Study of the Efficacy and Safety of NST-1024 Versus Placebo in Subjects With Hypertriglyceridemia
Study Details
Study Description
Brief Summary
This is a Phase IIa,multicentre proof of concept study consisting of 2 study periods to study Treatment with NST-1024 as an adjunct to diet to reduce triglyceride (TG) levels in subjects with TG levels of ≥500 mg/dL and ≤2000 mg/dL; determined by percentage change in TG from baseline after 28 days of treatment.
The two periods consist of:
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A 3-week screening period that includes a TG qualifying period, and
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A 28-days, double-blind, randomized, parallel group, placebo-controlled treatment period.
Subjects will return to the study site for a follow-up visit 2 weeks after the last dose.
Approximately 50 subjects will be randomized at approximately 15-20 centres in USA.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Matched Placebo
|
Other: Placebo
matched placebo to active arm
|
| Active Comparator: NST-1024 NST-1024 400 mg BID |
Drug: NST-1024
400 mg BID
|
Outcome Measures
Primary Outcome Measures
- Evaluate the efficacy of NST-1024 by percentage change in TG [4 weeks]
Evaluate the efficacy of NST-1024 400 mg BID by assessment of the percentage change in TG from baseline after 28 days of treatment
Secondary Outcome Measures
- Percent Change in Cholesterol Values [4 weeks]
Percent changes in TC, HDL-C, LDL-C, calculated. non-HDL-C, and VLDL-C from baseline to Week 4
- Percent change in Apolipoprotein B and Apolipoprotein C3 [4 weeks]
Percent changes in ApoB and ApoC3 from baseline to Week 4.
- Percent Change in Lipoprotein a [4 weeks]
Percent change in Lp(a) from baseline to Week 4.
- Percent Change in remnant-like particle cholesterol (RLP-C) [4 weeks]
Percent Change in RLP-C from baseline to Week 4.
- Changes in fasting plasma glucose, fasting plasma insulin, and HbA1c [4 weeks]
Changes in fasting plasma glucose (FPG), fasting plasma insulin (FPI) and HbA1c from baseline to Week 4
- Change in insulin resistance. [4 weeks]
Change in insulin resistance, as assessed by the homeostasis model index insulin resistance, from baseline to Week 4
- Change in lipoprotein associated phospholipase A2 [4 weeks]
Percent change in lipoprotein associated phospholipase A2 from baseline to Week 4
- Change in hsCRP [4 weeks]
Change in hsCRP from baseline to Week 4
- Safety Assessments [~ 8 weeks]
Incidence of Treatment-Emergent Adverse Events and abnormalities in clinical laboratory measurements (chemistry, haematology, and urinalysis), 12-lead ECGs, blood pressure, and physical examinations will be evaluated and monitored for any safety events through the study duration from screening through follow up.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Understanding of the study procedures, willing to adhere to the study schedules, and agreement to participate in the study by giving written informed consent prior to screening (Visit 1Week -3]) assessments;
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Men or women 18 to 79 years of age, inclusive;
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Women may be enrolled if all 3 of the following criteria are met
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They are not pregnant,
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They are not breastfeeding, and
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They do not plan on becoming pregnant during the study.
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Women of childbearing potential must have a negative urine pregnancy test at screening (Visit 1 [Week -3]). Note: Women are not considered to be of childbearing potential if they meet 1 of the following criteria as documented by the investigator:
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They have had a complete hysterectomy or tubal ligation prior to signing the informed consent form or
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They are post-menopausal, defined as ≥1 year since their last menstrual period or have a follicle-stimulating hormone (FSH) level in menopausal range.
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Women of childbearing potential and men whose partners are of childbearing potential must agree to use a highly effective method of avoiding pregnancy from screening to the end of the study.
o Highly effective methods of avoiding pregnancy are contraceptive methods used consistently and correctly and include:
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Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation.
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Oral
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Intravaginal
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Transdermal
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Progestogen-only hormonal contraception associated with inhibition of ovulation.
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Oral
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Injectable
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Implantable
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Intrauterine device (IUD)
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Intrauterine hormone-releasing system
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Bilateral tubal occlusion
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Vasectomised partner
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Sexual abstinence
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On statin or non-statin lipid-altering therapy, such as ezetimibe, niacin >200 mg/day, bempedoic acid, fibrates, prescription omega-3 products, other consumer products containing omega-3 fatty acids, or other herbal products or dietary supplements with potential lipid and glucose-altering effects. Subjects must be stable for ≥28 days prior to the first TG baseline qualifying measurement (i.e., Visit 1 [Week -1]), and should remain stable thereafter for the duration of study participation;
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Fasting TG levels ≥500 mg/dL and ≤2000 mg/dL (based on an average [arithmetic mean] of Visit 1 and Visit 2). Note: In cases in which a subject's average TG level from Visit 1 and Visit 2 falls outside the range for entry into the study, an additional visit (Visit 2a) can be arranged up to 7 days after Visit 2 for an additional measurement of fasting TG levels. If a third sample is collected, entry into the double-blind treatment period will be based on the average of the highest TG value from Visit 1 and 2 and the Visit 2a value. Neither one of the two values used for the arithmetic mean can be less than 400 mg/dL;
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Maintain stable dose of all oral and injectable weight loss drugs (e.g., GLP-1 receptor agonists) for at least 3 months prior to study period.
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Willingness to maintain stable diet and physical activity level throughout the study
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If a smoker, no plans to change smoking habits during the study period.
Exclusion Criteria:
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Body mass index >40 kg/m2;
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Participation in another clinical study involving an investigational agent within 30 days prior to screening or 5 ½ half-lives whichever is longer(Visit 1 [Week -3]);
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Type 1 diabetes mellitus;
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HbA1c > 8.5% at screening (Visit 1 [Week -3]); Note: Subjects with elevated A1c >7% and not previously diagnosed with type 2 diabetes mellitus at screening will be excluded from the study and should be referred to their primary care physician for further treatment.
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History of stroke, myocardial infarction, life-threatening arrhythmia, or coronary revascularization within 6 months prior to screening;
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History of Acute or chronic pancreatitis;
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History of symptomatic gallstone disease unless treated with cholecystectomy;
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History of nephrotic range (>3 g/day) proteinuria;
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Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2
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QTcF interval of >450ms.
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A history of additional risk factors for torsades de pointes (TdP) (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome)
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The use of concomitant medications that prolong the QT/QTc interval (Table 1);
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History or evidence of major and clinically significant hepatic, pulmonary, renal, hematologic, gastrointestinal (including clinically significant malabsorption), endocrine, immunologic, dermatologic, neurologic, psychiatric, oncologic, or allergic (including drug allergies, but excluding untreated or treated seasonal allergies at the time of dosing) disease that would interfere with the conduct of the study or interpretation of the data;
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Known lipoprotein lipase impairment or deficiency (Fredrickson Type I), apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type III);
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Requirement for peritoneal dialysis or haemodialysis for renal insufficiency;
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History of malignancy, except subjects who have been disease-free for >5 years, or whose only malignancy has been treated basal or squamous cell skin carcinoma;
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History of bariatric surgery;
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Uncontrolled hypertension;
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Known to be infected with human immunodeficiency virus (HIV);
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Positive test for HIV antibody, hepatitis B surface antigen, hepatitis B Core Total or hepatitis C antibody at screening (Visit 1 [Week -3]), except for those who have been successfully treated for hepatitis C infection and have achieved sustained virologic response for ≥1 year or who have a negative reflex HCV RNA test;
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Anticipation of major surgery during the screening or double-blind treatment periods of the study;
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Treatment with chronic prescription pharmacotherapy for metabolic or CV disease management or risk factor modification (e.g., antihypertensive and antidiabetic medications) that has not been stable for ≥28 days prior to screening (Visit 1 [Week -3]);
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Ongoing treatment with HIV-protease inhibitors, cyclophosphamide, or isotretinoin;
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Treatment with tamoxifen, estrogens, or progestins that has not been stable for ≥28 days prior to screening (Visit 1 [Week -3]);
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Routine or anticipated use of all systemic corticosteroids. Use of local injectable, inhaled, nasal administration or topical corticosteroids is permitted;
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Thyroid-stimulating hormone (TSH) > 2.0 x upper limit of normal (ULN), clinical evidence of hypothyroidism, or thyroid hormone therapy that has not been stable for ≥6 weeks prior to screening (Visit 1 [Week -3]);
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Alanine aminotransferase or AST >2.5 x ULN, unless exercise-related;
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Unexplained CK concentration >5 × ULN or CK elevation due to known muscle disease (e.g., polymyositis, mitochondrial dysfunction);
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Other recent or current serious disease that may interfere with the conduct of the study (renal, ophthalmic, pulmonary, hepatic, biliary, gastrointestinal, mental disorder, infectious disease, or cancer);
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Blood donation of ≥1 pint (0.5 L) within 30 days prior to screening (Visit 1 [Week -3]), or plasma donation within 7 days prior to screening (Visit 1 [Week -3]);
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History of illicit drug use or alcohol abuse within 1 year of screening. Alcohol consumption is defined as >21 standard drinks per week in men and >14 standard drinks per week in women, on average;
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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;
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Poor mental function or any other reason to expect subject difficulty in complying with the requirements of the study; or in the investigator's opinion, not able to comply with study procedures.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- NorthSea Therapeutics B.V.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NST-1024-03