Randomized, Double-blind, Parallel Group, Single-center, Placebo-controlled Study to Evaluate Efficacy and Safety of Analgesic Combo in Prevention and Treatment of Post-surgical Dental Pain in Healthy Subjects
Phase: PHASE2
Conditions: Dental Pain
Sponsor: Nevakar, Inc.

 
 
 
Pr ot oc ol  
Offici al Title:  A ra n d o mize d, d o u ble- bli n d, parallel gr o u p, si n gle- ce nter, place b o  c o ntr olle d 
st u d y t o e val uate t he efficac y a n d safet y of a n aceta mi n o p he n -pre ga b ali n 
c o m bi nati o n i n t he pre ve nti o n a n d treat me nt  of p ost-s ur gical de ntal pai n i n 
healt h y patie nts 
 
N C T N u m ber:  N C T 0 3 6 5 2 8 1 8 
Versi o n:  3. 0 
D ate:  0 9 J u ne 2 0 1 8 
 
 

N e v a k ar, I nc.  
C O N FI D E N TI AL  
Pr ot oc ol C P -N V K 0 0 9 -0 0 0 1( 3 ) 9 J u n 2 0 1 8 
Pr e g a b ali n D e nt al St u dy  
C o nfi d e n ti al a n d Pr o pri et ary I nf or m ati o n 
P a g e 9 o f 6 4  
0 9 J u n e 2 0 1 8  
as PI a n d P R will be c ollecte d at t hat ti me . Patie nts w h o d o n ot e x perie nce 
a n y pai n relief after D ose 2 will be e nc o ura ge d, b ut n ot re q uire d, t o wait at 
least 1 h o ur bef ore usi n g resc ue t hera p y. Patie nt Gl o bal E val uati o n of t he 
st u d y me dicati o n will be c ollecte d at  1 2. 2 5 h o urs p ost -s ur ger y or at t he ti me 
of first resc ue me dicati o n a d mi nistrati o n or at t he ti me of patie nt wit h dra wal , 
w hic he ver occ urs first, wit h a 0 -4 cate g orical rati n g scale: ( 0) p o or, ( 1) fair, 
( 2) g o o d, ( 3) ver y g o o d, a n d ( 4) e xcelle nt.
E F FI C A C Y 
M E A S U R E M E N T S:  
•
Cate g orical Pai n I nte nsit y: ( o nl y at Baseli ne pri or t o D ose 2)
N o ne ( 0)  
Mil d ( 1)  
M o derate ( 2)   
Se vere ( 3)
•
N u merical Rati n g Scale Pai n I nte nsit y:  ( PI-N R S)
( 0 = n o pai n a n d 1 0 = w orst i ma gi na ble pai n)
•
N u merical Rati n g Scale Pai n Relief ( P R -N R S)
( 0 = n o relief a n d 1 0 = c o m plete relief)
•
St o p Watc hes:  First Perce pti ble a n d Mea ni n gf ul Relief
( F P R = First Perce pti ble Relief, M P R = Mea ni n gf ul Pai n Relief  a n d F P R-
C = F P R t hat is c o nfir me d b y M P R)
•
Gl o bal E val uati o n:
P o or ( 0) 
Fair ( 1)   
G o o d ( 2)   Ver y G o o d ( 3)  E xcelle nt ( 4)
Effic ac y P ar a meters : 
•
S PI D 0 - 6, 0- 8, 0- 1 2 a n d 0- 2 4 ( Ti me wei g hte d S u m Pai n I nte nsit y
Differe nce Sc ores o ver 6 , 8, 1 2 a n d 2 4 h o urs base d o n t he 0 - 1 0 PI -N R S );
•
T O T P A R 0 - 6, 0- 8, 0- 1 2 a n d 0- 2 4 ( Ti me wei g hte d T otal Pai n Relief o ver
6, 8, 1 2 a n d 2 4 h o urs base d o n t he 0- 1 0 P R -N R S);
•
Ti me fr o m e n d of s ur ger y (last s ut ure) t o a d mi nistrati o n of D ose 2;
•
Pai n I nte nsit y Differe nce Rati n g ( PI D): sc ore d o n t he 0- 1 0 PI -N R S at
eac h o bser vati o n ti me after D ose 2 a d mi nistrati o n;
•
Pai n I nte nsit y Rati n g ( PI): sc ore d o n t he 0- 1 0 PI -N R S at eac h o bser vati o n
ti me after D ose 2 a d mi nistrati o n;
•
Pai n Relief Rati n g ( P R): sc ore d o n t he 0- 1 0 P R - N R S at eac h o bser vati o n
ti me after D ose 2 a d mi nistrati o n;
•
S PI 0 - 6, 0- 8, 0- 1 2 a n d 0- 2 4 ( Ti me wei g hte d T otal Pai n I nte nsit y Sc ores
o ver 6, 8, 1 2 a n d 2 4 h o urs base d o n t he 0 - 1 0 PI-N R S);
S T U D Y D E SI G N: 
(c o nt.) 

N e v a k ar, I nc.  
C O N FI D E N TI AL  
Pr ot oc ol C P -N V K 0 0 9 -0 0 0 1( 3 ) 9 J u n 2 0 1 8 
Pr e g a b ali n D e nt al St u dy  
C o nfi d e nt i al a n d Pr o pri et ary I nf or m ati o n 
P a g e 1 0  of 6 4  
0 9 J u n e 2 0 1 8  
•
D urati o n of pai n re d ucti o n, as meas ure d b y t he ti me t o treat me nt fail ure
(i.e. ti me t o first d ose of resc ue me dicati o n after D ose 2 or wit h dra w fr o m
t he st u d y d ue t o lac k of efficac y pri or t o resc ue);
•
C u m ulati ve % of patie nts wit h o nset of First Perce pti ble Relief
C o nfir me d a n d Mea ni n gf ul Pai n Relief after D ose 2;
•
T he c u m ulati ve pr o p orti o n of treat me nt fail ures o ver ti me after D ose 2
a d mi nistrati o n (fail ure defi ne d as re q u iri n g resc ue a nal gesic me dicati o n
or wit h dra w fr o m t he st u d y d ue t o lac k of efficac y);
•
Patie nt Gl o bal E val uati o n of st u d y treat me nt;
•
T otal d oses of resc ue a nal gesi a at 1 2. 2 5 a n d 2 4 h o urs .
O T H E R  
M E A S U R E M E N T S:  
F oll o wi n g s i g ni n g of t he i nf or me d c o nse nt/asse nt f or ms (I C F) u ntil t he 
c o m pleti o n of t he st u d y, patie nts will be m o nit ore d f or safet y. Vital si g ns will 
be c ollecte d at  Scree ni n g, Pri or t o D ose 1, E n d of S ur ger y a n d e ver y 4 h o urs 
f oll o wi n g e n d of s ur ger y or i m me diatel y pri or t o D ose 2, w hic he ver occ urs 
first, an d e ver y 4 h o urs f oll o wi n g D ose 2 t hr o u g h o ut t he 2 4- h o ur p ost-
o perati ve m o nit ori n g peri o d . F or s u bject's n ot recei vi n g D ose 2, 
a d diti o nal vital si g ns will be ta ke n at disc h ar ge.  Patie nts will c o nti n ue t o 
be peri o dicall y m o nit ore d t hr o u g h o ut t h e 2 4- h o ur sta y at t he C R U a n d all 
a d verse e ve nts s p o nta ne o usl y re p orte d b y t he patie nts or o bser ve d b y t he 
researc h c o or di nat ors will be rec or de d. 
E F FI C A C Y 
M E A S U R E M E N T S: 
(c o nt.) 

N e v a k ar, I nc.  
C O N FI D E N TI AL  
Pr ot oc ol C P -N V K 0 0 9 -0 0 0 1( 3 ) 9 J u n 2 0 1 8 
Pr e g a b ali n D e nt al St u dy  
C o nfi d e n ti al a n d Pr o pri et ary I nf or m ati o n 
P a g e 1 3  of 6 4  
0 9 J u n e 2 0 1 8  
I N C L U SI O N 
C RI T E RI A :  
(c o nt.) 
scree ni n g a n d uri ne o n da y of s ur ger y 1) pre g na nc y test a n d n ot be 
breastfee di n g;  
9.
Patie nts m ust ha ve a ne gati ve uri ne dr u g scree n f or dr u gs of a b use
(i ncl u di n g c oti ni ne) at Scree ni n g a n d at t he da y of s ur ger y.
a. 
S u bj ects wit h a p ositi ve dr u g scree n w h o are ta ki n g a n all o we d,
prescri be d me dicati o n t hat is k n o w n t o res ult i n a p ositi ve dr u g test
(e. g., a m p heta mi ne a n d de xtr oa m p heta mi ne f or atte nti o n-
deficit/ h y peracti vit y dis or der) ma y be eli gi ble f or partici pati o n i n t he
st u d y if t he y ha ve bee n o n a sta ble d ose f or > 3 0 da ys fr o m
scree ni n g.
b. Patie nts w h o di d n ot re p ort c o nc o mita nt me dicati o n use, w hic h is
later i de ntifie d d uri n g t he uri ne dr u g scree n, ca n n ot be e nr olle d i n
t he st u d y.
c.
S u bj ects ta ki n g me dical marij ua na are n ot all o we d t o partici pate i n
t he st u d y.
1 0. At t he discreti o n of t he PI, a p ositi ve dr u g scree n res ult ma y be per mitte d
if t he patie nt has bee n o n a sta ble d ose of a n all o we d me dicati o n f or > 3 0
da ys fr o m scree ni n g;
1 1. Patie nts w h o are sc he d ule d t o u n der g o t he s ur gical re m o val of u p t o 4
t hir d m olars of w hic h at least t w o ha ve t o be ma n di b ular m olars wit h a
diffic ult y rati n g of 4 or 5 a n d meeti n g t he f oll o wi n g criteria:
•
t w o f ull b o n y i m pacti o ns
•
t w o partial  b o n y i m pacti o ns
•
o ne f ull b o n y i m pacti o n i n c o m bi nati o n wit h o ne partial b o n y i m pacti o n
(see A p pe n di x  1 f or I m pacti o n Diffic ult y  Rati n g Scale);
1 2. Pa tie nts a ble t o c o m pre he n d a n d f oll o w t he re q uire me nts of t he st u d y
(i ncl u di n g a vaila bilit y o n sc he d ule d visit dates) base d u p o n t he researc h
site’s j u d g me nt.
E X C L U SI O N 
C RI T E RI A:  
1.
Patie nt s wit h a hist or y of a n y si g nifica nt me dical c o n diti o n t hat, i n t he
o pi ni o n of t he PI or his desi g nee, w o ul d place t he patie nt at i ncrease d ris k
s uc h as: he patic, re nal, e n d ocri ne, car diac, ne ur ol o gical, ps yc hiatric,
gastr oi ntesti nal, p ul m o nar y, he mat ol o gic, or meta b olic dis or ders,
i ncl u di n g gla uc o ma, dia betes, e m p h yse ma, a n d c hr o nic br o nc hitis;
2.
Patie nts s h o ul d n ot be e x perie nci n g a n y oral i nfecti o ns or s y m pt o ms of a
c o nc o mita nt ill ness (e. g., res pirat or y tract i nfecti o n) at t he ti me of a
sc he d ule d s ur ger y;

N e v a k ar, I nc.  
C O N FI D E N TI AL  
Pr ot oc ol C P -N V K 0 0 9 -0 0 0 1( 3 ) 9 J u n 2 0 1 8 
Pr e g a b ali n  D e nt al St u dy 
C o nfi d e nti al a n d Pr o pri et ary I nf or m ati o n  
P a g e 1 6  o f 6 4  
0 9 J u n e 2 0 1 8  
R E S C U E 
A N A L G E SI C : 
I b u pr ofe n 4 0 0 mg will be use d a s t he resc ue a nal gesic. Patie nts ca n resc ue at 
a n y ti me after recei vi n g D ose 2 of t he st u d y me dicati o n wit h t he resc ue 
a nal gesic, b ut n ot m ore ofte n t ha n e ver y 4 h o urs or m ore t ha n f o ur d oses i n 
2 4 h o urs. At t he ti me t he  patie nt ta kes t he first d ose of res c ue a nal gesic, PI 
a n d P R sc ores a n d Gl o bal E val uati o n (if pri or t o t he 1 2. 2 5-h o ur assess me nt)  
will be rec or de d.  
S u bj ects recei vi n g resc ue me dicati o n will c o nti n ue t o be assesse d f or b ot h 
efficac y a n d safet y at t he re g ularl y sc he d ule d o bser vati o n ti me p oi n ts 
t hr o u g h o ut t he e ntire 2 4 - h o ur o bser vati o n peri o d ( Ti me “ 0” will re mai n 
ass ociate d wit h D ose 2) .  
I n t he e ve nt a s u bject d oes n ot ha ve s ufficie nt pai n relief fr o m 4 0 0 m g 
i b u pr ofe n, t he PI ma y a d mi nister a d diti o nal resc ue ( o x yc o d o ne 5 m g; faili n g 
t hat, oral  tra ma d ol 5 0 m g).  

 
 
 
Statistical Analysis Plan (SAP) 
Official Title: A randomized, double-blind, parallel group, single-center, placebo controlled 
study to evaluate the efficacy and safety of an acetaminophen-pregabalin 
combination in the prevention and treatment of post-surgical dental pain in 
healthy patients 
 
NCT Number: NCT03652818 
Version: 1.0 
Date: 10 September 2018