Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Epanova™ QD (2 x 1 g capsules), Epanova® (omega-3 carboxylic acids), omega-3 free fatty acids, AZD0585, omefas
Epanova · 9 trials · 5 indications
To demonstrate the efficacy of AZD0585 2 g and 4 g compared to placebo (corn oil) in Japanese patients with hypertriglyceridemia.
To evaluate the long-term (up to 52 weeks) safety of AZD0585 in Japanese patients with hypertriglyceridemia.
MACE components include: cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, emergent/elective coronary revascularization, or hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
This primary endpoint was tested in parallel together with the first of the secondary endpoints, each at 0.025 Type I error rate.
For Part A, the distribution of serum TG levels by the degree of pancreatic exocrine insufficiency (PEI) was assessed in patients with Type 2 Diabetes Mellitus (T2DM).
Baseline corrected AUC(0-last) was measured for total EPA following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.
Baseline corrected AUC(0-last) was measured for total DHA following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.
Baseline corrected AUC(0-last) was measured for the sum of EPA and DHA (total EPA+DHA) following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.
Baseline corrected Cmax was measured for total EPA following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.
Baseline corrected Cmax was measured for total DHA following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.
Baseline corrected Cmax was measured for the sum of EPA and DHA (total EPA+DHA) following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.
The primary endpoints are the differences in mean percent changes from baseline to end-of-treatment in triglycerides between placebo and the 2g/day, 3g/day and 4g/day Epanova groups
Analyses of the outcome measures presented are for baseline-adjusted data for total (esterified and unesterfied) EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation.
Analyses of the outcome measures presented are for baseline-adjusted data for total (esterified and unesterfied) EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation.
Analyses of the outcome measures presented are for baseline-adjusted data for total (esterified and unesterfied) EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation.
AUC0-24: Area under the plasma concentration versus time curve, from time 0 to 24 hours after start of the meal
Cmax: Maximum measured plasma concentration over the time span specified
Area under the plasma concentration versus time curve (AUC0-tau)for simvastatin and beta- hydroxysimvastatin acid, measured over the 24 hour period after the 14th dose
Maximum measured plasma concentration for simvastatin and beta- hydroxysimvastatin acid,during the 0-24 hour dosing interval for the 14th simvastatin dose (Day 14)measured over the 24 hour period after the 14th dose.
The primary endpoints of this study will be the area under the curve (AUC)0-t, AUC0-inf, and maximum concentration (Cmax) of R- and S warfarin and the maximum International Normalized Ratio (INRmax) over 168 hours postdose and INR AUC0-168 when warfarin is administered with and without Epanova®.
The INRmax over 168 hours postdose and INR AUC0-168 when warfarin is administered with and without Epanova®.
| Arm | Type | Description |
|---|---|---|
| AZD0585 2g group | EXPERIMENTAL | AZD0585 1g × 2 capsules and AZD0585 placebo 1g × 2 capsules once daily |
| AZD0585 4g group | EXPERIMENTAL | AZD0585 1g × 4 capsules once daily |
| Placebo control group | PLACEBO_COMPARATOR | AZD0585 placebo 1g × 4 capsules once daily |
| EPANOVA | EXPERIMENTAL | Epanova + statin, once daily |
| Corn oil | ACTIVE_COMPARATOR | Corn oil + Statin |
| Epanova 2 g/day | EXPERIMENTAL | Arm 1 |
| Olive Oil 2 g/day | PLACEBO_COMPARATOR | Arm 2 |
| Sequence AB | EXPERIMENTAL | A single dose of EPANOVA® 4 g (administered as 4 x 1 g capsules) at Visit 4, followed by 10 to 14 days washout, followed by a single dose of OMACOR® 4 g (administered as 4 x 1 g capsules) at Visit 7. |
| Sequence BA | EXPERIMENTAL | A single dose of OMACOR® 4 g (administered as 4 x 1 g capsules) at Visit 4, followed by 10 to 14 days washout, followed by a single dose of EPANOVA® 4 g (administered as 4 x 1 g capsules) at Visit 7. |
| placebo | PLACEBO_COMPARATOR | - |
| Epanova 2 g | EXPERIMENTAL | - |
| Epanova 3 g | EXPERIMENTAL | - |
| Epanova 4 g | EXPERIMENTAL | - |
| Epanova-Lovaza-Epanova-Lovaza | ACTIVE_COMPARATOR | - |
| Lovaza-Epanova-Lovaza-Epanova | ACTIVE_COMPARATOR | - |
| E4:L4 | ACTIVE_COMPARATOR | Crossover Sequence |
| L4:E4 | ACTIVE_COMPARATOR | Crossover Sequence |
| E2:L4 | ACTIVE_COMPARATOR | Crossover Sequence |
| L4:E2 | ACTIVE_COMPARATOR | Crossover Sequence |
| Epanova and Simvastatin | EXPERIMENTAL | - |
| Simvastatin | ACTIVE_COMPARATOR | - |
| Warfarin and Epanova | EXPERIMENTAL | - |
| Lovaza | ACTIVE_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| AZD0585 | DRUG | 1g soft capsule |
| AZD0585 placebo | DRUG | 1g soft capsule |
| Epanova® (omega-3 carboxylic acids) | DRUG | Adjunct to statin therapy and diet in high risk adult patients for the prevention and reduction of major adverse cardiovascular events (MACE) |
| corn oil control | DRUG | corn oil control arm |
| Epanova | DRUG | 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 Oil | DRUG | 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. |
| Omacor® (omega-3-acid ethyl esters) | DRUG | 4 g (administered orally as 4 x 1 g capsules) |
| placebo | DRUG | 4 capsules (1g) daily for 12 weeks |
| omefas | DRUG | 2 capsules (1g) + 2 placebo daily for 12 weeks |
| Epanova (4 g) and Lovaza (4 g) | DRUG | Single dose of Epanova (omefas), 4x1g capsules, taken with low-fat meals, 7 day washout followed by single dose of Lovaza (omega-3-acid ethyl esters), 4x1g capsules, taken with low-fat meals, 7 day washout followed by single dose of Epanova (omefas), 4x1g capsules, taken with high-fat meals, 7 day washout followed by single dose of Lovaza (omega-3-acid ethyl esters, 4x1g capsules, taken with high-fat meals |
| Lovaza (4 g) and Epanova (4 g) | DRUG | Single dose of Lovaza (omega-3-acid ethyl esters), 4x1g capsules, taken with low-fat meals, 7 day washout followed by single dose of Epanova (omefas), 4x1g capsules, taken with low-fat meals, 7 day washout followed by single dose of Lovaza (omega-3-acid ethyl esters,4x1g capsules, taken with high-fat meals, 7 day washout followed by single dose ofEpanova (omefas),4x1g capsules, taken with high-fat meals |
| Lovaza | DRUG | - |
| Simvastatin | DRUG | 40 mg (1 tablet) simvastatin once a day |
| acetylsalicylic acid (ASA) | DRUG | 81 mg aspirin (1 tablet), once a day, co-administered with simvastatin |
| warfarin | DRUG | A single 25 mg dose of warfarin |
| omega-3-acid ethyl esters | DRUG | 4 x 1 g capsule dose of Lovaza® |
Key Inclusion Criteria: * Japanese men or women, ≥20 years of age. * Subjects must meet all of the following criteria; 1. Fasting triglyceride level: average of Visit 2 and Visit 3 must be in the range 150 - 499 mg/dL 2. %TG change between Visit 2 and Visit 3 must be within 30% 3. %LDL-C cha...
Epanova is an omega-3 carboxylic acids product studied for lowering very high triglycerides in hypertriglyceridemia and severe hypertriglyceridemia. It has also been studied in patients with type 2 diabetes and in adults considered high risk for atherosclerotic cardiovascular disease. Its clinical program includes trials in pancreatitis-related severe hypertriglyceridemia and in type 2 diabetes with exocrine pancreatic insufficiency.
Epanova is developed by AstraZeneca PLC, which trades on the Nasdaq under the ticker AZN. AstraZeneca is the sponsor of the Epanova clinical trial program, including the cardiovascular outcomes study and the triglyceride-lowering studies conducted across North America, Europe, and Asia.
Epanova has been studied across Phase 1, Phase 2, and Phase 3 clinical trials, all of which are now completed. It is an investigational omega-3 carboxylic acids product and is not described as approved. The largest study, a Phase 3 cardiovascular outcomes trial, enrolled 13,078 participants.
Epanova has been evaluated in completed trials including NCT02104817, a Phase 3 outcomes study in high cardiovascular risk patients with hypertriglyceridemia that enrolled 13,078 participants, NCT02009865 (EVOLVE II), a Phase 3 hypertriglyceridemia study with 379 participants, NCT02370537, a Phase 2 study in type 2 diabetes and exocrine pancreatic insufficiency with 490 participants, and NCT02189252, a Phase 1 bioavailability study with 30 participants.
Epanova and Lovaza are different products. Epanova is an omega-3 carboxylic acids formulation, while Lovaza is a separate omega-3 product. The two have been compared directly in a Phase 1 open-label crossover study, NCT02189252, which assessed relative bioavailability, efficacy, and safety in men and women with a history of pancreatitis and severe hypertriglyceridemia.
Across its completed clinical trials, Epanova has been studied in a total of 13,078 enrolled participants. The largest contribution comes from the Phase 3 cardiovascular outcomes trial NCT02104817, which alone enrolled 13,078 patients. The remaining studies in type 2 diabetes, hypertriglyceridemia, and pancreatitis enrolled smaller numbers of participants.