Trial Outcomes & Findings for Epanova® for Lowering Very High Triglycerides II (EVOLVE II) (NCT NCT02009865)
NCT ID: NCT02009865
Last Updated: 2019-09-10
Results Overview
This primary endpoint was tested in parallel together with the first of the secondary endpoints, each at 0.025 Type I error rate.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
379 participants
Primary outcome timeframe
From Baseline to Week 12 Endpoint
Results posted on
2019-09-10
Participant Flow
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.
In total, 379 subjects were screened from the 43 sites.
Participant milestones
| Measure |
Epanova
2g once daily (QD)
|
Olive Oil
2g once daily (QD)
|
|---|---|---|
|
Overall Study
STARTED
|
81
|
81
|
|
Overall Study
COMPLETED
|
80
|
76
|
|
Overall Study
NOT COMPLETED
|
1
|
5
|
Reasons for withdrawal
| Measure |
Epanova
2g once daily (QD)
|
Olive Oil
2g once daily (QD)
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
2
|
|
Overall Study
Protocol Violation
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
Epanova® for Lowering Very High Triglycerides II (EVOLVE II)
Baseline characteristics by cohort
| Measure |
Epanova
n=81 Participants
2g once daily (QD)
|
Olive Oil
n=81 Participants
2g once daily (QD)
|
Total
n=162 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.3 Years
STANDARD_DEVIATION 10.60 • n=5 Participants
|
50.0 Years
STANDARD_DEVIATION 10.88 • n=7 Participants
|
50.2 Years
STANDARD_DEVIATION 10.71 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
65 Participants
n=5 Participants
|
62 Participants
n=7 Participants
|
127 Participants
n=5 Participants
|
|
Lipid-altering drug use
Yes
|
36 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Lipid-altering drug use
No
|
45 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
89 Participants
n=5 Participants
|
|
At least 1 qualifying TG category > 885 mg/dL
Yes
|
53 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
105 Participants
n=5 Participants
|
|
At least 1 qualifying TG category > 885 mg/dL
No
|
28 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Baseline to Week 12 EndpointPopulation: Full Analysis Set (FAS)
This primary endpoint was tested in parallel together with the first of the secondary endpoints, each at 0.025 Type I error rate.
Outcome measures
| Measure |
Epanova
n=81 Participants
2g once daily (QD)
|
Olive Oil
n=81 Participants
2g once daily (QD)
|
|---|---|---|
|
Percent Change in Triglyceride for All Subjects
|
-28.1 Percentage of change (%)
Interval -42.1 to -5.5
|
-10.2 Percentage of change (%)
Interval -36.4 to 23.0
|
SECONDARY outcome
Timeframe: From Baseline to Week 12 EndpointPopulation: FAS
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.
Outcome measures
| Measure |
Epanova
n=53 Participants
2g once daily (QD)
|
Olive Oil
n=52 Participants
2g once daily (QD)
|
|---|---|---|
|
Percent Change in Triglycerides for Subjects With at Least 1 Qualifying Triglyceride >885 mg/dL
|
-37.5 Percentage of change (%)
Interval -46.1 to -18.1
|
-9.3 Percentage of change (%)
Interval -36.3 to 27.0
|
SECONDARY outcome
Timeframe: From Baseline to Week 12 EndpointPopulation: FAS
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.
Outcome measures
| Measure |
Epanova
n=81 Participants
2g once daily (QD)
|
Olive Oil
n=81 Participants
2g once daily (QD)
|
|---|---|---|
|
Percent Change in Non-High-Density Lipoprotein Cholesterol (mg/dL)
|
-8.8 Percentage of change (%)
Interval -15.7 to -1.4
|
0.4 Percentage of change (%)
Interval -13.5 to 14.2
|
SECONDARY outcome
Timeframe: From Baseline to Week 12 EndpointPopulation: FAS
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.
Outcome measures
| Measure |
Epanova
n=81 Participants
2g once daily (QD)
|
Olive Oil
n=81 Participants
2g once daily (QD)
|
|---|---|---|
|
Percent Change in High-Density Lipoprotein Cholesterol (mg/dL)
|
3.4 Percentage of change (%)
Interval -5.1 to 12.5
|
3.1 Percentage of change (%)
Interval -6.3 to 10.9
|
SECONDARY outcome
Timeframe: From Baseline to Week 12 EndpointPopulation: FAS
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.
Outcome measures
| Measure |
Epanova
n=55 Participants
2g once daily (QD)
|
Olive Oil
n=57 Participants
2g once daily (QD)
|
|---|---|---|
|
Percent Change in Triglyceride(mg/dL) in Subjects With Biochemically Defined Fredrickson Type V (Triglyceride/Very-Low-Density Lipoprotein Cholesterol ≥6)
|
-24.7 Percentage of change (%)
Interval -43.3 to -2.8
|
-12.4 Percentage of change (%)
Interval -38.8 to 14.2
|
Adverse Events
Epanova
Serious events: 1 serious events
Other events: 29 other events
Deaths: 0 deaths
Olive Oil
Serious events: 2 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Epanova
n=81 participants at risk
2g once daily (QD)
|
Olive Oil
n=81 participants at risk
2g once daily (QD)
|
|---|---|---|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Gastrointestinal disorders
Pancreatitis
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
Other adverse events
| Measure |
Epanova
n=81 participants at risk
2g once daily (QD)
|
Olive Oil
n=81 participants at risk
2g once daily (QD)
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
5/81 • Number of events 5
|
6.2%
5/81 • Number of events 6
|
|
Gastrointestinal disorders
Eructation
|
3.7%
3/81 • Number of events 3
|
0.00%
0/81
|
|
Gastrointestinal disorders
Constipation
|
2.5%
2/81 • Number of events 2
|
0.00%
0/81
|
|
Gastrointestinal disorders
Dyspepsia
|
1.2%
1/81 • Number of events 1
|
1.2%
1/81 • Number of events 1
|
|
Gastrointestinal disorders
Flatulence
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Gastrointestinal disorders
Food poisoning
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Gastrointestinal disorders
Nausea
|
1.2%
1/81 • Number of events 1
|
2.5%
2/81 • Number of events 2
|
|
Gastrointestinal disorders
Pancreatitis
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Gastrointestinal disorders
Toothache
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Gastrointestinal disorders
Vomiting
|
1.2%
1/81 • Number of events 1
|
1.2%
1/81 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/81
|
1.2%
1/81 • Number of events 2
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Gastrointestinal disorders
All
|
14.8%
12/81 • Number of events 17
|
8.6%
7/81 • Number of events 15
|
|
Infections and infestations
ALL
|
12.3%
10/81 • Number of events 11
|
7.4%
6/81 • Number of events 7
|
|
Infections and infestations
Nasopharyngitis
|
3.7%
3/81 • Number of events 3
|
1.2%
1/81 • Number of events 1
|
|
Infections and infestations
Bronchitis
|
1.2%
1/81 • Number of events 1
|
1.2%
1/81 • Number of events 1
|
|
Infections and infestations
Erysipelas
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Infections and infestations
Gastroenteritis viral
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Infections and infestations
Influenza
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Infections and infestations
Respiratory tract infection viral
|
1.2%
1/81 • Number of events 2
|
0.00%
0/81
|
|
Infections and infestations
Sialoadenitis
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Infections and infestations
Urinary tract infection
|
1.2%
1/81 • Number of events 1
|
3.7%
3/81 • Number of events 3
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/81
|
2.5%
2/81 • Number of events 2
|
|
Nervous system disorders
ALL
|
6.2%
5/81 • Number of events 5
|
3.7%
3/81 • Number of events 6
|
|
Nervous system disorders
Dysgeusia
|
2.5%
2/81 • Number of events 2
|
0.00%
0/81
|
|
Nervous system disorders
Dizziness
|
1.2%
1/81 • Number of events 1
|
2.5%
2/81 • Number of events 3
|
|
Nervous system disorders
Headache
|
1.2%
1/81 • Number of events 1
|
1.2%
1/81 • Number of events 3
|
|
Nervous system disorders
Hypoaesthesia
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Nervous system disorders
Syncope
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Investigations
ALL
|
4.9%
4/81 • Number of events 5
|
3.7%
3/81 • Number of events 4
|
|
Investigations
Alanine aminotransferase increased
|
1.2%
1/81 • Number of events 1
|
1.2%
1/81 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Investigations
Blood creatinine increased
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Investigations
Blood glucose increased
|
1.2%
1/81 • Number of events 1
|
1.2%
1/81 • Number of events 1
|
|
Investigations
Gastric pH decreased
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/81
|
2.5%
2/81 • Number of events 2
|
|
Vascular disorders
ALL
|
3.7%
3/81 • Number of events 3
|
1.2%
1/81 • Number of events 1
|
|
Vascular disorders
Hypertension
|
3.7%
3/81 • Number of events 3
|
0.00%
0/81
|
|
Vascular disorders
Flushing
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
ALL
|
3.7%
3/81 • Number of events 4
|
2.5%
2/81 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.2%
1/81 • Number of events 1
|
2.5%
2/81 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergi
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
General disorders
ALL
|
3.7%
3/81 • Number of events 3
|
2.5%
2/81 • Number of events 3
|
|
General disorders
Fatigue
|
2.5%
2/81 • Number of events 2
|
1.2%
1/81 • Number of events 1
|
|
General disorders
Chills
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
General disorders
Feeling hot
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
General disorders
Oedema peripheral
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ALL
|
1.2%
1/81 • Number of events 1
|
1.2%
1/81 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
|
1.2%
1/81 • Number of events 1
|
1.2%
1/81 • Number of events 1
|
|
Metabolism and nutrition disorders
ALL
|
1.2%
1/81 • Number of events 1
|
6.2%
5/81 • Number of events 5
|
|
Metabolism and nutrition disorders
Gout
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.00%
0/81
|
2.5%
2/81 • Number of events 2
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Psychiatric disorders
ALL
|
1.2%
1/81 • Number of events 1
|
1.2%
1/81 • Number of events 1
|
|
Psychiatric disorders
Depression
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Cardiac disorders
ALL
|
1.2%
1/81 • Number of events 1
|
1.2%
1/81 • Number of events 2
|
|
Cardiac disorders
Coronary artery disease
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Cardiac disorders
Palpitations
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Hepatobiliary disorders
ALL
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Skin and subcutaneous tissue disorders
ALL
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Skin and subcutaneous tissue disorders
Acne
|
1.2%
1/81 • Number of events 1
|
0.00%
0/81
|
|
Ear and labyrinth disorders
ALL
|
0.00%
0/81
|
2.5%
2/81 • Number of events 2
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
ALL
|
0.00%
0/81
|
6.2%
5/81 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Gouty arthritis
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Renal and urinary disorders
ALL
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Injury, poisoning and procedural complications
ALL
|
0.00%
0/81
|
2.5%
2/81 • Number of events 2
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
0.00%
0/81
|
1.2%
1/81 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place