A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of ISIS 304801 Administered Subcutaneously to Patients with Hypertriglyceridemia
- Conditions
- hypertriglyceridemia10013317
- Registration Number
- NL-OMON43654
- Lead Sponsor
- IONIS Pharmaceuticals, Inc
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
1. Must give written informed consent to participate in the study (signed and dated) and any authorizations by law
2. Age * 18 years at time of informed consent
3. BMI * 45kg/m²
4. Stable weight (+/- 4kg) for >6 weeks prior to screening
5. Fasting TG * 500mg/dL (* 5.7mmol/L)at Screening. If the fasting TG value at Screening is < 500mg/dL (< 5.7mmol/L) but *350mg/dL (* 4.0mmol/L) up to two additional tests may be performed in order to qualify
6. If on statin or fibrate, patients must be on stable, labeled dose for at least 3 months prior to screening that is not anticipated to change during the study treatment period. Patients not receiving these drugs within 4 weeks prior to screening are also eligible.
7. Fasting TG * 500mg/dL at Qualification Visit. IF fasting TG is < 500mg/dL but * 350mg/dL (* 4.0mmol/L) up to two additional tests may be performed in order to qualify.
8. Willing to maintain their customary activity level and to follow the NCEP ATP III TLC diet or similar with weight maintenance during the study.
9. Satisfy one of the following:
a. Females: Non-pregnant and non-lactating; surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), post-menopausal (defined as 12 months of spontaneous ameorrhea in females > 55 years of age or, in females * 55 years, 12 months of spontaneous ameorrhea without an alternative medical cause and FSH levels in the postmenopausal range for the laboratory involved), abstinent*, or if engaged in sexual relations and of child-bearing potential, patient is using an acceptable contraceptive method from time of signing the informed consent form until 13 weeks after the last dose of Study Drug administration
b. Males: Surgically sterile, abstinent* or if engaged in sexual relations with a female of child-bearing potential, patient is utilizing an acceptable contraceptive method from the time of signing the informed consent form until 13 weeks after the last dose fo Study Drug administration.
* Abstinence is only acceptable as true abstinence, i.e., when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception
1. Type 1 diabetes mellitus
2. Type 2 Diabetes mellitus with any of the following:
a. Newly diagnosed within 12 weeks of screening
b. HbA1c * 9.0% at Screening
c. Recent change in anti-diabetic pharmacotherapy (change in dosage or addition of new medication within 12 weeks of screening [with the exception of +/- 10 units of insulin])
d. Anticipated need to change dose or type of medication during the treatment period of the Study (with the exception of +/- 10 units of insulin)
e. Current use of GLP-1 agonists, if patient has history of pancreatitis
3. Acute pancreatitis within 3 months of screening
4. History within 6 months of screening of acute or unstable cardiac ischemia (myocardial infarction, acute coronary syndrome, new onset angina), stroke, transient ischemic attack or unstable congestive cardiac failure requiring a change in medication or major surgery within 3 months of screening
5. Any of the following laboratory values at Screening:
a. Hepatic: Total bilirubin > upper limit of normal (ULN), unless prior diagnosis and documentation of Gilbert's syndrome in which case total bilirubin must be * 3mg/dL; ALT > 2.0x ULN; AST > 2.0 x ULN
b. Renal: Persistently positive (2 out of 3 tests * 1+) for protein on urine dipstick. In the event of positive test eligibility may be confirmed by a quantative total urine protein measurement of < 500mg/24hrs; Persistently positive (2 out of 3 tests * trace positive) for blood on urine dipstick. In the event of a positive test eligibility may be confirmed with urine microscopy showing * 5 red blood cells per high power field; Estimated creatinine clearance calculated according to the formula of Cockcroft and Gault < 50mL/min
c. Cardiac troponin I > ULN at Screening
d. LDL-C > 130mg/dL (> 3.4 mmol/L) at Screening for all patients and LDL-C > 100mg/dL (> 2.6 mmol/L) for patients with T2DM or history of MACE
e. any other laboratory abnormalities which, in the opinion of the Investigator or the Sponsor, would make the patient unsuitable for inclusion
6. Uncontrolled hypothyroidism (abnormal thyroid function tests should be approved by Study medical monitor)
7. Uncontrolled hypertension (BP > 160/100 mm Hg)
8. History of bleeding diathesis or coagulopathy or clinically significant abnormality in coagulation parameters at Screening
9. History of heart failure with NYHA greater than Class II
10. History of gastrointestinal malabsorption (e.g., uncontrolled Crohn's disease, etc.) or history of a gastric bypass or other diversional bariatric surgery
11. Gastric banding procedure within 1 year of screening
12. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1
13. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B
14. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
15. Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational agent, whichever is longer
16. History within 6 months of screening of drug or alcohol abuse
17. Unwilling to comply with lifestyle requirements
18. Use of any of the following medications:
a. Omega-3 fatty acids (prescription or OTC preparations) within 4 weeks of
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Efficacy evaluations include percent change from baseline and absolute change<br /><br>from baseline as compared with placebo in fasting TG as well as other lipid<br /><br>parameters, and measures of insulin sensitivity for ISIS 304801 as compared to<br /><br>placebo. Analysis of response will also be conducted using a range of fasting<br /><br>plasma TG thresholds for determination of responder status.<br /><br><br /><br>The primary endpoint is the % change in fasting TG from baseline as measured at<br /><br>the primary analysis time point.</p><br>
- Secondary Outcome Measures
Name Time Method <p>_Absolute change from baseline in fasting TG<br /><br>_Proportion of patients who achieve * 40% reduction from baseline in fasting TG<br /><br>_Percent change from baseline in HDL-C<br /><br>_Proportion of patuents who achieve fasting TG < 150mg/dL<br /><br>_Change from baseline in HOMA-IR<br /><br>_Change from baseline in HbA1c in T2DM patients</p><br>