Trial | NCT00500682

Trial | NCT00500682 Report issue

Title

A Study of AST-120 for Evaluating Prevention of Progression In Chronic Kidney Disease (EPPIC-1)

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of AST-120 for Prevention of Chronic Kidney Disease Progression in Patients With Moderate to Severe Chronic Kidney Disease

Phase
Phase 3

Lead Sponsor
Mitsubishi Tanabe

Study Type
Interventional

Status
Completed Results Posted

Indication/Condition
Chronic Kidney Disease

Intervention/Treatment
kremezin ...
Placebo AST-120

Study Participants
1020

1) To evaluate the effectiveness of AST-120 (spherical carbon adsorbent) added to standard-of-care therapy in moderate to severe Chronic Kidney Disease (CKD), on time to first occurrence of any event of the triple composite outcome of initiation of dialysis, kidney transplant or doubling of serum creatinine (sCr) when compared with placebo; 2) To evaluate the safety and tolerability of long-term AST-120 therapy in patients with CKD; 3) To evaluate the effects of AST-120 versus placebo, on other measures of renal function.

Study Started

Jul 31

2007

Primary Completion

Oct 31

2011

Study Completion

Oct 31

2011

Results Posted

Mar 02

2015

Estimate

Last Update

Jun 07

2022

Drug Placebo

9g /day (3 times a day)

Drug AST-120

9g /day (3 times a day)

Placebo Placebo Comparator

Drug Placebo

AST-120 Experimental

Drug AST-120

Criteria

Inclusion Criteria:

Age 18 years or older
Moderate to severe CKD, not anticipated to require dialysis or renal transplant within the next 6 months
Patient survival expected to be no less than one year
Serum creatinine in men >= 2.0 mg/dL (>= 177 µmol/L) and <= 5.0 mg/dL (<= 442 µmol/L), and in women >= 1.5 mg/dL (>= 133 µmol/L) and <= 5.0 mg/dL (<= 442 µmol/L) at Screening
Urinary total protein to urinary total creatinine ratio must be >= 0.5 on a spot void at Screening
Blood pressure <= 160/90 mmHg at both Screening and Baseline. In addition, blood pressure, if measured, must have been stable in hypertensive patients over the 3 months prior to Screening, with no more than 1 blood pressure reading > 160/90 mmHg
In patients being treated for hypertension, they should be on a stable anti-hypertensive regimen

Exclusion Criteria:

Obstructive or reversible cause of kidney disease
Nephrotic syndrome defined as a ratio of urinary total protein to urinary creatinine of > 6.0 as measured on a spot void
Adult polycystic kidney disease
History of previous kidney transplant
History of recent (within the past 6 months) accelerated or malignant hypertension
Uncontrolled arrhythmia or severe cardiac disease within the past 6 months
History of malabsorption, inflammatory bowel disease, hiatal hernia, active peptic ulcer, or severe GI dysmotility, not attributable to the use of a phosphate binder
Received any investigational agent or participated in a clinical study within the previous 3 months
Presence of any significant medical condition that might create an undue risk with study participation, or significantly confound the collection of safety and efficacy data in this study

Summary

AST-120

Placebo

All Events

Event Type	Organ System	Event Term	AST-120	Placebo

Composite of Dialysis Initiation, Kidney Transplantation, and Serum Creatinine Doubling. Number of Participants Meeting the Criteria Are Reported.

AST-120

178.0

participants

Placebo

177.0

participants

Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events

AST-120

Treatment-emergent AE

Treatment-emergent SAE

Placebo

Treatment-emergent AE

Treatment-emergent SAE

Number of Participants Who Developed a Component of a Quadruple Composite Endpoint (Initiation of Dialysis, Kidney Transplant, Doubling of sCr, or Death)

AST-120

Placebo

Vitamin A Levels

AST-120

Baseline

1145.3

ng/mL (Mean)

Standard Deviation: 356.67

Early Term/Discontinuation

1167.2

ng/mL (Mean)

Standard Deviation: 401.08

Final Visit

1266.9

ng/mL (Mean)

Standard Deviation: 357.06

Week 108

1222.1

ng/mL (Mean)

Standard Deviation: 367.46

Week 12

1142.4

ng/mL (Mean)

Standard Deviation: 374.14

Week 120

1188.8

ng/mL (Mean)

Standard Deviation: 357.58

Week 132

1273.5

ng/mL (Mean)

Standard Deviation: 416.43

Week 144

1305.0

ng/mL (Mean)

Standard Deviation: 379.81

Week 156

1255.6

ng/mL (Mean)

Standard Deviation: 323.72

Week 168

1244.6

ng/mL (Mean)

Standard Deviation: 275.57

Week 180

1176.5

ng/mL (Mean)

Standard Deviation: 342.14

Week 192

1253.0

ng/mL (Mean)

Standard Deviation: 340.63

Week 24

1151.5

ng/mL (Mean)

Standard Deviation: 382.40

Week 36

1148.1

ng/mL (Mean)

Standard Deviation: 385.90

Week 48

1156.2

ng/mL (Mean)

Standard Deviation: 367.71

Week 60

1199.2

ng/mL (Mean)

Standard Deviation: 388.36

Week 72

1216.0

ng/mL (Mean)

Standard Deviation: 368.58

Week 84

1252.1

ng/mL (Mean)

Standard Deviation: 406.11

Week 96

1240.2

ng/mL (Mean)

Standard Deviation: 367.21

Placebo

Baseline

1164.2

ng/mL (Mean)

Standard Deviation: 387.08

Early Term/Discontinuation

1191.4

ng/mL (Mean)

Standard Deviation: 457.79

Final Visit

1320.1

ng/mL (Mean)

Standard Deviation: 444.09

Week 108

1305.7

ng/mL (Mean)

Standard Deviation: 421.64

Week 12

1177.9

ng/mL (Mean)

Standard Deviation: 404.21

Week 120

1234.7

ng/mL (Mean)

Standard Deviation: 397.81

Week 132

1284.1

ng/mL (Mean)

Standard Deviation: 411.37

Week 144

1277.9

ng/mL (Mean)

Standard Deviation: 336.23

Week 156

1174.8

ng/mL (Mean)

Standard Deviation: 347.46

Week 168

1185.9

ng/mL (Mean)

Standard Deviation: 402.00

Week 180

1203.5

ng/mL (Mean)

Standard Deviation: 271.98

Week 192

1189.3

ng/mL (Mean)

Standard Deviation: 152.33

Week 24

1193.6

ng/mL (Mean)

Standard Deviation: 363.36

Week 36

1215.1

ng/mL (Mean)

Standard Deviation: 406.78

Week 48

1210.1

ng/mL (Mean)

Standard Deviation: 396.91

Week 60

1232.1

ng/mL (Mean)

Standard Deviation: 419.86

Week 72

1265.5

ng/mL (Mean)

Standard Deviation: 428.28

Week 84

1292.8

ng/mL (Mean)

Standard Deviation: 435.80

Week 96

1314.8

ng/mL (Mean)

Standard Deviation: 433.70

Vitamin B12 Levels

AST-120

Baseline

688.1

pg/mL (Mean)

Standard Deviation: 1881.58

Early Term/Discontinuation

935.7

pg/mL (Mean)

Standard Deviation: 2400.94

Final Visit

626.7

pg/mL (Mean)

Standard Deviation: 1464.99

Week 108

544.1

pg/mL (Mean)

Standard Deviation: 1564.38

Week 12

597.3

pg/mL (Mean)

Standard Deviation: 1824.74

Week 120

590.0

pg/mL (Mean)

Standard Deviation: 1968.53

Week 132

923.7

pg/mL (Mean)

Standard Deviation: 3358.51

Week 144

460.5

pg/mL (Mean)

Standard Deviation: 291.19

Week 156

476.3

pg/mL (Mean)

Standard Deviation: 285.02

Week 168

563.9

pg/mL (Mean)

Standard Deviation: 528.25

Week 180

564.2

pg/mL (Mean)

Standard Deviation: 254.57

Week 192

489.0

pg/mL (Mean)

Standard Deviation: 306.00

Week 24

554.2

pg/mL (Mean)

Standard Deviation: 1654.52

Week 36

500.6

pg/mL (Mean)

Standard Deviation: 568.44

Week 48

530.6

pg/mL (Mean)

Standard Deviation: 759.54

Week 60

494.2

pg/mL (Mean)

Standard Deviation: 534.92

Week 72

545.9

pg/mL (Mean)

Standard Deviation: 1268.50

Week 84

497.6

pg/mL (Mean)

Standard Deviation: 923.15

Week 96

646.6

pg/mL (Mean)

Standard Deviation: 2012.14

Placebo

Baseline

620.5

pg/mL (Mean)

Standard Deviation: 1630.87

Early Term/Discontinuation

953.5

pg/mL (Mean)

Standard Deviation: 2914.40

Final Visit

747.1

pg/mL (Mean)

Standard Deviation: 2495.49

Week 108

682.2

pg/mL (Mean)

Standard Deviation: 1947.45

Week 12

570.0

pg/mL (Mean)

Standard Deviation: 1347.75

Week 120

638.4

pg/mL (Mean)

Standard Deviation: 1993.90

Week 132

714.2

pg/mL (Mean)

Standard Deviation: 2262.71

Week 144

472.6

pg/mL (Mean)

Standard Deviation: 283.43

Week 156

586.3

pg/mL (Mean)

Standard Deviation: 811.97

Week 168

493.7

pg/mL (Mean)

Standard Deviation: 342.53

Week 180

653.8

pg/mL (Mean)

Standard Deviation: 694.69

Week 192

974.0

pg/mL (Mean)

Standard Deviation: 898.28

Week 24

483.7

pg/mL (Mean)

Standard Deviation: 536.30

Week 36

581.6

pg/mL (Mean)

Standard Deviation: 1316.46

Week 48

500.2

pg/mL (Mean)

Standard Deviation: 940.36

Week 60

704.9

pg/mL (Mean)

Standard Deviation: 2338.15

Week 72

661.8

pg/mL (Mean)

Standard Deviation: 2014.14

Week 84

543.1

pg/mL (Mean)

Standard Deviation: 1246.14

Week 96

799.6

pg/mL (Mean)

Standard Deviation: 2767.12

25-Hydroxyvitamin D Levels

AST-120

Baseline

22.08

ng/mL (Mean)

Standard Deviation: 10.361

Early Term/Discontinuation

20.57

ng/mL (Mean)

Standard Deviation: 9.958

Final Visit

25.2

ng/mL (Mean)

Standard Deviation: 10.847

Week 108

21.85

ng/mL (Mean)

Standard Deviation: 11.324

Week 12

21.55

ng/mL (Mean)

Standard Deviation: 9.988

Week 120

22.15

ng/mL (Mean)

Standard Deviation: 11.189

Week 132

22.04

ng/mL (Mean)

Standard Deviation: 10.581

Week 144

23.29

ng/mL (Mean)

Standard Deviation: 11.051

Week 156

23.23

ng/mL (Mean)

Standard Deviation: 9.857

Week 168

25.45

ng/mL (Mean)

Standard Deviation: 12.045

Week 180

29.58

ng/mL (Mean)

Standard Deviation: 12.985

Week 192

33.1

ng/mL (Mean)

Standard Deviation: 6.651

Week 24

21.41

ng/mL (Mean)

Standard Deviation: 9.823

Week 36

21.7

ng/mL (Mean)

Standard Deviation: 10.539

Week 48

21.83

ng/mL (Mean)

Standard Deviation: 10.963

Week 60

21.78

ng/mL (Mean)

Standard Deviation: 11.076

Week 72

22.23

ng/mL (Mean)

Standard Deviation: 10.988

Week 84

21.79

ng/mL (Mean)

Standard Deviation: 10.759

Week 96

22.18

ng/mL (Mean)

Standard Deviation: 11.563

Placebo

Baseline

22.06

ng/mL (Mean)

Standard Deviation: 10.400

Early Term/Discontinuation

22.52

ng/mL (Mean)

Standard Deviation: 11.803

Final Visit

25.69

ng/mL (Mean)

Standard Deviation: 9.937

Week 108

21.62

ng/mL (Mean)

Standard Deviation: 10.679

Week 12

22.15

ng/mL (Mean)

Standard Deviation: 10.162

Week 120

22.45

ng/mL (Mean)

Standard Deviation: 9.344

Week 132

21.83

ng/mL (Mean)

Standard Deviation: 10.285

Week 144

22.95

ng/mL (Mean)

Standard Deviation: 11.046

Week 156

23.01

ng/mL (Mean)

Standard Deviation: 12.943

Week 168

24.44

ng/mL (Mean)

Standard Deviation: 11.403

Week 180

28.1

ng/mL (Mean)

Standard Deviation: 10.929

Week 192

31.38

ng/mL (Mean)

Standard Deviation: 9.606

Week 24

22.13

ng/mL (Mean)

Standard Deviation: 9.648

Week 36

21.7

ng/mL (Mean)

Standard Deviation: 9.926

Week 48

22.06

ng/mL (Mean)

Standard Deviation: 10.644

Week 60

21.56

ng/mL (Mean)

Standard Deviation: 10.425

Week 72

22.29

ng/mL (Mean)

Standard Deviation: 9.617

Week 84

22.75

ng/mL (Mean)

Standard Deviation: 10.528

Week 96

22.53

ng/mL (Mean)

Standard Deviation: 10.833

Vitamin E Levels

AST-120

Baseline

17.49

ug/mL (Mean)

Standard Deviation: 7.554

Early Term/Discontinuation

15.72

ug/mL (Mean)

Standard Deviation: 5.512

Final Visit

17.14

ug/mL (Mean)

Standard Deviation: 7.356

Week 108

17.6

ug/mL (Mean)

Standard Deviation: 6.580

Week 12

17.3

ug/mL (Mean)

Standard Deviation: 6.880

Week 120

18.18

ug/mL (Mean)

Standard Deviation: 7.293

Week 132

18.71

ug/mL (Mean)

Standard Deviation: 7.926

Week 144

18.02

ug/mL (Mean)

Standard Deviation: 6.653

Week 156

17.59

ug/mL (Mean)

Standard Deviation: 5.937

Week 168

16.6

ug/mL (Mean)

Standard Deviation: 5.946

Week 180

15.52

ug/mL (Mean)

Standard Deviation: 4.696

Week 192

14.0

ug/mL (Mean)

Standard Deviation: 3.568

Week 24

17.55

ug/mL (Mean)

Standard Deviation: 7.237

Week 36

17.42

ug/mL (Mean)

Standard Deviation: 6.474

Week 48

17.58

ug/mL (Mean)

Standard Deviation: 7.040

Week 60

17.77

ug/mL (Mean)

Standard Deviation: 7.376

Week 72

17.5

ug/mL (Mean)

Standard Deviation: 6.683

Week 84

17.7

ug/mL (Mean)

Standard Deviation: 6.779

Week 96

17.24

ug/mL (Mean)

Standard Deviation: 6.510

Placebo

Baseline

16.95

ug/mL (Mean)

Standard Deviation: 6.923

Early Term/Discontinuation

15.58

ug/mL (Mean)

Standard Deviation: 6.200

Final Visit

16.03

ug/mL (Mean)

Standard Deviation: 5.606

Week 108

17.07

ug/mL (Mean)

Standard Deviation: 6.126

Week 12

16.44

ug/mL (Mean)

Standard Deviation: 6.080

Week 120

17.17

ug/mL (Mean)

Standard Deviation: 6.416

Week 132

16.52

ug/mL (Mean)

Standard Deviation: 5.407

Week 144

16.47

ug/mL (Mean)

Standard Deviation: 6.805

Week 156

17.21

ug/mL (Mean)

Standard Deviation: 7.081

Week 168

18.0

ug/mL (Mean)

Standard Deviation: 8.052

Week 180

15.17

ug/mL (Mean)

Standard Deviation: 7.808

Week 192

16.45

ug/mL (Mean)

Standard Deviation: 5.341

Week 24

17.08

ug/mL (Mean)

Standard Deviation: 6.560

Week 36

17.22

ug/mL (Mean)

Standard Deviation: 6.445

Week 48

17.31

ug/mL (Mean)

Standard Deviation: 6.544

Week 60

17.7

ug/mL (Mean)

Standard Deviation: 6.880

Week 72

17.07

ug/mL (Mean)

Standard Deviation: 6.119

Week 84

17.27

ug/mL (Mean)

Standard Deviation: 6.440

Week 96

17.28

ug/mL (Mean)

Standard Deviation: 6.480

Vitamin K Levels

AST-120

Baseline

0.711

ng/mL (Mean)

Standard Deviation: 0.6276

Early Term/Discontinuation

0.735

ng/mL (Mean)

Standard Deviation: 0.7523

Final Visit

0.971

ng/mL (Mean)

Standard Deviation: 0.7657

Week 108

0.802

ng/mL (Mean)

Standard Deviation: 0.6797

Week 12

0.752

ng/mL (Mean)

Standard Deviation: 0.6601

Week 120

0.768

ng/mL (Mean)

Standard Deviation: 0.6708

Week 132

0.824

ng/mL (Mean)

Standard Deviation: 0.7655

Week 144

0.882

ng/mL (Mean)

Standard Deviation: 0.7630

Week 156

0.754

ng/mL (Mean)

Standard Deviation: 0.6129

Week 168

0.858

ng/mL (Mean)

Standard Deviation: 0.6494

Week 180

0.85

ng/mL (Mean)

Standard Deviation: 0.7162

Week 24

0.705

ng/mL (Mean)

Standard Deviation: 0.6006

Week 36

0.739

ng/mL (Mean)

Standard Deviation: 0.6726

Week 48

0.763

ng/mL (Mean)

Standard Deviation: 0.6630

Week 60

0.761

ng/mL (Mean)

Standard Deviation: 0.6868

Week 72

0.823

ng/mL (Mean)

Standard Deviation: 0.7291

Week 84

0.78

ng/mL (Mean)

Standard Deviation: 0.7174

Week 96

0.809

ng/mL (Mean)

Standard Deviation: 0.7156

Placebo

Baseline

0.721

ng/mL (Mean)

Standard Deviation: 0.6308

Early Term/Discontinuation

0.686

ng/mL (Mean)

Standard Deviation: 0.5772

Final Visit

0.844

ng/mL (Mean)

Standard Deviation: 0.6784

Week 108

0.768

ng/mL (Mean)

Standard Deviation: 0.7119

Week 12

0.769

ng/mL (Mean)

Standard Deviation: 0.6887

Week 120

0.814

ng/mL (Mean)

Standard Deviation: 0.7119

Week 132

0.76

ng/mL (Mean)

Standard Deviation: 0.5740

Week 144

0.78

ng/mL (Mean)

Standard Deviation: 0.6052

Week 156

0.816

ng/mL (Mean)

Standard Deviation: 0.6822

Week 168

1.031

ng/mL (Mean)

Standard Deviation: 0.8805

Week 180

0.97

ng/mL (Mean)

Standard Deviation: 0.9033

Week 24

0.706

ng/mL (Mean)

Standard Deviation: 0.6238

Week 36

0.748

ng/mL (Mean)

Standard Deviation: 0.6630

Week 48

0.704

ng/mL (Mean)

Standard Deviation: 0.6491

Week 60

0.778

ng/mL (Mean)

Standard Deviation: 0.7247

Week 72

0.722

ng/mL (Mean)

Standard Deviation: 0.6489

Week 84

0.725

ng/mL (Mean)

Standard Deviation: 0.6869

Week 96

0.768

ng/mL (Mean)

Standard Deviation: 0.6867

Serum Folate Levels

AST-120

Baseline

21.7

ng/mL (Mean)

Standard Deviation: 44.420

Early Term/Discontinuation

24.43

ng/mL (Mean)

Standard Deviation: 49.342

Final Visit

15.52

ng/mL (Mean)

Standard Deviation: 26.263

Week 108

13.5

ng/mL (Mean)

Standard Deviation: 18.491

Week 12

21.47

ng/mL (Mean)

Standard Deviation: 46.801

Week 120

12.52

ng/mL (Mean)

Standard Deviation: 16.033

Week 132

17.09

ng/mL (Mean)

Standard Deviation: 45.645

Week 144

18.13

ng/mL (Mean)

Standard Deviation: 41.386

Week 156

13.08

ng/mL (Mean)

Standard Deviation: 13.098

Week 168

15.13

ng/mL (Mean)

Standard Deviation: 12.776

Week 180

33.1

ng/mL (Mean)

Standard Deviation: 19.021

Week 24

18.16

ng/mL (Mean)

Standard Deviation: 34.095

Week 36

20.95

ng/mL (Mean)

Standard Deviation: 47.528

Week 48

19.3

ng/mL (Mean)

Standard Deviation: 44.798

Week 60

19.06

ng/mL (Mean)

Standard Deviation: 41.799

Week 72

16.12

ng/mL (Mean)

Standard Deviation: 32.761

Week 84

17.0

ng/mL (Mean)

Standard Deviation: 30.020

Week 96

14.47

ng/mL (Mean)

Standard Deviation: 25.918

Placebo

Baseline

21.78

ng/mL (Mean)

Standard Deviation: 47.064

Early Term/Discontinuation

17.14

ng/mL (Mean)

Standard Deviation: 24.122

Final Visit

22.66

ng/mL (Mean)

Standard Deviation: 50.498

Week 108

19.22

ng/mL (Mean)

Standard Deviation: 39.625

Week 12

20.94

ng/mL (Mean)

Standard Deviation: 45.093

Week 120

17.01

ng/mL (Mean)

Standard Deviation: 36.733

Week 132

18.85

ng/mL (Mean)

Standard Deviation: 44.240

Week 144

18.09

ng/mL (Mean)

Standard Deviation: 39.002

Week 156

15.13

ng/mL (Mean)

Standard Deviation: 20.162

Week 168

16.26

ng/mL (Mean)

Standard Deviation: 19.734

Week 180

22.23

ng/mL (Mean)

Standard Deviation: 25.137

Week 24

19.46

ng/mL (Mean)

Standard Deviation: 45.178

Week 36

18.54

ng/mL (Mean)

Standard Deviation: 41.653

Week 48

21.5

ng/mL (Mean)

Standard Deviation: 49.944

Week 60

19.72

ng/mL (Mean)

Standard Deviation: 45.119

Week 72

19.96

ng/mL (Mean)

Standard Deviation: 43.951

Week 84

20.95

ng/mL (Mean)

Standard Deviation: 46.184

Week 96

18.17

ng/mL (Mean)

Standard Deviation: 36.846

Total

1020

Participants

Age, Continuous

56.1

years (Mean)

Standard Deviation: 14.95