Epanova® for Lowering Very High Triglycerides II (EVOLVE II) - EVOLVEII

Study identifier:D5880C00001

ClinicalTrials.gov identifier:NCT02009865

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A 12-Week, Randomized, Double-Blind, Olive Oil-Controlled Phase 3 Study to Assess the Efficacy and Safety of EPANOVA™ in Subjects With Severe Hypertriglyceridemia (EVOLVE II)

Medical condition

Hypertriglyceridemia

Phase

Phase 3

Healthy volunteers

Study drug

Epanova, Olive Oil

Sex

All

Actual Enrollment

379

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 16 Dec 2013

Primary Completion Date: 23 Dec 2014

Study Completion Date: 23 Dec 2014

Study design

Allocation: Randomized
Endpoint Classification: Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Aug 2019 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Understanding of the study procedures, willingness to adhere to the study
schedule, and agreement to participate in the study by giving written
informed consent prior to screening;
2. Willing to use an appropriate and effective method of contraception;
3. Qualifying (average of Visit 1 or 1a + Visit 2 + Visit 2a [repeat
measurement]) serum TG ≥500 mg/dL (6 mMol/L) and <2500 mg/dL
(28 mMol/L);
4. Body mass index ≥20 kg/m2;
5. Untreated dyslipidemia or dyslipidemia treated with a statin, CAI, or
statin-CAI combination that has been stable for 6 weeks prior to
randomization; and
6. Willingness to maintain current physical activity level and follow the TLC
diet throughout the study.

Exclusion Criteria

1. Allergy or intolerance to omega-3 fatty acids, omega-3-acid ethyl esters, or
fish;
2. Known lipoprotein lipase impairment;
3. Known non-responder to omega-3 or fenofibrate therapy;
4. Use of any prescription medications containing EPA and/or DHA
(eg, Lovaza® or Vascepa®) within 8 weeks prior to randomization. Up to 1 g
capsule/day of an omega-3 dietary supplement will be permitted;
5. Unable to discontinue use of bile acid sequestrants, fibrates or niacin (other
than niacin-containing vitamins <200 mg), or any supplement used to alter
lipid metabolism including but not limited to dietary fiber supplements, red
rice yeast supplements, garlic supplements, soy isoflavone supplements,
sterol/stanol products, or policosanols at screening;
6. Use of tamoxifen, estrogens, or progestins that has not been stable for
>4 weeks at screening or is unstable prior to randomization;
7. Use of oral or injected corticosteroids or anabolic steroids prior to
randomization;
8. History of hospitalization for pancreatitis in the last 5 years;
9. Uncontrolled diabetes (hemoglobin A1c [HbA1c] >10%);
10. Uncontrolled hypothyroidism or thyroid-stimulating hormone (TSH)
>5 mIU/L;
11. History of cancer (other than basal cell carcinoma) in the past 2 years;
12. Cardiovascular event (ie, myocardial infarction, acute coronary syndrome,
new onset angina, stroke, transient heart attack, unstable congestive heart
failure requiring a change in treatment), revascularization procedure or
vascular surgery within 6 months of randomization;
13. Use of simvastatin 80 mg or Vytorin 10/80 mg;
14. Recent history (within 6 months of randomization) of significant nephrotic
syndrome, pulmonary, hepatic, biliary, gastrointestinal, or immunologic
disease;
15. Poorly controlled hypertension (systolic blood pressure ≥180 mmHg and/or
diastolic blood pressure ≥110 mmHg);
16. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
>3 × the upper limit of normal (ULN); if ALT/AST is >3 × ULN, the levels
have been stable for 3 months and are <5 × ULN;
17. Exposure to any investigational product within 4 weeks of randomization; or
18. Any condition or therapy which, in the opinion of the Investigator, might
pose a risk to the subject or make participation in the study not in the
subject's best interest.

[During the screening period and treatment period, all visits are to be within ±3 days of the scheduled time.] Screening Period: Visit 1 will occur at Week -8 for subjects requiring washout and/or statin, cholesterol-absorption inhibitor (CAI), or statin-CAI stabilization. This includes subjects who: • Were previously on omega-3 drugs/supplements; • Require adjustment to or addition of permitted statins, CAI, or statin-CAI combination; • Have not been on a permitted stable dose of statin, CAI, or statin-CAI combination for at least 4 weeks prior to Visit 1; and/or • Need to washout of bile acid sequestrants, fibrates, niacin, and other supplements known to alter lipid metabolism. For these subjects who require washout and/or statin, CAI, or statin-CAI stabilization, at Visit 1 (Week -8) screening procedures will be performed. Subjects will return at Visit 1a (Week -2) for their first qualifying lipid measurement. For subjects not requiring washout, Visit 1 will occur at Week -2. All screening procedures will be performed at this visit including the first qualifying lipid measurement. At Visit 2 (Week -1), all subjects will return for their second lipid qualifying measurement. If at Visit 2 the subject does not have an average TG ≥500 mg/dL (6 mmol/L) and <2500 mg/dL (28 mmol/L), the TG measurement may be repeated one additional time after Visit 2 (Visit 2a). The subject's qualifying measurement would be the average of Visit 1 or 1a + Visit 2 + Visit 2a (repeat measurement). To be eligible for randomization, the subject must have a qualifying TG ≥500 mg/dL (6 mmol/L) and <2500 mg/dL (28 mmol/L). Of the total number of subjects, approximately 50% will have a qualifying TG >885 mg/dL (10 mmol/L) and <2500 mg/dL (28 mmol/L). Once approximately 50% of the total subjects has been reached for each TG group, enrollment of subjects with that specific TG criterion will stop. Subjects will be equally allocated to each treatment group. [At the screening visit, all subjects will receive counseling regarding the National Cholesterol Education Program (NCEP) Therapeutic Lifestyle Changes (TLC) diet and will receive basic instructions on how to follow this diet. See Appendix C.] Treatment Period: At Visit 3 (Week 0), approximately 116 subjects will be randomized in a 1:1 ratio to receive daily olive oil 2 g or Epanova 2 g. Subjects will be stratified by lipid-altering drugs to ensure a balanced allocation of subjects who are users and non-users of the following permitted lipid-altering drugs in each treatment group: statin, CAI, or statin-CAI combination. During the treatment period, subjects will return to the site at Visit 4 (Week 6), Visit 5 (Week 10), and Visit 6 (Week 12) for efficacy and safety evaluations.

Location

Research Site

Chicoutimi, QC, Canada, G7H 7K9

Location

Research Site

Trutnov, Czech Republic, 541 21

Location

Research Site

Zlín, Czech Republic, 76275

Location

Research Site

Hradec Kralova, Czech Republic, 50005

Location

Research Site

Esbjerg, Denmark, 6700

Location

Research Site

Viborg, Denmark, 8800

Location

Research Site

Gentofte, Denmark, 2820

Location

Research Site

Herlev, Denmark, 2730

Arms	Assigned Interventions
Experimental: Epanova 2 g/day Arm 1	Drug: Epanova Epanova will be provided in 1 g polyacrylate-coated soft gel capsules. Two capsules will be taken once per day, without regard to meals, for 12 weeks. At clinic visits, study drug will be administered at the clinic after fasting blood draws are complete. Other Name: omega-3 free fatty acids
Placebo Comparator: Olive Oil 2 g/day Arm 2	Drug: Olive Oil Olive oil will be provided in 1 g polyacrylate-coated soft gel capsules. Two capsules will be taken once per day, without regard to meals, for 12 weeks. At clinic visits, study drug will be administered at the clinic after fasting blood draws are complete. Other Name: placebo comparator

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The recruitment was planned at 43 sites, and in total, 162 were randomized in a 1:1 ratio to two treatment groups, Epanova (n=81) and Olive Oil (n=81). Randomization of subjects was stratified by two factors: 1. use of lipid-altering drugs (yes, no), and 2. Qualifying triglycerides values below or above 885 mg/dL.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In total, 379 subjects were screened from the 43 sites.

Reporting Groups

	Description
Epanova	2g once daily (QD)
Olive Oil	2g once daily (QD)

Participant Flow: Overall Study

	Epanova	Olive Oil
STARTED	81	81
COMPLETED	80	76
NOT COMPLETED	1	5
Adverse Event	0	2
Protocol Violation	0	2
Withdrawal by Subject	1	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Epanova	2g once daily (QD)
Olive Oil	2g once daily (QD)

Baseline Measures

	Epanova	Olive Oil	Total
Number of Participants [units: Participants]	81	81	162
Age Continuous [units: Years] Mean ± Standard Deviation	50.3 ± 10.60	50.0 ± 10.88	50.2 ± 10.71
Gender, Male/Female [units: Participants]
Female	16	19	35
Male	65	62	127
Lipid-altering drug use [units: Participants]
Yes	36	37	73
No	45	44	89
At least 1 qualifying TG category > 885 mg/dL [units: Participants]
Yes	53	52	105
No	28	29	57

Outcome Measures

1. Primary Outcome Measure: Percent Change in Triglyceride for all Subjects [ Time Frame: From Baseline to Week 12 Endpoint ]

Measure Type	Primary
Measure Name	Percent Change in Triglyceride for all Subjects
Measure Description	This primary endpoint was tested in parallel together with the first of the secondary endpoints, each at 0.025 Type I error rate.
Time Frame	From Baseline to Week 12 Endpoint
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS)

Reporting Groups

	Description
Epanova	2g once daily (QD)
Olive Oil	2g once daily (QD)

Measured Values

	Epanova	Olive Oil
Number of Participants Analyzed [units:participants]	81	81
Percent Change in Triglyceride for all Subjects [units: Percentage of change (%)] Median (Inter-Quartile Range)	-28.1 (-42.1 to -5.5)	-10.2 (-36.4 to 23.0)

Statistical Analysis 1 for Percent Change in Triglyceride for all Subjects

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Wilcoxon (Mann-Whitney)
P-Value^[4]	0.017
Median Difference (Final Values)^[5]	-14.2
95% Confidence Interval	( -26.2 to -2.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Missing values were imputed using probabilities of missing estimated from logistic regression
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	The estimated median difference and its 95% CI were based on Hodges Lehmann procedure

2. Secondary Outcome Measure: Percent change in Triglycerides for subjects with at least 1 qualifying triglyceride >885 mg/dL [ Time Frame: From Baseline to Week 12 Endpoint ]

Measure Type	Secondary
Measure Name	Percent change in Triglycerides for subjects with at least 1 qualifying triglyceride >885 mg/dL
Measure Description	This first secondary endpoint in subjects with at least 1 qualifying triglyceride >885 mg/dL was tested in parallel together with the primary endpoint, each at 0.025 Type I error rate.
Time Frame	From Baseline to Week 12 Endpoint
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
Epanova	2g once daily (QD)
Olive Oil	2g once daily (QD)

Measured Values

	Epanova	Olive Oil
Number of Participants Analyzed [units:participants]	53	52
Percent change in Triglycerides for subjects with at least 1 qualifying triglyceride >885 mg/dL [units: Percentage of change (%)] Median (Inter-Quartile Range)	-37.5 (-46.1 to -18.1)	-9.3 (-36.3 to 27)

Statistical Analysis 1 for Percent change in Triglycerides for subjects with at least 1 qualifying triglyceride >885 mg/dL

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Wilcoxon (Mann-Whitney)
P-Value^[4]	0.0008
Median Difference (Final Values)^[5]	-26.3
95% Confidence Interval	( -40.5 to -11.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Main analysis with missing values imputed using probabilities of missing estimated from logistic regression
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	The estimated median difference and its 95% CI were based on Hodges Lehmann procedure.

3. Secondary Outcome Measure: Percent Change in Non-High-Density Lipoprotein Cholesterol (mg/dL) [ Time Frame: From Baseline to Week 12 Endpoint ]

Measure Type	Secondary
Measure Name	Percent Change in Non-High-Density Lipoprotein Cholesterol (mg/dL)
Measure Description	This secondary endpoint, together with the 3rd. and 4th secondary ones, was treated as the core secondary, and the p value from the hypothesis test on its treatment comparison was adjusted by using Hommel's procedure.
Time Frame	From Baseline to Week 12 Endpoint
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
Epanova	2g once daily (QD)
Olive Oil	2g once daily (QD)

Measured Values

	Epanova	Olive Oil
Number of Participants Analyzed [units:participants]	81	81
Percent Change in Non-High-Density Lipoprotein Cholesterol (mg/dL) [units: Percentage of change (%)] Median (Inter-Quartile Range)	-8.8 (-15.7 to -1.4)	0.4 (-13.5 to 14.2)

Statistical Analysis 1 for Percent Change in Non-High-Density Lipoprotein Cholesterol (mg/dL)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Wilcoxon (Mann-Whitney)
P-Value^[4]	0.0180
Median Difference (Final Values)^[5]	-9.0
95% Confidence Interval	( -14.8 to -2.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Missing values were imputed using probabilities of missing estimated from logistic regression
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Adjusted by using Hommel's procedure
[5]	Other relevant estimation information:
	The estimated median difference and its 95% CI were based on Hodges Lehmann procedure.

4. Secondary Outcome Measure: Percent Change in High-Density Lipoprotein Cholesterol (mg/dL) [ Time Frame: From Baseline to Week 12 Endpoint ]

Measure Type	Secondary
Measure Name	Percent Change in High-Density Lipoprotein Cholesterol (mg/dL)
Measure Description	This secondary endpoint, together with the 2nd. and 4th. secondary ones, was treated as the core secondary, and the p value from the hypothesis test on its treatment comparison was adjusted by using Hommel's procedure.
Time Frame	From Baseline to Week 12 Endpoint
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
Epanova	2g once daily (QD)
Olive Oil	2g once daily (QD)

Measured Values

	Epanova	Olive Oil
Number of Participants Analyzed [units:participants]	81	81
Percent Change in High-Density Lipoprotein Cholesterol (mg/dL) [units: Percentage of change (%)] Median (Inter-Quartile Range)	3.4 (-5.1 to 12.5)	3.1 (-6.3 to 10.9)

Statistical Analysis 1 for Percent Change in High-Density Lipoprotein Cholesterol (mg/dL)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Wilcoxon (Mann-Whitney)
P-Value^[4]	0.7117
Median Difference (Final Values)^[5]	-0.3
95% Confidence Interval	( -3.5 to 4.9 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Missing values were imputed using probabilities of missing estimated from logistic regression
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Adjusted by using Hommel's procedure
[5]	Other relevant estimation information:
	The estimated median difference and its 95% CI were based on Hodges Lehmann procedure.

5. Secondary Outcome Measure: Percent Change in Triglyceride(mg/dL) in Subjects With Biochemically Defined Fredrickson Type V (Triglyceride/Very-Low-Density Lipoprotein Cholesterol ≥6) [ Time Frame: From Baseline to Week 12 Endpoint ]

Measure Type	Secondary
Measure Name	Percent Change in Triglyceride(mg/dL) in Subjects With Biochemically Defined Fredrickson Type V (Triglyceride/Very-Low-Density Lipoprotein Cholesterol ≥6)
Measure Description	This secondary endpoint in subjects with Biochemically Defined Fredrickson Type V (Triglyceride/Very-Low-Density Lipoprotein Cholesterol ≥6), together with the 2nd. and 3rd.secondary ones, was treated as the core secondary, and the p value from the hypothesis test on its treatment comparison was adjusted by using Hommel's procedure.
Time Frame	From Baseline to Week 12 Endpoint
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
Epanova	2g once daily (QD)
Olive Oil	2g once daily (QD)

Measured Values

	Epanova	Olive Oil
Number of Participants Analyzed [units:participants]	55	57
Percent Change in Triglyceride(mg/dL) in Subjects With Biochemically Defined Fredrickson Type V (Triglyceride/Very-Low-Density Lipoprotein Cholesterol ≥6) [units: Percentage of change (%)] Median (Inter-Quartile Range)	-24.7 (-43.3 to -2.8)	-12.4 (-38.8 to 14.2)

Statistical Analysis 1 for Percent Change in Triglyceride(mg/dL) in Subjects With Biochemically Defined Fredrickson Type V (Triglyceride/Very-Low-Density Lipoprotein Cholesterol ≥6)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Wilcoxon (Mann-Whitney)
P-Value^[4]	0.3034
Median Difference (Final Values)^[5]	-10.3
95% Confidence Interval	( -23.9 to 3.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Missing values were imputed using probabilities of missing estimated from logistic regression
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Adjusted by using Hommel's procedure
[5]	Other relevant estimation information:
	The estimated median difference and its 95% CI were based on Hodges Lehmann procedure.

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Epanova	2g once daily (QD)
Olive Oil	2g once daily (QD)

Serious Adverse Events

Epanova

Olive Oil

Total, serious adverse events

# participants affected / at risk

1/81 (1.23%)

2/81 (2.47%)

Gastrointestinal disorders

Rectal haemorrhage¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Gastrointestinal disorders

Pancreatitis¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Injury, poisoning and procedural complications

Clavicle fracture ¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 16.1

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Epanova	2g once daily (QD)
Olive Oil	2g once daily (QD)

Other Adverse Events

Epanova

Olive Oil

Total, other (not including serious) adverse events

# participants affected / at risk

29/81 (35.80%)

28/81 (34.57%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

5/81 (6.17%)

# events

Gastrointestinal disorders

Eructation¹,^†

# participants affected / at risk

3/81 (3.70%)

0/81 (0.00%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

2/81 (2.47%)

0/81 (0.00%)

# events

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

1/81 (1.23%)

# events

Gastrointestinal disorders

Flatulence¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Gastrointestinal disorders

Food poisoning¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

1/81 (1.23%)

2/81 (2.47%)

# events

Gastrointestinal disorders

Pancreatitis¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Gastrointestinal disorders

Toothache¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

1/81 (1.23%)

# events

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Gastrointestinal disorders

Haemorrhoids ¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Gastrointestinal disorders

Rectal haemorrhage¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Gastrointestinal disorders

All¹,^†

# participants affected / at risk

12/81 (14.81%)

7/81 (8.64%)

# events

Infections and infestations

ALL¹,^†

# participants affected / at risk

10/81 (12.35%)

6/81 (7.41%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

3/81 (3.70%)

1/81 (1.23%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

1/81 (1.23%)

# events

Infections and infestations

Erysipelas¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Infections and infestations

Gastroenteritis viral¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Infections and infestations

Respiratory tract infection viral ¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Infections and infestations

Sialoadenitis¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

1/81 (1.23%)

3/81 (3.70%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

0/81 (0.00%)

2/81 (2.47%)

# events

Nervous system disorders

ALL¹,^†

# participants affected / at risk

5/81 (6.17%)

3/81 (3.70%)

# events

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

2/81 (2.47%)

0/81 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

1/81 (1.23%)

2/81 (2.47%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

1/81 (1.23%)

# events

Nervous system disorders

Hypoaesthesia¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Nervous system disorders

Paraesthesia¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Investigations

ALL¹,^†

# participants affected / at risk

4/81 (4.94%)

3/81 (3.70%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

1/81 (1.23%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Investigations

Blood creatinine increased¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Investigations

Blood glucose increased¹,^†

# participants affected / at risk

1/81 (1.23%)

# events

Investigations

Gastric pH decreased¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Investigations

Blood creatine phosphokinase increased¹,^†

# participants affected / at risk

0/81 (0.00%)

2/81 (2.47%)

# events

Vascular disorders

ALL¹,^†

# participants affected / at risk

3/81 (3.70%)

1/81 (1.23%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

3/81 (3.70%)

0/81 (0.00%)

# events

Vascular disorders

Flushing¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Respiratory, thoracic and mediastinal disorders

ALL¹,^†

# participants affected / at risk

3/81 (3.70%)

2/81 (2.47%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

1/81 (1.23%)

2/81 (2.47%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinitis allergi¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Upper respiratory tract congestion¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

General disorders

ALL¹,^†

# participants affected / at risk

3/81 (3.70%)

2/81 (2.47%)

# events

General disorders

Fatigue¹,^†

# participants affected / at risk

2/81 (2.47%)

1/81 (1.23%)

# events

General disorders

Chills¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

General disorders

Feeling hot¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

General disorders

Oedema peripheral¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

ALL¹,^†

# participants affected / at risk

1/81 (1.23%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lipoma¹,^†

# participants affected / at risk

1/81 (1.23%)

# events

Metabolism and nutrition disorders

ALL¹,^†

# participants affected / at risk

1/81 (1.23%)

5/81 (6.17%)

# events

Metabolism and nutrition disorders

Gout ¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Metabolism and nutrition disorders

Diabetes mellitus inadequate control¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Metabolism and nutrition disorders

Hypertriglyceridaemia ¹,^†

# participants affected / at risk

0/81 (0.00%)

2/81 (2.47%)

# events

Metabolism and nutrition disorders

Type 2 diabetes mellitus¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Psychiatric disorders

ALL¹,^†

# participants affected / at risk

1/81 (1.23%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Cardiac disorders

ALL¹,^†

# participants affected / at risk

1/81 (1.23%)

# events

Cardiac disorders

Coronary artery disease¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Cardiac disorders

Angina pectoris¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Cardiac disorders

Palpitations ¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Hepatobiliary disorders

ALL¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Hepatobiliary disorders

Cholelithiasis¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Skin and subcutaneous tissue disorders

ALL¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Skin and subcutaneous tissue disorders

Acne¹,^†

# participants affected / at risk

1/81 (1.23%)

0/81 (0.00%)

# events

Ear and labyrinth disorders

ALL¹,^†

# participants affected / at risk

0/81 (0.00%)

2/81 (2.47%)

# events

Ear and labyrinth disorders

Vertigo¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Ear and labyrinth disorders

Vertigo positional ¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Musculoskeletal and connective tissue disorders

ALL¹,^†

# participants affected / at risk

0/81 (0.00%)

5/81 (6.17%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Musculoskeletal and connective tissue disorders

Back pain ¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Musculoskeletal and connective tissue disorders

Gouty arthritis ¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Musculoskeletal and connective tissue disorders

Intervertebral disc protrusion¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Renal and urinary disorders

ALL¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Renal and urinary disorders

Renal impairment ¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Injury, poisoning and procedural complications

ALL¹,^†

# participants affected / at risk

0/81 (0.00%)

2/81 (2.47%)

# events

Injury, poisoning and procedural complications

Clavicle fracture ¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

Injury, poisoning and procedural complications

Tooth fracture¹,^†

# participants affected / at risk

0/81 (0.00%)

1/81 (1.23%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 16.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact

Name/Title:	Hong Yang, Study Statistician
Organization:	AstraZeneca AB
Phone	+46-(0)317762397
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

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Research Site

Research Site

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Research Site

Trial Results Summaries