Trial | NCT02463071  Report issue

Title

AZD0585 Phase III Long-term Study in Japan
A Randomised, Double-blind, Placebo Controlled, Parallel Group, Phase III Long-term Study to Evaluate Efficacy and Safety of 12 Weeks and 52 Weeks of AZD0585 Administration, Respectively, in Japanese Patients With Hyperlipidemia Accompanied by Hypertriglyceridemia.

  • Phase

    Phase 3

  • Study Type

    Interventional

  • Study Participants

    383
This study is a randomised, double-blind phase III long-term study to evaluate efficacy and safety of 12 weeks and 52 weeks of AZD0585 administration compared to placebo in patients with hyperlipidemia accompanied by hypertriglyceridemia .
Study Started
Jun 10
2015
Primary Completion
Mar 11
2017
Study Completion
Mar 11
2017
Results Posted
Oct 01
2018
Last Update
Oct 01
2018

Drug AZD0585

1g soft capsule

  • Other names: Epanova

Drug AZD0585 placebo

1g soft capsule

  • Other names: Corn oil

AZD0585 2g group Experimental

AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily

AZD0585 4g group Experimental

AZD0585 1g × 4 capsules once daily

Placebo control group Placebo Comparator

AZD0585 placebo 1g × 4 capsules once daily

Criteria 

Key Inclusion Criteria:

Japanese men or women, ≥20 years of age.

Subjects must meet all of the following criteria;

Fasting triglyceride level: average of Visit 2 and Visit 3 must be in the range 150 - 499 mg/dL
%TG change between Visit 2 and Visit 3 must be within 30%
%LDL-C change between Visit 2 and Visit 3 must be within 25%

Key Exclusion Criteria:

Allergy or intolerance to omega-3 fatty acids and omega-3-acid ethyl esters.
Known lipoprotein lipase impairment or deficiency, or Apolipoprotein C-II deficiency or familial dysbetalipoproteinemia.
Current or history of pancreatitis.
Type I diabetes mellitus, use of insulin, or haemoglobin A1c >10% at Visit 1.

Summary

AZD0585 2g Group

AZD0585 4g Group

Placebo Control Group

All Events

Event Type Organ System Event Term AZD0585 2g Group AZD0585 4g Group Placebo Control Group

Efficacy of AZD0585 by Assessment of Percent Change in Serum Triglycerides

To demonstrate the efficacy of AZD0585 2 g and 4 g compared to placebo (corn oil) in Japanese patients with hypertriglyceridemia.

AZD0585 2g Group

-15.57
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.70

AZD0585 4g Group

-21.78
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.95

Placebo Control Group

11.15
% (percent change from baseline) (Least Squares Mean)
Standard Error: 4.65

Safety of AZD0585 by Assessment of Adverse Events in Patients

To evaluate the long-term (up to 52 weeks) safety of AZD0585 in Japanese patients with hypertriglyceridemia.

AZD0585 2g Group

Any AE

127.0
Participants

Any AE leading to discontinuation of IP

6.0
Participants

Any AE with outcome = death

1.0
Participants

Any causally related AE

16.0
Participants

Any serious AE

6.0
Participants

Any severe AE

4.0
Participants

AZD0585 4g Group

Any AE

135.0
Participants

Any AE leading to discontinuation of IP

5.0
Participants

Any AE with outcome = death

Any causally related AE

36.0
Participants

Any serious AE

6.0
Participants

Any severe AE

1.0
Participants

Placebo Control Group

Any AE

55.0
Participants

Any AE leading to discontinuation of IP

1.0
Participants

Any AE with outcome = death

Any causally related AE

8.0
Participants

Any serious AE

4.0
Participants

Any severe AE

Efficacy of AZD0585 by Assessment of Percent Change in Serum Lipid Profile

To assess the efficacy of AZD0585 2 g and 4 g compared to placebo (corn oil). The serum lipid profile includes total cholesterol, High-density lipoprotein cholesterol, Low-density lipoprotein cholesterol,Very low-density lipoprotein cholesterol and Non-high-density lipoprotein cholesterol.

AZD0585 2g Group

High-density lipoprotein cholesterol

2.64
% (percent change from baseline) (Least Squares Mean)
Standard Error: 0.83

Low-density lipoprotein cholesterol

1.45
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.18

Non-high-density lipoprotein cholesterol

-1.33
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.05

Total cholesterol

-0.34
% (percent change from baseline) (Least Squares Mean)
Standard Error: 0.78

Very low-density lipoprotein cholesterol

-10.18
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.62

AZD0585 4g Group

High-density lipoprotein cholesterol

1.54
% (percent change from baseline) (Least Squares Mean)
Standard Error: 0.86

Low-density lipoprotein cholesterol

-2.17
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.91

Non-high-density lipoprotein cholesterol

-3.11
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.74

Total cholesterol

-1.95
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.29

Very low-density lipoprotein cholesterol

-18.35
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.73

Placebo Control Group

High-density lipoprotein cholesterol

1.33
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.22

Low-density lipoprotein cholesterol

2.9
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.10

Non-high-density lipoprotein cholesterol

3.05
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.83

Total cholesterol

2.31
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.31

Very low-density lipoprotein cholesterol

7.06
% (percent change from baseline) (Least Squares Mean)
Standard Error: 3.84

Efficacy of AZD0585 by Assessment of Percent Changes in Plasma Fatty Acids Profile.

To assess the efficacy of AZD0585 2 g and 4 g compared to placebo (corn oil) . The plasma fatty acids profile includes eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid and eicosapentaenoic acid per arachidonic acid rate.

AZD0585 2g Group

AA

-7.26
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.33

DHA

14.21
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.50

EPA

153.06
% (percent change from baseline) (Least Squares Mean)
Standard Error: 10.40

EPA/AA ratio

169.64
% (percent change from baseline) (Least Squares Mean)
Standard Error: 11.12

AZD0585 4g Group

AA

-10.0
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.39

DHA

20.1
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.45

EPA

265.34
% (percent change from baseline) (Least Squares Mean)
Standard Error: 15.86

EPA/AA ratio

319.9
% (percent change from baseline) (Least Squares Mean)
Standard Error: 20.02

Placebo Control Group

AA

0.86
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.82

DHA

0.13
% (percent change from baseline) (Least Squares Mean)
Standard Error: 4.13

EPA

3.6
% (percent change from baseline) (Least Squares Mean)
Standard Error: 10.25

EPA/AA ratio

-2.19
% (percent change from baseline) (Least Squares Mean)
Standard Error: 9.23

Efficacy of AZD0585 by Assessment of Percent Changes in Apolipoproteins Profile

To assess the efficacy of AZD0585 2 g and 4 g compared to placebo (corn oil) . Apolipoproteins include Apolipoprotein A-I, Apolipoprotein A-II, Apolipoprotein B, Apolipoprotein B48, Apolipoprotein C-II, Apolipoprotein C-III and Apolipoprotein E.

Placebo Control Group

Apo A-I

0.55
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.10

Apo A-II

0.31
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.01

Apo B

2.6
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.79

Apo B48

41.58
% (percent change from baseline) (Least Squares Mean)
Standard Error: 17.49

Apo C-II

5.49
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.45

Apo C-III

5.56
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.91

Apo E

9.67
% (percent change from baseline) (Least Squares Mean)
Standard Error: 3.08

AZD0585 2g Group

Apo A-I

0.39
% (percent change from baseline) (Least Squares Mean)
Standard Error: 0.84

Apo A-II

-3.2
% (percent change from baseline) (Least Squares Mean)
Standard Error: 0.85

Apo B

1.73
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.05

Apo B48

-2.87
% (percent change from baseline) (Least Squares Mean)
Standard Error: 4.86

Apo C-II

-2.98
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.82

Apo C-III

-2.5
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.03

Apo E

5.25
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.08

AZD0585 4g Group

Apo A-I

-0.42
% (percent change from baseline) (Least Squares Mean)
Standard Error: 0.83

Apo A-II

-5.01
% (percent change from baseline) (Least Squares Mean)
Standard Error: 0.80

Apo B

-0.3
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.07

Apo B48

0.94
% (percent change from baseline) (Least Squares Mean)
Standard Error: 5.26

Apo C-II

-6.2
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.26

Apo C-III

-5.47
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.20

Apo E

6.27
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.06

Efficacy of AZD0585 by Assessment of Percent Changes in Small Dense LDL and LDL-C/Apo B Ratio

To assess the efficacy of AZD0585 2 g and 4 g compared to placebo (corn oil).

AZD0585 2g Group

LDL-C/Apo B ratio

0.58
% (percent change from baseline) (Least Squares Mean)
Standard Error: 0.99

Small dense LDL

-0.49
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.08

AZD0585 4g Group

LDL-C/Apo B ratio

-1.77
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.63

Small dense LDL

-1.72
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.05

Placebo Control Group

LDL-C/Apo B ratio

0.66
% (percent change from baseline) (Least Squares Mean)
Standard Error: 1.41

Small dense LDL

5.19
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.91

Efficacy of AZD0585 by Assessment of Percent Changes in Lp(a), RLP-C, PCSK9, and Hs-CRP

To assess the efficacy of AZD0585 2 g and 4 g compared to placebo (corn oil).

AZD0585 2g Group

hs-CRP

119.94
% (percent change from baseline) (Least Squares Mean)
Standard Error: 59.65

Lp(a)

14.84
% (percent change from baseline) (Least Squares Mean)
Standard Error: 4.31

PCSK9

3.2
% (percent change from baseline) (Least Squares Mean)
Standard Error: 2.79

RLP-C

5.85
% (percent change from baseline) (Least Squares Mean)
Standard Error: 6.84

AZD0585 4g Group

hs-CRP

15.24
% (percent change from baseline) (Least Squares Mean)
Standard Error: 19.29

Lp(a)

22.69
% (percent change from baseline) (Least Squares Mean)
Standard Error: 3.97

PCSK9

0.51
% (percent change from baseline) (Least Squares Mean)
Standard Error: 3.10

RLP-C

54.86
% (percent change from baseline) (Least Squares Mean)
Standard Error: 55.30

Placebo Control Group

hs-CRP

69.61
% (percent change from baseline) (Least Squares Mean)
Standard Error: 42.95

Lp(a)

3.18
% (percent change from baseline) (Least Squares Mean)
Standard Error: 5.04

PCSK9

13.53
% (percent change from baseline) (Least Squares Mean)
Standard Error: 4.57

RLP-C

53.8
% (percent change from baseline) (Least Squares Mean)
Standard Error: 16.67

Total

382
Participants

Age, Continuous

56.9
Years (Mean)
Standard Deviation: 10.7

BMI

26.9
kg/m2 (Mean)
Standard Deviation: 4.0

Height

166.8
cm (Mean)
Standard Deviation: 8.0

Weight

75.0
kg (Mean)
Standard Deviation: 13.4

Baseline HDL-C

Baseline LDL-C

Baseline triglyceride

Concurrent use of statin

Diabetes

established CVD

Hypertension

Race/Ethnicity, Customized

Sex: Female, Male

Overall Study

AZD0585 2g Group

AZD0585 4g Group

Placebo Control Group

Drop/Withdrawal Reasons

AZD0585 2g Group

AZD0585 4g Group

Placebo Control Group