81
CARDIO-RENAL Advisory Committee Meeting EXTRANEAL™ (7.5% Icodextrin) Peritoneal Dialysis Solution NDA 21-321 Orphan Drug Designation 97-1056 August 9, 2001 Baxter Healthcare Corporation
CARDIO-RENALAdvisory Committee Meeting
EXTRANEAL™ (7.5% Icodextrin)
Peritoneal Dialysis SolutionNDA 21-321
Orphan Drug Designation 97-1056
August 9, 2001
Baxter Healthcare Corporation
2
Baxter Participants Marsha Wolfson, M.D.
Vice President, Global Clinical Affairs
Salim Mujais, M.D. Vice President, Global Medical Affairs
Frank Ogrinc, Ph.D. Clinical Statistician
Leo Martis, Ph.D. Vice President, Solution Development
James Moberly, Ph.D. Director, Solutions R&D
Richard Newman, Ph.D. Vice President, Global Product Development
Mary Kay Rybicki Associate Director, Regulatory Affairs
3
Consultants John Burkart, M.D.
Professor of Internal Medicine/Nephrology, Bowman Gray School of Medicine
Allan Collins, M.D. Professor of Medicine,
University of Minnesota, Director Nephrology Analytical Services, Minneapolis Medical Research Foundation
Marc DeBroe, M.D., Ph.D. Dept. of Nephrology &
Hypertension, University Hospital of Antwerp
Ram Gokal, M.D. Consultant Nephrologist,
University of Manchester
Karl Nolph, M.D. Curator Professor Emeritus,
University of Missouri, Columbia William Frishman, M.D.
Chairman & Professor of Medicine, New York Medical College, Department of Medicine
Peter O’Brien, Ph.D. Professor of Biostatistics, Mayo
Medical School, Department of Health Sciences Research
Robert Stern, M.D. Carl J. Herzog Professor of
Dermatology, Beth Israel Deaconess Medical Center
Jeff Trotter, M.M. President, Ovation Research
Group
4
Extraneal Development Milestones
First market approval UK 1992 by ML Labs
Licensed by Baxter 1996
Marketing approval in 31 countries
~8200 patients currently treated worldwide
30% of PD patients in Europe
US clinical trials began 1997
Orphan Drug designation granted 1997
NDA submitted December 2000
5
Proposed Indication
Extraneal is indicated for a single daily exchange for the long (8-16 hour) dwell during continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD) for the management of chronic renal failure.
6
Topics Identified in FDA Briefing Document & Questions
Dialysis Efficacy
Quality of Life
Size of Database
Safety Profile Mortality
Rash
Peritonitis
Membrane Transport Characteristics
7
AGENDACardio-Renal Advisory Committee
NDA 21-321 Extraneal (7.5% icodextrin)
Introduction and Rationale for ExtranealSalim Mujais, M.D., Vice President Global Medical Affairs, Baxter
Clinical Trial Experience with ExtranealMarsha Wolfson, M.D., Vice President Global Clinical Affairs, BaxterFrank Ogrinc, Ph.D., Clinical Statistician, Baxter
Conclusions Salim Mujais, M.D., Vice President Global Medical Affairs, Baxter
8
Icodextrin: A Polymer of Glucose
Main chain 1 4 linkage
O
CH2OH
O
CH2OH
O
CH2
O
CH2OH
O O O
O
CH2OH
O
O
CH2OH
O
9
Composition of Extraneal
DIANEAL EXTRANEAL
Dextrose (g/dL) 1.5, 2.5, 4.25 ---
Icodextrin (g/dL) --- 7.5
Sodium (mEq/L) 132.0 132.0
Chloride (mEq/L) 96.0 96.0
Calcium (mEq/L) 3.5 3.5
Magnesium (mEq/L) 0.5 0.5
Lactate (mEq/L) 40.0 40.0
Osmolality (mOsm/kg) 346-485 282-285
pH 5.2 5.2
10
Clinical Rationale for Extraneal
Unmet clinical need
Limitations of fluid management in PD
Limitations of current osmotic agents
Necessity of the long dwell
Kinetics of peritoneal ultrafiltration
Extraneal as a new osmotic agent
Kinetics matching clinical requirement
11
Unmet Clinical NeedLimitations of Current Fluid Management in PD
Symptomatic fluid retention occurs in 25% of all PD patients1. In these patients:
Lower extremity edema 98.6%
Pleural effusions 76.1%
Pulmonary congestion 80.3%
Similar clinical observations have been reported from Japan2, the Netherlands3 and Sweden4
1Tzamaloukas et al. JASN 1995; 2Kawaguchi et al. Kidney Int 1997;3Ho-dac-Pannekeet et al. Perit Dial Int 1997; 4Heimbürger et al. Perit Dial Int 1999
12
Limitations of Fluid Management in PD Hampered by Inflexibility
Complexity of dietary counseling
Hampered by compliance issues
May complicate management
Constrained renal excretion1
Gradual decline to anuria
Diuretic resistance
Peritoneal Ultrafiltration
Challenge of the long dwell
1 Medcalf et al, Kidney International 59:1128, 2001
13
The long dwell: an integral component of PD
Dwell3
Dwell2
Dwell4
Dwell1
Long dwell
AP
D
nighttime period daytime period
Long dwellday
dwellday
dwellday
dwell
CA
PD
Extraneal Use
Extraneal Use
14
Rationale for the long dwell in PD: Intersection of two imperatives
Toxin removal imperative:
Small solutes removal fluid flow dependent
Middle and large molecular weight toxins are time dependent
Continuously wet abdomen required for therapy success
Realistic therapy imperative
Logistic burden and compliance
15
Limitations of Current Osmotic Agents Dextrose Kinetics in PD: Rapid Dissipation
Mujais et al, Peritoneal Dialysis Int. 2001
0%
20%
40%
60%
80%
100%
120%
0 1 2 3 4 5
Dwell time (hr)
% D
ex
tro
se
re
ma
inin
g
+ 2SD
Mean
-2 SD
16
Limitations of Current Osmotic Agents Balance of opposing forces
-600
-400
-200
0
200
400
600
800
-30 0 30 60 90 120 150 180 210 240
Time (min)
Cu
mu
lati
ve
tra
ns
po
rt (
ml)
Absorption Transcapillary UF Net UF
Mactier et al, J Clinical Invest 80:1311, 1987Removal from peritoneum
17
Limitations of Current Osmotic Agents:Temporal Decline
-800
-600
-400
-200
0
200
400
600
800
1000
1200
0 2 4 6 8 10 12 14 16
Time (hr)
Ne
t U
F (
ml)
2.5% Dextrose
4.25% Dextrose
1.5% Dextrose
Negative UltrafiltrationHo-Dac-Pannekeet et al, Kid Int 1996; 50:979-86 Douma et al, Kid Int 1998; 53:1014-21
18
Limitations of Current Osmotic AgentsGlycemic Effect of 4.25% Dextrose
orali.p.
Delarue et al, Kidney Int. 45:1147, 1994
19
Limitations of Current Osmotic AgentsHyperinsulinemic Effect of 4.25% Dextrose
orali.p.
Delarue et al, Kidney Int. 45:1147, 1994
20
Contrasting Dextrose vs. Icodextrin Peritoneal Kinetics
0%
20%
40%
60%
80%
100%
120%
0 2 4 6 8 10 12 14
Dwell time (hr)
Pe
rce
nt
rem
ain
ing
Dextrose Icodextrin
Dextrose data from Mujais et al, PDI 2001; Icodextrin data from RD-99-CA-060
21
Plasma Levels of Total Icodextrin & MaltoseExtraneal 035 Study – APD
0
1000
2000
3000
4000
5000
6000
7000
Baseline Week 1 Week 6 Week 12 Week 13 Week 14
Pla
sm
a le
ve
l (m
g/L
)
IcodextrinMaltose
22
Contrasting Dextrose vs. Icodextrin Net UF Profile
Temporal Decline vs. Sustained Effect
-800
-600
-400
-200
0
200
400
600
800
1000
1200
0 2 4 6 8 10 12 14 16
Time (hr)
Ne
t U
F (
ml)
2.5% Dextrose
4.25% Dextrose
7.5% Icodextrin
1.5% Dextrose
Negative UltrafiltrationHo-Dac-Pannekeet et al, Kid Int 1996; 50:979-86 Douma et al, Kid Int 1998; 53:1014-21
23
Plasma Glucose and Insulin During an Extraneal Dwell
(060 Study)
0
20
40
60
80
100
0 2 4 8 12 16
Time (hr)
Pla
sma
Insu
lin
(U
U/m
l)
0
2
4
6
8
10
Plasm
a Glu
cose
(mm
ol/L
)Insulin
Glucose
24
Rationale for Extraneal
Fluid management in PD is constrained by the consequences of the underlying disease resulting in a necessary high reliance on peritoneal ultrafiltration.
With dextrose-based solutions a long dwell can compound the difficulties with fluid management
There is an unmet need in fluid management in PD
Extraneal is uniquely suited for successful ultrafiltration during the long dwell, and can contribute significantly to fluid management in these critically ill patients
Clinical Trial Experience with Extraneal Efficacy and Safety
Marsha Wolfson, MD, FACP
VP, Global Clinical Affairs
Francis G. Ogrinc, Ph.D.
Clinical Statistician
26
Presentation Plan
Efficacy of Extraneal Net Ultrafiltration
Peritoneal Clearance
Special Assessments in Study 131
Safety Profile of Extraneal Database
Observational Mortality Data
Adverse Events
Laboratory Values
27
Key Studies
216207TOTAL EFFICACY
Double Blind
8-16 hrs12 mos.
APD/CAPD
175112RD-97-CA-131 (2.5% dextrose)
8,12 hrs
12-16 hrs
8-16 hrs
Dwell Time/ Duration
Open6 mos.
CAPD
106103ML/IB/001 (MIDAS) (1.5% and 2.5/ 4.25% dextrose
Open4 mos.
APD
2019Pro-Renal-REG-035 (2.5% dextrose)
Double Blind
1 month
CAPD
9085RD-97-CA-130 (2.5% dextrose)
Study Design
Study Length/PD Therapy
Extraneal
(n)
Control
(n)
Study
28
Supportive Studies
10228TOTAL PATIENTS
OpenSingle Exchange-
PK
N/A130RD-99-CA-060
Open8-12 hrs5 weeksCAPD
120ML/IB/014(S-5)
Open8-12 hrs45 monthsCAPD
480ML/IB/004 (MIDAS-2)
Open14-16 hrs20 weeksAPD
109Ml/IB/020 (DELIA)
Open 12-16 hrs2 years APD
1919ML/IB/011 DIANA
Study Design
Dwell TimeStudy Length/ PD Therapy
ExtranealControlStudy
29
Age, Gender and RaceIntegrated Summary of Safety — Baseline Demographics for All
Studies
0
10
20
30
40
50
60
70
80
MEAN AGE
Control
Extraneal
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
MALE FEMALE
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Cauc.
Hisp.
Asian
Black
Oth
er
AGE GENDER RACE
30
Primary Renal DiagnosisIntegrated Summary of Safety — Baseline Demographics for All
Studies
0% 5% 10% 15% 20% 25%
Other
Autoimmune Disease
Obstructive Nephropathy
Interstitial Nephritis
Polycystic Kidney Disease
Glomerulonephritis
Hypertensive Nephropathy
Diabetic Nephropathy
ExtranealControl
31
Efficacy Endpoints
Primary Endpoint
Net Ultrafiltration
Secondary Endpoints
Peritoneal Creatinine Clearance
Peritoneal Urea Clearance
Special Assessments from Study 131
Edema
Body weight
QoL
32
Ultrafiltration Extraneal 130 Study — CAPD
8-16 hour Dwell, Mean Net UF – Change from Baseline
*significant within (p<0.001) and between (p<0.01) groups
**
Mea
n N
et U
F (
ml)
0
50
100
150
200
250
300
350
400
Week 2 Week 4
Control (2.5%)
Extraneal
33
Ultrafiltration Extraneal 035 Study — APD
12-16 Hour Dwell, Mean Net UF – Change from Baseline
Mea
n N
et U
F (
ml)
**
*significant within (p<0.001) and between (p<0.001) groups
*
-100
0
100
200
300
400
500
600
Week 1 Week 6 Week 12 Follow-up
Control (2.5%)
Extraneal
34
Ultrafiltration Extraneal MIDAS Study — CAPD
8 & 12-Hour Dwell 1.5% Dextrose, Mean Net UF – Change from Baseline
*significant within (p<0.001) and between (p<0.001) groups
Mea
n N
et U
F (
ml)
* * *
0
100
200
300
400
500
600
Week 4 Week 13 Week 21
* **
8 HOUR DWELL 12 HOUR DWELL
0
100
200
300
400
500
600
Week 3 Week 12 Week 20
Control
Extraneal
35
Ultrafiltration Extraneal MIDAS Study — CAPD
8 & 12-Hour Dwell 4.25% Dextrose, Mean Net UF – Change from Baseline
*significantly different from baseline
Mea
n N
et U
F(m
)
*
8 HOUR DWELL 12 HOUR DWELL
-400
-200
0
200
400
600
800
Week 4 Week 13 Week 21
Control
Extraneal
-400
-200
0
200
400
600
800
Week 3 Week 12 Week 20
Control
Extraneal
36
Percentage of Patients with Negative Net UF Extraneal 130 Study — CAPD
8-16 Hour Dwell
0%
10%
20%
Baseline Week 2 Week 4
Control (2.5%)
Extraneal
% p
atie
nts
wit
h N
egat
ive
Net
UF
**
* significant between treatment groups (p<0.005)
37
%
Pat
ien
ts w
ith
Neg
ati
ve
Ne
t U
FPercentage of Patients with Negative Net UF
Extraneal 035 Study — APD12-16 Hour Dwell
0%
10%
20%
30%
40%
50%
60%
70%
80%
Baseline Week 1 Week 6 Week 12 Follow-up
Control (2.5%)Extraneal
** *
*significant between treatment groups (p<0.001)
38
Percentage of Patients with Negative Net UF Extraneal MIDAS Study — CAPD 8-Hour Dwell & 12-Hour Dwell 1.5% Dextrose
0%
10%
20%
30%
40%
50%
Baseline Week 3 Week 12 Week 20
% P
ati
en
ts w
ith
Ne
ga
tiv
e N
et
UF
* * * 0%
10%
20%
30%
40%
50%
Baseline Week 4 Week 13 Week 21
Control
Extraneal
8-HOUR DWELL 12-HOUR DWELL
* * *
* significant between treatment groups (p<0.001)
39
Percentage of Patients with Negative Net UF Extraneal MIDAS Study — CAPD 8-Hour Dwell & 12-Hour Dwell 4.25% Dextrose
0%
10%
20%
30%
40%
50%
Baseline Week 3 Week 12 Week 20
% P
ati
en
ts w
ith
Ne
ga
tiv
e N
et
UF
0%
10%
20%
30%
40%
50%
Baseline Week 4 Week 13 Week 21
Control
Extraneal
8-HOUR DWELL 12-HOUR DWELL
40
Efficacy Endpoints
Primary Endpoint
Net Ultrafiltration
Secondary Endpoints
Peritoneal Creatinine Clearance
Peritoneal Urea Clearance
Special Assessments from Study 131
Edema
Body weight
QoL
41
Clearance of Creatinine & Urea Extraneal 130 Study — CAPD
Cle
aran
ce (
mL
/min
) fo
r th
e L
on
g D
wel
l
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
Week 2 Week 4
Control (2.5%)
Extraneal
p<0.001 p=0.001
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
Week 2 Week 4
Cle
aran
ce (
mL
/min
) fo
r th
e L
on
g D
wel
l
p=0.005 p=0.004
CREATININE UREA
** *
*
42
Special Assessments from Long-term Study 131
Edema
Body Weight
Quality of Life
43
Peripheral Edema Assessment Extraneal 131 Study — CAPD & APD
Usually assessed by same individual
0 - 3+ - Recorded on CRF
4+ - Recorded as Adverse Event
44
Adverse Events for Edema Extraneal 131 Study — CAPD & APD
10.3%13.4%Other Edema
6.3%17.9%Peripheral Edema (p=0.002)
ExtranealN=175
ControlN=112
COSTART Term
45
Special Assessments from Study 131
Edema
Body Weight
Quality of Life
46
Body Weight
Important parameter in ESRD
Assesses:
Fluid balance - short term
Body composition - long term
47
Body Weight – Before Drain Extraneal 131 Study — CAPD & APD
(N=47 Control, N=88 Extraneal)
Extraneal patients - maintained body weight at 52 weeks (mean change -0.03 kg)
Control patients - average increase of 2.33 kg at 52 weeks
(p=0.022 at 52 weeks)
48
Special Assessments from Long-term Study 131
Edema
Body Weight
Quality of Life
49
Quality of Life — KDQoL Extraneal 131 Study — CAPD & APD
Patients completing both Baseline and Week 52 (N=25 Control, 41 Extraneal):
Queried on 35 kidney-specific symptoms/problems
Short Form 36
50
Quality of Life — KDQoL Results - SF36
Change in SF-36 Score: Baseline to Week 52Patients with Baseline and Week 52 Forms
-25
-20
-15
-10
-5
0
5
PF RP BP GH VT SF RE MH
Mea
n C
han
ge
in S
core
Extraneal
Control
**
* clinically significant result favoring Extraneal, ** favoring Dianeal
*
**
*
51
Quality of Life — KDQOL Extraneal 131 Study — CAPD & APD
For patients completing both Baseline and Week 52 (N=25 Control, N=41 Extraneal):
35 Symptoms/Problems: 10 favored Extraneal, 5 favored Dextrose
Short Form 36
Domains: 4 favored Extraneal, 1 favored Dextrose
Health Transition Summary:
30% of Extraneal patients vs 4% of Control patients reported their health was much better as compared to one year ago (p=0.032)
52
Extraneal Efficacy Conclusions
Superior UF compared to 1.5% or 2.5% Dextrose and comparable to 4.25% Dextrose
Significantly reduced number of patients with negative net UF compared to both 1.5% and 2.5% Dextrose and comparable to 4.25% Dextrose
Significantly increased peritoneal clearance of urea and creatinine compared to 2.5% Dextrose
Potential benefit in preventing weight gain and edema, and improving quality of life
53
Safety Profile of Extraneal
Database
Observational Mortality Data
Adverse Events
Laboratory Values
Membrane Transport Characteristics
54
Extraneal Clinical Database
840 Total Patients 347 Control, 493 Extraneal
Exposure Control 174.3 days average
Extraneal 232.5 days average 215 (43.6%) Extraneal patients exposed greater
than 6 months
155 (31.4%) Extraneal patients exposed greater than 12 months
55
Patient Disposition (Withdrawals/Completions, All Studies)
7.5%4.9% Other
1.4%3.2% Protocol Violations
3.7%3.2% Deaths
13.4%11.8% Adverse Event
8.5%6.1% Transplantation
34.5%29.1%Prematurely Discontinued
65.5%70.9%Completed
EXTRANEAL N=493
CONTROL N=347
56
Safety Profile of Extraneal
Database
Observational Mortality Data
Adverse Events
Laboratory Values
Membrane Transport Characteristics
57
Observational MortalityExtraneal 131 Study: Original Data Collection
Each patient was followed until drop out or completion of 12 months.
Once a patient discontinued (early drop out or completer), he was observed for an additional 30 days to collect adverse events, including death.
Based on these data collection methods:
DeathsNumber of Patients
Treatment Group
%N
175
112
7.413EXTRANEAL
4.55Control
58
Observational Mortality Extraneal 131 Study: Additional Data
Collection Additional information on 13-month status (dead or alive 395 days
after enrollment) was obtained for the patients who had not died and had not completed the 12-month study.
12-Month Mortality Rate@
Number of Deaths
Number of Patients
Treatment Group
11.7%
7.2%
175
112
20EXTRANEAL
9Control
@ From Kaplan-Meier estimation (Not Sig.)
12-Month Mortality Rate@
Number of Deaths
Number of Patients
Treatment Group
11.7%
7.2%
175
112
20EXTRANEAL
9Control
59
0 25 50 75 100 125 150 175 200 225 250 275 300 325 350 375 400Days Until Death or Censor
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Pro
po
rtio
n S
urv
ivin
g
Treatment Group:ControlExtraneal
p=0.301 from the Log-Rank Test
All Follow-Up Time for Mortality Extraneal Study 131: Long-Term Safety Study in APD and
CAPD Patients
60
Observational MortalityAll Studies (Other Than MIDAS-2)
Because of the limited database in Study 131, mortality results from all studies, other than MIDAS-2, were combined to describe the overall mortality.
Intent-to-treat methods were applied and all deaths were included. Some of these were after study participation.
244
189
Total Follow-Up Time (Patient-Yrs)
Deaths per 1000 Pt-Year
Number of Deaths
Number of Patients
Treatment Group
107
106
366
285
26EXTRANEAL
20Control
61
Observational MortalityAll Studies (Other Than MIDAS-2)
Estimated Death Rates from the Kaplan-Meier Methods
27.6%
17.3%
10.4%
EXTRANEAL
0.51
0.36
1.32
Ratio of Death RatesControlMonth
7.9%12
54.0%
47.4%
24
18
62
100 200 300 400 500 600 700 800Time to Death (Days)
00
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Pro
po
rtio
n S
urv
ivin
g
Treatment Group:ControlExtraneal
p=0.929 from Log-Rank Test
Kaplan-Meier Survival Curves for Time to Death
Using All Mortality From ISS Except MIDAS-2 (Uncontrolled)
63
Observational MortalitySummary
Mortality information from all clinical studies was combined to better describe the experience for Extraneal.
There were 366 Extraneal patients in this integrated safety database.
These provide 244 patient-years of experience with Extraneal.
Survival times were comparable for Control and Extraneal Hazard Ratio: 1.03
90% Confidence Interval: [0.63, 1.68]
64
Safety Profile of Extraneal
Database
Observational Mortality Data
Adverse Events
Laboratory Values
Membrane Transport Characteristics
65
Extraneal All StudiesSafety - Adverse Events
0.29031.7%31.2%Pct. Of Patients with at least one Serious AE
p-ValueExtraneal (N=493)
Control (N=347)
0.33916.6%40.6%39.4%
3.5%
20.2%39.4%38.7%
1.7%
MildModerateSevereNot Reported
Most Severe AE
0.25040.1%28.2%31.7%
41.1%25.7%33.2%
NoneRelatedNot Reported
Most Related AE to Treatment
0.24087.0% 84.1%Pct. of Patients with at least one AE
66
Adverse Events
Peritonitis
Rash
67
Adverse Events
Peritonitis most frequent adverse event Control – 25.4%
Extraneal – 26.4%
Peritonitis most frequent serious adverse event - resulting in hospitalization Control - 8.6%
Extraneal - 5.3%
(p=0.013)
68
Adverse Events
Of all adverse events, only Rash showed greater than 5 percentage points difference between groups
69
Total Skin EventsIncidence Rates – All Studies, Unrelated and Related AEs
27.0%
10.1%
22.5%
4.6%
All SKIN EVENTS
RASH
1.8%0.3%DERM EXFOL
Extraneal (N=493)
Control (N=347)
COSTART Code
70
Total Skin EventsIncidence Rates – All Studies, Related AEs
1.6%0.0%DERM EXFOL
5.5%1.7%RASH
9.9%4.0%All SKIN EVENTS
Extraneal (N=493)
Control(N=347)
COSTART Code
71
Outcomes for Rash in Clinical Trials
6 patients withdrew/discontinued for rash, 1 for exfoliative dermatitis
All were in the Extraneal Group
No patient was hospitalized for rash
All rash events resolved
No anaphylaxis
No Stevens-Johnson Syndrome
72
Safety Profile of Extraneal
Database
Observational Mortality Data
Adverse Events
Laboratory Values
Membrane Transport Characteristics
73
Laboratory Value ChangesAt Last Visit, Between Groups
INCREASED:
Alkaline Phosphatase (130, 131 and 035 studies)
DECREASED:
Amylase-Assay Interference
Sodium
Chloride
74
Serum Alkaline Phosphatase (U/L)
(130, 131 and 035 Studies)
Mean change
+4.039 Control
+19.073 Extraneal
Patients above normal range (31.0 - 115.0 U/L)
23.6% Control
33.5% Extraneal
Adverse Events for increased Alk. Phos.
1.7% Control
2.8% Extraneal
75
Serum Sodium (mmol/L)All Studies
Mean change -0.272 Control
-2.771 Extraneal
Patients below normal range (135-148 mmol/L) 15.8% Control
32.5% Extraneal
Adverse Events for Hyponatremia 2.0% Control
2.2% Extraneal
76
Serum Chloride (mmol/L)All Studies
Mean change +0.610 Control
-2.003 Extraneal
Patients below normal range (96-112 mmol/L) 32.9% Control
51.7% Extraneal
Adverse Events for hypochloremia 0.9% Control
1.6% Extraneal
77
Safety Profile of Extraneal
Database
Observational Mortality Data
Adverse Events
Laboratory Values
Membrane Transport Characteristics
78
Membrane Transport CharacteristicsMTAC for Creatinine, Urea and Glucose
*significantly different from baseline within group‡ significantly different between groups
0
10
20
Baseline Week 26 Week 52
Control
Extraneal
0
10
20
Baseline Week 26 Week 52
Control
Extraneal
0
10
20
Baseline Week 26 Week 52
Control
Extraneal
** ‡
CR
EA
TIN
INE
(m
L/m
in)
UR
EA
(m
L/m
in)
GL
UC
OS
E(m
L/m
in)
79
Summary of Clinical Trial Results
EFFICACY
Increased Ultrafiltration
Reduced percentage of patients with negative net UF
Increased peritoneal creatinine and urea clearance
Potential benefit in preventing weight gain and edema, and improving quality of life
SAFETY
Safety profile comparable to current therapy
Rash most frequent related AE
Increases in alkaline phosphatase, decreases in sodium and chloride, with no known clinical relevance
80
ExtranealOverall Summary
Patients on PD have limited therapy options for fluid management
Extraneal provides patients and their physicians a new dialysis solution that expands these options by sustaining effective ultrafiltration during the long dwell
The enhanced efficacy of the new solution is coupled with a safety profile comparable to existing solutions
81
Proposed Indication
Extraneal is indicated for a single daily exchange for the long (8-16 hour) dwell during continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD) for the management of chronic renal failure.
