HypertriglyceridemiaPhase 3EVOLVEIINCT02009865
Epanova® for Lowering Very High Triglycerides II (EVOLVE II)
A Phase 3 study testing Epanova and Olive Oil in people with Hypertriglyceridemia, run by AstraZeneca at 40 sites in 7 countries.
Trial summary
This is a double-blind, randomized, olive oil-controlled study to investigate the efficacy and safety of Epanova as an adjunct therapy to diet for reduction of TG levels in subjects with severe hypertriglyceridemia. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Hypertriglyceridemia
- What is being tested?
- Epanova and Olive Oil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 379 participants
- Where
- 40 sitesin 7 countries
- Study dates
- 16 Dec 2013to 23 Dec 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
- Willing to use an appropriate and effective method of contraception;
- 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);
- Body mass index ≥20 kg/m2;
- Untreated dyslipidemia or dyslipidemia treated with a statin, CAI, or statin-CAI combination that has been stable for 6 weeks prior to randomization; and
- Willingness to maintain current physical activity level and follow the TLC diet throughout the study.
Who cannot join
- Allergy or intolerance to omega-3 fatty acids, omega-3-acid ethyl esters, or fish;
- Known lipoprotein lipase impairment;
- Known non-responder to omega-3 or fenofibrate therapy;
- 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;
- 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;
- Use of tamoxifen, estrogens, or progestins that has not been stable for >4 weeks at screening or is unstable prior to randomization;
Show all 18Show fewer
- Use of oral or injected corticosteroids or anabolic steroids prior to randomization;
- History of hospitalization for pancreatitis in the last 5 years;
- Uncontrolled diabetes (hemoglobin A1c [HbA1c] >10%);
- Uncontrolled hypothyroidism or thyroid-stimulating hormone (TSH) >5 mIU/L;
- History of cancer (other than basal cell carcinoma) in the past 2 years;
- 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;
- Use of simvastatin 80 mg or Vytorin 10/80 mg;
- Recent history (within 6 months of randomization) of significant nephrotic syndrome, pulmonary, hepatic, biliary, gastrointestinal, or immunologic disease;
- Poorly controlled hypertension (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg);
- 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;
- Exposure to any investigational product within 4 weeks of randomization; or
- 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.
Trial locations and contacts
40 sites in 7 countries.
40 sites in 7 countries
United States15 sites
Research Site
Addison, Illinois, 60101
Research Site
Bristol, Tennessee, 37620
Research Site
Cincinnati, Ohio, 45227
Research Site
Cincinnati, Ohio, 45246
Research Site
Columbus, Ohio, 43213
Research Site
Houston, Texas, 77074
Research Site
Katy, Texas, 77450
Research Site
Kettering, Ohio, 45429
Research Site
Los Angeles, California, 90057
Research Site
Louisville, Kentucky, 40213
Research Site
Lyndhurst, Ohio, 44124
Research Site
Oklahoma City, Oklahoma, 73103
Research Site
Orangeburg, South Carolina, 29118
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
St. Petersburg, Florida, 33709
Hungary8 sites
Research Site
Baja, 6500
Research Site
Balatonfüred, 8230
Research Site
Budapest, 1062
Research Site
Debrecen, 4031
Research Site
Debrecen, 4032
Research Site
Sátoraljaújhely, 3980
Research Site
Székesfehérvár, 8000
Research Site
Szikszó, 3800
Russia7 sites
Research Site
Barnaul, 656055
Research Site
Kemerovo, 650002
Research Site
Moscow, 121551
Research Site
Moscow, 121552
Research Site
Saint Petersburg, 196601
Research Site
Tomsk, 634012
Research Site
Yekaterinburg, 620219
Denmark4 sites
Research Site
Esbjerg, 6700
Research Site
Gentofte Municipality, 2820
Research Site
Herlev, 2730
Research Site
Viborg, 8800
Czechia3 sites
Research Site
Hradec Kralova, 50005
Research Site
Trutnov, 541 21
Research Site
Zlín, 76275
Netherlands2 sites
Research Site
Alkmaar, 1815JD
Research Site
Amsterdam, 1105 AZ
About this study
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)
This is a double-blind, randomized, olive oil-controlled study to investigate the efficacy and safety of Epanova as an adjunct therapy to diet for reduction of TG levels in subjects with severe hypertriglyceridemia. The study consists of an approximately 8-week screening period that includes a diet and lifestyle stabilization and washout period and a 12-week treatment period.
Read the detailed description
[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.
- Conditions
- Hypertriglyceridemia
- Being tested
- Epanova, Olive Oil
- Keywords
- Hypertriglyceridemia, Dyslipidemia, Eicosapentaenoic acid, EPA, Docosahexaenoic acid, DHA
- Medical subject headings
- Hypertriglyceridemia, Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpanovaDrug
Also called omega-3 free fatty acids
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.
Olive OilDrug
Also called placebo comparator
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.
| Study group | Role | What they receive |
|---|---|---|
| Epanova 2 g/day | Experimental | Arm 1 Receives: Drug: Epanova |
| Olive Oil 2 g/day | Placebo comparator | Arm 2 Receives: Drug: Olive Oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Triglyceride for All Subjects
This primary endpoint was tested in parallel together with the first of the secondary endpoints, each at 0.025 Type I error rate.
Measured: From Baseline to Week 12 Endpoint
Secondary outcomes (4)
Percent Change in Triglycerides for Subjects With at Least 1 Qualifying Triglyceride >885 mg/dL
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.
Measured: From Baseline to Week 12 Endpoint
Percent Change in Non-High-Density Lipoprotein Cholesterol (mg/dL)
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.
Measured: From Baseline to Week 12 Endpoint
Percent Change in High-Density Lipoprotein Cholesterol (mg/dL)
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.
Measured: From Baseline to Week 12 Endpoint
Percent Change in Triglyceride(mg/dL) in Subjects With Biochemically Defined Fredrickson Type V (Triglyceride/Very-Low-Density Lipoprotein Cholesterol ≥6)
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.
Measured: From Baseline to Week 12 Endpoint
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2013 (estimated)
- Study start16 Dec 2013
- Primary completion23 Dec 2014
- Study completion23 Dec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypertriglyceridemiaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 379 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02009865
- Sponsor's protocol ID
- D5880C00001
- Other IDs
- OM-EPA-011
- Acronym
- EVOLVEII
- Status last verified
- Aug 2019
- First submitted
- 9 Dec 2013
- Last updated
- 10 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02009865
- Acronym / sponsor ID
- EVOLVEII / D5880C00001
- Conditions
- Hypertriglyceridemia
- Keywords
- Hypertriglyceridemia, Dyslipidemia, Eicosapentaenoic acid, EPA, Docosahexaenoic acid, DHA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 379 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 16 Dec 2013 (actual)
- Primary completion
- 23 Dec 2014 (actual)
- Study completion
- 23 Dec 2014 (actual)
- First posted
- 12 Dec 2013 (estimated)
- Results
- Posted 15 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a double-blind, randomized, olive oil-controlled study to investigate the efficacy and safety of Epanova as an adjunct therapy to diet for reduction of TG levels in subjects with severe hypertriglyceridemia. The study consists of an approximately 8-week screening period that includes a diet and lifestyle stabilization and washout period and a 12-week treatment period.
Detailed description
[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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Epanova 2 g/day | Experimental | Drug: EpanovaArm 1 |
| Olive Oil 2 g/day | Placebo comparator | Drug: Olive OilArm 2 |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
- Willing to use an appropriate and effective method of contraception;
- 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);
- Body mass index ≥20 kg/m2;
- Untreated dyslipidemia or dyslipidemia treated with a statin, CAI, or statin-CAI combination that has been stable for 6 weeks prior to randomization; and
Key exclusion criteria (18 listed)
- Allergy or intolerance to omega-3 fatty acids, omega-3-acid ethyl esters, or fish;
- Known lipoprotein lipase impairment;
- Known non-responder to omega-3 or fenofibrate therapy;
- 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;
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EpanovaAlso: omega-3 free fatty acidsEpanova 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. | Drug | Epanova 2 g/day |
| Olive OilAlso: placebo comparatorOlive 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. | Drug | Olive Oil 2 g/day |
Primary outcome
Percent Change in Triglyceride for All Subjects
Time frame: From Baseline to Week 12 Endpoint
This primary endpoint was tested in parallel together with the first of the secondary endpoints, each at 0.025 Type I error rate.
4 secondary outcomes
Percent Change in Triglycerides for Subjects With at Least 1 Qualifying Triglyceride >885 mg/dL
Time frame: From Baseline to Week 12 Endpoint
Percent Change in Non-High-Density Lipoprotein Cholesterol (mg/dL)
Time frame: From Baseline to Week 12 Endpoint
Percent Change in High-Density Lipoprotein Cholesterol (mg/dL)
Time frame: From Baseline to Week 12 Endpoint
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
40 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Epanova and Olive Oil in people with Hypertriglyceridemia, run by AstraZeneca at 40 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States, Hungary, Russia, Denmark, Czechia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Triglyceride for All Subjects (time frame: From Baseline to Week 12 Endpoint). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2019; AzTrials last refreshed its copy on 26 Oct 2026.