or osis ( S hi va ne et al., 2 0 1 2). 
St u di es i n dicate a p pr o xi matel y 8 0 -9 0 % of hi p fract u re patie nts i n I n dia are vita mi n D deficie nt 
( D ha n wal et al., 2 0 1 3 ; K ha d ga wat et al., 2 0 1 3). T he hi g h rate of vita mi n D deficie nc y ma y be 
d ue t o se veral ca uses s uc h as l o w s u n e x p os ure, i na de q uate dietar y  vita mi n D i nta ke, la c k of fo o d 
f ortificati on, pi g m e nte d s ki n, e n vir o n me ntal p o ll uti on a n d cl ot hi n g ha b bits ( Mit hal et al., 2 0 0 9). 
St u di es ha ve s h o w n t hat desira ble ser u m le vels of Vita mi n D ( 2 5( O H) D) is bet wee n 2 5 t o 4 5 
n g/ m L ( 5 0 t o 1 0 0 n m o l/ L) base d o n be neficial effects o n b o ne healt h s uc h as pre ve nti on of  fall 
a n d fract ure ris k ( F ulei ha n et al., 2 0 1 5) . C o nsi deri n g t hat m ore t ha n 8 0 % of ur ba n I n dia ns 
(acr oss a ge gr o u ps) ha ve ser u m 2 5( O H) D le vels bel o w 2 0 n g/ m L ( Mithal et al., 2 0 1 4) a n d t hat 
f or e ver y 1 0 0 I U ( 2. 5 mc g) a d ditio nal  Vita mi n D eac h da y o ver se veral m ont hs, ser u m 2 5( O H) D 
ca n be e x pecte d t o rise b y a b o ut 1 n g/ m L ( Hea ne y, 2 0 0 8), si g nifica nt a m o u nt of Vita mi n D are 
re q uire d t o be a d de d fr o m t he s u p ple me nts t o attai n a de q uate ser u m le vels.
He nce, t here e xists a nee d f or a p pr o priate s u p ple me nts c o n tai ni n g Calci u m, Vita mi n D a n d ot her 
os te o ge nic n utrie nts t o i m pr o ve b o ne healt h acr oss life -sta ges. Pre me n o pa usal w ome n is a n 
i m p orta nt tar get gr o u p as t he y ma y st ill ha ve t he o p p ort u nit y t o i ncrease t heir pea k b o ne mass. 
T here i s e vi de nce t hat p h ysicall y act i ve 2 0 t o 5 0 year ol d w o me n wit h a g o o d lifeti me calci u m 
i nta ke ca n i ncrease t heir pea k b o ne mass ( Hali o ua & A n ders o n et al., 1 9 8 9). F urt her, 
s u p ple me ntatio n d uri n g pre me n o pa usal years hel ps t o mai ntai n b o ne mass s uc h t hat w o me n e nter 
me n o pa use ( peri o d of  accelerate d b o ne l oss d ue t o estr o ge n deficie nc y) wit h hi g her b o ne st ores. 
Data i n I n dia n p o p ulati o n ha ve re veale d t hat a vera ge a ge f or me n o pa use i n I n dia is 4 7 y ears a n d 
t hat sig nifica nt i ncrease i n B o ne t ur n o ver is o bser ve d after t he a ge of 4 0 y ears d ue t o h or m o n al  
c ha n ges ( Desai et al., 2 0 0 7). O nce t he h or m o nal c ha n ges set -i n, b o ne meta b olis m bec o me s less 
a me na ble t o n utritio nal  int er ve nt i ons. He nce, n utriti o nal s u p ple me nts t o i m pr o ve b o ne mass i n 
sec o n d a n d t hir d deca des of life are partic ularl y be neficial t o h elp attai n a de q uate pea k b o ne 
mass a n d mai ntai n t he sa me t hr o u g h t he pre me n o pa usal years. S uc h strate gies w o ul d g o a l o n g 
w a y  t o re d uce t he mor bi di t y of oste o p or osis later i n life. It is re p orte d t hat a 1 0 % i ncrease i n 
P B M c orres p o n ds t o a gai n of  o ne sta n dar d de viati o n i n b o ne mi neral de nsity i n a d ulth o o d & 
os te o p or otic fract ure ris k ma y be re d uce d b y u p t o 5 0 % ( Mars hall et al., 1 9 9 6)
G S K I n dia c o ns u mer healt hcare has de vel o pe d a c ust o mise d pr o d uct desi g ne d t o i m pr o ve b o ne 
healt h i n I n dia n W ome n. It i s ric h i n g o o d q ualit y pr otei n a n d se veral oste o ge nic n utrie nts li ke 
Calci u m, Vita mi n D, Vita mi n K, Ma g nesi u m, Sele ni u m, Vita mi n C etc. Greater details o n t he 
pr o d uct are disc usse d i n sect i on 3. T he o bject i ve of t his st u d y is t o test t he efficac y of t his 
s u p ple me nt o n b o ne healt h b y vali date d met h o ds. 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 2 2 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 2 3 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

O bjecti ve s a n d E n d p oi nts
O bjecti ves
E n d p oi nts
Pri m ar y
T o c o m pare t he c ha n ges i n B o ne Res or pti o n 
mar ker : ser u m C-t elo p e pti de of t y pe 1 
c olla ge n (s-C T X - 1)  at  e n dli ne 6 m o nt hs fr o m 
baseli ne i n test a n d c o ntr ol gr o u ps 
C ha n ge fr o m baseli ne i n s -C T X -1 at 6 m o nt hs
T o c o m pare t he c ha n ges i n t he ratio of  
car b o x ylate d (c-O C) t o u n der -car b o x ylate d 
Oste ocal ci n ( uc-O C)  at  e n dli ne 6 m o nt hs 
fr om baseli ne i n test a n d c o ntr ol gr o u ps
C ha n ge fr o m baseli ne i n t he rati o of c -O C t o 
uc- O C at 6 m o nt hs
Sec o n d ar y
T o c o m pare t he c ha n ges i n B o ne Res or pti o n 
mar ker : ser u m C-t elo p e pti de of t y pe 1 
c olla ge n (s-C T X - 1) at mi dli ne 3 m o nt hs fr om 
baseli ne i n test a n d c o ntr ol gr o u ps 
C ha n ge fr o m baseli ne i n s -C T X -1 at 3 m o nt hs
T o c o m pare t he c ha n ges i n t he ratio of  
car b o x ylate d (c-O C) t o u n der -car b o x ylate d 
Oste ocal ci n ( uc-O C)  at mi dli ne 3 m o nt hs f r o m 
baseli ne i n test a n d c o ntr ol gr o u ps
C ha n ge fr o m baseli ne i n t he rati o of c -O C t o 
uc- O C at 3 m o nt hs
T o c o m pare t he c ha n ges i n B o ne Res or pti o n 
mar ker : uri nar y C T X -1  at mi dli ne 3 m o nt hs 
a n d e n dli ne 6 m o nt hs fr o m baseli ne i n test a n d 
c o ntr ol gr o u ps
C ha n ge fr o m baseli ne i n Uri nar y C T X -1 at 3 
a n d 6 mo nt hs
T o c o m pare t he c ha n ges i n B o ne Res or pti o n 
m ar ker: ser u m N-ter mi nal tel o pe pti de of t ype 1 
c olla ge n (s-N T X -1) at mi dli ne 3 m o nt hs a n d 
e n dli ne 6 m o nt hs fr o m baseli ne i n test a n d 
c o ntr ol gr o u ps
C ha n ge fr o m baseli ne i n s -N T X -1 at 3 a n d 6 
m o nt hs
T o c o m pare c ha n ges i n B o ne f or mat i on m ar ker
ser u m pr oc olla ge n t y pe 1 N -ter mi nal 
pr o pe pti de (s- P 1 N P ), b o ne s pecific al kali ne 
C ha n ge fr o m baseli ne i n s -P 1 N P, B S A P at 3 
a n d 6 mo nt hs
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 2 3 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 2 4 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

p h os p hatase (B S A P ) at baseli ne, at mi d li ne 3 
m o nt hs a n d e n dli ne 6 m o nt hs i n test a n d 
c o ntr ol gr o u ps
T o c o m pare Calci u m Stat us usi n g s-P T H & 
U rinar y  Calciu m, Ser u m  Ca, P a n d t otal 
alkali ne p h os p hatase ( A L P)  at mi dli ne 3 
m o nt hs a n d e n dli ne 6 m o nt hs t o see c ha n ge i n 
le vel fr om baseli ne i n b ot h t he gr o u ps
C ha n ge fr o m baseli ne i n s -P T H & U rinar y  
C alciu m, Ser u m  Ca, P a n d t otal al kali ne 
p h os p hatase ( A L P)  at 3 a n d 6 m o nt hs
T o c o m pare t he c ha n ges i n Vi t ami n D s t at us
usi n g ser u m 2 5- h y dr o x yc h o lecalcifer ol ( 2 5 O H 
D 3)  at mi dli ne 3 m o nt hs a n d e n dli ne 6 m o nt hs 
fr om baseli ne i n test a n d c o ntr ol gr o u ps
C ha n ge fr o m baseli ne i n 2 5-
h y dr o x yc h o lecalcifer ol ( 2 5 O H D 3) at 3 a n d 6 
m o nt hs
T o c o m pare t he c ha n ges i n Micr o n utri e nt 
Pr ofile st at us usi n g ser u m Se, Z n , F olic acid, 
B 6 a n d B 1 2 A N D P L A S M A Z n A N D B 6
stat us  at mi dli ne 3 m o nt hs a n d e n dli ne 6 
m o nt hs fr om baseli ne i n test a n d c o ntr ol 
gr o u ps
C ha n ge fr o m baseli ne i n Ser u m Se, Z n , F olic 
acid, B 6 a n d B 1 2 A N D P L A S M A Z n A N D 
B 6 stat us at 3 a n d 6 m o nt hs
E x pl or at or y
T o c o m pare t he c ha n ges i n Gr o wt h Mar kers
I G F-1 at mi dli ne 3 m o nt hs a n d e n dli ne 6 
m o nt hs fr om baseli ne i n test a n d c o ntr ol 
gr o u ps
C ha n ge fr o m baseli ne i n I G F -1 at 3 a n d 6 
m o nt hs
St u d y Desi g n
O ver all Desi g n
T his is a d o u bl e bli n d, si n gle- ce ntre, ra n d o mize d -c o ntr olle d trial testi n g t he effect of f ortifie d 
be vera ge o n b o ne t ur n o ver mar kers as c o m pare d t o pl ace b o c o ntr ol i n 2 5 -4 5 y rs old 
pr e m e n o pa usal w o me n.
Gr o u p 1: - Pr otei n ric h be vera ge p o w der f ortifie d wit h M M N 
Gr o u p 2:- L o w pr otei n n o n -f ortifie d is o-calori c be vera ge p o w der
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 2 4 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 2 5 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

St atistic al Met h o ds
T he c o -pri mar y efficac y varia ble s of  t he st u d y are t he c ha n ge fr o m baseli ne i n b o ne res or pti o n 
mar ker (s -C T X -1) after 6 m o nt hs a n d t he c ha n ge fr o m baseli ne i n t he rati o of car b o x ylate d t o 
u n der car b o x ylate d ostea ocalci n ( C o C/ u C oc) after 6 m o nt hs . 
Eac h of t hese c o -pri mar y efficac y varia bles will be a nal yze d usi n g t he a nal ysis of c o varia nce 
( A N C O V A). T he A N C O V A will ha ve treat me nt as fi xe d effect a n d t he c orres p o n di n g baseli ne 
as c o variate. A dj uste d mea ns, 9 5 % c o nfi de nce i nter vals, wit hi n treat me nt p -val ues f or eac h 
treat me nt gr o u p, treat me nt gr o u p differe nce, 9 5 % c o nfi de nce i nter val o f t he differe nce a n d t he 
bet wee n -treat me nt p-va l ues base d o n t he statistical mo d el  descri be d a b o ve will als o be 
prese nte d. S t atistical tests t o c o mpare treat m e nts will be t w o- side d a n d will e m pl o y a le vel of 
sig nifica nce of α = 0. 0 2 5.
T he setti n g of t he si g nifica nce le vel o f 0. 0 2 5 f or t hese 2 c o -pri mar y e n d p oi nts will e ns ure t hat 
t he o verall si g nifica nce le vel f or t he pri mar y e n d p oi nt is less t ha n or e q ual t o 0. 0 5.
Ass u m pt i ons of n or malit y a n d h o m o ge nei t y of varia nces will be e val uate d. If vi o lati o ns are 
o bser ve d t he n s uita ble data tra nsf or mat i ons will be tri e d t o ac hie ve t he ass u m pti o ns. If s uita ble 
tra nsf or mati o ns ca n n ot be f o u n d, n o n-para metric a nal yses will be perf or me d.
T he sec o n dar y  a nd e x pl orat or y  a nal yses will be perf or me d i n a si milar wa y as t he pri mar y 
a nal yses, t h o u g h t here will be n o a dj ust me nt s ma de f or mul tiplici t y.  
1. I N T R O D U C TI O N
It is well d oc u me nte d t hat i n t he fiel d of n utriti on, val ua ble i nf or mat i on c o ul d be o btai ne d fr o m 
ra n d omise d c o ntr olle d trials t hat ha ve B o ne t ur n o ver mar kers ( B T Ms) as e n d p o i nts t o 
d e m o nstrate c ha n ges i n b o ne meta b olis m a n d t hat s uc h data c o ul d be use d as scie ntific s u p p ort 
f or clai ms o n f o o ds or n utrie nts t hat i nfl ue nce b o ne meta b olis m ( B o nj o ur et al., 2 0 1 4). B T M are 
pr o d ucts release d i nt o t he bl o o dstrea m d uri n g b o ne f or mat i on a n d res or pti o n a n d ca n be use d as 
s urr o gate mar kers of b o ne t ur n o ver. T hese mar kers i ncl u de b o ne -s pecific al kali ne p h os p hatase 
( A L P), PI N P ( N-ter mi nal pr o pe pti de of t ype I pr oc olla ge n), oste ocalci n ( O C), uri nar y  le vels o f 
p y ridi n o li nes a n d de o x yp yri di n oli nes, ser u m le vels of t y pe I c olla ge n tel o pe pti des ; N -ter mi nal 
cr oss-li n ki n g telo p e pti de of t y pe I c olla ge n, N T X -I a n d C-ter mi nal cr oss-li n ki n g tel o pe pti de of 
t ype I c olla ge n, C T X -I  etc. T hese mar kers are se nsiti ve a n d res p o n d q uic kl y t o n utriti o n or dr u g 
i nter ve nt i ons. I n s h ort -t er m st u dies, t he meas ure me nt of bi oc he mical mar kers t o assess b o ne 
t ur n o ver offers a n acce pte d mea ns of deter mi ni n g t he effect of a treat me nt or dietar y s u p ple me nt 
o n b o ne meta b o lis m bef ore a n y si g nifica nt c ha n ge i n act ual b o ne de nsit y ca n be detecte d (et al., 
2 0 0 0). Se veral st u dies ha ve n o w s h o w n t hat i ncrea se d le vels o f b o ne res or pti o n m ar kers are 
ass ociate d wit h a n i ncrease d ris k of fract ure s u g gesti n g t hat i ncrease d b o ne res or pti o n lea ds t o 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 2 5 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 2 6 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

micr o -arc hitect ural deteri orati o n of b o ne tiss ue d ue t o perf orati o n of t he tra bec ulae ( Gar ner o et 
al., 1 9 9 6). I n S o uth East Asia n pre me n o pa usal w o me n, f ortifie d mil k wit h Calci u m, vita mi n D or 
K 1 ha ve s h o w n t o ra pi dl y re d uce b o ne res or pti o n a n d b o ne t ur n o ver mar kers wit hi n wee ks of 
starti n g s u p ple me ntati o n ( Kr u ger et al., 2 0 0 6). T his e m p hasises t he i m p orta nce of b o ne t urn o ver 
mar ker res p o nse i n m o nit ori n g treat me nt effects i n t he s h ort- t o me di u m-t er m. As B T Ms ca n 
pi c k c ha n ges q uite earl y, t he y are a ver y hel pf ul t o ol t o mo d ul ate t he treat me nt/i nter ve nt i on i n 
s u bjects w h o d o n ot s h o w t he e x pecte d res p o nse, if necessar y. On t he ot her ha n d, B M D c ha n ges 
ma y ta ke 1 8 m o nt hs t o bec o me si g nifica nt; t h us, it ta kes ver y  lo n g t o detect treat m e nt fail ure 
usi n g t he D E X A. F urt her, i n cli nical trials, bi oc he mical mar kers pr o vi de a s u peri or si g nal -t o-
n o ise ratio, a n d t heref ore, t hese ma y be use d t o s h orte n d urati o n of trials a n d t o decrease st u d y  
c o h orts i n size. I n a st u d y of treat me nt of p ost me n o pa usal oste o p or osis wit h ale n dr oa nte, it was 
re p orte d t hat t he si g nal t o n oise rati o f or t he b o ne t ur n o ver mar ker N T X was 4. 9 w hereas t he 
r atio f or lu m bar s pi ne B M D was o nl y  1. 3 ( after 6 m ont hs of treat me nt) ( Mac ha d o, 1 9 9 9).
I nsi g hts o n rele va nce of B T M assess me nt i n yo u n g pre me n o pa usal w o m e n is pr o vide d b y t w o 
pr os pecti ve c o h ort st u dies w hic h ha ve s h o w n t hat B T Ms assess me nt i n pre me n o pa usal w o me n 
ca n pre dict fract ure ris k later i n life ( d uri n g p ost me n o pa usal years) (i) Ca ule y et al., ( 2 0 1 2) i n a 7 
year st u d y  s h o we d t hat t hat hi g her uri nar y N T X-I e xcreti on meas ure d bef ore me n o pa use a n d 
acr oss me n o pa usal tra nsit i on is ass ociate d wit h a hi g her ris k of  fract ure. T he st u d y c o mprise d of 
2, 3 0 5 w o me n ( 4 2 t o 5 2 y ears) w h o were eit her pre me n o pa usal or earl y peri me n o pa usal at 
baseli ne. Ser u m O C a n d uri nar y N T X -I were meas ure d at baseli ne. N T X-I was meas ure d at eac h 
a n n ual f o ll ow- u p. W o me n w h o e x perie nce d fra ct ures ( n = 1 8 4) ha d a b o ut a 1 0 % hi g her baseli ne 
me dia n N T X -I ( P = 0. 0 0 1), b ut t here was n o differe nce i n O C. F urt her, t he w o me n wit h a 
baseli ne N T X- I greater t ha n t he me dia n ha d a 4 5 % hi g her ris k of fract ure, m ulti varia ble-a dj uste d 
( H R, 1. 4 6; 9 5 % CI, 1. 0 5-2. 2 6). (ii) Ja pa nese P o p ulati o n -base d Oste o p or osis St u d y  re p orte d t hat 
bi oc he mical mar kers of b o ne t ur n o ver pre dicte d b o ne l oss i n peri me n o pa usal w o me n b ut n ot i n 
p ost m e n o pa usal w o me n. A c o h ort of 1, 2 8 3 w o me n a ge d 1 5 – 7 9 y ears was selecte d ra n d o ml y 
fr om t he i n ha bita nts of t hree areas i n Ja pa n a n d f o ll owe d f or 6 y ears. T he a n n ual c ha n ges i n b o ne 
de nsit y at t he s pi ne, t otal hi p, a n d distal ra di us a n d c ha n ges i n b o ne t ur n o ver mar kers i ncl u di n g 
ser u m O C a n d b o ne-s pecific al kali ne p h os p hatase ( b o ne A L P), free a nd t otal  t D P D , uri nar y 
C T X -I were meas ure d. Peri me n o pa usal w ome n a ge d 4 5 y ears or older wi t h ele vate d le vels o f 
O C, b o ne A L P, C T X -I, or t D P D s h o we d si g nifica ntl y greater b o ne l oss at m ost s keletal sites 
d uri n g t he f o ll ow- u p peri o d t ha n t h ose wi t h lo wer le v els, after a djust me nt  for t he effects of a ge, 
hei g ht, wei g ht, dietar y  calci u m int a ke, re g ular e xercise, a n d c urre nt s m o ki n g (I ki et al., 2 0 0 6). 
I nter nati o nal Oste o p or osis f o u n dati on (I O F) rec o m me n ds t he use of s -P 1 N P as t he refere nce 
b o ne f or m at i on mar ker a n d C T X-1 as t he refere nce b o ne res or pti o n mar ker t o assess c ha n ges i n 
b o ne meta b o lis m p ost i nter ve nti on ( Vasi kara n et al., 2 0 1 1). G R E E S pa nel ( Gr o u p f or res pect of 
et hics a n d e xcelle nce i n Scie nce; o ne of t he m ost pr o mi ne nt scie ntific gr o u ps w or ki n g i n 
pers pecti ve of i m pr o vi n g patie nt well- bei n g) als o s u p p orts I O F rec o m me n dati o ns t o  meas ure 
c ha n ges i n B T Ms t o s u p p ort clai ms o n f o o d pr o d ucts f or b o ne healt h ( Br u y ere et al., 2 0 1 2)
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 2 6 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 2 7 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

He nce, f or t he prese nt st u d y , t hese t w o refere nce B o ne t ur n o ver mar kers C T X a n d P 1 N P 
rec o m me n de d b y I O F will be utilise d t o  assess t he i m pact of W o me n’s H orlic ks (a c ust o mise d 
n utri tio nal s u p ple me nt f or b o ne healt h ric h i n oste o ge nic n utrie nts ) i n I n dia n healt h pre -
me n o pa usal w o me n t he a ge gr o u p 2 5 -4 5 y ears(i ncl usi ve), f oll o wi n g si x m ont hs s u p ple me ntati o n. 
I ncl u di n g w o me n bet wee n 2 5-4 5 y ears pr o vides a n o p p ort u ni t y t o test t he efficac y of t he 
s u p ple me nt i n i m pr o vi n g Pea k b o ne mass ac q uisit i o n as b o ne accr ual c o nti n ues d uri n g t he a ge 
p eri o d 2 0 -3 0 years. He nce, we pr o p ose t o i ncl u d e a s u b-a nal ysis f or 'attai n me nt of pea k b o ne 
mass' a n d 'attai ne d pea k b o ne mass'. T he peri o d of attai n me nt of pea k b o ne mass i ncl u des b o ne 
m o delli n g as well as re m o delli n g a n d t he pr ocess is de pe n de nt o n I G F -I. N utrie nts s uc h as 
pr otei n a n d zi nc ha ve bee n s h o w n t o i ncrease I G F-I a n d s o c o ul d i ncrease b o ne f or mati o n 
( PI N P). F urt her, W o me n are pr o ne t o vita mi n D deficie nc y d uri n g t his peri o d a n d s o a be neficial 
effect of vita mi n D a n d calci u m s u p ple me nts ma y s h o w itself t hr o u g h l o wer P T H a n d b o ne 
mar kers ( C T X, PI N P). T he peri o d of attai ne d pea k b o ne mass i ncl u des m ost l y b o ne re m o delli n g 
a n d s o a be nefit w o ul d be best s h o w n wit h a decrease i n b o ne res or pti o n ( C T X). He nce, C T X is 
pr o p ose d as t he pri mar y  o bjecti ve f or t he st u d y, t he sec o n dar y bei n g, c ha n ges i n P I N P a n d ot her 
b o ne mar kers.
T he st u d y  will b e fu n de d b y Gla x o S mit h Kli ne C o ns u mer Healt hcare ( G S K C H) a n d will be r u n 
i n I n dia as a ra n d omise d d o u bl e bli n d, c o ntr olle d st u d y .  
2. O B J E C TI V E S A N D E N D P OI N T S
O bjecti ves
E n d p oi nts
Pri m ar y
T o c o m pare t he c ha n ges i n B o ne Res or pti o n 
mar ker : ser u m C-t elo p e pti de of t y pe 1 
c olla ge n (s-C T X - 1)  at  e n dli ne 6 m o nt hs fr o m 
baseli ne i n test a n d c o ntr ol gr o u ps 
C ha n ge fr o m baseli ne i n s -C T X -1 at 6 m o nt hs
T o c o m pare t he c ha n ges i n t he ratio of  
car b o x ylate d (c-O C) t o u n der -car b o x ylate d 
Oste ocal ci n ( uc-O C)  at  e n dli ne 6 m o nt hs 
fr om baseli ne i n test a n d c o ntr ol gr o u ps
C ha n ge fr o m baseli ne i n t he rati o of c -O C t o 
uc- O C at 6 m o nt hs
Sec o n d ar y
T o c o m pare t he c ha n ges i n B o ne Res or pti o n 
mar ker : ser u m C-t elo p e pti de of t y pe 1 
c olla ge n (s-C T X - 1) at mi dli ne 3 m o nt hs fr om 
baseli ne i n test a n d c o ntr ol gr o u ps 
C ha n ge fr o m baseli ne i n s -C T X -1 at 3 m o nt hs
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 2 7 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 2 8 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

T o c o m pare t he c ha n ges i n t he ratio of  
car b o x ylate d (c-O C) t o u n der -car b o x ylate d 
Oste ocal ci n ( uc-O C)  at mi d li ne 3 mo nt hs f r o m 
baseli ne i n test a n d c o ntr ol gr o u ps
C ha n ge fr o m baseli ne i n t he rati o of c -O C t o 
uc- O C at 3 m o nt hs
T o c o m pare t he c ha n ges i n B o ne Res or pti o n 
mar ker : uri nar y C T X -1  at mi dli ne 3 m o nt hs 
a n d e n dli ne 6 m o nt hs fr o m baseli ne i n test a n d 
c o nt r ol gr o u ps
C ha n ge fr o m baseli ne i n Uri nar y C T X -1 at 3 
a n d 6 mo nt hs
T o c o m pare t he c ha n ges i n B o ne Res or pti o n 
mar ker: ser u m N -ter mi nal tel o pe pti de of t ype 1 
c olla ge n (s-N T X -1) at mi dli ne 3 m o nt hs a n d 
e n dli ne 6 m o nt hs fr o m baseli ne i n test a n d 
c o ntr ol gr o u ps
C ha n ge fr o m baseli ne i n s -N T X -1 at 3 a n d 6 
m o nt hs
T o c o m pare c ha n ges i n B o ne f or mat i on m ar ker
ser u m pr oc olla ge n t y pe 1 N -ter mi nal 
pr o pe pti de (s- P 1 N P ), b o ne s pecific al kali ne 
p h os p hatase (B S A P ) at baseli ne, at mi d li ne 3 
m o nt hs a n d e n dli ne 6 m o nt hs i n test a n d 
c o ntr ol gr o u ps
C ha n ge fr o m baseli ne i n s -P 1 N P, B S A P at 3 
a n d 6 mo nt hs
T o c o m pare Calci u m Stat us usi n g s-P T H & 
Uri nar y  Calciu m, Ser u m  Ca, P a n d t otal 
alkali ne p h os p hatase ( A L P) at  mi dli ne 3 
m o nt hs a n d e n dli ne 6 m o nt hs t o see c ha n ge i n 
le vel fr om baseli ne i n b ot h t he gr o u ps
C ha n ge fr o m baseli ne i n s -P T H & Uri nar y  
Calci u m, Ser u m  Ca, P a n d t otal alkali ne 
p h os p hatase ( A L P)  at 3 a n d 6 m o nt hs
T o c o m pare t he c ha n ges i n Vi t ami n D s t at us
usi n g ser u m 2 5- h y dr o x yc h o lecalcifer ol ( 2 5 O H 
D 3)  at mi dli ne 3 m o nt hs a n d e n dli ne 6 m o nt hs 
fr om baseli ne i n test a n d c o ntr ol gr o u ps
C ha n ge fr o m baseli ne i n 2 5-
h y dr o x yc h o lecalcifer ol ( 2 5 O H D 3) at 3 a n d 6 
m o nt hs
T o c o m pare t he c ha n ges i n Micr o n utri e nt 
P r ofile st at us usi n g ser u m Se, Z n , F olic acid, 
B 6 a n d B 1 2 stat us  A N D P L A S M A Z n A N D 
B 6 at mi dli ne 3 m o nt hs a n d e n dli ne 6 m o nt hs 
fr om baseli ne i n test a n d c o ntr ol gr o u ps
C ha n ge fr o m baseli ne i n Ser u m Se, Z n , F olic 
acid, B 6 a n d B 1 2 A N D P L A S M A Z n A N D 
B 6 stat us at  3 a n d 6 m o nt hs
E x pl or at or y
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 2 8 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 2 9 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

T o c o m pare t he c ha n ges i n Gr o wt h Mar kers
I G F-1 at mi dli ne 3 m o nt hs a n d e n dli ne 6 
m o nt hs fr om baseli ne i n test a n d c o ntr ol 
gr o u ps
C ha n ge fr o m baseli ne i n I G F -1 at 3 a n d 6 
m o nt hs
3. S T U D Y P L A N
3. 1. St u d y Desi g n
O ver all Desi g n
T his is a d o u ble -bli n d, si n gle -ce ntre, ra n d o mize d -c o ntr olle d trial testi n g t he effect of f ortifie d 
be vera ge o n b o ne t ur n o ver mar kers as c o m pare d t o pl ace b o c o ntr ol i n 2 5 -4 5 y rs old 
pr e m e n o pa usal w o me n.
Gr o u p 1: - Pr otei n ric h be vera ge p o w der f ortifie d wit h M M N 
Gr o u p 2: - L o w pr otei n n o n -f ortifie d is o-calori c be vera ge p o w der
Visit 1 - Scree ni n g Visit
T he f o ll owi n g assess me nt s will be c o n d ucte d i n t he writte n or der
I nf or me d c o nse nt 
D e m o gra p hics
Me dical hist or y
C urre nt/c o nc o mita nt me dicati o n
Ge neral p h ysical e xa mi nat i on
Vi t al si g ns
H b assess me nt usi n g Pr o n t o
A nt hr o p o m etric meas ur e me nts ( hei g ht, weig ht a n d B MI)
I ncl usi on/ e xcl usi o n cri t eria e val uat i on
S u bject eli gi bilit y
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 2 9 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 3 0 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

Ra n d o misat i on 
Pre g na nc y test
7- d a y  F o o d int a ke diar y ha n d o ver t o partici pa nt 
Visit 2 - B aseli ne Visit ( + 7 d a ys t o 1 0 d a ys p ost scree ni n g)
T he f o ll owi n g assess me nts will be c o n d ucte d i n t he writte n or der
C urre nt a n d c o nc o mita nt me dicat i on
C o nti n ue d eli gi bilit y
Pre g na nc y Test
R A N D O MI S A TI O N
7- d a y  diar y c o llecti on f or assess me nt of dietar y int a ke of calci u m, pr otei n & ot her ke y 
micr o n utrie nts. 
G E N E R A L P H Y SI C A L E X A MI N A TI O N
VI T A L SI G N S
H B A S S E S S M E N T U SI N G P R O N T O
Pre g na nc y Test
S a m ple c ollect i on f or a nal ysis of ser u m C T X-1, N T X -1, P 1 N P, B S A P, t otal O C, c O C, u O C, 
P T H, 2 5 ( O H) D, Ca, P, t otal A L P, I G F- 1, Z n , Se, vit a mi n B 6, vita mi n B 1 2 a n d F olic aci d, 
P L A S M A F O R Z n A N D VI T A MI N B 6
S a m ple c ollect i on f or a nal ysis of uri nar y  calci u m, creati ni ne a n d C T X- 1
Pr o d uct a d mi nistrati o n a n d dis pe nsat i on
A d verse e ve nts m o nit ori n g
Visit 3 – F oll o w -u p visit ( 4 5 d a ys +/ - 7 d a ys fr o m visit 2)
T he f o ll owi n g assess me nts will be c o n d ucte d i n t he or der writte n:
C urre nt a n d c o nc o mita nt me dicat i on
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 3 0 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 3 1 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

C o nti n ue d eli gi bilit y
Pre g na nc y test
G E N E R A L P H Y SI C A L E X A MI N A TI O N
VI T A L SI G N S
H B A S S E S S M E N T U SI N G P R O N T O
Pr o d uct a d mi nistrati o n a n d dis pe nsat i on 
C ollect i on of ret ur n sac het (e m pt y + u nc o ns u me d)
A d verse e ve nts m o nit ori n g
Visit 4 – Mi dli ne visit ( 9 0 d a ys +/ -  7 d a ys fr o m b aseli ne )
T he f o ll owi n g assess me nts will be c o n d ucte d i n t he or der writte n:
C urre nt a n d c o nc o mita nt me dicat i on
C o nti n ue d eli gi bilit y
Pre g na nc y test
G E N E R A L P H Y SI C A L E X A MI N A TI O N
VI T A L SI G N S
H B A S S E S S M E N T U SI N G P R O N T O
S a m ple c ollect i on f or a nal ysis of ser u m C T X-1, N T X -1, P 1 N P, B S A P, t otal O C, c O C, u O C, 
P T H, 2 5 ( O H) D, Ca, P, t otal A L P, I G F- 1, Z n , Se, vit a mi n B 6, vita mi n B 1 2 a n d F olic aci d, 
P L A S M A F O R Z n A N D VI T A MI N B 6
S a m ple c ollect i on f or a nal ysis of uri nar y  calci u m, creati ni ne a n d C T X- 1
Pr o d uct a d mi nistrati o n a n d dis pe nsat i on 
C ollect i on of ret ur n sac het (e m pt y + u nc o ns u me d)
A d verse e ve nts m o nit ori n g
Visit 5 – F oll o w -u p visit ( 1 3 5 d a ys +/ - 7 d a ys fr o m b aseli ne)
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 3 1 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 3 2 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

T he f o ll owi n g assess me nts will be c o n d ucte d i n t he or der writte n:
C urre nt a n d c o nc o mita nt me dicat i on
C o nti n ue d eli gi bilit y
Pre g na nc y test
G E N E R A L P H Y SI C A L E X A MI N A TI O N
VI T A L SI G N S
H B A S S E S S M E N T U SI N G P R O N T O
Pr o d uct a d mi nistrati o n a n d dis pe nsat i on 
C ollect i on of ret ur n sac het (e m pt y + u nc o ns u me d)
A d verse e ve nts m o nit ori n g
7- d a y  F o o d int a ke diar y ha n d o ver t o partici pa nt (t here will be tele p h o nic re mi n der 8 -1 0 pri or t o 
visit 6 t o start filli n g diar y  acc or di n g t o i nstr uctio n)
Visit 6 – E n d of st u d y ( 1 8 0 d a ys / L S L V +/ - u p t o 7 d a ys fr o m b aseli ne)
P R O D U C T A D MI NI S T R A TI O N ( T O B E C O N S U M E D U N TI L L A S T E V E NI N G 
B E F O R E VI SI T -6 N O T A C T U A L L Y O N T H E D A Y B E C A U S E W E A R E D R A WI N G 
L A S T B L O O D S A M P L E F A S TI N G A N D A F T E R T H A T I T I S N O T N E E D E D)
T he f o ll owi n g assess me nts will be c o n d ucte d i n t he or der writte n:
C urre nt a n d c o nc o mita nt me dicat i on
Ge neral p h ysical e xa mi nat i on
Vi t al si g ns
C o nti n ue d eli gi bilit y 
P R E G N A N C Y T E S T
G E N E R A L P H Y SI C A L E X A MI N A TI O N
VI T A L SI G N S
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 3 2 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 3 3 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

H B A S S E S S M E N T U SI N G P R O N T O
C ollect i on of ret ur n sac het (e m pt y + u nc o ns u me d)
7- d a y  diar y c o llecti on f or assess me nt of dietar y int a ke of calci u m, pr otei n & ot her ke y 
micr o n utrie nts
Pre g na nc y Test
S a m ple c ollect i on f or a nal ysis of ser u m C T X-1, N T X -1, P 1 N P, B S A P, t otal O C, c O C, u O C, 
P T H, 2 5 ( O H) D, Ca, P, t otal A L P, I G F- 1, Z n , Se, vit a mi n B 6, vita mi n B 1 2 an d F o lic aci d, 
P L A S M A F O R Z n A N D VI T A M I N B 6
S a m ple c ollect i on f or a nal ysis of uri nar y  calci u m, creati ni ne a n d C T X- 1
A d verse e ve nts m o nit ori n g
St u d y  c o nclusi o n / Me dical si g n off
3. 2. S u bject Restricti o ns
Lifest yle/ Diet ar y
Lifest yle : T he f o ll owi n g lifest yle restrict i on a p plies d uri n g t he st u d y  int er ve nt i on peri o d; f r o m 
baseli ne/start of pr o d uct a d mi nistrati o n t o e n d of st u d y visit:
P arti cip a nt m ust a gree t o a bstai n fr o m use of a n y heal t h fo o d dri n ks/ be vera ges a n d a n y  
s u p ple me nts, i ncl u di n g her bal s u p ple me nts a n d n utriti o nal s u p ple me nts, i ncl u di n g healt h f oo d 
s u p ple me nts.
P arti cipa nts s h o ul d m ai nt ai n t heir re g ular acti vities b ut m ust n ot i ncl u de a n y s pecial p h ysical 
acti vit y.
Me dic ati o ns a n d Tre at me nts
T here are n o restrict i ons wit h re gar ds t o me dicat i on use a n d me dical treat me nt.
H o we ver use of dr u gs s uc h as gl uc oc ortic o i ds, a nti-c o n v ulsa nts, se lecti ve estr o ge n rece pt or 
m o d ulat ors (e. g. ral o xife ne etc), bis p h os p h o nates (e. g. ale n dr o nate etc) (f or m ore t ha n a 7 da ys) 
or a n y  ot her me dicat i on w hic h ca n i m pact o verall b o ne healt h, d uri n g t he c o urse of st u d y  p ost 
scree ni n g, will be c o nsi dere d a pr ot ocol  viol at i on a n d will res ult i n t he re m o val of t he s u bject 
fr om t he efficac y a nal yses.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 3 3 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 3 4 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

3. 3. T y pe a n d Pl a n ne d N u m ber of S u bjects
A p pr o xi matel y  1 3 5 parti ci pa nts will be scree ne d t o ra n d o mise a p pr o xi matel y 1 0 8 part ici pa nts
( 5 4 per treat me nt ar m) i n or der t o o btai n at least 8 8 partici pa nts c o m plet i n g t he st u d y.
3. 4. St u d y Desi g n a n d D ose J ustific ati o n
T his is a d o u ble bli n d, t w o -ar m, parallel gr o u p, stratifie d (f or a ge ba n ds), ra n d o mize d, 
c o ntr olle d, st u d y in w o me n 2 5 -4 5 y rs, i ncl usi ve. T he st u d y ce ntre will ai m t o recr uit a tar get 
r atio of  5 0 % 2 5-3 5 y ears a ge a n d 5 0 % 3 5 -4 5 years wit h a mi ni m u m o f 4 0 % of  eit her a ge ba n d. 
Ra n d o mizati o n of  t he s u bjects will e ns ure t hat bias is mi ni mize d b y distri b uti n g t he 
c haracterist ics of s u bjects t hat ma y infl ue nce o utc o me ra n d o ml y bet wee n treat me nt gr o u ps, s o 
t hat a n y differe nce i n o utc o me ca n be e x plai ne d o nl y b y treat me nt. T he c o ntr ol gr o u p will all o w 
t he deter mi nat i on of w het her i m pr o ve me nt i n o utc o mes, if a n y , is relate d t o i nter ve nt i on pr o d uct.
T o e ns ure c o m plia nce, t he c o ns u m pt i on of t he st u d y  pr o d uct will be mo ni t or e d b y t he st u d y 
staff.
T he st u d y  will be d o u ble bli n de d wit h res pect t o t he s u bject a n d t he st u d y staff (t h ose i n v ol ve d i n 
assess me nt) t o e ns ure t here is n o bias i n t he assess me nts. T he s u bjects i n t his st u d y  will b e 
ra n d oml y assi g ne d t o eit her t he test treat me nt or t he c o ntr ol treat me nt.
4. S E L E C TI O N O F S T U D Y P O P U L A TI O N A N D WI T H D R A W A L 
C RI T E RI A
Fe males , a ge d bet wee n 2 5 t o 4 5 years i ncl usi ve will be i n vite d t o partici pate i n t his st u d y .
S pecific i nf or mati o n re gar di n g war ni n gs, preca uti o ns, c o ntrai n dicati o ns, a d verse e ve nts, a n d 
ot her perti ne nt i nf or mati o n o n t he G S K i n vest i gati o nal pr o d uct or ot her st u d y treat me nt t hat ma y 
i m pact s u bject eli gi bility is pr o vi de d i n t he S af et y State m e nt .
De viat i ons fr o m  incl usi o n a n d e xcl usi o n cri t eria are n ot all o we d beca use t he y ca n p ote ntiall y 
je o par dize t he scie nt ific i nte grit y of t he st u d y, re g ulat or y acce pta bility or s u bject safet y.  
T heref ore, a d here nce t o t he criteria as s pecifie d i n t he pr ot oc ol is esse ntial.
4. 1. I ncl usi o n Cr iteri a
A s u bject will be eli gi ble f or i ncl usi o n i n t his st u d y o nl y if all of t he fol l owi n g criteria a p pl y:
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 3 4 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 3 5 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

1. C O N S E N T
D e m o nstrates u n dersta n di n g of t he st u d y  pr oce d ures, restricti o ns a n d willi n g ness t o partici pate 
as e vi de nce d b y v o l unt ar y writte n i nf or me d c o nse nt a n d has recei ve d a si g ne d a n d date d c o p y of 
t he i nf or me d c o nse nt f or m. 
2. A G E
A ge d bet wee n 2 5 a n d 4 5 years i ncl usi ve.
3. G E N D E R
S u bject is fe male.
4. G E N E R A L H E A L T H
G o o d ge neral a n d me ntal healt h wi t h, i n t he o pi ni on of t he i n vest i gat or or me dicall y q ualifie d 
desi g nee n o cli nicall y si g nifica nt a n d rele va nt a b n or malit ies i n me dical hist or y or u p o n p h ysical 
e xa mi nat i on.
5. W EI G H T/ B MI/ Z S C O R E S 
B MI bet wee n 1 8. 0 - 3 0 ( k g/ m2) i ncl usi ve.
6. C O M P LI A N C E
W o me n w h o u n dersta n d, willi n g, a ble a n d li kel y t o c o m pl y wi t h all st u d y pr oce d ures a n d 
restrict i ons.
4. 2. E xcl usi o n Criteri a
A s u bject will n ot be eli gi ble f or i ncl usi o n i n t his st u d y if a n y of t he f oll owi n g crit eria a p pl y:
1. P R E G N A N C Y
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 3 5 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 3 6 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

W o me n w h o are k n o w n t o be pre g na nt or w h o are i nte n di n g t o bec o me pre g na nt o ver t he 
d urati o n of  t he st u d y. 
O R
W o me n w h o ha ve a p osit i ve uri ne pre g na nc y test. 
2. M E N O P A U S E
W o me n w h o ha ve attai ne d p h ysi o l ogical me n o pa use defi ne d as t h ose w h o ha ve n ot 
ha d a me nstr ual peri o d f or c o nsec ut i ve 1 2 m o nt hs.
3. B R E A S T -F E E DI N G
W o me n w h o are breast -fee di n g
4. C O N C U R R E N T M E DI C A TI O N/ M E DI C A L HI S T O R Y 
A.
C urre nt ( wit hi n 1 4 da ys of t he start of t he st u d y ) or re g ular use of a n y prescri pti o n, o ver -
t he- c o u nter ( O T C), vita mi n s u p ple me nts her bal me dici ne u nless t he me dicat i on has bee n 
a p pr o ve d b y t he st u d y p h ysicia n. 
B.
Treat me nt wit h bis p h os p h o nates (a n y d ose wit hi n t he pre vi o us 2 y ears) or ot her 
me dicat i ons k n o w n t o affect b o ne ( wit hi n t he pre vi o us 6 m o nt hs),
C.
H istor y  of meta b o lic b o ne disease
D.
A n y h or m o nal dis or ders or di st ur ba nces
E.
B o ne fract ure i n last 1 2 m o nt hs
5. A L L E R G Y/ I N T O L E R A N C E
A.
K n o w n or s us pecte d i nt olera nce or h y perse nsi tivi t y t o t he st u d y mat erials ( or closel y 
r elate d c o mp o u n ds) or a n y  of t heir state d i n gre die nts.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 3 6 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 3 7 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

B.
S u bject is lact ose i nt olera nt.
6 . C LI NI C A L S T U D Y/ E X P E R M E N T A L P R O D U C T
A.
P articip ati o n i n a n ot her cli nical st u d y  (i ncl u di n g c os metic st u dies) or recei pt of a n 
i n vesti gati onal dr u g wi t hi n 3 0 da ys of  t he scree ni n g visit.
B.
Pre vi o us partici pat i on i n t his st u d y.
7 . S U B S T A N C E A B U S E
A.
R ece nt hist or y ( wit hi n t he last 1 year ) of alc o h o l or ot her s u bsta nce a b use.
B.
M ore t ha n 2 U nits of alc o h o l per da y
C.
S m o kers 
8 . F O O D/ B E V E R A G E
A.
C urre nt l y ta ki n g a n y ot her health f oo d dri n ks/ be vera ges or s u p ple me nts (i ncl u di n g 
n utri tio nal s u p ple me nts e. g. m ult i vita mi ns a n d/ or her bal s u p ple me nts e. g. gi n k g o) or has 
bee n o n s u p ple me nts wit hi n a m o nt h pri or t o st u d y start.
B.
W o me n w h o use d me dicat i on k n o w n t o i nfl ue nce b o ne mass a n d t he use of calci u m, 
vit a mi n D, a n d mul tivit a mi n s u p ple me nts o n a re g ular basis were st o p pe d 2 m o nt hs 
bef ore t he o nset of t he trial.
9 . P E R S O N N E L
A n e m pl o yee of t he s p o ns or or t he st u d y  sit e or me m bers of t heir i m me diate fa mil y.
1 0 . DI A G N O S TI C A S S E S S M E N T S A N D O T H E R C RI T E RI A
A.
O n g o i n g c o n diti ons k n o w n t o ca use a b n or malit ies of calci u m meta b olis m or s keletal 
healt h, m ala bs or ptio n s y n dr o m es (s uc h as c oeliac or Cr o h n ’s disease), h y pert h yr oidis m, 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 3 7 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 3 8 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

h y per parat h y r oidis m, h y p o - or h y percalcae mia, oste o malacia, Pa get ’s disease, dia betes, 
B.
Fract ure i n t he past 1 2 m o nt hs, 
C.
K n o w n c hr o nic ki d ne y disease, alc o h o lis m, 
D.
O bes ity w o me n ( B MI > 3 0) a n d T hi n ness i.e. B MI < 1 8 k g/ m 2
E.
Se verel y  a ne mic ( H b < 8 g/ dl m g % )
F.
U n derta ki n g e xcessi ve e xercise ( > 2 stre n u o us * e xercise sessi o ns per wee k)  
G.
C o ntrace pti ve i nject i ons wit hi n t he pre vi o us y ear.
H.
K n o w n hist ori es of s ur geries s uc h as bilateral  o o p hrect o m y (s ur gical re mo v al  of o varies)
I.
Di a g n ose d h y p o g o n dal states s uc h as T ur ner s y n dr o me, Kli nfelter s y n dr o me, Kall ma n 
s y n dr ome, a n ore xia ner v osa, h y p ot hala mic a me n orr hea or h y per pr ol act i ne mia
J.
He m ot ol o gi cal dis or ders e. g. He m o p hilia, Le u ke mi a a n d l y m p h o ma s mo n o cl o nal 
m ult i ple m yel oma, sic kle cell disease, T halasse mia etc.
K.
R he u mat ol o gical a n d a ut oi m m u ne dis or ders s uc h as a n k yl osi n g s p o n d ylit is, r he u mat oi d 
art hritis, s yste mic l u p us etc.
L.
Miscella ne o us c o n dit i ons a n d diseases s uc h as HI V/ AI D S, a lc oh o lis m, a m yl oi d osis, 
c hr o nic meta b olic aci d osis, C O P D, c o n gesti ve heart fail ure, de pressi o n etc.
* Resista nce trai ni n g, r u n ni n g a n d at hlet ic acti vities
4. 3. Scree ni n g/ B aseli ne F ail ures
Scree n fail ures are defi ne d as s u bjects w h o c o nse nt t o partici pate i n t he st u d y  b ut are ne ver 
s u bse q ue ntl y ra n d omize d.  I n or der t o e ns ure tra ns pare nt re p orti n g of scree n fail ure s u bjects, a 
mi ni mal set of scree n fail ure i nf or mati o n is re q uire d i ncl u di n g D e mo gra p h y , Scree n Fail ure 
details, Eli gi bilit y Cri t eria, a n d a n y Serio us A d verse E ve nts. Re -scree ni n g of s u bjects will n ot be 
all o we d i n t his st u d y.
4. 4. Wit h dr a w al/ St o p pi n g Criteri a
A s u bject m a y wit hdra w fr o m  t he st u d y at a n y time at his/ her o w n re q uest, or ma y be wit h dra w n 
at a n y ti me at t he discreti on of t he i n vesti gat or f or safet y,  be ha vio ur al  or a d mi nistrati ve reas o ns. 
If a s u bject wit h dra ws or is wit h dra w n fr om t he st u d y, all hu ma n bi ol o gical  sa m ples c ollecte d 
bef ore t he y  left will be a nal yze d a n d re p orte d u nless t he s u bject re q uests ot her wise. A s u bject 
ma y re q uest f or t heir h u ma n bi o l ogical  sa m ples t o be destr o ye d. I n t hese cases, t he i n vest i gat or 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 3 8 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 3 9 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

m ust d oc u m e nt t his i n t he site st u d y rec or ds a n d t he sa m ples s h o ul d n ot be use d f or a n y furt her 
researc h.
If t he reas o n f or re m o val of a s u bject fr o m t he st u d y is a n A E or a n a b n or mal la b orat or y  test 
res ult, t he pri nci pal s pecific e ve nt or test will be rec or de d o n t he electr o nic case re p ort f or m 
( C R F).  If a s u bject is with dra w n fr o m t he st u d y  beca use of a pr o d uct li miti n g A E, t h or o u g h 
eff orts s h o ul d be clearl y ma de t o d oc u me nt t he o utc o me. A n y A Es o n g oi n g at t he fi nal visit will 
be f oll owe d u p u nt il res ol ve d, t he c o n diti on sta bilizes, is ot her wise e x plai ne d, or t he s u bject is 
l ost t o f ollo w - u p.
T he f o ll owi n g acti o ns m ust be ta ke n i n relati o n t o a s u bject w h o fails t o atte n d t he cli nic f or a 
re q uire d st u d y visit:
T he site m ust atte m pt t o c o ntact t he s u bject a n d re -sc he d ule t he misse d visit as s o o n as p ossi ble. 
T he site m ust c o u nsel t he s u bject o n t he i m p orta nce of mai ntai ni n g t he assi g ne d visit sc he d ule 
a n d ascertai n w het her or n ot t he s u bject wis hes t o a n d/ or s h o ul d c o nti n ue i n t he st u d y. 
I n cases w here t he s u bject is deeme d ‘l ost t o f oll o w u p’, t he i n vest i gat or or desi g nee m ust ma ke 
e ver y eff ort t o re gai n c o ntact wit h t h e s u bject ( w here p ossi ble, at least 2 tele p h o ne calls). T he 
c o ntact atte m pt s h o ul d be d oc u me nte d i n t he s u bject’s rec or d. 
S h o ul d t he s u bject c o nti n ue t o be u nreac ha ble, o nl y t he n will he/s he be c o nsi dere d t o ha ve 
wi t hdra w n fr o m  t he st u d y wit h a pri mar y reas o n of “ L ost t o F oll o w-u p”.
4. 5. S u bject Re pl ace me nt
S u bjects w h o wit h dra w fr o m t he st u d y p ost -ra n d o mizati on will n ot be re place d.
4. 6. S u bject a n d St u d y C o m pleti o n
A c o m p lete d s u bject is o ne w h o has c om p lete d all p hases of t he st u d y incl u di n g t he f o ll ow- u p 
visit.
T he e n d o f t he st u d y is defi ne d as t he date of t he last s u bject’s last visit.
5. P R O D U C T I N F O R M A TI O N
5. 1. St u d y Pr o d uct
T he f oll owi n g st u d y  pr o d ucts will be s u p plie d b y t he Cli nical S u p plies De part me nt, G S K C H:
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 3 9 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 4 0 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

Test Pr o d uct 1
Refere nce Pr o d uct 1
Pr o d uct N a me 
Cereal base d f ortifie d 
Be vera ge ( Pr o prietar y  
f oo d)
L o w pr otei n n o n f ortifie d 
is ocal oric be vera ge
Pr o d uct F or m ul ati o n 
C o de ( M F C)
D ose
6 0 gra ms dail y i n t w o 
di vi de d d oses
6 0 gra ms dail y i n t w o 
di vi de d d oses
R o ute of 
A d mi nistr ati o n
Oral  
Oral  
D osi n g I nstr ucti o ns
3 0 gra ms p o w der ma de u p 
i n 2 0 0 m L water, 
a d mi nistere d t wice dail y
3 0 gra ms p o w der m a de u p 
i n 2 0 0 m L water 
a d mi nistere d t wice dail y
Ot her ite ms t o be s u p plie d b y t he Cli nical S u p plies De part me nt, G S K C H:
N a me of Ite m
P ur p ose
Gra d uate d t u m blers
D ose pre parati o n
Sti rrers 
D ose pre parati o n
5. 2. D ose Sc he d ule
P arti cipa nts will be a d mi nistere d t w o  d oses of t he dri n k (a p pr o x 2 00 m L eac h) dail y f or 6 
m o nt hs. Eac h da y o ne d ose will  be a d mi nistere d first i n t he m or ni n g a n d t he sec o n d d ose will be 
a d mi nistere d prefera bl y i n e ve ni n g
5. 3. D ose A d mi nistr ati o n
T he gra d uate d t u m bler will be fille d wit h water u p t o t he 2 0 0 m L mar k. T he e nt ire c o nte nts of 
o ne sac het will be gra d uall y e m pt ie d i n t he water fille d t u m bler wit h i nter mitte nt stirri n g t o a v oi d 
f or mat i on of l u m ps. T he r ec o nstit ute d test pr o d uct will be c o ns u me d b y t he partici pa nts 
i m me diatel y orall y.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 4 0 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 4 1 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI
C CI
C CI

5. 4. D ose M o dific ati o n
N o d ose m o dificat i on is per mitte d i n t his st u d y. A n y v ari at i on fr om t he d osi n g re gi me n will be 
re p orte d t o t he st u d y site pers o n nel a n d details will be e ntere d o n t he test pr o d uct a d mi nistrati o n 
l og a n d t he n e ntere d i nt o t he C R F.
5. 5 . Pr o d uct C o m pli a nce
Ra n d o m h o me vis its will be ma de b y site staff t o e ns ure c o m p lia nce of pr o d uct c o ns u m pti o n at 
h o m e. Details o f misse d pr o d uct c o ns u m pt i on will be rec or de d i n c o m plia nce re gister later will 
be e ntere d i n t he C R F.
P arti cip a nt will nee d t o e nter details i n t he S U B J E C T DI A R Y C A R D F O R D O S E 
C O M P LI A N C E Pr o d uct C o m plia nce Re p ort . Site staff will dis pe nse as ma n y bla n k S U B J E C T 
DI A R Y C A R D S re p orts as a p pr o priate f or rec or di n g details. Eac h S U B J E C T DI A R Y C A R D
re p ort will be n u m bere d i n a n asce n di n g or der (f or eac h partici pa nt) a n d rec or ds s h o ul d be 
mai ntai ne d t o trac k t he t otal n u m ber of re p orts dis pe nse d a n d c ollecte d . Partici pa nt will be 
c o nsi dere d as n o n-c o m p lia nt if t he partici pa nt c o ns u m es less t ha n 8 0 % of t he t otal a m o u nt of 
rec o m me n de d (f or t he e ntire st u d y d urati o n) d ose.
5. 6 . Prec a uti o ns
N o s pecial preca ut i ons are necessar y  pr o vi de d t he test pr o d uct is use d i n acc or da nce wit h t he 
pr ot oc ol  a n d t he usa ge i nstr ucti o ns.
5. 7 . O ver d ose
A n o ver d ose is a deli berate or i na d verte nt a d mi nistrati o n of a pr o d uct at a d ose hi g her t ha n 
s pecifie d i n t he pr ot oc ol.
O ver d ose is n ot li kel y t o occ ur i n t his st u d y .  Li mit ed q ua nt ities of t he pr o d uct will be s u p plie d, 
a n d cl osel y m o nit ore d b y  t he sit e for eac h s u bject.
O ver d ose per se is n ot a n A E.  H o we ver, a n y  cli nical se q uelae of a n o ver d ose s h o ul d be re p orte d 
as a n A E (a n d seri o us a d verse e ve nt ( S A E), if a p pr o priate).  F or re p orti n g, f oll ow t he A E a n d 
S A E re p orti n g i nstr ucti o ns.
5. 8 . Resc ue T her a p y
N o resc ue t hera p y  is re q uire d i n t his st u d y.
5. 9 . Pr o d uct Assi g n me nt
S u bjects will be assi g ne d t o st u d y  pr o d uct i n acc or da nce wi t h t he ra n d o mizati on sc he d ule 
ge nerate d b y  t he Bios t atistics De partme nt , G S K C H, pri or t o t he start of t he st u d y, usi n g 
vali date d i nter nal s o ftware.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 4 1 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 4 2 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

5. 9 . 1 R a n d o miz ati o n
A u ni q ue scree ni n g n u m ber will i de nt if y eac h s u bject scree ne d f or st u d y partici pati o n.  
Scree ni n g n u m bers will be assi g ne d i n asce n di n g n u merical or der as eac h s u bject si g ns t heir 
c o nse nt f or m.  S u bjects w h o meet all i ncl usi o n a n d e xcl usi o n cri t eria will be assi g ne d t o o ne of 
t he t w o st u d y tr e at me nts acc or di n g t o a ra n d o misati o n sc he d ule pr o vi de d b y t he Bi ostatist ics 
De part m e nt, G S K C H. T he st u d y  pr o d ucts will be la belle d with ra n d o misat i on n u m bers 
acc or di n g t o t his ra n d o misat i on s c he d ule. S u bjects will be ra n d o mise d i n a n asce n di n g n u merical 
or der as t he y  q ualif y f or st u d y e ntr y stratifie d b y t h eir a ge gr o u p.
T he strata are as f oll o ws:
Strat u m 1: A ge ≥ 2 5 years; a ge < 3 5 y ears
Strat u m 2: A ge ≥ 3 5 years; a ge ≤ 4 5 y ears.
T he ra n d omisa tio n sc he d ule wi t h treat me nt dec o des will be pr o vi de d t o t he site i n a seale d 
e n vel o pe a n d will be a vaila ble f or e mer ge nc y use o nl y.  All ra n d o misat i on n u m bers will be 
mas ke d wit h scratc h -off pa nels. O nl y t he pa nels re q uire d f or e mer ge nc y s u bject u n bli n di n g
s h o uld be re m o ve d.
5. 9 . 2 Bli n di n g
T he st u d y  is a d o u ble-bli n d tri al; neit her t he s p o ns or, s p o ns or’s re prese ntati ve, i n vesti gat or/site 
staff, n or t he partici pat i n g s u bject will k n o w w hic h treat me nt a n i n di vi d ual is ra n d omise d.
5. 9 . 3 C o de Bre a ks
T he bli n d m ust o nl y be br o ke n i n a n e mer ge nc y w here it is esse nt ial t o k n o w w hic h pr o d uct a 
s u bject recei ve d i n or der t o gi ve t he a p pr o priate me dical care.  W here ver p ossi ble t he 
I n vesti gat or ( or desi g nee) m ust c o ntact t he S p o ns or pri or t o brea ki n g t he bli n d.  T he i n vesti gat or 
m ust d oc u m e nt t he reas o n f or brea ki n g t he c o de a n d si g n a n d date t he a p pr o priate d oc u me nt.
T he ra n d omizat i on sc he d ule m ust be ret ur ne d t o G S K C H at t he e n d of t he st u d y .
5. 1 0 . P ac k a gi n g a n d L a belli n g
T he c o nte nts of t he la bel will be i n acc or da nce wit h all a p plica ble re g ulat or y  re q uire me nts a n d 
will be t he res p o nsi bilit y of  t he Cli nical S u p plies De part me nt, G S K C H.
T he test a n d refere nce pr o d ucts will be s u p plie d i n plai n pac ka gi n g wit h st u d y la bels affi xe d t o 
eac h sa m ple.  T he st u d y ce ntre will be s u p plie d a la belle d m ont hl y s u bject cart o n f or eac h 
parti ci pa nt c o ntai ni n g s ufficie nt sac hets f or t he peri o d of use.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 4 2 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 4 3 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

Care s h o ul d be ta ke n wit h t he s u p plie d pr o d ucts a n d t heir la bels s o t hat t he y ar e mai ntai ne d i n 
g o o d c o n di tio n.  It i s i m p orta nt t hat all la bels re mai n i ntact a n d le gi ble f or t he d urati o n of t he 
st u d y. S u bjects s h o uld be i nstr ucte d t o n ot re m o ve or deface a n y part of t he st u d y la bel.
5. 1 0 . 1. Acc o u nt a bilit y of Pr o d uct
All pr o d ucts s u p plie d are f or use o nl y i n t his cli nical st u d y  a n d s h o uld n ot be use d f or a n y  ot her 
p ur p ose.
T he i n vest i gat or or desi g nee will mai ntai n a f ull rec or d of st u d y pr o d uct acc o u nta bility.  A 
Pr o d uct Dis pe nsi n g L o g m ust be ke pt c urre nt a n d will c o ntai n t he f o ll owi n g i nf or mati o n:
T he i de nt ificati on of t he s u bject t o w h o m t he st u d y pr o d uct was dis pe nse d.
T he date a n d q ua nt ity of  t he st u d y pr o d uct dispe nse d t o t he s u bject.
T he date a n d q ua nt ity of  t he st u d y pr o d uct ret ur ne d b y t he s u bject (if a p plica ble).
T he i n ve nt or y  must be a vaila ble f or i ns pect i on b y t he st u d y  mo ni t or d uri n g t he st u d y. At t he e n d 
of  t he st u d y, st u d y pr o d uct s u p plies will be verified b y  t h e mo ni t or.  St u d y pr o d uct s u p plies will 
t he n be eit her c o llecte d b y t he st u d y m o nit or or ret ur ne d b y t he i n vesti gat or or desi g nee t o t he 
G S K C H Cli nical S u p plies De part me nt or desi g nate d ve n d or.
5. 1 0 . 2. St or a ge of Pr o d uct
St u d y  pr o d uct s u p plies m ust be st ore d i n c o m plia nce wit h t he la bel re q uire me nts i n a sec ure 
pl ace wit h li mite d or c o ntr olle d access.
6. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S
T his sect i on lists t he pr oce d ures a n d para meters of eac h pla n ne d st u d y assess me nt.  T he e xact 
ti mi n g of eac h assess me nt is liste d i n t he Sc he d ule of E ve nts secti o n.
A d here nce t o t he st u d y  desi g n re q uire me nts, i ncl u di n g all assess me nts a n d pr oce d ures are 
esse nt ial a n d re q uire d f or st u d y c o n d uct.
6 . 1. Tele p h o ne Scree ni n g
Pri or t o t he scree ni n g visit, tele p h o ne scree ni n g of i ntereste d s u bjects will be c o n d ucte d usi n g a 
t ele p h o ne scri pt. T his will be c o n d ucte d b y t he site recr uit me nt staff or desi g nee.   
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 4 3 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 4 4 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

6 . 2. I nf or me d C o nse nt
T he i n vest i gat or, or desi g nee, m ust o btai n writte n (si g ne d a n d date d b y t he s u bject) i nf or me d 
c o nse nt fr o m eac h s u bject partici pat i n g i n t his st u d y after a de q uate e x pla nati on of t he ai ms, 
met h o ds, o bjecti ves, a n d p ote nti al hazar ds of t he st u d y.
G S K a n d t he i n vest i gat or m ust a gree o n t he pr ocess f oll o we d t o e ns ure t hat t he a p pr o priate 
meas ures are ta ke n t o esta blis h le gall y  acce pta ble re prese ntati ve or i m partial wi t ness is 
c o mplia nt wi t h lo c al  re g ulat or y or c or p orate e x pectati o ns pri or t o st u d y start.
T he i n vest i gat or, or desi g nee, m ust als o e x plai n t o t he s u bjects t hat t he y are c o m pletel y free t o 
ref use t o e nter t he st u d y or t o wit hdra w fr o m  it at a n y time.  A p pr o priate f or ms f or d oc u me nt i n g 
a writte n c o nse nt will be pr o vide d b y t he i n vest i gat or or b y G S K C H.  T he i n vesti gat or, or 
desi g nee, s h o ul d si g n a n d date t he c o nse nt f or m t o c o nfir m t hat t he c o nse nt pr ocess was 
c o mplete d c orrectl y.  T he s u bject will be pr o vi de d wi t h a c o p y of t heir si g ne d a n d date d c o nse nt 
f or m a n d a n y ot her writte n i nf or mati o n w hic h t he y s h o ul d be i nstr ucte d t o retai n.
If, d uri n g a s u bject’s partici pati on i n t he st u d y, a n y ne w i nf or mati o n bec ome s a vaila ble t hat ma y 
affect t he s u bject’s willi n g ness t o partici pate i n t he st u d y , eac h o n g oi n g s u bject s h o uld recei ve a 
c o p y of t his ne w i nf or mati o n a n d be re-c o nse nte d i nt o t he st u d y. S u bjects s h o uld be pr o vi de d 
wi t h a c o p y of t he si g ne d a n d date d a me n de d c o nse nt f or m. T he date of c o nse nt will be rec or de d 
o n t he C R F.
6. 3. De m o gr a p hics
T he f o ll owi n g de m o gra p hic para meters will be ca pt ure d b y  t he I n vestigat or or desi g nee a n d 
rec or de d o n t he C R F: ye ar of birt h, ge n der a n d race.
6. 4. Me dic al Hist or y a n d C o nc o mit a nt Me dic ati o n
Me dical hist or y  will be assesse d as relate d t o t he i ncl usi o n/e xcl usi on cri t eria b y t he I n vest i gat or 
or m e dicall y q ualifie d desi g nee.  Details of a n y  rele va nt me dical or s ur gical hist or y incl u di n g 
aller gies or dr u g se nsit i vity will  be rec or de d o n t he C R F.  A n y c o nc o mita nt t hera p y ta ke n i n t he 
pri or t o t he S cree ni n g Visit a n d t hr o u g h o ut t he st u d y will als o be rec or de d.
6. 5 . Ge ner al P h ysic al E x a mi n ati o n
T he I n vesti gat or or t heir desi g nee will perf or m a p h ysical e xa mi nat i on w hic h s h o ul d i ncl u de 
assess me nt of t he f o ll owi n g b o d y  s yste ms as a p pr o priate: Ce ntral Ne r vo us S y st e m ( C N S); e yes; 
ears, n ose a n d t hr oat ( E N T); res pirat or y; car di o vasc ular; GI ; m u sc ulos keletal; ne ur ol o gi cal; 
e n d ocri ne/ meta b o lic; Ge ni t o uri nar y; hae mat o p oi etic/l y m p hat ic; der mat olo gi cal.
T he o utc o me o f t hese assess me nts will be d oc u me nte d i n t he C R F a n d a n y a b n or malit ies will be 
descri be d. T he I n vest i gat or ca n i nter pret i n di vi d ual fi n di n gs base d o n t he partici pa nt’s a ge, 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 4 4 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 4 5 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

p h ysical state a n d le vel of fit ness. Parti ci pa nts wit h cli nicall y si g nifica nt fi n di n gs o utsi de t he 
n or m al ra n ge s h o uld be e xcl u d e d fr o m t he st u d y base d o n i n vesti gat or’s discreti on. T his decisi o n 
will be d oc u me nte d o n t he C o m me nts pa ge of t he C R F.
6. 6. Vit al Si g ns
Q ualifie d site staff will rec or d partici pa nt’s heart rate , B L O O D P R E S S U R E a n d oral b o d y 
t e mperat ure w he n part ici pa nts are resti n g i n a sitti n g p ositi on, c hec ke d a gai nst t he f o ll owi n g 
n or m al ra n ges ( w hic h are gi ve n as a g ui de) a n d rec or de d i n a p pr o priate f or ms.
He art r ate:
6 0- 1 0 0 beats per mi n ute.
Or al b o d y Te m per at ure:
9 7. 7 – 9 9. 5 ° F
Bl o o d Press ure
S y st olic: < 1 4 0 m m H g; Diast olic: < 9 0 m m H g
T he I n vesti gat or ca n i nter pret i n di vi d ual fi n di n gs base d o n t he partici pa nt’s a ge, p h ysical state 
a n d le vel o f fitness. Parti cip a nts wi t h cli nicall y si g nifica nt rea di n gs o utsi de t he n or mal ra n ge 
s ho ul d be e xcl u de d fr o m  t he st u d y base d o n i n vesti gat or’s discreti o n. T his decisi o n will  be 
d oc u m e nte d o n t he C o m me nts pa ge of t he e C R F.
6. 7. A nt hr o p o metric Me as ure me nts ( Hei g ht, Wei g ht, a n d B MI)
All a nt hr o p o metric meas ure me nts will be perf or me d usi n g t he g u i deli nes a d o pte d at t he Nati o nal 
I nstitute of Healt h s p o ns ore d Arlie C o nfere nce ( L o h ma n et al., 1 9 8 8).
H ei g ht will be meas ure d usi n g a p orta ble sta di o -meter ( S E C A 2 1 3), wit h t he s u bject sta n di n g 
bare -f oot, t o t he nearest 0. 1 c m.  A n a vera ge of 3 meas ure me n ts will be rec or de d.  
Wei g ht will be meas ure d i n sta n dar d cl ot hi n g o n sta n dar dise d wei g hi n g scale ( S E C A 8 7 4 8 0 3 ) t o 
t he nearest 0. 1 k g. Wei g ht will be meas ure d i n t he u nit k g a n d a n a vera ge of 3 meas ure me nts will 
be rec or de d.
6. 8. H b Assess me nt
A n o n i n vasi ve s pectr o p h ot o metr y base d i nstr u me nt ( Masi m o Pr o nt o 7 P ul se C O-O xi me ter) will 
be use d f or H b assess me nt. T he Masi m o Pr o nt o 7 P ulse C O -O xi meter uses si g nal e xtracti o n 
tec h n ol og y  p ulse o xi metr y. 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 4 5 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 4 6 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

Si te staff will select a n a p pr o priate size d se ns or. T he se ns or will be place d o n t he nail of rin g 
fi n ger of t he left ha n d, f oll o we d b y assess me nt of hae m o gl obi n b y  pressi n g t he test b utt o n. 
A p pr o priate care will be ta ke n b y t he site staff t o e ns ure t hat t he partici pa nt’s test fi n ger nail 
d oes n ot c o ntai n a n y n ail pai nt.
6. 9 . L a b or at or y assess me nt 
Bl o o d sa m ple will  be c ollecte d F A S TI N G 1 2 H O U R S , c ollecti on, tra ns p ortati o n a n d st ora ge 
will be d o ne strictl y acc or di n g t o la b ma n ual P R O VI D E D B Y Q 2 L A B f or t he res pecti ve test. 
SI T E WI L L B E T R AI N E D B Y L A B A T T H E I NI TI A TI O N VI SI T R E G A R DI N G A L L 
O F T H E A B O V E. 
A F T E R A P P LI C A TI O N O F A N A N E S T H E TI C P A T C H/ OI N T M E N T E. G. LI D O C AI N, 
T E T R A C AI N E T C T O R E D U C E DI S C O M F O R T, A T O T A L V O L U M E O F 
A P P R O XI M A T E L Y 5 7. 5 m L ( E A C H A T B A S E LI N E VI SI T ( 2), MI D LI N E ( VI SI T 4) 
A N D E N D LI N E ( VI SI T 6) T O T A L O F A P P R O XI M A T E L Y 1 7 2. 5 m L) O F W H O L E 
B L O O D WI L L B E C O L L E C T E D F R O M E A C H P A R TI CI P A N T B Y A C E R TI FI E D 
P H L E B O T O MI S T F O R BI O C H E MI C A L A N D MI C R O N U T RI E N T A N A L Y SI S.
T H E P A R TI CI P A N T WI L L B E M A D E T O LI E D O W N O N B E D O R SI T
C O M F O R T A B L Y O N A C H AI R WI T H HI S A R M S T R E T C H E D O N T H E T A B L E. S H E 
WI L L B E A S K E D T O E X E R CI S E T H E A R M S O A S T O M A K E T H E A N T E -C U BI T A L 
V EI N P R O MI N E N T. A T O U R NI Q U E T WI L L B E TI E D A B O U T 2 I N C H E S A B O V E 
T H E V EI N O N T H E U P P E R A R M. T H E V EI N WI L L B E P A L P A T E D, A N D T H E A R E A 
WI L L B E S T E RI LI S E D. T H E V EI N WI L L B E P R I C K E D A N D V A C U T AI N E R 
P L A C E D I N P O SI TI O N T O C O L L E C T S A M P L E.
U RI N E S A M P L E C O L L E C TI O N, 
S P O T U RI N E F O R T E S T: C T X -1 U RI N E ; U RI N A R Y C A L CI U M A N D C R E A TI NI N E
(C R E A TI NI N E T O N O R M A LI S E U RI N A R Y C A L CI U M)
C ollect sec o n d v o i de d uri ne sa m ple i n t he m or ni n g after a n o ver ni g ht fast. Site t o ali q u ot 0. 5 ml 
of  uri ne i nt o tra ns p ort t u be a n d se n d fr oze n.
2 4 h o urs uri ne: 
P ati e nt is s u p plie d wit h 2 4 hr uri ne b ottle a n d is pr o vi de d b y  site staff i nf or mati o n of w he n t o 
start t he c ollecti on. Pati e nt must n ot use fi rst v oid of  t he da y t o start c ollecti o n. Patie nt c ollects 
uri ne i n sa me b ottle, a n d refri gerates after eac h v oi d. T he last sa m ple c ollecte d m ust be t he first 
s peci me n v oi de d t he f oll owi n g m or ni n g at t he sa me ti me as pre vi o us da ys first v oi d. Site t o 
ali q u ot 1 0 ml of uri ne i nt o tra ns p ort t u be a n d se n d at a m bie nt te m perat ure.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 4 6 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 4 7 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

T he a nal yt ical met h o d, assa y vali dat i on, a n d a nal ytical re p ort f or t his st u d y  will be pr o vide d b y  
t he a nal ytical in vest i gat or. I n a d diti on, t he a nal y tic al re p ort will i ncl u de a state me nt re gar di n g 
t he sta bility of  t h e fr oze n sa m ples, li mit of q ua ntificati o n, rec o ver y, a n d a s u m mar y of t he 
sta n dar d c ur ves. I n a d diti on, t he re p ort will i ncl u de re prese ntati ve c hr o mat o gra ms (if a n y) .
I M M E DI A T E L Y A F T E R C O L L E C TI O N, S A M P L E S WI L L B E F R O Z E N A T O R 
B E L O W -2 0° C ( F O R S E R U M C E N T RI F U G E B E F O R E S T O R A G E ). I F F R E E ZI N G I S 
N O T P O S SI B L E, T H E Y WI L L B E R E F RI G E R A T E D I M M E DI A T E L Y A T O R B E L O W 
4° C A N D M AI N T AI N E D A T T HI S T E M P E R A T U R E F O R N O L O N G E R T H A N 2 
H O U R S B E F O R E F R E E ZI N G A T O R B E L O W -7 0° C B E T W E E N - 6 00 T O - 8 00 C . 
All sa m ples ( baseli ne a n d e n d-li ne) will be a nal yse d i n batc hes. T E S T S R U N A T T H E 
BI O M A R K E R L A B WI L L B E A N A L Y S E D I N B A T C H E S F O R C T X -1 S E R U M, c O C, 
u O C, C T X -1 U RI N E . O T H E R S A M P L E S WI L L B E T E S T E D W H E N T H E Y A R E 
R E C EI V E D I N T H E L A B.
H B S T O B E S T O R E D TI L L I T I S P R O P E R L Y D I S P O S E D O F A T T H E E N D O F I T S 
R E T E N TI O N P E RI O D (I. E. 1 4 D A Y S F R O M L A S T E A C H S A M P L E A N A L Y SI S TI L L 
S T U D Y R E P O R T I S I S S U E D ), O R U P O N R E C EI P T O F A R E Q U E S T T O D E S T R O Y 
T H E H B S D U E T O WI T H D R A W A L O F C O N S E N T.
St ora ge of bi o l ogical sa m ple will be hel d till 1 4 D A Y S F R O M L A S T S A M P L E A N A L Y S E D 
2 m o nt h past fi nal re p ort is o ut, l on ger st ora ge i s n ot a d vise d beca use of sta bilit y of mar kers 
a nal yze d.
6. 1 0. Diet ar y assess me nt ( 7 d a y f o o d di ar y)
T he parti ci pa nts t o re gister all f oo d, water a n d be vera ge c o ns u me d d uri n g o ne c o m plete wee k. 
T he di ar y incl u de (te m plate i n A p pe n di x III) t he differe nt meal times (at wa ki n g u p/ bef ore 
brea kfast, d uri n g brea kfast, d uri n g m or ni n g/ bef ore mai n meal, d uri n g mai n meal, d uri n g 
after n o o n/ bef ore di n ner, d uri n g di n ner, a n d bef ore g oi n g t o be d), a s pace t o s pecif y t he t yp e of  
f oo d i t e m c o ns u me d, t he a mo u nt c o ns u me d d uri n g t he da y  I N G R A M S b ot h i n m L a n d p orti o n 
sizes usi n g sta n dar d meas ure U SI N G W EI G HI N G S C A L E W E N S A R KI T C H E N 
B A L A N C E T T B 3 M O D E L gi ve n wit h di ar y, a n d t he bra n d (i n case it was a c o m mercial f o o d 
pr o d uct ). T o i ncrease t he acc urac y o f t he re p orte d p ortio n si ze, i nter vie wers will visit t o re p ort
i nta ke wit h t he s u bjects at e ver y visit usi n g sta n dar d meas ure me nt c u ps. Dietar y  assess me nt will 
be d o ne usi n g sta n dar d n utrit i on i nta ke pr o gra m DI E T S O F T S O F T W A R E  U SI N G L A T E S T 
V E R SI O N B A S E D NI N, I N DI A F O O D G UI D E. 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 4 7 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 4 8 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

6. 1 1 . St u d y C o ncl usi o n
S u bjects will be e val uate d t o deter mi ne if t he y c o m plete d all st u d y pr oce d ures or if t he y were 
di sc o nti n ue d fr om t he st u d y earl y.  If t he s u bject disc o nti n ue d at a n y p oi nt d uri n g t he st u d y, t he 
pri mar y  reas o n f or wit hdra wal  s h o uld be rec or de d o n t he St u d y  C o ncl usi on pa ge of t he C R F b y 
selecti n g o ne of t he o pti o ns bel o w.
1.
S u bject di d n ot meet st u d y  crit eria
2.
A d verse E ve nt
3.
L ost t o F oll o w U p
4.
Pr ot oc ol  Viol at i on
5.
Wit h dra wal o f C o nse nt
6.
Ot her
6. 1 2 . Cli nic al S afet y L a b or at or y Assess me nts
All pr ot oc ol re q uire d la b orat or y  assess me nts, must be c o n d ucte d i n acc or da nce wit h t he 
La b orat or y  Ma n ual or acc or di n g t o t he la b orat or y secti on of t he Pr ot oc ol, a n d Pr ot oc ol Sc he d ule 
of  E ve nts.  Sa mples m ust be cl earl y la bele d wi t h t he s u bject n u m ber, pr oto c ol  nu m ber, 
site/ce ntre n u m ber, a n d visit date.  Details f or t he pre parati o n a n d s hi p me nt of sa m ples will be 
pr o vi de d b y t he la b orat or y . Refere nce ra n ges f or all safet y para m eters will be pr o vi de d t o t he site 
b y t he l a b orat or y res p o nsi ble f or t he assess ment s.
If a d diti onal n o n- pr ot oc ol  s pecifie d la b orat or y assess me nts are perf or me d at t he i nstit uti o n’s 
l ocal la b orat or y a n d res ult in a c ha n ge i n s u bject ma na ge me nt or are c o nsi dere d cli nicall y 
sig nifica nt or a b n or mal b y  t he i n vestigat or (e. g., S A E or A E or d ose m o dificat i on) t he res ults 
m ust be rec or de d i n t he C R F. If t he cli nicall y  sig nifica nt a b n or m al la b is ass ociate d wit h a 
di a g n osis, t he dia g n osis s h o ul d be rec or de d o n t he C R F.
7. S A F E T Y A S S E S S M E N T S
7. 1. Defi niti o ns of a n A d verse E ve nt a n d Seri o us A d verse E ve nt 
7. 1. 1. A d verse E ve nts
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 4 8 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 4 9 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

T he i n vesti gat or or site staff will be res p o nsi ble f or detecti n g, d oc u me nti n g a n d re p orti n g e ve nts 
t hat meet t he defi nit i on of a n A E or S A E.
A d verse E ve nt Defi niti o n:
A n A E i s a n y u nt o war d me dical occ urre nce i n a patie nt or cli nical i n vesti gati o n 
s u bject, te mp orall y ass oci ate d wit h t he use of a n i n vesti gati o nal or was h o ut pr o d uct, 
w het her or n ot c o nsi dere d relate d t o t he i n vest i gati o nal or was h o ut pr o d uct.
N O T E: A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n 
a b n or mal la b orat or y fi n di n g), s y m pt o m, or disease ( ne w or e xacer bate d) te m p orall y 
ass ociate d wit h t he use of a n i n vesti gati onal or was h o ut pr o d uct.
E ve nts meeti n g A E defi niti o n i ncl u de:
A n y a b n or mal la b orat or y test res ults (if a p plica ble) or ot her safety assess me nts, 
i ncl u di n g t h ose t hat w orse n fr om baseli ne, a n d felt t o be cli nicall y  sig nifica nt i n t he 
me dical a n d scie nt ific j u d g me nt of t he i n vesti gat or.
E xacer bat i on of a c hr o nic or i nter mi tt e nt pre-e xist i n g c o n diti on i ncl u di n g eit her a n 
i ncrease i n fre q ue nc y a n d/ or i nte nsity of  t he c o n ditio n .
Ne w c o n dit i on(s) detecte d or dia g n ose d after st u d y pr o d uct a d mi nistrati o n e ve n 
t ho u g h it m a y ha ve bee n prese nt pri or t o t he start of t he st u d y.
Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d i nteracti o n.
Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y  
pr o d uct or a c o nc o mita nt me dicat i on ( o ver d ose per se will n ot be re p orte d as a n 
A E/ S A E).
E ve nts N O T meeti n g defi niti o n of a n A E i ncl u de:
A n y cli nicall y  sig nifica nt a b n or mal la b orat or y  fi n di n gs (if a p plica ble) or ot her 
a b n or mal s af et y assess me nts w hic h are ass ociate d wit h t he u n derl yi n g disease, u nless 
j u d ge d b y t he i n vesti gat or t o be m ore se vere t ha n e x pecte d for t he s u bject’s c o n dit i on. 
T he disease/ dis or der/ c o n dit i on bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or 
s y m pt o ms of t he disease/ dis or der bei n g st u die d, u nless m ore se vere t ha n e x pecte d f or 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 4 9 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 5 0 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

t he s u bject’s c o n dit i on.. 
Me dical or s ur gical pr oce d ure (e. g ., e n d osc o p y, a p pe n dect o m y): t he c o n diti on t hat 
lea ds t o t he pr oce d ure is a n A E.
Si t u atio ns w here a n u nt o war d me dical occ urre nce di d n ot occ ur (s ocial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital).
A nt ici pate d da y-t o-da y fl uct uati o ns of pre-e xist i n g disease(s) or c o n diti on(s) prese nt 
or detecte d at t he start of t he st u d y  t hat d o n ot w orse n.
7. 1. 2. Seri o us A d verse E ve nts
Seri o us A d verse E ve nt is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose:
Res ults i n de at h
Is life-t hre ate ni n g
N O T E: T he ter m 'life -t hreate ni n g' i n t he defi niti on of 'seri o us' refers t o a n e ve nt i n w hic h t he 
s u bject was at ris k of deat h at t he ti me of t he e ve nt.  It d oes n ot refer t o a n e ve nt, w hic h 
h y p ot heti call y mi g ht ha ve ca use d deat h, if it were m ore se vere.
Re q uires h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h os pit aliz ati o n
N O T E: I n ge neral, h os pitalizat i on si g nifies t hat t he s u bject has bee n detai ne d ( us uall y i n v ol vi n g 
at least a n o ver ni g ht sta y) at t he h os pit al or e mer ge nc y war d f or o bser vat i on a n d/ or treat me nt 
t hat w o uld n ot ha ve bee n a p pr o priate i n t he p h ysicia n’s office or o ut -patie nt setti n g.  
C o m plicat i ons t hat occ ur d uri n g h os pitalizati o n are A Es.  If a c o mplicat i on pr ol o n gs 
h os pi talizatio n or f ulfills a n y  ot her serio us cri t eria, t he e ve nt is serio us.  W he n i n d o u bt as t o 
w het her “ h os pitalizat i on” occ urre d or was necessar y , t he A E s h o uld be c o nsi dere d seri o us.
H os pitalizati o n f or elect i ve treat me nt of a pre -e xisti n g c o n dit i on t hat di d n ot w orse n fr o m 
baseli ne is n ot c o nsi dere d a n A E.
Res ults i n dis a bilit y/i nc a p acit y
N O T E: T he ter m disa bilit y mea ns a s u bsta nt ial disr u ptio n of  a pers o n’s a bility t o c o n d uct n or mal 
life f u ncti ons.
T his defi nit i on is n ot i nte n de d t o i ncl u de e x perie nces of relat i vel y mi n or me dical si g nifica nce 
s uc h as u nc om p licate d hea dac he, na usea, v omit i n g, diarr hea, i nfl ue nza, a n d acci de ntal tra u ma 
(e. g. s prai ne d a n kle) w hic h ma y i nterfere or pre ve nt e ver yd a y  lif e fu nct i ons b ut d o n ot c o nstit ute 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 5 0 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 5 1 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

a s u bsta ntial disr u pt i on.
Is a c o n ge nit al a n o m al y/ birt h defect
Ot her Sit u ati o ns
Me dical or scie nt ific j u d g me nt s h o ul d be e xercise d i n deci di n g w het her re p orti n g is a p pr o priate 
i n ot her sit uati o ns, s uc h as i m p orta nt me dical e ve nts t hat ma y n ot be i m me diatel y life-
t hreate ni n g or res ult i n deat h or h os pitalizati on b ut ma y je o par dize t he s u bject or ma y re q uire 
me dical or s ur gical i nter ve nt i on t o pre ve nt o ne of t he ot her o utc o mes liste d i n t he a b o ve 
defi nit i on. T hese s h o ul d als o be c o nsi dere d seri o us.
E xa m ples of s uc h e ve nts are i n vasi ve or mali g na nt ca ncers, i nte nsi ve treat me nt i n a n e mer ge nc y 
r o o m or at h o me for aller gic br o nc h os pas m, bl o o d d y scrasias or c o n v ulsi o ns t hat d o n ot res ult i n 
h os pi talizatio n or de vel o p m e nt of dr u g de pe n de nc y or dr u g a b use or re p orts of s p o nta ne o us 
a b ortio n.
7. 2. Rec or di n g A d verse E ve nts a n d Seri o us A d verse E ve nts
Rec or di n g of a d verse e ve nts a n d seri o us a d verse e ve nts:
T he i n vest i gat or or site staff will be res p o nsi ble f or detecti n g, d oc u me nti n g a n d re p orti n g e ve nts 
t hat meet t he defi nit i on of a n A E or S A E. 
T he i n vest i gat or or site staff will t he n rec or d all rele va nt i nf or mati on re gar di n g a n A E/ S A E i n 
t he C R F.
T here m a y be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are re q ueste d b y G S K.  
I n t his i nsta nce, all s u bject i de ntifiers, wit h t he e xce pti o n of t he s u bject n u m ber, will be bli n de d 
o n t he c o pies of t he me dical rec or ds pri or t o s u b missi o n of t o G S K.
T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, s y m pt o ms, 
a n d/ or ot her cli nical i nf or mat i on.  I n s uc h cases, t he dia g n osis will be d oc u me nte d as t he 
A E/ S A E a n d n ot t he i n di vi d ual si g ns/s y m pt o ms. Cli nical A Es will be descr i be d b y dia g n osis a n d 
n ot b y  s y m pt o ms w he n p ossi ble (e. g., u p per res pirat or y tract infect i on, seas o nal aller g y , etc. 
i nstea d of r u n n y nose).
A Es will be c o llecte d fr om t he start of t he a n d u ntil 7 da ys f o ll owi n g last a d mi nistrati o n of t he 
st u d y pr o d uct.
S A Es will be c ollecte d o ver t he sa me ti me peri o d as state d a b o ve f or A Es.  H o we ver, a n y S A Es 
assesse d as rel ate d t o st u d y partici patio n (e. g., i n vesti gati o nal pr o d uct, pr ot oc ol ma n date d 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 5 1 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 5 2 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

pr oce d ures, i n vasi ve tests, or c ha n ge i n e xist i n g t hera p y) or relate d t o a G S K c o nc o mita nt 
me dicat i on will be rec or de d fr o m t he ti me a s u bject c o nse nts t o partici pate i n t he st u d y  u p t o a n d 
i ncl u di n g a n y fol l ow -u p c o ntact.  
Me dical c o n dit i ons re p orte d pri or t o t he ti me peri o d f or re p orti n g A Es/ S A Es s h o ul d be rec or de d 
as par t of t he s u bject’s me dical hist or y.
7. 3. E v al u ati n g A d verse E ve nts a n d Seri o us A d verse E ve nts
Assess me nt of I nte nsit y:
T he i n vest i gat or or desi g nee will ma ke a n assess me nt of i nte nsity f or eac h A E a n d S A E re p orte d 
d uri n g t he st u d y a n d will assi g n it t o o ne of t he f oll o wi n g cate g ories:
Mil d:  A n e ve nt t hat is easil y t olerate d b y  t he s u bject, ca usi n g mi ni mal disc o mf ort a n d n ot 
i nterferi n g wit h e ver y da y acti vities.
M o derate:  A n e ve nt t hat is s ufficie nt l y disc omf o rti n g t o i nterfere wit h n or mal e ver y da y 
acti vit ies
Se vere:  A n e ve nt t hat pre ve nts n or mal e ver y da y acti vit ies. - a n A E t hat is assesse d as se vere will 
n ot be c o nf use d wit h a n S A E. Se verit y is a cate g or y utilize d f or rati n g t he i nte nsity of  a n e ve nt; 
a n d b ot h A Es a n d S A Es ca n be assesse d as se vere.
N ote: A n e ve nt is defi ne d as ‘seri o us’ w he n it meets at least o ne of t he pre -defi ne d o utc o mes as 
descri be d i n t he defi nit i on o f a n S A E.
Assess me nt of C a us alit y:
T he i n vest i gat or is o bli gate d t o assess t he relati o ns hi p bet wee n st u d y  pr o d uct a n d t he 
occ urre nce of eac h A E/ S A E.
A "reas o na ble p ossi bilit y" is me a nt t o c o n ve y t hat t here are facts/e vi de nce or 
ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat her t ha n a relat i ons hi p ca n n ot be r ul e d 
o ut.
T he i n vest i gat or will use cli nical j u d g me nt t o deter mi ne t he relati ons hi p.
Alt er nat i ve ca uses, s uc h as nat ural hist or y of t he u n derl yi n g diseases, c o nc o mita nt 
t hera p y, ot her ris k fact ors, a n d t he te m p oral relati ons hi p of t he e ve nt t o t he st u d y  
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 5 2 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 5 3 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

pr o d uct will be c o nsi dere d a n d i n vest i gate d.
T he i n vest i gat or will als o c o ns ult t he I n vesti gat or Br oc h ure (I B) a n d/ or Pr o d uct 
I nf or mat i on, f or mar kete d pr o d ucts, i n t he deter mi nat i on of his/ her assess me nt.
F or eac h A E/ S A E t he i n vesti gat or m ust d oc u me nt i n t he me dical n otes (s o urce 
d oc u me nt) or C R F t hat he/s he has re vie we d t he A E/ S A E a n d has pr o vi de d a n 
assess me nt of ca usalit y.
T here m a y be sit u atio ns w he n a n S A E has occ urre d a n d t he i n vest i gat or has mi ni mal 
i nf or mat i on t o i ncl u de i n t he i nit ial re p ort t o G S K.  H o we ver, it is ver y i m p ort a nt 
t h at the i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y f or e ver y e ve nt 
pri or t o t he i niti al tr a ns missi o n of t he S A E d at a t o G S K.
T he i n vest i gat or ma y c ha n ge his/ her o pi ni on of ca usalit y i n li g ht of f oll ow- u p 
i nf or mat i on, a m e n di n g t he S A E data c ollect i on t o ol acc or di n gl y.
T he ca usalit y assess me nt is o ne of t he crit eria use d w he n deter mi ni n g re g ulat or y 
re p orti n g re q uire me nts.
7. 4. Re p orti n g A d verse E ve nts a n d Seri o us A d verse E ve nts
A E Re p orti n g t o G S K C H:
A Es will be rec or de d i n t he A E sect i on of t he C R F. 
Me dical c o n dit i ons rec or de d b y  t he s u bject o n a diar y car d or si milar d oc u me nt t hat meet t he 
defi nit i on o f a n A E m ust al s o be rec or de d i n t he A E secti o n of t he C R F, if n ot pre vi o usl y well-
c haracterize d b y t he i n vesti gat or i n t he s u bject’s me dical hist or y. 
A Es elicite d b y t he i n vest i gat or i n a sta n dar d ma n ner at t he st u d y visits s h o ul d als o be rec or de d 
i n t he A E secti on of t he C R F.  T he i n vesti gat or or desi g nee m ust as k t he s u bject t he f o ll owi n g 
q uesti o n d uri n g eac h visit i ncl u di n g a n y f o ll ow- u p visit s:  “ H ave y o u felt u n well, e x perie nce d 
a ny sy m pt o ms or t a ke n a ny me dic ati o n (si nce y o ur l ast visit) (t o d ay) (si nce y o ur l ast d ose) 
(si nce t he l ast sessi o n) ? ”
T he m e dicall y q ualifie d i n vesti gat or s h o ul d re vie w a d verse e ve nts i n a ti mel y  ma n ner; t his 
re vie w s h o ul d be d oc u m e nte d i n writin g i n t he s o urce d oc u me nt or i n t he C R F. 
After t he st u d y  is c o mplete d at a gi ve n site, a n d t he site has recei ve d t heir st u d y  data o n C o mpact 
Di scs ( C Ds), t he electr o nic data c ollecti on t o ol  will b e r e mo ve d fr o m  t he i nter net t o pre vent  t he 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 5 3 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 5 4 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

e ntr y of ne w data or c ha n ges t o e xisti n g data.
S A E Re p orti n g t o G S K C H:
A pa per c o p y  of t he S A E f or m pr o vide d i n t he i n vesti gat or st u d y  master file s h o ul d 
be c o m p lete d as f ull y as p ossi ble. 
It is esse ntial t o e nter t he f oll o wi n g i nf or mati on: 
Pr ot oc ol  a n d s u bject ide nt ifiers
S u bject’s de m o gra p h y
Descri pt i on of e ve nts, wit h dia g n osis if a vaila ble
I n vesti gat or o pi ni on of relati o ns hi p t o st u d y  pr o d uct (see secti o n 8. 3)
Cri t erio n f or s eri o us ness.
T he f o ll owi n g are desira ble a n d are of partic ular rele va nce f or i n vesti gat or a n d 
G S K C H assess me nt of t he S A E re p ort:
Date of o nset of A E 
Date A E st o p pe d, if rele va nt
St u d y  pr o d uct start date
St u d y  pr o d uct e n d date if rele va nt
Act i on ta ke n o n st u d y  pr o d uct
O utc o m e if k n o w n
T he S A E f or m, c o m plete d as f ull y as p ossi ble, a n d S A E fa x c o ver s heet m ust be 
fa xe d or e-maile d t o t he a p pr o priate G S K C H st u d y ma na ger as s o o n as p ossi ble, b ut 
n ot l ater t ha n 2 4 h o urs after st u d y site pers o n nel lear n of t he e ve nt. T he G S K C H 
st u d y ma na ger s h o uld be n otifie d o f t he sit u atio n b y  tele p h o ne or e mail.
Fa x seri o us a d verse e ve nts t o:
I n dia: 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 5 4 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 5 5 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI
C CI

T he G S K C H st u d y  ma na ger will be res p o nsi ble f or f or war di n g t he S A E f or m t o t he 
case ma na ge me nt gr o u p, gl o bal cli nical safet y a n d p ha mac o vi gila nce, t he me dical 
di rect or res p o nsi ble f or t he st u d y a n d ot her G S K C H pers o n nel as a p pr o priate via 
e mail.
T he i nit ial re p ort will be f oll owe d u p wi t h more i nf or m at i on as rele va nt, or as 
re q ueste d b y t he G S K C H st u d y ma na ger.
7. 5. F oll o w - u p of A d verse E ve nts a n d Seri o us A d verse E ve nts
F oll o w -u p of A Es a n d S A Es:
After t he i nit ial re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y f oll ow u p wi t h eac h s u bject a n d 
pr o vi d e f urt her i nf or m at i on o n t he s u bject’s c o n diti o n.
All A Es/ S A Es will be f o ll owe d u nt il res ol uti on, u ntil t he c o n dit i on sta bilizes, u nt il t he e ve nt is 
ot her wi se e x plai ne d, or u ntil t he s u bject is l ost t o f oll o w-u p.  
T he i n vest i gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
meas ure me nts a n d/ or e val uat i ons as ma y be i n dicate d or as re q ueste d b y  G S K t o elu ci date as 
f ull y as p ossi ble t he nat ure a n d/ or ca usality of  t he A E or S A E.
I n vesti gat ors are n ot o bli ge d t o acti vely see k A Es or S A Es i n f or mer s u bjects.  H o we ver, if t he 
i n vesti gat or lear ns of a n y S A E, i ncl u di n g t he deat h, at a n y ti me after a s u bject has bee n 
di sc har ge d fr o m t he st u d y, a n d c o nsi ders t he e ve nt reas o na bl y relate d t o t he i n vesti gati onal 
pr o d uct or st u d y  parti ci pat i on, t he i n vest i gat or will pr o m ptl y n otif y  G S K C H.
T he i n vest i gat or will s u b mit a n y u p date d S A E data t o G S K wit hi n t he desi g nate d re p orti n g ti me 
fra mes.
Re g ul at or y a n d et hics re p orti n g re q uire me nts f or S A Es:
T he i n vest i gat or will pr om ptl y re p ort all S A Es t o G S K C H withi n t he desi g nate d 
re p orti n g ti mefra mes ( wit hi n 2 4 h o urs of lear ni n g of t he e ve nt).  G S K C H has a le gal 
res p o nsi bility t o n otif y, as a p pr o priate, t he l ocal re g ulat or y  a ut h orit y a n d ot her 
re g ulat or y a ut h orities a b o ut t he safety of a pr o d uct u n der cli nical i n vest i gati on.  
Pr o m pt n otificat i on of S A Es b y t he i n vest i gat or t o G S K C H is esse ntial s o t hat le gal 
o bli gat i ons a n d et hical res p o nsi bilit ies t o war ds t he safety of  s u bjects are met.
G S K C H will c o m p l y wit h c o u ntr y s pecific re g ulat or y re q uire me nts relati n g t o safety 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 5 5 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 5 6 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

re p orti n g t o t he re g ulat or y a ut h orit y, I R B/I E C a n d i n vesti gat ors.
I n vesti gat or safety re p orts are pre pare d acc or di n g t o G S K C H p olic y a n d are 
f or war de d t o i n vesti gat ors as necessar y.  A n i n vesti gat or safet y re p ort is pre pare d for 
a S A E(s) t hat is b ot h attri b uta ble t o i n vest i gati onal pr o d uct a n d u ne x pecte d.  T he 
p ur p ose of t he re p ort is t o f ulfill s pecific re g ulat or y a n d G C P re q uire me nts, re gar di n g 
t he pr o d uct u n der i n vesti gati o n.
A n i n vesti gat or w h o recei ves a n i n vesti gat or safet y re p ort descri bi n g a S A E(s) or 
ot her s pecific safet y i nf or mati on (e. g., s u m mar y  of listi n g of S A Es) fr o m G S K C H 
will file it wit h t he I n vesti gat or Br oc h ure ( or safet y state me nt) a n d will n otif y t he 
I E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts.
7. 7. C ollecti o n of Pre g n a nc y I nf or m ati o n
7. 7. 1. Ti m e Peri o d f or C ollecti n g of Pre g n a nc y I nf or m ati o n
C ollecti o n of Pre g n a nc y I nf or m ati o n:
Pre g na nc y i nf or mat i on will be c o llecte d o n all pre g na ncies re p orte d f oll owi n g a d mi nistrati o n of 
a n y i n vesti gati onal pr o d uct .
I nf or mati o n o n pre g na nc y i de ntifie d d uri n g t he scree ni n g p hase a n d pri or t o i n vesti gati onal 
pr o d uct a d mi nistrati o n d oes n ot nee d t o be c ollecte d.
7. 7. 2. Acti o n t o be T a ke n if Pre g n a nc y Occ urs
Acti o n t o be T a ke n:
T he i n vest i gat or will c ollect pre g na nc y i nf or mati o n o n a n y s u bject w h o bec omes pre g na nt w hile 
parti ci pat i n g i n t he st u d y after a d mi nistrati o n of t he i n vesti gati on al pr o d uct. T he i n vest i gat or 
will rec or d pre g na nc y  inf or m at i on o n t he a p pr o priate f or m a n d s u b mit it t o G S K C H wit hi n 2 
wee ks of lear ni n g o f t he s u bject bec o mi n g pre g na nt. T he s u bject will be f o ll owe d t o deter mi ne 
t he o utc o me of t he pre g na nc y. I nf or mati on o n t he stat us of t he m ot her a n d i nfa nt / ne o nate 
(incl u di n g c o nc o mit a nt me dicat i ons ta ke n b y t he m ot her d uri n g t he pre g na nc y) will be 
f or war de d t o G S K C H. Ge nerall y, fol l ow- u p will be n o l o n ger t ha n 6 t o 8 wee ks f o ll owi n g t he 
esti mate d deli ver y date. A n y ter mi nati on of t he pre g na nc y wil l be re p orte d.
W hile pre g na nc y  itself is n ot c o nsi dere d t o be a n A E, a n y pre g na nc y c o mplicat i on or el ect i ve 
ter mi nati o n f or me dical reas o ns will be rec or de d as a n A E or S A E.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 5 6 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 5 7 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

A s p o nta ne o us a b orti o n is al wa ys c o nsi dere d t o be a n S A E a n d will be re p orte d as s uc h. A n S A E 
occ urri n g i n ass ociat i on wi t h a pre g na nc y, br o u g ht t o t he i n vesti gat or’s atte nti o n after t he s u bject 
c o mplete d t he st u d y  a n d c o nsi dere d b y t he i n vesti gat or as p ossi bl y relate d t o t he i n vesti gat i onal 
pr o d uct, m ust be pr o m ptl y f or war de d t o G S K.
W hile t he i n vest i gat or is n ot o bli ge d t o acti vel y see k t his i nf or mati o n i n f or mer st u d y 
parti ci pa nts, he or s he ma y lear n of a n S A E t hr o u g h s p o nta ne o us re p orti n g.
If t he s u bject bec omes pre g na nt d uri n g t he st u d y t he y s h o ul d be wit h dra w n fr o m t he st u d y a n d 
this s h o ul d be rec or de d i n t he a p pr o priate secti o n of t he C R F.
8. D A T A M A N A G E M E N T
F or t hi s st u d y s u bject data will be e ntere d i nt o a n electr o nic case re p ort f or m, usi n g a G S K C H 
vali date d data s y st e m.
8. 1. S o urce D oc u me nts/ D at a
T he s o urce d oc u me nts (e. g. h os pital rec or ds, cli nical a n d office c harts, la b orat or y  notes, 
me m ora n da, s u bjects’ diaries or e val uati o n c hec klists, p har mac y dis pe nsi n g rec or ds, rec or de d 
data fr o m  a ut o mate d i nstr u me nts, micr o fic hes, p h ot o gra p hic ne gati ves, micr ofil m or ma g net ic 
me dia, x -ra ys, s u bject files a n d rec or ds ke pt at t he p har mac y, at t he la b orat or y a n d at t he me dic o -
tec h nical de partme nt s i n v ol ve d i n t he cli nical st u d y) w hic h c o ntai n t he s o urce of data rec or de d i n 
t he C R F s h o ul d be s pecifie d i n t he S o urce D oc u me nt Desi g nat i on F or m .  I n s o me cases t he C R F 
ca n be use d as a s o urce d oc u me nt.
Eac h s u bject will be assi g ne d a n d i de nt ifie d b y a u ni q ue Scree ni n g N u m ber. A n y refere nce ma de 
t o a n i n di vi d ual s u bject wit hi n t he st u d y must be d o ne usi n g t he u ni q ue Scree ni n g N u m ber.
8. 2. Electr o nic C ase Re p ort F or m
A C R F is a pri nte d, o ptical, or electr o nic d oc u me nt desi g ne d t o rec or d all of t he pr ot oc ol 
re q uire d i nf or mat i on t o be re p orte d t o t he s p o ns or o n eac h trial s u bject.
F or eac h s u bject w h o has gi ve n i nf or me d c o nse nt/asse nt a n d has bee n scree ne d, C R F m ust be 
c o mplete d a n d si g ne d b y t he Pri nci pal I n vest i gat or ( or a ut h orize d desi g nee) t o certif y t hat t he 
data are c o m plete a n d c orrect.  
Ma na ge me nt of cli nical data will be perf or me d i n acc or da nce wit h a p plica ble G S K C H sta n dar ds 
a n d data clea ni n g pr oce d ures t o e ns ure t he i nte grit y o f t he data e. g. re m o vi n g err ors a n d 
i nc o nsiste ncies i n t he data. 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 5 7 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 5 8 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

I n or der t o pr otect t he pri vac y of s u bjects, n o Pers o nall y I de ntifia ble I nf or mat i on ( PII) (i ncl u di n g 
t he s u bject's na me or i nit ials or birt h date) is t o be rec or de d i n t he C R F or as part of t he q uer y 
te xt.
A d verse e ve nts a n d c o nc o mit a nt me dicat i ons ter ms (if a p plica ble) will be c o de d usi n g Me d D R A 
( Me dic al Dicti onar y  for Re g ulat or y  Act i vities) an d a n i nter nal vali date d me dicat i on dict i onar y , 
G S K Dr u g.  
S u bject data will be e ntere d i nt o G S K C H defi ne d C R Fs a n d tra ns mitte d electr o nicall y t o 
G S K C H i n a vali date d ( 2 1 C F R Part 1 1 c o m plia nt) we b- base d electr o ni c data ca pt ure s yste m 
(I n F or mT M ).
All C R F p a ges s h o uld be c o m plete d d uri n g a s u bject assess me nt w he n t he C R F has bee n 
desi g nate d as t he s o urce.  Data t hat is s o urce d else w here s h o ul d be e ntere d i nt o t he C R F i n a n 
a gree d u p o n ti mefra me bet wee n t he I n vest i gat or a n d S p o ns or.  
T he C R Fs (i ncl u di n g q uer ies, q uer y res p o nses a n d a u dit trails) will be retai ne d b y G S K C H. Sit e 
data arc hi ve d c o m pact discs ( C D(s)) pre pare d b y  a t hir d part y will be se nt t o t he i n vesti gat or t o 
mai ntai n as t he i n vesti gat or c o p y  fol l owi n g t he dec o m missi o ni n g of t he st u d y .
8. 3. D at a H a n dli n g
D oc u m e ntatio n of  all d at a ma na ge me nt acti vit ies s h o ul d all o w ste p- b y-ste p retr os pecti ve 
assess me nt of data q ualit y a n d st u d y p erfor ma nce. A n y c ha n ges or c orrecti o ns t o data will be 
perf or m e d i n t he Electr o nic Data Ca pt ure ( E D C) S yste m, a n d it will i ncl u de r atio nale f or 
c ha n ges. T he E D C s yste m has a n a u dit trail, w hic h will pr o vi de a c o m p lete rec or d of t he c ha n ges 
a n d c orrecti o ns e n d orse d b y t he I n vesti gat or.
8. 3. 1. D at a Q ueries
Pr o gra m me d e dit c hec ks will be ge nerate d a ut o maticall y , as t he data is bei n g e ntere d i nt o t he 
s yste m. Data Ma na ge me nt will als o r u n re p orts a n d listi n gs o n t he C R F data, i n a d diti on t o t he 
q ueri es alrea d y pr o gra m me d a n d ge nerate d b y t he s yste m, t o rais e ma n ual q ueries as nee de d f or 
sit e clarificatio n or c orrecti o n. T he Cli nical Dict i onar y  D e v elo p me nt a n d Ma na ge me nt Gr o u p 
will raise q ueries as nee de d o n safet y data t o c o de t he ter ms ( A d verse E ve nts a n d Dr u gs) are 
re p orte d a p pr o priatel y. 
T he st u d y  mo ni t or at t he st u d y sit e will re vie w t he C R Fs i n acc or da nce wit h t he m o nit ori n g pla n, 
a n d a n y q u eries will be ge nerate d i n t he E D C S yste m t o t he I n vesti gat or or desi g nee, e na bli n g 
t he err ors t o be a d dresse d i n parallel wit h Data Ma na ge me nt re vie w. M o nit or ca n als o r u n re p orts 
a n d list i n gs o n t he C R Fs, t o raise ma n ual q ueries as nee de d f or site clarificati on or c orrecti o n
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 5 8 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 5 9 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

8. 4. Pr ocessi n g P atie nt Re p orte d O utc o mes
P ati e nt re p orte d o utc o me ( P R O) data are c ollecte d direct l y fr om t he s u bject P R O meas ures e. g. 
di ar y car ds, q uestio n naires etc, a n d e ntere d i nt o t he s p o ns or’s cli nical data ma na ge me nt s y st e m 
( D M S) b y t he st u d y site re prese ntati ve. I n i nsta nces w here t he P R O data i s e ntere d i nt o t he D M S 
b y G S K C H, t he P R Os will be a n o n y mise d, a n d f or war de d t o G S K C H f or e ntr y , as a gree d a n d 
d oc u m e nte d a hea d of t he st u d y starti n g. P R Os t hat are s o urce will be retai ne d b y t he i n vesti gat or 
a n d certifie d c o pies will be se nt t o G S K C H. 
I n or der t o pr otect t he pri vac y of partici pa nts, n o Pers o nall y I de ntifia ble I nf or mati o n ( PII) 
(incl u di n g t he s u bject's na me or i nit ials or birt h date) is t o be rec or de d o n all P R O’s t hat will be 
f or war de d t o G S K C H.
8. 5. E xter n al D at a
E xter nal Data are s u bject data o btai ne d e xter nall y  t o t he C R F. T hese data are ge nerate d fr o m 
la b orat or y instr u m e nts, c o mp uters or ot her s o urces a n d t he n tra nscri be d i nt o a file a n d f or mat 
a gree d u p o n b y G S K C H t o ide ntif y t he s u bject a n d ti me p o i nt refere nce d i n t he C R F a n d/ or 
pr ot oc ol . 
A n a gree d u p o n q ualit y c o ntr ol pr ocess is perf or me d a gai nst t he tra nscri be d data t o t he s o urce t o 
e ns ure t he acc urac y of t he tra nscript i on. T he tra nscri be d data is tra ns mitte d i n a n a gree d u p o n 
f or mat t o G S K C H via sec ure d we b p ortal or C D/ D V D via mail carrier wit h trac ki n g ca pa bilit ies. 
Pr o per rec o nciliat i on will be perf or me d bet wee n t he tra nscri be d data a n d t he cli nical data base t o 
e ns ure s u bject a n d ti me p oi nt refere nce d i n t he Cli nical Data base matc h bef ore Cli nical Data b ase 
Freeze (l oc ki n g of t he data base) ca n occ ur.
9. S T A TI S TI C A L C O N SI D E R A TI O N S A N D D A T A A N A L Y S E S
9. 1 S a m ple Size Deter mi n ati o n
T he first pri mar y o bject i ve f or t his st u d y is c ha n ges i n s-C T X -1 le vels. Na yl or et al. ( 2 0 1 5) use d 
b o ne t ur n o ver mar kers t o i de nt if y w o me n w h o res p o n de d t o bis p h os p h o nate treat me nt f or 
os te o p or osis. T he c ha n ge i n C T X wit h rise dr o nate (a b o ve t he effect of t he calci u m a n d vita mi n 
D s u p pl e me nt) was 3 0 %. T h us, we ca n sa y t hat a 3 0 % re d uctio n has bee n s h o w n t o be ass ociate d 
wi t h a re d uctio n i n fract ures. He nce, a re d ucti o n of 2 0 % i n test pr o d uct as c o m pare d t o place b o 
c o uld be c o nsi dere d as a cli nicall y si g nifica nt differe nce. 
Esti mates of mea n s-C T X -1 a n d varia bilit y fr om Kr u ger et al, 2 0 0 6 were as f oll o ws:
Esti mates of s-C T X -1 a n d varia bilit y fr om Kr u ger et al, 2 0 0 6 ( Mea n ± S D 1)
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 5 9 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 6 0 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

E n d p oi nt
Test pr o d uct
C o ntr ol Pr o d uct
C T X - 1
Baseli ne
0. 4 5 ± 0. 1 6 6
0. 4 4 ± 0. 0 3 2
P os t-Baseli ne 
( Wee k 1 6)
0. 3 0 ± 0. 0 9 4
0. 4 6 ± 0. 0 9 2
C ha n ge fr o m baseli ne
-0. 1 5 ± 0. 1 4 4
0. 0 2 ± 0. 1 4 2
1: S E val ues were re p orte d i n t he pa per. S D was calc ulate d as S E * S Q R T ( N).
S D val ues f or c ha n ge fr o m baseli ne were n ot re p orte d i n t he pa per. T hese were calc ulate d usi n g 
f oll owi n g f or m ula c o nsi deri n g c orrelat i on c o efficie nt bet wee n baseli ne a n d p ost -baseli ne val ues 
as 0. 5: 
S D E, C ha n ge = S D f or c ha n ge fr o m baseli ne
S D E, Baseli ne = S D f or baseli ne
S D E,fi nal = S D f or p ost -baseli ne
C orr = c orrelati o n c oefficie nt bet wee n baseli ne a n d fi nal val ues
C o nsi deri n g si milar ba seli ne val ues a n d 2 0 % cli nicall y rele va nt decrease i n test pr o d uct (l o wer 
val ues are better) fr o m baseli ne, -0. 0 9 will be use d as c ha n ge fr o m baseli ne val ue i n test pr o d uct. 
T his gi ves a treat me nt differe nce of - 0. 1 1.
Base d o n t he a b o ve est i mates of treat me nt differe nce a n d ta ki n g t he lar ger esti mate f or 
varia bilit y (i.e S D = 0. 1 4 4), to be a ble t o ac hie ve 9 0 % p o wer, 4 4 partici pa nts per treat me nt ar m 
( T otal =8 8 ) will be re q uire d t o c o mplete t he st u d y . T his ass u mes 0. 0 2 5 % l e vel of si g nifica nce 
(t w o taile d t-test).
T o all o w f or 2 0 % dr o p -o ut rate, a t otal of 5 4 partici pa nts ( T otal= 1 0 8) will be ra n d o mise d per 
treat me nt ar m.
T he c o -pri mar y o bject i ve f or t his st u d y is c ha n ges i n ( c- OC/ u c- OC) le vels. Fr o m Bi n kle y et al . 
t he f o ll owi n g data rel ate d t o t he e n d p oi n t was recei ve d. 
Fr o m  t he esti mates of % uc -O C , a n d T otal O C fr o m Bi n kle y  et al ( Mea n), t he esti mates of c - OC 
ha ve bee n calc ulate d. Fr o m t he a vaila ble data t he f oll o wi n g ta ble has bee n ta b ulate d.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 6 0 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 6 1 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

E n d p oi nt
Test pr o d uct
C o ntr ol Pr o d uct
c- OC/ u c- O C
Baseli ne
1 1. 7 2 0 6
1 1. 9 6
P os t-Baseli ne 
( Wee k 2)
3 1. 8 6 8
1 8. 6 0
C ha n ge fr o m baseli ne
2 0. 1 4
7. 5 3
C o nsi deri n g t he delta val ue as 1 2. 5 a n d t he S D as 1 3 usi n g Ta yl or series e x pa nsi o n t he sa m ple 
size to be a ble t o ac hie ve 9 0 % p o wer, 3 0 partici pa nts per treat me nt ar m ( T otal = 6 0 ) will be 
re q uire d t o c o mplete t he st u d y . T his ass u mes 0. 0 2 5 % l e vel of si g nifica nce (t w o taile d t -test).
T o all o w f or 2 0 % dr o p -o ut rate, a t otal of 3 6 partici pa nts ( T otal= 7 2) will be ra n d o mise d per 
treat me nt ar m.
H o we ver, t he s a mple size f or t he first pri mar y  e n d p oi nt is lar ger s o t he sa m ple size will be 
re q uir e d for t hi s st u d y is 1 0 8 i n t otal.
T he sa m ple size is base d o n t he pri mar y e n d p o i nt. N o sa m ple size c o nsi derati o ns ha ve bee n 
ta ke n i nt o acc o u nt for sec o n dar y  o bjecti ves.
A p pr o xi matel y  1 3 5 parti ci pa nts will be scree ne d t o ra n d o mise a p pr o xi matel y 1 0 8 part ici pa nts i n 
or der t o o btai n 8 8 parti ci pa nts c o mplet i n g t he st u d y.
F o ll owi n g ass u m pt i ons ha ve bee n ta ke n f or sa m ple size esti mat i on:
Esti mates of s-C T X -1 will be si milar i n I n dia n W o me n as c o m pare d t o Ne w Zeala n d P o p ulat i on 
( Kr u ger et al, 2 0 0 6).
Pr o d uct use d i n Kr u ger et al, 2 0 0 6 a n d i n t he pr o p ose d st u d y  will pr o vi de si milar esti mates of s-
C T X - 1.
V al ues at 6 m o nt hs i n t he pr o p ose d st u d y  will be si milar t o val ues at 4 m o nt hs fr o m Kr u ger et al, 
2 0 0 6.
W o me n 2 5 - 3 5 years o l d will ha ve si milar esti mates of s-C T X -1 as 3 6 - 45 y ears old f r o m Kr u ger 
et al.
Vi ta mi n K s u p ple me ntati o n re d uces ser u m c o nce ntrati o ns of u n der car b o x ylate d oste ocalci n i n 
healt h y y o u n g a n d el derl y a d ults fr o m Bi n kle y  et al.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 6 1 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 6 2 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

9. 2. Ge ner al C o nsi der ati o ns
9. 2. 1. Defi niti o n of A n al ysis P o p ul ati o ns
All a nal yses of safety will be m a de o n t he safet y p o p ul at i on w hic h will be defi ne d as all s u bjects 
w h o are ra n d o mize d a n d ha ve recei ve d at least o ne d ose of st u d y treat me nt.  T he safet y 
p o p ul at i on will be a nal yze d as per treat me nt recei ve d.
T he i nte nt -t o-treat (I T T) p o p ulati on w hic h will be defi ne d as all ra n d o mize d s u bjects wi t h at 
least o ne p ost treat me nt efficac y assess me nt.
T he pre -pr ot oc ol ( P P) p o p ulat i on is defi ne d as t h ose s u bjects i n t he I T T p o p ulati on f or w h om all 
p ost baseli ne effica c y meas ures are n ot dee me d t o be affecte d b y pr ot oc ol viol atio ns.
Stati stical a nal yses of t he efficac y para meters will be base d o n t he I T T p o p ulati on. T he P P 
a nal ysis will be perf or me d f or t he pri mar y e n d p o i nt if m ore t ha n 1 0 % of t he s u bjects i n t he I T T 
p o p ulat i on are re m o ve d fr o m  t he P P p o p ulatio n. P ost baseli ne efficac y assess me nts dee me d t o be 
affecte d b y pr ot oc ol viol at i ons will be re m o ve d f or t he per -pr ot oc ol a nal ysis.
9. 2. 2. E xcl usi o n of D at a fr o m A n al ysis
T he f o ll owi n g will be re vie we d a n d t h ose pr ot oc ol vi o lati ons c o nsi dere d t o affect efficac y  
assess me nts will lea d t o e xcl usi o n of eit her s u bject or data fr o m P P a nal yses:
Vi ol at i on of i ncl usi on or e xcl usi o n cri t eria
Si g nifica nt n o n c o m plia nce wi t h assi g ne d treat me nt
Efficac y assess me nts o utsi de t he s pecifie d ti me wi n d o ws
Use of pr o hi bite d treat me nt  or me dicatio n bef ore or d uri n g t he st u d y
A n y ot her reas o n i de nt ifie d w hic h ma y affect t he efficac y assess me nts.
All pr ot o c o l vi o lati ons a n d t heir i m pact o n efficac y  a nal yses will be deter mi ne d bet wee n t he 
Bi ost ati sticia n a n d Cli nical Researc h Di rect or or desi g nee, a hea d of data base l oc k a n d 
u n bli n di n g.
9. 2. 4. Criteri a f or Assessi n g Effic ac y
T he pri mar y  s uccess crit eria is t o o bser ve a statist icall y si g nifica ntl y greater re d ucti o n i n s-C T X -
1 f or t he test pr o d uct t ha n t he refere nce pr o d uct or t o o bser ve a statist icall y si g nifica ntl y greater 
i ncrease i n c- OC/ u c- OC f or t he test pr o d uct t ha n t he refere nce pr o d uct, after 6 m o nt hs of 
treat me nt.
9. 2. 5. Criteri a f or Assessi n g T oler a bilit y
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 6 2 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 6 3 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

T he assess me nt f or safet y will be base d o n t he A Es re p orte d b y s u bjects f oll o wi n g d osi n g wi t h 
st u d y tr e at me nt .
9. 3. St atistic al Met h o ds a n d A n al ytic al Pl a n
A d di tio n al details of t he pr o p ose d statistical a nal ysis will be d oc u me nte d i n t he statistical 
a nal ysis pla n ( S A P), w hic h will be writte n f o ll owi n g fi nalizat i on of t he pr ot oc ol a n d pri or t o 
st u d y u n bli n di n g.
9. 3. 1. De m o gr a p hic a n d B aseli ne C h ar acteristics
Descri pt i ve statistics ( n u m ber of s u bjects, mea n, sta n dar d de viat i on, me dia n, mi ni m u m a n d 
ma xi m u m f or c o nti n u o us varia bles, a n d fre q ue nc y a n d perce nta ge f or cate g orical varia bles) will 
be pr o vi de d f or de m o gra p hic a n d baseli ne data.
9 . 3.2. Pri m ar y A n al ysis
T he c o -pri mar y efficac y varia ble s of  t he st u d y are t he c ha n ge fr o m baseli ne i n b o ne res or pti o n 
mar ker (s -C T X -1) after 6 m o nt hs a n d t he c ha n ge fr o m baseli ne i n t he rati o of car b o x ylate d t o 
u n der car b o x ylate d ostea ocalci n (c -o C/ uc -O C ) after 6 mo nt hs . 
Eac h of t hese c o -pri mar y efficac y varia bles will be a nal yze d usi n g t he a nal ysis of c o varia nce 
( A N C O V A). T he A N C O V A will ha ve treat me nt as fi xe d effect a n d t he c orres p o n di n g baseli ne 
as c o variate. A dj uste d mea ns, 9 5 % c o nfi de nce i nter vals, wi t hi n treat me nt p-val ues f or eac h 
treat me nt gr o u p, treat me nt gr o u p differe nce, 9 5 % c o nfi de nce i nter val o f t he differe nce a n d t he 
bet wee n -treat me nt p-val ues base d o n t he statist ical mo d el  descri be d a b o ve will als o be 
prese nte d. Statistical tests t o c o m par e treat me nts will be t w o-side d a n d will e m pl o y a le vel of 
sig nifica nce of α = 0. 0 2 5.
T he setti n g of t he si g nifica nce le vel o f 0. 0 2 5 f or t hese 2 c o -pri mar y e n d p oi nts will e ns ure t hat 
t he o verall si g nifica nce le vel f or t he pri mar y e n d p oi nt is less t ha n or e q u al  t o 0. 0 5.
Ass u m pt i ons of n or malit y a n d h o m o ge nei t y of  varia nces will be e val uate d. If vi o lati o ns are 
o bser ve d t he n s uita ble data tra nsf or mat i ons will be trie d t o ac hie ve t he ass u m pti o ns. If s uita ble 
tra nsf or mati o ns ca n n ot be f o u n d, n o n-para metric a nal ys es will be perf or me d.
9. 3. 3. Sec o n d ar y A n al ysis
T he sec o n dar y  efficac y varia bles are:
C ha n ge fr o m baseli ne i n s -C T X -1 af ter 3 mo nt hs of treat m e nt
C ha n ge fr o m baseli ne i n c- O C/ uc -O C after 3 mo nt hs of treat m e nt
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 6 3 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 6 4 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

C ha n ge fr o m baseli ne i n uri nar y C T X -1 after 3 a n d 6 m o nt hs of treat me nt
C ha n ge fr o m baseli ne i n s -N T X -1 after 3 a n d 6 m o nt hs of treat me nt
C ha n ge fr o m baseli ne i n s -P 1 N P after 3 a n d 6 m o nt hs of treat me nt
C ha n ge fr o m baseli ne i n B S A P af ter 3 a n d 6 mo nt hs of treat m e nt
C ha n ge fr o m baseli ne i n s -P T H after 3 a n d 6 m o nt hs o f treat me nt
C ha n ge fr o m baseli ne i n Uri nar y Calci u m U SI N G C R E A TI NI N E I N S P O T T E S T T O 
N O R M A LI S E after 3 a n d 6 m o nt hs of treat me nt
C ha n ge fr o m baseli ne i n Ser u m Ca after 3 a n d 6 m o nt hs of treat me nt
C ha n ge fr o m baseli ne i n Ser u m P after 3 a n d 6 m o nt hs of treat me nt
C ha n ge fr o m baseli ne i n Ser u m A L P after 3 a n d 6 m o nt hs of treat me nt
C ha n ge fr o m baseli ne i n 2 5 O H D 3 after 3 a n d 6 m o nt hs of treat me nt
C ha n ge fr o m baseli ne i n Ser u m Se after 3 a n d 6 m o nt hs of treat me nt
C ha n ge fr o m baseli ne i n Ser u m P L A S M A Z n after 3 a n d 6 m o nt hs of treat me nt
C ha n ge fr o m baseli ne i n Ser u m F o lic aci d after 3 a n d 6 m o nt hs of treat me nt
C ha n ge fr o m baseli ne i n Ser u m P L A S M A B 6 after 3 a n d 6 m o nt hs of  treat me nt
C ha n ge fr o m baseli ne i n Ser u m B 1 2 after 3 a n d 6 m o nt hs oftreat me nt
Sec o n dar y  efficac y varia bles will be a nal yse d i n a si milar wa y as t he c o-pri mar y efficac y 
varia bles. T he o nl y  differe nce will be t hat all si g nifica nce le vels f or testi n g of h y pot h eses will be 
5 %.
9. 3. 3. E x pl or at or y A n al ysis
T he c ha n ge fr o m baseli ne i n I G F -1 af ter 3 a n d 6 m o nt hs of treat me nt will be a nal yse d i n a 
si milar wa y as t he c o-pri mar y efficac y varia bles, t he o nl y differe nce bei n g t hat t he si g nifica nce 
le vel will be 5 % f or all tests of h y p ot heses. 
9. 3. 4. S afet y A n al ysis
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 6 4 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 6 5 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

Treat me nt e mer ge nt A Es a n d treat me nt e mer ge nt treat me nt relate d A Es will be s u m marise d.  
A Es will be c o nsi dere d treat me nt e mer ge nt if t he y occ ur o n or after t he date a n d ti me of t he first 
d ose of st u d y  treat me nt .  
A Es will be liste d.  N o i nfere nt ial a nal yses will be perf or me d t o c o m pare treat me nts wit h res pect 
t o safety data.
1 0. S T U D Y G O V E R N A N C E C O N SI D E R A TI O N S
1 0. 1. P osti n g of I nf or m ati o n o n P u blicl y A v ail a ble Cli nic al Tri als Re gisters
St u d y  inf or m at i on fr om t his pr ot oc ol will be p oste d o n p u blicl y a vaila ble cli nical trial re gisters 
bef ore e nr oll me nt of s u bjects be gi ns.
1 0. 2. Re g ul at or y a n d Et hic al C o n si der ati o ns, I ncl u di n g t he I nf or me d C o nse nt
T he st u d y  will be c o n d ucte d i n acc or da nce wit h all a p plica ble re g ulat or y re q uire me nts, a n d wit h 
G S K p olic y.
T he st u d y  will als o be c o n d ucte d i n acc or da nce wit h I C H G o o d Cli nical Pract ice ( G C P), all 
a p plica ble s u bject pri vac y re q uire me nts, a n d t he g ui di n g pri nci ples o f t he c urre nt versi o n of t he 
Declarati o n of Helsi n ki.  T his i ncl u des, b ut is n ot li mite d t o, t he f o ll owi n g:
Bef ore i nit iati n g a trial, t he i n vest i gat or/i nstit uti o n s h o ul d ha ve writte n a n d date d 
a p pr o val/fa v ora ble o pi ni on fr o m t he I E C f or t he trial pr ot oc ol (i ncl u di n g a me n d me nts), writte n 
i nf or me d c o nse nt f or m, c o nse nt f or m u p dates, s u bject recr uitme nt  pr oce d ures (e. g., 
a d vert ise me nts), i n vesti gat or br oc h ure/ safet y state me nt (i ncl u di n g a n y u p dates) a n d a n y ot her 
wri tte n i nf or mat i on t o be pr o vi de d t o s u bjects. A letter or certificate of a p pr o val will be se nt b y  
t he i n vest i gat or t o t he s p o ns or pri or t o i nitiati on of t he st u d y , a n d als o w he n s ubse q ue nt 
a me n d me nts t o t he pr ot oc ol are ma de.
Si g ne d i nf or me d c o nse nt  t o be o btai ne d f or eac h s u bject bef ore partici pati o n i n t he st u d y  (a n d 
f or a me n d me nts as a p plica ble)
I n vesti gat or re p orti n g re q uire me nts (e. g. re p orti n g of A Es/ S A Es/ pr ot oc ol de viati ons t o I E C
G S K will pr o vi de f ull details o f t he a b o ve pr oce d ures, eit her ver ball y, i n writ i n g, or b ot h.
1 0. 3. Q u alit y C o ntr ol ( St u d y M o nit ori n g)
I n acc or da nce wit h a p plica ble re g ulati o ns i ncl u di n g G C P, a n d G S K pr oce d ures, G S K or 
desi g nee (i.e. t hir d part y ve n d or) mo ni t ors will c o ntact t he site prior t o t he start of t he st u d y  t o 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 6 5 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 6 6 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

re vie w wit h t he site staff t he pr ot oc ol, st u d y re q uir e me nts, a n d t heir res p o nsi bilities t o satisf y 
re g ulat or y, et hical, a n d G S K re q uire me nts.
W he n re vie wi n g data c o llecti on pr oce d ures, t he disc ussi o n will i ncl u de i de nt ificati o n, a gree me nt 
a n d d oc u me ntatio n of  data it e ms for w hic h t he C R F will ser ve as t he s o urce d oc u me nt.
G S K or desi g nee will m o nit or t he st u d y  a n d site acti vit y t o verif y t hat t he:
Data are a ut he ntic, acc urate, a n d c o m plete.
S af et y a n d rig hts of  s u bjects are bei n g pr otecte d.
St u d y  is c o n d ucte d i n acc or da nce wit h t he c urre nt l y a p pr o ve d pr ot oc ol a n d a n y ot her st u d y 
a gree me nts, G C P, a n d all a p plica ble re g ulat or y r e q uire me nts.
T he e xte nt a n d nat ure of m o ni t ori n g will be descri be d i n a writte n m o nit ori n g pla n o n file at 
G S K C H. T he i n vest i gat or ( or desi g nee) a grees t o all o w t he m o nit or direct access t o all rele va nt 
d oc u m e nts a n d a grees t o c o -o perate wi t h t h e mo ni t or t o e ns ure t hat a n y pr o ble ms detecte d i n t he
c o urse of t hese m o nit ori n g visit s are res ol ve d.
1 0. 4. Q u alit y Ass ur a nce
T o e ns ure c o m plia nce wit h G C P a n d all a p plica ble re g ulat or y  re q uire me nts, G S K ma y c o n d uct a 
q ualit y ass ura nce assess me nt a n d/ or a u dit of t he site rec or ds, a n d t he re g ulat or y a ge ncies ma y 
c o nd uct a re g ulat or y  ins pect i on at a n y  ti me d uri n g or after c o m pleti on of t he st u d y . 
I n t he e ve nt of a n assess me nt, a u dit or i ns pecti on, t he i n vest i gat or (a n d i nstitut i on) m ust a gree t o 
gra nt t he a d vis or(s), a u dit or(s) a n d i ns pect or(s) direct access t o all r ele va nt d oc u me nts a n d t o 
all ocate t heir ti me a n d t he ti me o f t heir staff t o disc uss t he c o n d uct of t he st u d y, a n y 
fi n di n gs/rele va nt iss ues a n d t o i m ple me nt a n y c orrecti ve a n d/ or pre ve ntati ve acti ons t o a d dress 
a n y fi n di n gs/iss ues i de nt ifie d.
T he s p o ns or wi ll be a vaila ble t o hel p i n vesti gat ors pre pare f or a n i ns pecti o n.
1 0. 5. C o n diti o ns f or Ter mi n ati n g t he St u d y
U p o n c o m plet i on or pre mat ure disc o nt i n uati on of t he st u d y , t he G S K C H mo ni t or will c o n d uct 
sit e clos ure acti vit ies with t he i n vest i gat or or si te staff, as a p pr o priate, i n acc or da nce with 
a p plica ble re g ulat i ons i ncl u di n g G C P, a n d G S K C H Sta n dar d O perati n g Pr oce d ures.
B ot h G S K C H a n d t he I n vest i gat or reser ve t he ri g ht t o te m p oraril y s us pe n d or pre mat urel y 
di sc o nti n ue t his st u d y at a n y time f or reas o ns i ncl u di n g, b ut n ot li mite d t o, safety or et hi cal 
iss ues or se vere n o n-c o m p lia nce. F or m ultice nter st u dies (if a p plica ble), t his ca n occ ur at o ne or 
m o re or at all sites.  
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 6 6 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 6 7 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

If t he trial is pre mat urel y ter mi nate d or s us pe n de d f or a n y reas o n, t he i n vesti gat or site s h o ul d 
pr o m ptl y i nf or m t he trial s u bjects a n d s h o ul d ass ure a p pr o priate t hera p y / fol l ow- u p f or t he 
s u bjects. W here re q uire d b y t he a p plica ble re g ulat or y re q uire me nts, G S K C H s h o ul d i nf or m t he 
re g ulat or y a ut h orit y(ies). 
I n a d diti on: 
If t he i n vesti gat or ter mi nates or s us pe n ds a trial wit h o ut pri or a gree me nt of G S K C H, t he 
i n vesti gat or site s h o ul d pr o m ptl y i nf or m t he s p o ns or a n d t he I E C, a n d s h o ul d pr o vi de t he 
s p o ns or a n d t he I E C a detaile d writte n e x pla nat i on of t he ter mi nat i on or s us pe nsi o n .
If t he G S K C H ter mi nates or s us pe n ds a trial, t he i n vesti gat or s h o uld pr o m pt l y i nf or m t he I E C
a n d pr o vi de t he I E C a detaile d writte n e x pla nat i on of  t he ter mi nati on or s us pe nsi o n. 
If t he I E C ter mi nates or s us pe n ds its a p pr o val/fa v ora ble o pi ni on of a tri al, t he i n vesti gat or s h o ul d 
pr o m ptl y n otif y t he G S K C H a n d pr o vi de G S K C H wit h a detaile d writte n e x pla nat i on of t he 
ter mi nati o n or s us pe nsi on.
1 0. 6 . Rec or ds Rete nti o n
F o ll owi n g cl os ure of t he st u d y , t he i n vesti gat or m ust mai ntai n all site st u d y rec or ds (e xce pt f or 
t hose re q ui re d b y lo c al  re g ulati ons t o be mai ntai ne d else w here), i n a safe a n d sec ure l ocati o n.  
T he rec or ds (st u d y / sit e master file) m ust be mai nt ai ne d t o all o w eas y a n d ti mel y retrie val, w he n 
nee de d (e. g., f or a G S K a u dit or re g ulat or y  ins pecti o n) a n d m ust be a vaila ble f or re vie w i n 
c o nju nct i on wi t h assess me nt of t he facility,  s u p p orti n g s yste ms, a n d rele va nt site staff.
W here per mitte d b y  lo c al  la ws/re g ulatio ns or i nsti t utio nal  p olic y, s o me or all of t hese rec or ds 
ca n be mai ntai ne d i n a f or mat ot her t ha n har d c o p y (e. g., micr o fic he, sca n ne d, electr o nic); 
h o we ver, ca uti o n nee ds t o be e xercise d bef ore s uc h act i on is ta ke n. 
T he i n vest i gat or m ust e ns ure t hat all re pr o d ucti o ns are le gi ble a n d are a tr ue a n d acc urate c o p y of 
t he origi nal a n d m eet accessi bilit y a n d retrie val sta n dar ds, i ncl u di n g re-ge nerat i n g a har d c o p y, if 
re q uire d.  F urt her m ore, t he i n vesti gat or m ust e ns ure t here is a n acce pta ble bac k-u p of  t hese 
re pr o d uctio ns a n d t hat a n acce pta ble q ualit y c o ntr ol pr ocess e xists f or ma ki n g t hese 
re pr o d uctio ns.
T he i n vest i gat or m ust ass ure t hat t he s u bject’s a n o n y mity will  b e mai ntai ne d.  O n C R Fs or ot her 
d oc u m e nts s u b mitte d t o G S K C H, s u bjects s h o ul d n ot be i de n tifie d b y t heir na mes or i nitials, b ut 
b y a n ide nt ificati on c o de. T he i n vest i gat or s h o ul d kee p a se parate l o g of s u bjects’ c o des, na mes 
a n d a d dresses.  D oc u me nts n ot f or s u b missi o n t o G S K C H, e. g. s u bjects’ writte n c o nse nt f or ms, 
s h o uld be mai ntai ne d b y t he i n vesti gat or i n strict c o nfi de nce.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 6 7 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 6 8 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

G S K will i nf or m t he i n vest i gat or of t he ti me peri o d f or retai ni n g t hese rec or ds t o c o m pl y with all 
a p plica ble re g ulat or y re q uire me nts ( G S K C H rec o m me n ds t hat d oc u me nts be ke pt f or 1 0 years). 
T he i n vest i gat or is als o re q uire d t o kee p s u bje ct ide nt ificati on c o des o n file f or at least 1 5 y ears 
after c o mplet i on or di sc o nti n uati on of t he st u d y . T he mi ni m u m rete nti o n ti me will meet t he 
strictest sta n dar d a p plica ble t o t hat site f or t he st u d y, as dictate d b y a n y inst ituti o nal  
re qui re me nts or lo c al  la ws or re g ulat i ons, G S K sta n dar ds/ pr oce d ures, a n d/ or i nst ituti o nal  
re q uire me nts.  
N o st u d y  d oc u me nt s h o ul d be destr o ye d wit ho ut a pri or wri tte n a gree me nt bet wee n G S K C H a n d 
t he i n vest i gat or. T he i n vesti gat or m ust n otif y G S K of a n y c ha n ges i n t he arc hi val arra n ge me nts, 
i ncl u di n g, b ut n ot li mite d t o, arc hi val at a n off-site facilit y or tra nsfer of o w ners hi p of t he rec or ds 
i n t he e ve nt t he i n vesti gat or is n o l o n ger ass ociate d wit h t he site.
1 0. 7 . Pr o visi o n of St u d y Res ults t o I n vesti g at ors, p osti n g of I nf or m ati o n o n P u blicl y
A v ail a ble Cli nic al Tri als Re gisters a n d P u blic ati o n
W here re q uire d b y  a p plica ble re g ulat or y re q uire me nts, a n i n vesti gat or si gnat or y  will be 
i de ntifie d f or t he a p pr o val of t he cli nical st u d y re p ort.  T he i n vesti gat or will be pr o vi de d 
reas o na ble access t o statistical ta bles, fi g ures, a n d rele va nt re p orts a n d will ha ve t he o p p ort u nit y 
t o re vie w t he c o mplete st u d y  res ults at a G SK site or ot her m ut uall y -a greea ble l ocat i on.
G S K will als o pr o vi de t he i n vest i gat or wit h t he f ull s u m mar y of t he st u d y res ults.  T he 
i n vesti gat or is e nc o ura ge d t o s hare t he s u m mar y res ults wit h t he st u d y s u bjects, as a p pr o priate.
T he pr oce d ures a n d ti mi n g f or p u blic discl os ure of t he res ults s u m mar y a n d f or de vel o p me nt of a 
ma n uscri pt f or p u blicati o n will be i n acc or da nce wit h G S K P olic y .
A ma n uscri pt will be pr o gresse d f or p u blicat i on i n t he scie nt ific literat ure if t he res ults pr o vi de 
i m p orta nt scie ntific or m e dical k n o wle d ge.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 6 8 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 6 9 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

1 1. R E F E R E N C E S
A bra ha m, G. E. T he I m p orta nce of Ma g nesi u m i n t he Ma na ge me nt of Pri mar y P ost me n o pa usal 
Oste o p or osi s. J. N utr. Me d . 1 9 9 1; 2 ( 2) : 1 6 5-1 7 8. 
A n derse n, R., M o l gaar d, C., S k o v gaar d, L. T., Br ot, C., Cas h ma n, K. D., Ja k o bse n, J., La m ber g -
Allar dt, C., O vese n, L. . Effect of vita mi n D s u p ple me ntati o n o n b o ne a n d vita mi n D stat us 
a mo n g pa kista ni i m mi gra nts i n de n mar k: A ra n d o mise d d o u ble -bli n de d place b o -c o nt r olle d 
i nter ve nt i on st u d y . Br J N utr. 2 0 0 8; 1 0 0( 1) : 1 9 7 -2 0 7.
Ar ya, V., B ha m bri, R., G o d b ole, M. M., & Mit hal, A. Vita mi n D stat us a n d its relat i ons hi p wit h 
b o ne mi neral de nsit y i n heal t h y asia n i n dia ns. Oste o p or osis I nt . 2 0 0 4; 1 5( 1) : 5 6 -6 1. 
Beasle y, J. M., L a Cr oi x, A. Z., Lars o n, J. C., H ua n g, Y., Ne u h o user, M. L., Ti n ker, L. F., Jac ks o n, 
R., S netselaar, L., J o h ns o n, K. C., Eat o n, C. B., a n d  Pre ntice, R. L.
Bi o m ar ker -cali brate d pr otei n i nta ke a n d b o ne healt h i n t he W ome n’ s Health I nit iati ve cli nical 
trials a n d o bser vatio n al  st u d y. A m. J. Cli n. N utr . 2 0 1 4; 9 9 : 9 3 4– 9 4 0.
Be ule ns, J. W., B ots, M. L., Ats ma, F., Barteli n k, M. L., Pr o k o p, M., Geleij nse, J. M., Witte ma n, 
J. C., Gr o b bee, D. E., Va n der Sc h o u w, Y. T. Hi g h dietar y me na q ui n o ne i nta ke is ass ociate d wit h 
re d uce d c or o nar y calcificati on. At her oscler osis. 2 0 0 9 A pr; 2 0 3 ( 2) : 4 8 9 – 4 9 3. 
Be ule ns, J. W., B o ot h, S. L., Va n de n He u vel , E. G.,  St oec kli n, E., Ba ka, A., Ver meer, C., T he 
r ole of me na q ui n o nes ( vita mi n K 2) i n h u ma n healt h. Br J N utr. 2 0 1 3 Oct ;1 1 0( 8): 1 3 5 7 - 1 3 6 8
Bi kle, D. D. Vi ta mi n D a n d B o ne . C urr Oste o p or os Re p . 2 0 1 2 J u ne; 1 0( 2): 1 5 1– 1 5 9.
B o o ne n, S. , Mari n, F., O ber ma yer -Pi etsc h, B., Si m ões, M. E., Bar ker, C., Glass, E. V., Ha dji, P., 
L y ritis, G., Oertel, H. , Nic kelse n, T., Mc Clos ke y , E. V. Effects of pre vi o us a ntires or pti ve 
t hera p y o n t he b o ne mi neral de nsity res p o nse t o t w o years of teri parati de treat me nt i n 
p ost m e n o pa usal w o me n wit h oste o p or osis. J Cli n E n d ocri n ol Met a b o 2 0 0 8 Mar ; 9 3( 3): 8 5 2 -
8 6 0. 
B o nj o ur, J. P., K o hrt, W., Le vasse ur, R., Warre n, M., W hit i n g, S., a n d Krae nzli n, M. 
Bi oc he mical  mar kers f or assess me nt of calci u m ec o n o m y a nd b o ne meta b o lis m: a p plicati o n i n 
cli nical trials fr o m p har mace ut ical a ge nts t o n utriti o nal pr o d ucts . Nut  Res. Re v. 2 0 1 4; 2 7 : 
2 5 2 – 2 6 7.
B o ot h S L, Br oe K E, Peters o n J W Ass ociat i ons bet wee n vita mi n K bi oc he mical meas ures a n d 
b o ne mi neral de nsit y i n me n a n d w o m e n. J Cli n E n d ocri n ol Met a b. 2 0 0 4 Oct; 8 9 ( 1 0) : 4 9 0 4 -
4 9 0 9.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 6 9 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 7 0 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

Br u y ère, O.,  Rizz oli, R.,  C o xa m, V., A v o uac, B., C he valier, T., Fa bie n -S o ul é, V., Ka nis, J. A., 
Ka uf ma n, J. M., Ts o u der os, Y.,  Re gi nster, J. Y. Assess me nt of healt h clai ms i n t he fiel d o f b o ne: 
a vie w of t he Gr o u p f or t he Res pect of Et hics a n d E xcelle nce i n Scie nce ( G R E E S). Oste o p or os 
I nt 2 0 1 2, 2 3: 1 9 3 – 1 9 9.
Ca ule y  J A, Da niels o n M E, Gree n dale G A, Fi n kelstei n J S, C ha n g Y F, L o J C, Cra n dall CJ, Neer 
R M, R u p pert K, Me y n L, Prairie B A, S o wers M R. B o ne Res or pti o n a n d fract ure acr oss t he 
me n o pa usal tra nsit i on: t he St u d y  of Wo me n’s Healt h Acr oss t he Nati o n. Me n o p a use
2 0 1 2 
N o v; 1 9( 1 1) : 1 2 0 0 -1 2 0 7.
C hi n, K. Y. a n d  I ma -Ni r wa na, S. T he Effects of α-T oc o p her ol  o n B o ne: A D o u ble-E d ge d 
S w or d? N utrie nts 2 0 1 4 A pr 1 0; 6( 4) : 1 4 2 4 - 1 4 4 1
C oc ka y ne, S., A da ms o n, J., La n ha m -Ne w., S, S hearer, M.J., Gil b o d y , S., T or gers o n, D.J. Vita mi n 
K a n d t he pre ve nt i on of fract ures: s y ste matic re vie w a n d meta-a nal ysis of ra n d o mize d c o ntr olle d 
trials. Arc h I nter n Me d. 2 0 0 6 J u n 2 6; 1 6 6 ( 1 2): 1 2 5 6 – 1 2 6 1. 
Dal meijer, G. W., Va n der Sc h o u w, Y. T., Ma g dele y ns, E., A h me d, N., Ver meer, C., Be ule ns, 
J. W. T he effect of me na q ui n one -7 s u p ple me ntati o n o n ci rc ulati n g s pecies of matri x Gla pr otei n. 
At her oscler osis 2 0 1 2 Dec; 2 2 5( 2): 3 9 7- 4 0 2.
Darli n g, A. L., Mil l war d, D. J., T or gers o n, D. J., He witt, C. E., & La n ha m-Ne w, S. A. Dietar y  
pr otei n a n d b o ne healt h: A s yste matic re vie w a n d meta -a nal ysis. A m J  Cli n N utr. 2 0 0 9 Dec; 
9 0( 6) : 1 6 7 4 -1 6 9 2. 
Da ws o n -H u g hes B, Harri s S S. Calci u m int a ke i nfl ue nces t he ass ociat i on of pr otei n i nta ke wit h 
rates of b o ne l oss i n el derl y me n a n d w ome n. A m J Cli n N utr 2 0 0 2 A pr; 7 5 ( 4): 7 7 3 - 7 7 9.
Del mas P D, Eastell R, Gar ner o P, Sei bel MJ, Ste pa n J. T he use of bi oc he mical m ar kers of b o ne 
meta b o lis m i n oste o p or osis. Oste o p or os I nt 2 0 0 0; 1 1 S u p pl 6: S 2 – S 1 7. 
Desai M. P, K hat k hata y M.I, B ha n u Pra kas h K. V , Sa var de kar L. S a n d S ha h R. S, A nsari Z. 
H or m o nal  pr ofiles a n d bi oc he mical i n dices of b o ne t ur n o ver i n I n dia n w o me n. Oste o p or os I nt  
2 0 0 7; 1 8: 9 2 3 – 9 2 9. 
De S o uza Ge nar o, P. a n d  Marti ni, L. A. Effect of pr otei n i nta ke o n b o ne a n d m uscle mass i n t he 
elderl y . N ut Re v 2 0 1 0 ; 6 8( 1 0), 6 1 6 -6 2 3.
D ha n wal D K, Sa h o o S, Ga uta m V K, Sa ha R. Hi p fract ure patie nts i n I n dia ha ve vit a mi n D 
deficie nc y a n d sec o n dar y  h y per parat h yr oidis m . Oste o p or os I nt 2 0 1 3; 2 4: 5 5 3 -5 5 7. 
Di pl oc k , A. T. A nt i oxi da nt n utrie nts a n d disease pre ve nt i on: a n o ver vie w. A m J Cli n N utr.
1 9 9 1 Ja n; 5 3 ( 1 S u p pl): 1 8 9 S- 1 9 3 S.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 7 0 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 7 1 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

El -Hajj F ulei ha n, G., B o uill o n, R., Clar ke, B., C ha k ht o ura, M ., C o o per, C., Mc Cl u n g, M., & 
Si n g h, R. J. Ser u m 2 5 -h y dr o x y vita mi n D le vels: Varia bilit y,  k n o wle d ge ga ps, a n d t he c o nce pt of 
a desira ble ra n ge. J B o ne Mi n Res . 2 0 1 5 J ul; 3 0( 7) : 1 1 1 9 -1 1 3 3. 
E ma us , N. , Gjes dal, C. G., Al mas, B. Vita mi n K 2 s u p ple me ntati o n d oes n ot i nfl ue nce b o ne l oss 
i n earl y me n o pa usal w o me n: a ra n d o mise d d o u ble -bli n d place b o -c o ntr olle d trial. Oste o p or os I nt 
2 0 0 9; 2 1 : 1 7 3 1 -1 7 4 0.
Ferrar, L., Va n der Hee, R. M., Berr y , M., Wats o n, C., Miret, S., Wil ki ns o n, J., Bra d b ur n, M.,  
Eastell, R.  Effects of calci u m -f ortifie d ice crea m o n mar kers of b o ne health. Oste o p or osis I nt
2 0 1 0 Oct ; 2 2( 1 0) : 2 7 2 1 - 2 7 3 1.
Fre u de n hei m, J. L., J o h ns o n, N. E., & S mit h, E. L. Rel at i ons hi ps bet wee n us ual n ut rie nt i nta ke 
a n d b o ne-mi neral c o nte nt of w o me n 3 5 -6 5 y ears of a ge: L o n git u di nal a n d cr oss-secti o nal 
a nal ysis. A m J Cli n N utr 1 9 8 6; 4 4( 6) : 8 6 3 - 8 7 6.
F ujita, Y., I ki M., Ta ma ki, J., K o u da, K., Y ura, A., Ka d o wa ki, E., Sat o, Y. , M o o n, J. S., 
T o mi o ka, K., O ka m ot o, N., K ur u mata ni, N. Ass ociat i on bet wee n vita mi n K i nta ke fr o m 
fer me nte d s o y bea ns, natt o, a n d b o ne mi neral de nsit y in el derl y  Ja pa nese me n: t he F uji wara -k y o 
Oste o p or osi s Ris k i n Me n ( F O R M E N) st u d y. Oste o p or os I nt. 2 0 1 2 Fe b; 2 3( 2): 7 0 5 -7 1 4.
Ga n d hi a n d S h u k la. E val uati on of B M D of w o me n a b o ve 4 0 y ears of a ge. J O bstet G y nec ol 
I n di a 2 0 0 5; 5 5 ( 3): 2 6 5 -2 6 7. 
Gar ner o P, Ha uss her E, C ha p u y  M C, Marcelli C, Gra n djea n H, M uller C et al. Mar kers of b o ne 
res or ptio n pre di cts hi p fract ure ris k i n el derl y w o me n. T he E PI DO S Pr os pecti ve St u d y . J B o ne 
Mi n Res 1 9 9 6; 1 1: 1 5 3 1 – 1 5 3 8.
G el eij nse, J. M., Ver meer, C., Gr o b bee, D. E., Sc h ur gers L.J., K na pe n, M/ H., Va n der Meer I M, 
H of ma n A, Witte ma n, J. C. Dietar y  int a ke of me na q ui n o ne is ass ociate d wit h a re d uce d ris k of 
c or o nar y heart disease: t he R otter da m St u d y. J N utr 2 0 0 4 N o v; 1 3 4 ( 1 1): 3 1 0 0 – 3 1 0 5. 
Hall, S. L., & Gree n dale, G. A.  T he relat i on of dietar y  vita mi n C i nta ke t o b o ne mi neral de nsity:  
Res ults fr o m t he P E PI st u d y. C alcif Tiss ue I nt 1 9 9 8 Se p; 6 3( 3): 1 8 3 - 1 8 9.
Hali o ua L a n d A n ders o n JJ. Lifeti me calci u m i nta ke a n d p h ysical act i vity ha bits: i n de pe n de nt 
a n d c o m bi ne d effects o n t he ra dial b o ne of healt h y pre me n o pa usal Ca ucasia n w o me n. A m J 
Cli n N utr . 1 9 8 9 Mar; 4 9( 3): 5 3 4-5 4 1.
Ha mi di, M. S; C ore y , P. N.; C he u n g, A. M. Effects of vita mi n E o n b o ne t ur n o ver mar kers a m o n g 
us p ost me n o pa usal w o me n. J. B o ne Mi ner. Res. 2 0 1 2, 2 7, 1 3 6 8 – 1 3 8 0.
Hari nara ya n C V, Ra mala ks h mi T, Prasa d U V. Hi g h Pre vale nce of l o w dietar y
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 7 1 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 7 2 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

calci u m, hi g h p h ytate c o ns u mpt i on a n d vita mi n D deficie nc y  in heal t hy s o ut h 
I n dia ns. A m J Cli n N utr 2 0 0 7; 8 5: 1 0 6 2 -1 0 6 7. 
Hea ne y  R. P. Vita mi n D i n Healt h a n d Disease. Cli n J A m S oc Ne p hr ol . 2 0 0 8 Se p; 3( 5): 1 5 3 5-
1 5 4 1
Hea ne y  R P, D o well M S, Hale C A, Be n dic h A. Calci u m a bs or pti o n varies withi n t he refere nce 
ra n ge f or ser u m 2 5-h y dr o x y vita m i n D. J A m C oll N utr 2 0 0 3a; 2 2: 1 4 2 – 6. 
Hea ne y  R P. Vita mi n D de pletio n a n d effect i ve calci u m a bs or pti o n. J B o ne Mi ner Res 
2 0 0 3 b; 1 8: 1 3 4 2 (letter). 
Herz ber g, M., F ol des, J., Stei n ber g, R., & Me nczel, J. ( 1 9 9 0). Zi nc e xcret i on i n oste o p or otic 
w o m e n. J B o ne Mi n Res . 1 9 9 0; 5( 3) : 2 5 1 -2 5 7.
H ol stei n J H, Herr ma n n M, S plett C, Herr ma n n W, Garcia P, Hist i n g T, Grae ber S, O n g M F, 
K urz K, Sie bel T, Me n ger M D, P o hle ma n n T. L o w ser u m f o late a n d vita mi n B-6 are ass oci ate d 
wi t h a n altere d ca ncell o us b o ne str uct ure i n h u ma ns. A m J Cli n N utr . 2 0 0 9 N o v; 9 0( 5): 1 4 4 0-
1 4 4 5
H o ut k o o per L B, Rite n ba u g h C, Aic ki n M, L o h ma n T G, G oi n g S B, We ber J L, Grea ves K A, 
B o y de n T W, Pa m e nter R W, Hall M C: N utrie nts, b o d y c o mp osi tio n a n d e xercise are relate d t o 
c ha n ge i n b o ne mi neral de nsit y i n pre me n o pa usal w o m e n. J N utr. 1 9 9 5; 1 2 5: 1 2 2 9 – 1 2 3 7
H oe g, A., G o ga k os, A., M ur p h y , E., M ueller, S., K ö hrle, J.,  Reid, D., Gl üer, C. C,  Fel se n ber g, 
D., R o u x, C. , Eastell, R., Sc h o m b ur g, L., Willia ms, G. R. B o ne t ur n o ver a n d b o ne mi neral 
de nsit y are i n de pe n de nt l y relate d t o sele ni u m stat us i n healt h y e ut h yr oi d p ost me n o pa usal 
w o m e n. J Cli n E n d ocri n Met a b 2 0 1 2 N o v; 9 7 ( 1 1) : 4 0 6 1 - 4 0 7 0.
I ki , M., M orita, A., I ke da, Y., Sat o, Y., A ki ba, T., Mats u m ot o, T., Nis hi n o, H., Ka ga mi m ori, S., 
Ka ga wa, Y., Y o nes hi ma, H.  Bi oc he mical mar kers of b o ne t ur n o ver pre dict b o ne l oss i n 
peri me n o pa usal w o me n b ut n ot i n p ost me n o pa usal w o me n- t he Ja pa nese P o p ulat io n -base d 
Oste o p or osi s (J P O S) C o h ort St u d y. Oste o p or os I nt 2 0 0 6 ; 1 7: 1 0 8 6 – 1 0 9 5.
I ke da Y, I ki M, M orita A et al. I nta ke of fer me nte d s o y bea ns, natt o, is ass ociate d wit h re d uce d 
b o ne l oss i n p ost me n o pa usal w o me n: Ja pa nese P o p ulat i on- Base d Oste o p or osis (J P O S) St u d y . J 
N utr 2 0 0 6 Ma y; 1 3 6 ( 5) : 1 3 2 3 -1 3 2 8.
Je, S. H., J o o, N.S., C h o i,B. H., Ki m, K. M., Ki m, B. T., Par k, S. B., C h o, D. Y., Ki m, K. N., Lee, D.   
Vi ta mi n K s u p ple me nt al o n g wit h vita mi n D a n d calci u m re d uce d ser u m c o nce ntrati o n of 
u n dercar b o x ylate d oste ocalci n w hile i ncreasi n g b o ne mi neral de nsit y i n k orea n p ost me n o pa usal 
w o m e n o ver si xt y- years -ol d. J K ore a n Me d Sci 2 0 1 1 A u g; 2 6( 8) : 1 0 9 3 -1 0 9 8.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 7 2 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 7 3 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

Ka da m N, C hi pl o n kar S, K ha dil kar A, Di vate U, k ha dil kar V. L o w b o ne mass i n ur ba n I n dia n 
w o m e n a b o ve 4 0 years of a ge: pre vale nce a n d ris k fact ors. G y nec ol E n d ocri n ol 2 0 1 0 Dec; 
2 6( 1 2): 9 0 9 - 9 1 7.
Kats u ya ma, H., I de g uc hi, S., F u k u na ga, M., Saij o h, K., S u na mi, S. Us ual dietar y i nta ke of 
fer me nte d s o y bea ns ( Natt o) is ass ociate d wit h b o ne mi neral de nsity i n pre me n o pa usal w ome n. J 
N utr Sci Vit a mi n ol ( T o k y o) 2 0 0 2 J u n; 4 8( 3) : 2 0 7 - 2 1 5.
Kerstetter, J. E., O' Bri e n, K. O. , I n s o g n a, K. L. Dietar y  pr otei n, calci u m meta b olis m, a n d s keletal 
h o me o stasis re visite d. A m J Cli n N utr 2 0 0 3; 7 8 ( 3 S U P P L.) : 5 8 4 S - 5 9 2 S
K ha d ga wat R, Mar wa ha R K, Gar g M K, Ra m ot R, O ber o i A K, Sree ni vas V, et al. I mpact of 
vit a mi n D f ortifie d mil k s u p ple me ntati o n o n vita mi n D stat us of healt h y sc h o ol c hil dre n. 
Oste o p or os I nt 2 0 1 3; 2 4: 2 3 3 5 -2 3 4 3. 
Ki n d mar k, A., T or ma, H., J o ha nss o n, A., Lj u n g hall, S., Mel h us, H. Re verse tra nscri pt i on-
p ol y merase c hai n react i on assa y de m o nstrates t hat t he 9 -cis reti n o ic aci d rece pt or al p ha is 
e x presse d i n h u ma n oste o blasts. Bi oc he m Bi o p h ys Res C o m m u n. 1 9 9 3; 1 9 2: 1 3 6 7 – 1 3 7 2.
K na pe n, M. H., Dr u m me n, N. E., S mit, E., Ver meer, C., T he u wisse n, E. T hree -year l o w -d ose 
me na q ui n o ne -7 s u p ple me ntati o n hel ps decrease b o ne l oss i n healt h y p ost me n o pa usal w o me n. 
Oste o p or os I nt 2 0 1 3 Se p; 2 4 ( 9): 2 4 9 9 -2 5 0 7.
K na pe n , M. H.J., Braa m, L. A.J. L. M., Te u nisse n , K.J., Z wijse n, R. M. L., T he u wisse n , E. a n d 
V er m eer , C. Y o g urt dri n k f ortifie d wit h me na q ui n one -7 i m pr o ves vita mi n K stat us i n a healt h y 
p o p ul at i on. J N S, 2 0 1 5, 4, e 3 5 d oi: 1 0. 1 0 1 7/ j ns. 2 0 1 5. 2 5. 
Kr u ger M C, B o ot h C L, C oa d J, Sc h oll u m L M, S herl oc k B K, a n d S hearer MJ.  Effect of calci u m 
f ortifie d mil k s u p ple me ntati o n wit h or wit h o ut vita mi n K o n bi oc he mical mar kers of b o ne 
t ur n o ver i n pre me n o pa usal w ome n.  N utriti o n 2 0 0 6 N o v - Dec; 2 2 ( 1 1-1 2): 1 1 2 0 – 1 1 2 8.
Mac ha d o, A. B. D. C., Ha n n o n , R., & Eastell, R. ( 1 9 9 9). M o nit ori n g ale n dr o nate t hera p y for 
os te o p or osis. J B o ne Mi n er Res. 1 9 9 9 A pr; 1 4( 4) : 6 0 2-6 0 8. 
Mars hall D, J o h nell O, We del H. Meta- a nal ysis o f h o w well meas ures of b o ne mi neral de nsit y 
pre di ct occ urre nce of oste o p or otic fract ur es. B M J 1 9 9 6 Ma y  1 8 ; 3 1 2 ( 7 0 4 1): 1 2 5 4-1 2 5 9. 
Maj  Agar wal, T a n d Bri g b Ver m a, A. k. Cr oss secti o nal st u d y of oste o p or osis a mo n g w o m e n. 
Me d J Ar me d F orces I n di a
2 0 1 3; 6 9( 2): 1 6 8 – 1 7 1.
Mel h us, H., Mic haelss o n, K., Ki n d mar k, A., Ber gstr o m, R., H ol m ber g, L., Mall mi n, H., W ol k, 
A., Lj u n g hall , S. E xcessi ve diet ar y int a ke of vita mi n A is ass ociate d wit h re d uce d b o ne mi neral 
de nsit y a n d i ncrease d ris k f or hi p fract ure. A n n I nter n Me d. 1 9 9 8 N o v 1 5; 1 2 9( 1 0): 7 7 0 – 7 7 8.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 7 3 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 7 4 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

Mel h us, H., Mic haelss o n, K.; H ol m ber g, L.; W ol k, A.; Lj u n g hall , S. S mo ki n g, a nt i oxi da nt 
vit a mi ns, a n d t he ris k o f hi p fract ure. J. B o ne Mi ner. Res. 1 9 9 9; 1 4: 1 2 9 – 1 3 5.
Mi tt al, A., D hi n gra, V., La u, E.,  T he Asia n A u dit: E pi de mi ol og y , c osts a n d b ur de n of 
os te o p or osis i n Asia. I nt Oste o p or os F o u n d ati o n 2 0 0 9; 2 4 - 2 9.
M ithal A, Ba nsal B, K yer C. S, E beli n g P. I . T he Asia- Pacific Re gi o nal A u di t-E pi de mi ol o g y, 
C osts, a n d B ur de n of Oste o p or osis i n I n dia 2 0 1 3: A re p ort of I nter nat i onal Oste o p or osis 
F o u n dat i on. I n di a n J E n d ocri n ol Met a b. 2 0 1 4; 1 8( 4): 4 4 9– 4 5 4.
M orri s H A. Vita mi n D Acti vities f or Healt h O utc o mes. A n n L a b Me d 2 0 1 4; 3 4: 1 8 1 - 1 8 6.
M osc h o nis, G., Ka nella kis, S., Pa pai oa n n o u, N., Sc haafs ma, A., Ma ni os, Y. P ossi ble site -
s pecific effect of a n i nter ve nt i on c o m bi ni n g n utrit i o n a n d lifestyle c o u nselli n g wit h c o ns u m pti o n 
of  fortifie d dair y pr o d ucts o n b o ne mass: t he P ost me n o pa usal Healt h St u d y  II. J B o ne Mi ner 
Met a b 2 0 1 1 J ul ; 2 9( 4) : 5 0 1 - 5 0 6.
M u k herj ee A & Mat h ur A. P o p ulatio n base d refere nce sta n dar ds of pea k b o ne mi neral de nsit y of  
I n dia n males a n d fe males: An I C M R m ult i-ce nter tas k f orce st u d y . I C M R B ulleti n 2 0 1 1; 4 1 ( 4) 
: 2 1- 2 8.
Na yl or, K. E., Jac q ues, R. M., Pa g gi osi, M., G ossiel, F., Peel, N. F. A., Mc Cl os ke y , E. V., 
Wals h, J. S., Eastell, R. Res p o nse of b o ne t ur n o ver mar kers t o t hree oral bis p h os p h o nate 
thera pies i n p ost me n o pa usal oste o p or osis: T he T RI O st u d y  Oste o p or os I nt   2 0 1 5 Ma y 2 0. d oi
1 0. 1 0 0 7/s 0 0 1 9 8 - 0 1 5- 3 1 4 5-7 
Ne w, S. A., B olt o n -S mit h, C., Gr u b b, D. A., & Rei d, D. M. N utrit i onal i nfl ue nces o n b o ne 
mi neral de nsit y:  A cr oss-secti onal st u d y in pre me n o pa usal w o me n. A m J Cli n N utr 1 9 9 7 ; 6 5( 6) 
: 1 8 3 1- 1 8 3 9.
Ni else n, F. H., L u kas ki, H. C., J o h ns o n, L. K., & R o u g hea d, Z. K. ( 2 0 1 1). Re p orte d zi nc, b ut n ot 
c o p per, i nta kes i nfl ue nce w h o le-b o d y  bo ne de nsit y, mi neral c o nte nt a n d T sc ore res p o nses t o 
zi nc a n d c o p p er s u p ple me ntati o n i n healt h y p ost me n o pa usal w o me n. Br J N utr . 2 0 1 1 Dec; 
1 0 6( 1 2): 1 8 7 2 - 1 8 7 9.
N or di n B E. Calci u m a n d oste o p or osis. N utriti o n 1 9 9 7; 1 3: 6 6 4 -6 8 6. 
Ost ma n, B.; Mic haelss o n, K.; Hel merss o n, J.; B y ber g, L.; Gee b or g, R.; Mel h us, H.; Bas u, S. 
O xi dat ive stress a n d b o ne mi neral de nsit y i n el derl y me n: A nti oxi da nt acti vit y of α -t o co p her ol . 
Free R a dic. Bi ol. Me d. 2 0 0 9, 4 7, 6 6 8 – 6 7 3
R o gers, A., Gl o ver, S. J., & Eastell, R. A ra n d o mise d, d o u ble -bli n de d, place b o -c o ntr olle d, trial 
t o deter mi ne t he i n di vi d ual res p o nse i n b o ne t ur n o ver mar kers t o las of o xife ne t hera p y . B o ne. 
2 0 0 9; 4 5( 6): 1 0 4 4 -1 0 5 2.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 7 4 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 7 5 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

R ua n J , G o n g X,  K o n g J,  Wa n g H,  Z he n g X , C he n  Effect of B Vita mi n ( F olate, B 6, a n d B 1 2) 
S u p pl e me ntatio n o n Oste o p or otic Fract ure a n d B o ne T ur n o ver Mar kers: A Meta -A nal ysis. Me d 
Sci M o nit, 2 0 1 5; 2 1: 8 7 5 - 8 8 1.
R u de R K: Ma g nesi u m deficie nc y : a ca use of heter o ge ne o us dis- ease i n h u ma ns. J B o ne Mi ner 
Res. 1 9 9 8; 1 3: 7 4 9 – 7 5 8.
Sa h ni, S., Ha n na n, M. T., Ga g n o n, D., Bl u m ber g, J., C u p ples, L. A., Kiel, D. P., & T uc ker, K. L. 
( 2 00 9). Pr otecti ve effect of t otal a n d s u p ple me ntal vita mi n C i nta ke o n t he ris k of hi p fract ure -a 
1 7- year f oll ow- u p fr o m t he fra mi n g ha m oste o p or osis st u d y. Oste o p or os I nt 2 0 0 9; 2 0( 1 1) : 
1 8 5 3- 1 8 6 1.
S al ari, P., A b d olla hi, M., Hes h mat, R.,  Me y b o di, H. A. a n d  Razi, F. Effect of f olic aci d o n b o ne 
meta b o lis m: a ra n d omize d d o u ble bli n d cli nical trial i n p ost me n o pa usal oste o p or otic w o me n. 
D ar u 2 0 1 4 Se p 1 6; 2 2: 6 2.
Sa nes hi ge S, Ma n o H, Tez u ka K, Ka k u d o S, M ori Y, H o n da Y, Ita bas hi A, Ya ma da T, Mi yata 
K, Ha ke da Y. Reti n o ic aci d directl y sti m ulates oste oclast ic b o ne res or pti o n a n d ge ne e x pres-
sio n of  cat he psi n K/ O C-2. Bi oc he m J . 1 9 9 5 A u g 1; 3 0 9 ( pt 3): 7 2 1– 7 2 4
Sc h ur ger s, L.J., Te u nisse n, K.J, Ha mul ya k, K. , K na pe n, M. H., Vi k, H., Ver meer, C. Vit a mi n K-
c o ntai ni n g dietar y s u p ple me nts: c o mparis o n of s y nt hetic vita mi n K 1 a n d natt o -deri ve d 
me na q ui n o ne -7. Bl o o d 2 0 0 7 A pr 1 5; 1 0 9( 8) : 3 2 7 9 - 3 2 8 3.
Sc h ü rc h, M., Rizz o li, R., Sl os ma n, D., Va das, L., Ver g na u d, P., & B o nj o ur, J. P. Pr otei n 
s u p ple me nts i ncrease ser u m i ns uli n-li ke gr o wt h fact or-I le vels a n d atte n uate pr o xi mal fe m ur 
b o ne l oss i n patie nts wit h rece nt hi p fract ure. A ra n d omize d, d o u ble -bli n d, p lace b o-c o ntr olle d 
trial. A n n I nter Me d, 1 9 9 8 Ma y 1 5; 1 2 8( 1 0) : 8 0 1 -8 0 9. 
S hi va ne, V. K., Sarat hi, V., Lila, A. R., Ba n d gar , T., J os hi, S., Me n o n, P. S., S ha h, N. S.  Pea k B o ne 
Mi neral De nsit y a n d Its Deter mi na nts i n a n Asia n I n dia n P o p ulat i on. J Cli n De ns it o m. 2 0 1 2 
A pr -J u n; 1 5( 2): 1 5 2-1 5 8. 
Si l va n us, V., G h osal, K., Be hera, A. a n d S u bra ma nia n, P.  Scree ni n g f or Oste o pe nia a n d 
Oste o p or osi s i n a n Ur ba n C o m m u nity i n I n dia. Ne p al Me d C oll J 2 0 1 2 Se p; 1 4( 3): 2 4 7 -2 5 0.
S os uls ki, F. W., I mafi d o n, G.I., 1 9 9 0. A mi n o aci d c o m p osi tio n a n d nitr o ge n -t o-pr otei n 
c o n versi o n fact ors f or a ni mal a n d pla nt f o o ds. J. A gric. F o o d C he m . 3 8: 1 3 5 1– 1 3 5 6. 
S pr o n k H M, S o ute B A, Sc h ur gers LJ,  Tiss ue - s pecific utilizati on of me na q ui n o ne -4 res ul ts i n 
t he pre ve n- tio n of  arterial calcificati on i n warfari n -treate d rats. J V asc Res. 2 0 0 3; 4 0 : 5 3 1 – 5 3 7. 
S z ul c, P. , Arlot, M., C ha p u y , M. C. Ser u m u n dercar b o x ylate d oste ocalci n c orrelates wit h hi p 
b o ne mi neral de nsit y i n el derl y w o me n. J B o ne Mi ner Res. 1 9 9 4; 9: 1 5 9 1 - 1 5 9 5.
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 7 5 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 7 6 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

S z ul c, P., C ha p u y, M. C, Me u nier, P.J., Del mas, P. D. Ser u m u n dercar b o x ylate d oste ocalci n is a 
mar ker of t he ris k of hi p fract ure i n el derl y w o me n. J Cli n I n vest 1 9 9 3 A pr; 9 1( 4): 1 7 6 9 - 1 7 7 4.
S z ul c, P., C ha p u y, M. C., Me u nier, P.J., Del mas, P. D. Ser u m u n dercar b o x ylate d oste ocalci n is a 
mar ker of  t he ris k of hi p fract ure: a t hree year fol l ow- u p st u d y . B o ne 1 9 9 6 Ma y ; 1 8 ( 5), 4 8 7- 4 8 8.
Ta n g, B. M., Eslic k, G. D., N o ws o n, C. S mit h, C., Be ns o ussa n, A. Use of calci u m or calci u m i n 
c o m bi nat i on wi t h vita mi n D s u p ple me ntatio n t o pre ve nt fract ures a n d b o ne l oss i n pe o ple a ge d 
5 0 years a n d ol der: a meta- a nal ysis. L a ncet 2 0 0 7 A u g 2 5 ; 3 7 0 ( 9 5 8 8): 6 5 7 -6 6 6.
T uc ker, K. L., Ha n na n, M. T., C he n, H., C u p ples. L. A., Wils o n, P. W. , Kiel, D. P. P otassi u m, 
ma g nesi u m, a n d fr uit a n d ve geta ble i nta kes are ass ociate d wit h greater b o ne mi neral de nsit y i n 
elderl y  me n a n d w o me n. A m J Cli n N utr. 1 9 9 9; 6 9: 7 2 7 – 7 3 6.
Vasi kara n S, Eastell R, Br u y ere O, F oldes AJ, Gar ner o P, Gri es mac her A, Mc Cl u n g M, M orris 
H A, Sil ver ma n S, Tre nti T, Wa hl D A, C o o per C, Ka nis J A; I O F -I F C C B o ne Mar ker Sta n dar ds 
W o r ki n g Gr o u p. P ositi on Pa per. Mar kers of b o ne t ur n o ver f or t he pre dict i on of fract ure ris k a n d 
m o nit ori n g of oste o p or osis treat me nt: a nee d f or i nter nati o nal refere nce sta n dar ds. Oste o p or os 
I nt 2 0 1 1; 2 2( 2): 3 9 1 - 4 2 0.
Ver g na u d, P., Gar ner o, P., Me u nier, P.J., Breart, G., Ka mi ha gi, K., Del mas, P. D. 
U n dercar b o x ylate d oste ocalci n meas ure d wit h a s pecific i m m u n oassa y pre dicts hi p fract ure i n 
elderl y  w o me n: t he E PI D O S St u d y. J Cli n E n d ocri n ol Met a b 1 9 9 7 Mar; 8 2( 3): 7 1 9 - 7 2 4.
W o lf, R. L.; Ca ule y, J. A.; Petti n ger, M.; Jac ks o n, R.; Lacr oi x, A.; Le b off, M. S.; Le wis, C. E.; 
Ne vitt, M. C.; Si m o n, J. A.; St o n e, K. L. Lac k of a relat i on bet wee n vita mi n a n d mi neral 
a nt i oxi da nts a n d b o ne mi neral de nsit y: Res ults fr o m t he w o me n’s healt h i nitiati ve. A m. J. Cli n. 
N utr. 2 0 0 5, 8 2, 5 8 1 – 5 8 8
W o o, J., La u, W., X u, L., La m, C. W. K., Z ha o, X., Y u, W., Xi n g, X., La u, E., K u h n -S herl oc k, 
B., P oc oc k, N., Eastell, R. Mil k s u p ple me ntati o n a n d b o ne healt h i n y o u n g a d ult c hi nese w o me n. 
J W o me ns He alt h ( L arc h mt) . 2 0 0 7 J u n; 1 6( 5):  6 9 2-7 0 2. 
W u, A, H ua n g, C, Li n, Z, Tia n, N, Ni, W, Wa n g, X, C hi, Y. T he relati o ns hi p bet wee n vita mi n a 
a n d ris k of fract ure: Meta-a nal ysis o f pr os pecti ve st u di es. J B o ne Mi n Res , 2 0 1 4, 2 9( 9) : 2 0 3 2-
2 0 3 9.
Yaz da n pa na h, N.; Zilli ke ns, M. C.; Ri va de neira, F.; De J o n g, R.; Li n de ma ns, J.; Uitterli n de n, 
A. G.; P ols, H. A.; Va n Me urs, J. B. Effect of dietar y B vita mi ns o n b m d a n d ris k of fract ure i n 
elderl y  me n a n d w o me n: T he R otter da m St u d y. B o ne 2 0 0 7; 4 1: 9 8 7 – 9 9 4. 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 7 6 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 7 7 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

Y a m a u c hi M, Ya ma g uc hi T, Na wata K et al. Relatio n s hi ps bet wee n u n dercar b o x ylate d 
os te ocalci n a n d vita mi n K i nta kes, b o ne t ur n o ver, a n d b o ne mi neral de nsit y i n healt h y w o me n. 
Cli n N utr 2 0 1 0 Dec; 2 9( 6): 7 6 1 - 7 6 5.
Z ha n g, J.; M u n ger, R. G.; West, N. A.; C ut ler, D. R.; We n gree n, H.J.; C orc ora n, C. D. A nti oxi da nt 
i nta ke a n d ris k of oste o p or otic hi p fract ure i n Uta h: A n effect m o difie d b y s m o ki n g stat us. A m. 
J. E pi de mi ol. 2 0 0 5, 1 6 3, 9 – 1 7
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 7 7 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 7 8 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

1 2. A P P E N DI C E S
1 2. 1. A p pe n di x 1 – Pr o d uct N utriti o n al Pr ofile
N utri tio nal  C o m p osi tio n 
of  Test a n d Place b o
Test - N utrit i onal 
S u p pl e me nt
Pl ace b o
N utri e nt 
I C M R/ W H O 
R D A 
A m o u nt ( per 
dail y  ser ve, 6 0 g)
% 
R D A
A M O U N T ( P E R 
D AI L Y S E R V E, 6 0 G)
E ner g y  
N A
2 1 5. 9 Kcal
N A
2 1 5. 9 Kcal
Car b o h y drate
Of  w hic h s u gar
N A
4 0. 9 g m
0
N A
4 7 g m
1 0 . 8 g m (a p pr o x)
Fat
N A
2 g m  ( ma x)
N A
2 g m ( ma x)
T ot al  Pr otei n ( g o o d q uality 
pr otei n)
    9 g ( 6 g)
3 g m ( m a x) 2 -5 g %
( T B D)
Vi ta mi n A
6 0 0 mc g 
1 9 8
3 3
Vi ta mi n D
4 0 0 I U ( 1 0 
mc g)
4 0 0    I U   ( 1 0 
mc g)
1 0 0
Vi ta mi n E
7. 5 m c g
2. 5
3 3
Vi ta mi n K 2- 7
5 5 mc g
5 5
1 0 0
Vi ta mi n B 1
1 m g
0. 3 3
3 3
Vi ta mi ns B 2
1. 1 m g
1. 1
1 0 0
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 7 8 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 7 9 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

N utri tio nal  C o m p osi tio n 
of  Test a n d Place b o
Test - N utrit i onal 
S u p pl e me nt
Pl ace b o
Ni aci n
1 2 m g 
4
3 3
Vi ta mi n B 6
2 m g
2
1 0 0
Vi ta mi n B 1 2
1 mc g
1
1 0 0
F o lic aci d
1 2 0 mc g
1 2 0 mc g 
1 0 0
Bi oti n
3 0 mc g
9. 9
3 3
Pa nt ot he nic aci d
5 m g
1. 7
3 3. 6
Vi ta mi n C
4 0 m g 
4 0
1 0 0
Calci u m
6 0 0 m g
6 0 0
1 0 0
I o di ne
1 5 0 mc g
4 9. 5
3 3
Ma g nesi u m
3 1 0 m g
7 2. 6
2 3
Zi nc
1 0 m g
1. 6 2 
1 6. 2
S el e ni u m
2 6 mc g
2 6
1 0 0
P O T A S SI U M 
3 2 2 5
3 2 5. 0 1
1 0. 0 8
1 2. 2. A p pe n di x II - A b bre vi ati o ns
A E
A d verse E ve nt
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 7 9 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 8 0 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

C D
C o m pact Di s c
C R F
Case Re p ort F or m
E D C
Electr o nic Data Ca pt ure
G C P
G o o d Cli nical Pract ice
G S K C H
Gl a x o S mit hKli ne C o ns u mer Healt hcare
I C H
I nter nati o nal C o nfere nce o n Har m o nizati on of Tec h nical Re q uire me nts f or 
Re gistrati o n o f P har mace ut icals f or H u ma n Use
I E C
I n de pe n de nt Et hics C o m mittee
I R B
I nstituti o nal  Re vie w B oar d
I T T
I nte nti o n t o Treat
PII
Pers o nall y I de nt ifia ble I nf or mati on
P P
Per Pr ot oc ol
S A E
S eri o us A d verse E ve nt
P R O
Pati e nt Re p orte d O utc o me
s-C T X - 1
Ser u m  C-ter mi nal cr oss-li n ki n g tel o pe pti de of t ype I c olla ge n
N T X - 1  
N-t er mi nal cr oss-li n ki n g tel o pe pti de of t ype I c olla ge n
C T X - 1 
C-ter mi nal cr oss-li n ki n g tel o pe pti de of t ype I c olla ge n
s-P 1 N P
N- t er mi nal pr o pe pti de of t ype I pr oc olla ge n
s-O C
Ser u m  Oste ocalci n
s-uc O C
Ser u m  u n der-car b o x ylate d oste ocalci n
s-P T H
Ser u m  Parat h yr oid H or m o n e
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 8 0 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 8 1 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

1 2. 3. A p pe n di x III - 7 d a y f o o d di a r y te m pl ate
W e e k #
S u n d a y
M o n d a y
T u e s d a y
W e d n e s d a y
T h ur s d a y
Fri d a y
S at ur d a y
N ot e s
C o m m e nt s
8: 0 0: 0 0
9: 0 0: 0 0
1 0: 0 0: 0 0
1 1: 0 0: 0 0
1 2: 0 0: 0 0
1 3: 0 0: 0 0
1 4: 0 0: 0 0
1 5: 0 0: 0 0
1 6: 0 0: 0 0
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 8 1 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 8 2 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

1 7: 0 0: 0 0
1 8: 0 0: 0 0
1 9: 0 0: 0 0
2 0: 0 0: 0 0
2 1: 0 0: 0 0
2 2: 0 0: 0 0
2 3: 0 0: 0 0
2 4: 0 0: 0 0
I nstr ucti o n t o use di ar y: T he partici pa nts t o re gister all f o o d, water a n d be vera ge c o ns u me d 
d uri n g o ne c o m plete wee k. T he diar y i ncl u de t he differe nt meal t i mes (at wa ki n g u p/ bef ore 
brea kfast, d uri n g brea kfast, d uri n g m or ni n g/ bef ore mai n meal, d uri n g mai n meal, d uri n g 
after n o o n/ bef ore di n ner, d uri n g di n ner, a n d bef ore g oi n g t o be d), a s pace t o s pecif y t he t yp e of  
f oo d i t e m c o ns u me d, t he a mo u nt c o ns u me d d uri n g t he da y  ( b ot h i n m L a n d porti o n sizes usi n g 
sta n dar d meas ure gi ve n wit h diar y), a n d t he bra n d (i n case it was a c o m mercial f o o d pr o d uct). T o 
i ncrease t he acc urac y of t he re p orte d p orti o n size, i nter vie wers will visit t o re p ort i nta ke wit h t he 
s u bjects at e ver y visit usi n g sta n dar d meas ure me nt c u ps , B O W L A N D S P O O N. 
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 8 2 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
C CI
Pa ge 8 3 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
C CI
C CI

 
 
SI G N A T U R E P A G E 
 
  
 
D ate  
Si g ne d B y
 
J ustific ati o n  
 
 
 
D ate  
Si g ne d B y
 
J ustific ati o n  
 
 
 
D ate  
Si g ne d B y
 
J ustific ati o n  
 
 
 
D ate  
Si g ne d B y
 
J ustific ati o n  
 
 
 
D ate  
Si g ne d B y
 
 
J ustific ati o n  
 
 
 
D ate  
Si g ne d B y
 
 
J ustific ati o n  
 
 
2 7- J ul- 2 0 1 7 2 2: 0 6: 0 9
 
Bi o st ati sti c s A p pr o v al
2 8- J ul- 2 0 1 7 0 8: 0 6: 0 8
Cli ni c al O p er ati o n s A p pr o v al
2 7- J ul- 2 0 1 7 1 0: 5 6: 0 2
A p pr o v e d
A p pr o v e d
Pr ot o c ol  
 2 0 7 1 9 2
2 7- J ul- 2 0 1 7 1 0: 0 3: 4 4
 
D oc u m e nt N a m e  
 
T y p e  
V ersi o n  
D oc u m e nt I d e ntifi er  
Eff ecti v e D at e  
 
 
 
 
R e as o n F or Iss u e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 1- J ul- 2 0 1 7 0 6: 4 3: 3 0
 
el d o _ cli ni c al _ d o c
4. 0; M o st- R e c e nt; Eff e cti v e; C U R R E N T
Pr ot o c ol  
 2 0 7 1 9 2
a p pr o v e d b y all a p pr o v er s b ut n ot ci n v ert e d i nt o eff e cti v e b y it s o w n r at h er s h o wi n g a p pr o v e d.
0 9 0 0 3 2 d 5 8 0 d 7 6 d 6 5
Pa ge 8 3 of 8 3
F ortifie d H F D
 2 0 7 1 9 2
P P D
Pa ge 8 4 of 8 4
Te m plate Versi o n Effecti ve: 3 0 J u n 2 0 1 7
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
P P D
P P D
P P D
C CI
C CI
C CI
C CI