E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Hypertriglyceridemia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020870 |
E.1.2 | Term | Hypertriglyceridemia |
E.1.2 | System Organ Class | 100000004861 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of ISIS 304801 (300 mg once weekly) as compared to placebo on the percent change in fasting TG from baseline. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of ISIS 304801 as compared to placebo on the following: -Absolute change from baseline in fasting TG -Proportion of patients who achieve ≥ 40% reduction from baseline in fasting TG -Percent change from baseline in HDL-C -Proportion of patients who achieve fasting TG < 150 mg/dL -Change from baseline in HOMA-IR -Change from baseline in HbA1c in T2DM patients |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. BMI ≤ 45 kg/m2
2. Fasting TG ≥ 500 mg/dL (≥ 5.7 mmol/L) at Screening.
3. If on statin or fibrate, patients must be on stable, labeled dose for at least 3 months prior to screening. Patients not receiving these drugs within 4 weeks prior to screening are also eligible. |
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E.4 | Principal exclusion criteria |
1. Type 1 Diabetes mellitus
2. Newly diagnosed type 2 diabetes mellitus (within 12 weeks of screening) or HbA1c ≥ 9.0% at Screening
3. Acute pancreatitis within 3 months of screening
4. Acute Coronary Syndrome within 6 months of screening
5. Gastric banding procedure within 1 year of screening
6. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin of carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
7. Treatment with another investigational drug, biological agent, or device within one month of screening.
8. Prior exposure to ISIS 304801
9. Have any other conditions in the opinion of the investigator which could interfere with the patient participating in our completing the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The % change in fasting TG from baseline as measured at the primary analysis time point. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis time point is at the end of Month 3 where the value is defined as the average of Week 12 and Week 13 fasting assessments |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints include: -Absolute change from baseline in fasting TG -Proportion of patients who achieve ≥ 40% reduction from baseline in fasting TG -Percent change from baseline in HDL-C -Proportion of patients who achieve fasting TG < 150 mg/dL -Change from baseline in HOMA-IR -Change from baseline in HbA1c in T2DM patients |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of Month 3 where the value is defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Germany |
Netherlands |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |