Trial Outcomes & Findings for AZD0585 Phase III Long-term Study in Japan (NCT NCT02463071)

Last Updated: 2018-10-01

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

383 participants

Primary outcome timeframe

From baseline to Week12

Results posted on

2018-10-01

Participant Flow

This study was conducted in 26 sites in Japan between 10 June 2015 and 08 March 2017.

The study duration was up to 60 weeks, consisting of an initial screening period of 8 weeks and a 52-week treatment period.

Participant milestones

Participant milestones
Measure	AZD0585 2g Group AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily	AZD0585 4g Group AZD0585 1g × 4 capsules once daily	Placebo Control Group AZD0585 placebo 1g × 4 capsules once daily
Overall Study STARTED	152	154	77
Overall Study COMPLETED	140	138	71
Overall Study NOT COMPLETED	12	16	6

Reasons for withdrawal

Reasons for withdrawal
Measure	AZD0585 2g Group AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily	AZD0585 4g Group AZD0585 1g × 4 capsules once daily	Placebo Control Group AZD0585 placebo 1g × 4 capsules once daily
Overall Study Adverse Event	3	5	1
Overall Study Death	1	0	0
Overall Study Eligibility criteria not fulfilled	1	0	0
Overall Study Reason not specified	7	9	4
Overall Study Protocol Violation	0	2	0
Overall Study Lost to Follow-up	0	0	1

Baseline Characteristics

AZD0585 Phase III Long-term Study in Japan

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD0585 2g Group n=152 Participants AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily	AZD0585 4g Group n=154 Participants AZD0585 1g × 4 capsules once daily	Placebo Control Group n=76 Participants AZD0585 placebo 1g × 4 capsules once daily	Total n=382 Participants Total of all reporting groups
Age, Continuous	56.9 Years STANDARD_DEVIATION 10.1 • n=99 Participants	56.5 Years STANDARD_DEVIATION 11.2 • n=107 Participants	57.4 Years STANDARD_DEVIATION 10.9 • n=206 Participants	56.9 Years STANDARD_DEVIATION 10.7 • n=7 Participants
Sex: Female, Male Female	41 Participants n=99 Participants	29 Participants n=107 Participants	13 Participants n=206 Participants	83 Participants n=7 Participants
Sex: Female, Male Male	111 Participants n=99 Participants	125 Participants n=107 Participants	63 Participants n=206 Participants	299 Participants n=7 Participants
Race/Ethnicity, Customized Asian	152 Participants n=99 Participants	154 Participants n=107 Participants	76 Participants n=206 Participants	382 Participants n=7 Participants
Weight	74.5 kg STANDARD_DEVIATION 12.8 • n=99 Participants	75.8 kg STANDARD_DEVIATION 14.1 • n=107 Participants	74.4 kg STANDARD_DEVIATION 13.2 • n=206 Participants	75.0 kg STANDARD_DEVIATION 13.4 • n=7 Participants
BMI	26.9 kg/m2 STANDARD_DEVIATION 4.0 • n=99 Participants	26.9 kg/m2 STANDARD_DEVIATION 4.0 • n=107 Participants	26.8 kg/m2 STANDARD_DEVIATION 3.9 • n=206 Participants	26.9 kg/m2 STANDARD_DEVIATION 4.0 • n=7 Participants
Height	166.1 cm STANDARD_DEVIATION 7.8 • n=99 Participants	167.6 cm STANDARD_DEVIATION 7.7 • n=107 Participants	166.4 cm STANDARD_DEVIATION 9.0 • n=206 Participants	166.8 cm STANDARD_DEVIATION 8.0 • n=7 Participants
Baseline triglyceride < 300 mg/dL	132 Participants n=99 Participants	127 Participants n=107 Participants	64 Participants n=206 Participants	323 Participants n=7 Participants
Baseline triglyceride >= 300 mg/dL	20 Participants n=99 Participants	27 Participants n=107 Participants	12 Participants n=206 Participants	59 Participants n=7 Participants
Concurrent use of statin Yes	79 Participants n=99 Participants	78 Participants n=107 Participants	38 Participants n=206 Participants	195 Participants n=7 Participants
Concurrent use of statin No	73 Participants n=99 Participants	76 Participants n=107 Participants	38 Participants n=206 Participants	187 Participants n=7 Participants
Baseline LDL-C < 140 mg/dL	134 Participants n=99 Participants	141 Participants n=107 Participants	66 Participants n=206 Participants	341 Participants n=7 Participants
Baseline LDL-C >= 140 mg/dL	18 Participants n=99 Participants	13 Participants n=107 Participants	10 Participants n=206 Participants	41 Participants n=7 Participants
Baseline HDL-C < 40 mg/dL	43 Participants n=99 Participants	52 Participants n=107 Participants	22 Participants n=206 Participants	117 Participants n=7 Participants
Baseline HDL-C >= 40 mg/dL	109 Participants n=99 Participants	102 Participants n=107 Participants	54 Participants n=206 Participants	265 Participants n=7 Participants
Hypertension Yes	97 Participants n=99 Participants	103 Participants n=107 Participants	44 Participants n=206 Participants	244 Participants n=7 Participants
Hypertension No	55 Participants n=99 Participants	51 Participants n=107 Participants	32 Participants n=206 Participants	138 Participants n=7 Participants
Diabetes Yes	60 Participants n=99 Participants	68 Participants n=107 Participants	29 Participants n=206 Participants	157 Participants n=7 Participants
Diabetes No	92 Participants n=99 Participants	86 Participants n=107 Participants	47 Participants n=206 Participants	225 Participants n=7 Participants
established CVD Yes	22 Participants n=99 Participants	13 Participants n=107 Participants	9 Participants n=206 Participants	44 Participants n=7 Participants
established CVD No	130 Participants n=99 Participants	141 Participants n=107 Participants	67 Participants n=206 Participants	338 Participants n=7 Participants

PRIMARY outcome

Timeframe: From baseline to Week12

Population: The Full Analysis Set included all randomized patients who had both any baseline and any post-baseline efficacy measurements.

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

Outcome measures

Outcome measures
Measure	AZD0585 2g Group n=152 Participants AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily	AZD0585 4g Group n=154 Participants AZD0585 1g × 4 capsules once daily	Placebo Control Group n=76 Participants AZD0585 placebo 1g × 4 capsules once daily
Efficacy of AZD0585 by Assessment of Percent Change in Serum Triglycerides	-15.57 % (percent change from baseline) Standard Error 1.70	-21.78 % (percent change from baseline) Standard Error 1.95	11.15 % (percent change from baseline) Standard Error 4.65

PRIMARY outcome

Timeframe: From baseline to Week52

Population: The Safety Analysis Set included all patients who took at least 1 dose of double-blind investigational product.

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

Outcome measures

Outcome measures
Measure	AZD0585 2g Group n=152 Participants AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily	AZD0585 4g Group n=154 Participants AZD0585 1g × 4 capsules once daily	Placebo Control Group n=77 Participants AZD0585 placebo 1g × 4 capsules once daily
Safety of AZD0585 by Assessment of Adverse Events in Patients Any AE	127 Participants	135 Participants	55 Participants
Safety of AZD0585 by Assessment of Adverse Events in Patients Any AE with outcome = death	1 Participants	0 Participants	0 Participants
Safety of AZD0585 by Assessment of Adverse Events in Patients Any serious AE	6 Participants	6 Participants	4 Participants
Safety of AZD0585 by Assessment of Adverse Events in Patients Any AE leading to discontinuation of IP	6 Participants	5 Participants	1 Participants
Safety of AZD0585 by Assessment of Adverse Events in Patients Any causally related AE	16 Participants	36 Participants	8 Participants
Safety of AZD0585 by Assessment of Adverse Events in Patients Any severe AE	4 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline to Week12

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.

Outcome measures

Outcome measures
Measure	AZD0585 2g Group n=152 Participants AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily	AZD0585 4g Group n=154 Participants AZD0585 1g × 4 capsules once daily	Placebo Control Group n=76 Participants AZD0585 placebo 1g × 4 capsules once daily
Efficacy of AZD0585 by Assessment of Percent Change in Serum Lipid Profile Total cholesterol	-0.34 % (percent change from baseline) Standard Error 0.78	-1.95 % (percent change from baseline) Standard Error 1.29	2.31 % (percent change from baseline) Standard Error 1.31
Efficacy of AZD0585 by Assessment of Percent Change in Serum Lipid Profile Low-density lipoprotein cholesterol	1.45 % (percent change from baseline) Standard Error 1.18	-2.17 % (percent change from baseline) Standard Error 1.91	2.90 % (percent change from baseline) Standard Error 2.10
Efficacy of AZD0585 by Assessment of Percent Change in Serum Lipid Profile High-density lipoprotein cholesterol	2.64 % (percent change from baseline) Standard Error 0.83	1.54 % (percent change from baseline) Standard Error 0.86	1.33 % (percent change from baseline) Standard Error 1.22
Efficacy of AZD0585 by Assessment of Percent Change in Serum Lipid Profile Non-high-density lipoprotein cholesterol	-1.33 % (percent change from baseline) Standard Error 1.05	-3.11 % (percent change from baseline) Standard Error 1.74	3.05 % (percent change from baseline) Standard Error 1.83
Efficacy of AZD0585 by Assessment of Percent Change in Serum Lipid Profile Very low-density lipoprotein cholesterol	-10.18 % (percent change from baseline) Standard Error 2.62	-18.35 % (percent change from baseline) Standard Error 2.73	7.06 % (percent change from baseline) Standard Error 3.84

SECONDARY outcome

Timeframe: From baseline to Week12

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.

Outcome measures

Outcome measures
Measure	AZD0585 2g Group n=151 Participants AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily	AZD0585 4g Group n=154 Participants AZD0585 1g × 4 capsules once daily	Placebo Control Group n=76 Participants AZD0585 placebo 1g × 4 capsules once daily
Efficacy of AZD0585 by Assessment of Percent Changes in Plasma Fatty Acids Profile. EPA	153.06 % (percent change from baseline) Standard Error 10.40	265.34 % (percent change from baseline) Standard Error 15.86	3.60 % (percent change from baseline) Standard Error 10.25
Efficacy of AZD0585 by Assessment of Percent Changes in Plasma Fatty Acids Profile. DHA	14.21 % (percent change from baseline) Standard Error 2.50	20.10 % (percent change from baseline) Standard Error 2.45	0.13 % (percent change from baseline) Standard Error 4.13
Efficacy of AZD0585 by Assessment of Percent Changes in Plasma Fatty Acids Profile. AA	-7.26 % (percent change from baseline) Standard Error 1.33	-10.00 % (percent change from baseline) Standard Error 1.39	0.86 % (percent change from baseline) Standard Error 1.82
Efficacy of AZD0585 by Assessment of Percent Changes in Plasma Fatty Acids Profile. EPA/AA ratio	169.64 % (percent change from baseline) Standard Error 11.12	319.90 % (percent change from baseline) Standard Error 20.02	-2.19 % (percent change from baseline) Standard Error 9.23

SECONDARY outcome

Timeframe: From baseline to Week12

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.

Outcome measures

Outcome measures
Measure	AZD0585 2g Group n=151 Participants AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily	AZD0585 4g Group n=154 Participants AZD0585 1g × 4 capsules once daily	Placebo Control Group n=76 Participants AZD0585 placebo 1g × 4 capsules once daily
Efficacy of AZD0585 by Assessment of Percent Changes in Apolipoproteins Profile Apo E	5.25 % (percent change from baseline) Standard Error 2.08	6.27 % (percent change from baseline) Standard Error 2.06	9.67 % (percent change from baseline) Standard Error 3.08
Efficacy of AZD0585 by Assessment of Percent Changes in Apolipoproteins Profile Apo C-II	-2.98 % (percent change from baseline) Standard Error 1.82	-6.20 % (percent change from baseline) Standard Error 2.26	5.49 % (percent change from baseline) Standard Error 2.45
Efficacy of AZD0585 by Assessment of Percent Changes in Apolipoproteins Profile Apo C-III	-2.50 % (percent change from baseline) Standard Error 2.03	-5.47 % (percent change from baseline) Standard Error 2.20	5.56 % (percent change from baseline) Standard Error 2.91
Efficacy of AZD0585 by Assessment of Percent Changes in Apolipoproteins Profile Apo A-I	0.39 % (percent change from baseline) Standard Error 0.84	-0.42 % (percent change from baseline) Standard Error 0.83	0.55 % (percent change from baseline) Standard Error 1.10
Efficacy of AZD0585 by Assessment of Percent Changes in Apolipoproteins Profile Apo A-II	-3.20 % (percent change from baseline) Standard Error 0.85	-5.01 % (percent change from baseline) Standard Error 0.80	0.31 % (percent change from baseline) Standard Error 1.01
Efficacy of AZD0585 by Assessment of Percent Changes in Apolipoproteins Profile Apo B	1.73 % (percent change from baseline) Standard Error 1.05	-0.30 % (percent change from baseline) Standard Error 1.07	2.60 % (percent change from baseline) Standard Error 1.79
Efficacy of AZD0585 by Assessment of Percent Changes in Apolipoproteins Profile Apo B48	-2.87 % (percent change from baseline) Standard Error 4.86	0.94 % (percent change from baseline) Standard Error 5.26	41.58 % (percent change from baseline) Standard Error 17.49

SECONDARY outcome

Timeframe: From baseline to Week12

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

Outcome measures

Outcome measures
Measure	AZD0585 2g Group n=151 Participants AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily	AZD0585 4g Group n=154 Participants AZD0585 1g × 4 capsules once daily	Placebo Control Group n=76 Participants AZD0585 placebo 1g × 4 capsules once daily
Efficacy of AZD0585 by Assessment of Percent Changes in Small Dense LDL and LDL-C/Apo B Ratio Small dense LDL	-0.49 % (percent change from baseline) Standard Error 2.08	-1.72 % (percent change from baseline) Standard Error 2.05	5.19 % (percent change from baseline) Standard Error 2.91
Efficacy of AZD0585 by Assessment of Percent Changes in Small Dense LDL and LDL-C/Apo B Ratio LDL-C/Apo B ratio	0.58 % (percent change from baseline) Standard Error 0.99	-1.77 % (percent change from baseline) Standard Error 1.63	0.66 % (percent change from baseline) Standard Error 1.41

SECONDARY outcome

Timeframe: From baseline to Week12

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

Outcome measures

Outcome measures
Measure	AZD0585 2g Group n=151 Participants AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily	AZD0585 4g Group n=154 Participants AZD0585 1g × 4 capsules once daily	Placebo Control Group n=76 Participants AZD0585 placebo 1g × 4 capsules once daily
Efficacy of AZD0585 by Assessment of Percent Changes in Lp(a), RLP-C, PCSK9, and Hs-CRP Lp(a)	14.84 % (percent change from baseline) Standard Error 4.31	22.69 % (percent change from baseline) Standard Error 3.97	3.18 % (percent change from baseline) Standard Error 5.04
Efficacy of AZD0585 by Assessment of Percent Changes in Lp(a), RLP-C, PCSK9, and Hs-CRP hs-CRP	119.94 % (percent change from baseline) Standard Error 59.65	15.24 % (percent change from baseline) Standard Error 19.29	69.61 % (percent change from baseline) Standard Error 42.95
Efficacy of AZD0585 by Assessment of Percent Changes in Lp(a), RLP-C, PCSK9, and Hs-CRP RLP-C	5.85 % (percent change from baseline) Standard Error 6.84	54.86 % (percent change from baseline) Standard Error 55.30	53.80 % (percent change from baseline) Standard Error 16.67
Efficacy of AZD0585 by Assessment of Percent Changes in Lp(a), RLP-C, PCSK9, and Hs-CRP PCSK9	3.20 % (percent change from baseline) Standard Error 2.79	0.51 % (percent change from baseline) Standard Error 3.10	13.53 % (percent change from baseline) Standard Error 4.57

Adverse Events

AZD0585 2g Group

Serious events: 6 serious events

Other events: 127 other events

Deaths: 1 deaths

AZD0585 4g Group

Serious events: 6 serious events

Other events: 135 other events

Deaths: 0 deaths

Placebo Control Group

Serious events: 4 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Torbjorn Lundstrom, MD, PhD

AstraZeneca

Phone: +46 31 706 4100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	AZD0585 2g Group n=152 participants at risk AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily	AZD0585 4g Group n=154 participants at risk AZD0585 1g × 4 capsules once daily	Placebo Control Group n=77 participants at risk AZD0585 placebo 1g × 4 capsules once daily
Infections and infestations Meningitis bacterial	0.66% 1/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Infections and infestations Sinusitis	0.00% 0/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	1.3% 1/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Infections and infestations Urinary tract infection	0.00% 0/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.65% 1/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.66% 1/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.65% 1/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.66% 1/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Urethral cancer	0.66% 1/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Ear and labyrinth disorders Vertigo	0.00% 0/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.65% 1/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Cardiac disorders Atrioventricular block complete	0.66% 1/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Cardiac disorders Myocardial ischaemia	0.00% 0/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.65% 1/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Gastrointestinal disorders Abdominal pain	0.00% 0/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	1.3% 1/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Gastrointestinal disorders Large intestine polyp	0.00% 0/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.65% 1/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.66% 1/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	1.3% 1/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	1.3% 1/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.65% 1/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Injury, poisoning and procedural complications Fracture displacement	0.66% 1/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.

Measure	AZD0585 2g Group n=152 participants at risk AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily	AZD0585 4g Group n=154 participants at risk AZD0585 1g × 4 capsules once daily	Placebo Control Group n=77 participants at risk AZD0585 placebo 1g × 4 capsules once daily
Infections and infestations Bronchitis	7.2% 11/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	7.8% 12/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	6.5% 5/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Infections and infestations Gastroenteritis	5.9% 9/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	5.8% 9/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	2.6% 2/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Infections and infestations Influenza	3.9% 6/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	3.2% 5/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Infections and infestations Nasopharyngitis	36.8% 56/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	36.4% 56/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	36.4% 28/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Infections and infestations Oral herpes	3.3% 5/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.65% 1/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Infections and infestations Pharyngitis	3.9% 6/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	5.2% 8/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	6.5% 5/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Infections and infestations Upper respiratory tract infection	3.3% 5/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	1.9% 3/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	3.9% 3/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Metabolism and nutrition disorders Diabetes mellitus	2.6% 4/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	3.2% 5/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	6.5% 5/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Eye disorders Cataract	0.00% 0/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	3.2% 5/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	1.3% 1/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Vascular disorders Hypertension	4.6% 7/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	2.6% 4/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	1.3% 1/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.65% 1/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	3.9% 3/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Gastrointestinal disorders Abdominal discomfort	2.6% 4/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	3.9% 6/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Gastrointestinal disorders Dental caries	3.9% 6/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	3.2% 5/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Gastrointestinal disorders Diarrhoea	9.9% 15/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	18.2% 28/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	2.6% 2/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Skin and subcutaneous tissue disorders Eczema	2.0% 3/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	4.5% 7/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	0.00% 0/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Musculoskeletal and connective tissue disorders Arthralgia	3.3% 5/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	3.9% 6/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	5.2% 4/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.
Musculoskeletal and connective tissue disorders Back pain	8.6% 13/152 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	4.5% 7/154 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.	7.8% 6/77 • AEs, brief physical findings/clinical assessments, laboratory measurements, vital signs ,and ECGs were assessed throughout the 52-treatment period.