Clinical trial NCT01516151: Assess the Safety and Efficacy of NKPL66 (CaPre™) in the Treatment of Mild-to-high Hypertriglyceridemia
Official title: A Randomized Open-label Dose-ranging, Multi-center Trial to Assess the Safety and Efficacy of NKPL66(CaPre™) in the Treatment of Mild-to-high Hypertriglyceridemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertriglyceridemia
Keywords: Hypertriglyceridemia
Lead sponsor: Grace Therapeutics Inc.
Sponsor class: INDUSTRY
Collaborators: name: JSS Medical Research Inc.
First posted: 2012-01-24
Enrollment: 289
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy of 0.5, 1.0, 2.0 and 4.0 g/ day of CaPre™ in reducing fasting plasma serum triglycerides over a four week period in patients with mild-to-high hypertriglyceridemia as compared to the standard of care alone.

Detailed description: The data generated from preclinical studies, as well as data accumulated from preclinical and clinical studies conducted with the precursor of CaPre™, NKO® , a natural health product (NPN: 80006416), have shown that CaPre™ is a safe product and well tolerated. In addition, there are preclinical data demonstrating that CaPre™ is effective in reducing circulating plasma concentrations of triglycerides. This effect is also accompanied by the regulation of other blood lipids, glucose tolerance and inflammatory biomarkers. These studies have been conducted in several preclinical adult phenotypes: (1) Healthy Sprague-Dawley (SD) rats, (2) obese and dyslipidemic Zucker Diabetic Fatty (ZDF) rats and(3-5) in three distinct murine phenotypes (normal wild-type C57BL/6, human ApoA-I transgenic mice and homozygous LDL-receptor knockout).

As the prevalence of cardiometabolic disorders progressively increase over the years, it is expected that there will be an augmentation in the necessity for new anti-dyslipidemic medications that can most importantly be added in combination to other treatments. Current treatment methods address a specific target indication, but do not offer complete management of dyslipidemia.

We are now left with the option to either inadequately treat patients suffering from cardiovascular and metabolic disorders or, to prescribe combination treatments hoping to address the risk factors while mitigating their known side effects. A treatment gap exists since there is no medication that increases HDL-cholesterol and reduces triglycerides while reducing LDL-cholesterol without side effects.

At present there is a need to assess the effectiveness of CaPre™ in reducing triglycerides in patients with high hypertriglyceridemia. The current study will address these issues and will generate the evidence that will be required to determine whether this product could be effectively used in the clinical management of this patient population.

Eligibility criteria: Inclusion Criteria:

* Male and female adults aged 18 to 75 years;
* Fasting plasma levels of TG \> 2.28 and \< 10 mmol/L (200 and 877 mg/dL) on two occasions within 2 weeks (screening and baseline/part 1 visits).
* Patients who are currently not on pharmacotherapy for hyperlipidemia and according to the judgement of the physician and Canadian Guidelines for the Diagnosis and Treatment of Dyslipidemia initiation of drug therapy is not indicated for the duration of the study.

OR

* Patients currently treated with statins and according to the judgement of the physician and the Canadian Guidelines for the Diagnosis and Treatment of Dyslipidemia a change in their current drug regimen is not indicated for the duration of the study.
* Patients treated with statin must be on stable dose for at least 6 weeks prior to screening;
* Patients are willing to follow the NCEP Step 1 Diet (see Appendix 4) for the duration of the study;
* Female participants of childbearing potential (i.e. not surgically sterilized or post-menopausal greater than one year) must have negative serum pregnancy test and must be using an effective birth control method, defined as:

  * continuous use of oral or long acting injected contraceptive for at least 2 months prior to study entry, or;
  * use of an intra-uterine device or implantable contraceptive, or;
  * use of double barrier methods of birth control

Exclusion Criteria:

* Any concomitant medication which in the opinion of the investigator would preclude the patient from successfully participating in the study;
* Women who are pregnant or that are breast feeding;
* Participation in another clinical trial within 30 days from initiation of the study;
* Participants with a high risk for cardiovascular disease; (The definition of high-risk individuals will follow that of the 2009 Canadian Guidelines and include a) FRS \>= 20% 10-year risk; b) All patients with uncontrolled diabetes (DCA guidelines) and c) Evidence of atherosclerosis -when this evidence was ascertained when clinically indicated);
* Systolic blood pressure \> 140 mmHg and/or diastolic blood pressure \> 90 mmHg. In diabetic patients, systolic blood pressure \> 130 mmHg and/or diastolic blood pressure \> 90 mmHg.
* History of stroke, intermittent claudication or transient ischemic attack;
* Known unstable (uncontrolled) cardiac disease, within the last 6 months:
* Patient with a clinically significant abnormal ECG at screening.
* Patients with uncontrolled diabetes mellitus, with HbA1c \> 7.0%;
* Known diagnosis of hypoglycemia
* Evidence of active renal disease indicated by a fasting estimated glomerular filtration rate (eGFR) of \< 60 ml/min per 1.73 m2;
* Increased plasma levels (\>ULN) of amylase (as per respective lab upper limits) and / or lipase (\>160 IU/L) or any indication of pancreatitis (increased alcohol consumption, gallstones);
* History of pancreatitis;
* Use of any lipid lowering medication other than statins (e.g niacin, fibrates or ezetimibe) and/or lipid lowering NHP within 6 weeks prior to the screening visit;
* Intake of \> 2 servings per week of fish or regimented use of fish oil/omega-3 supplements within 6 weeks prior to the screening visit;
* Intake of fortified foods containing plant sterols within 6 weeks prior to the screening visit;
* Known HIV or Hepatitis B or C positive;
* Patients with osteoporosis and hormone sensitive conditions;
* Patients with uncontrolled asthma as defined by the 2010 Consensus Summary of the Canadian Thoracic Society;
* Known seafood allergy or allergy to any of the medicinal or non-medicinal ingredients of the study medication, including:

  * Omega-3 fatty acids (including EPA and DHA)
  * Phospholipids (mainly phosphatidylcholine)
  * Astaxanthin
  * Bovine gelatin
* Coagulopathy or on anticoagulants. Platelet aggregation inhibitors (such as aspirin or clopidogrel but not heparin) are permitted in the study; patients taking both aspirin and clopidogrel are not permitted in the study;
* Unable or unwilling to comply with the protocol;
* Patient reported weight must be stable for the past 6 months (within 3kg variation);
* Consumption of more than 14 standard alcoholic drinks a week.

Primary outcomes:
measure: Percent change in fasting blood circulating serum TGs
timeFrame: Between baseline and 4 weeks of treatment.
Secondary outcomes:
measure: Absolute change in fasting plasma TGs
timeFrame: Baseline, Week 4 and Week 8
measure: Patients achieving target TG fasting plasma levels
timeFrame: Baseline
measure: Change in fasting plasma LDL-C, VLDL-C, HDL-C, total cholesterol, hs-CRP and non-HDL
timeFrame: Between baseline and 4 and 8 weeks of treatment
measure: Change in fasting plasma concentrations of LDL-C, VLDL-C, HDL-C, total cholesterol, hs-CRP and non-HDL
timeFrame: Between baseline and 4 and 8 weeks of treatment
measure: Calculated ratios
timeFrame: The percent change in fasting blood circulating serum TGs Between baseline and 4 and 8 weeks of treatment.
measure: Change in fasting plasma concentrations of biomarkers
timeFrame: Between baseline and 4 and 8 weeks of treatment
Other outcomes:
Locations:
city: Red Deer
country: Canada
facility: Alberta Health Services Clinical Trials
state: Alberta
city: Abbotsford
country: Canada
state: British Columbia
city: Kelowna
country: Canada
state: British Columbia
city: Vancouver
country: Canada
facility: BC Diabetes
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Dieppe
country: Canada
state: New Brunswick
city: Aurora
country: Canada
facility: Entralogix Clinical Research
state: Ontario
city: Brampton
country: Canada
facility: Entralogix Clinical Research
state: Ontario
city: Cambridge
country: Canada
facility: Cambridge Cardiac Care Center
state: Ontario
city: Chatam
country: Canada
facility: Thamesview Ctr of Family Med
state: Ontario
city: Colingwood
country: Canada
facility: Moran Medical Centre
state: Ontario
city: Fort Erie
country: Canada
facility: C & L Research
state: Ontario
city: Hamilton
country: Canada
state: Ontario
city: Kitchener
country: Canada
facility: Entralogix Clinical Research
state: Ontario
city: Mississauga
country: Canada
facility: Entralogix Clinical Research
state: Ontario
city: Mississauga
country: Canada
facility: Malton Medical Research Group
state: Ontario
city: Niagara Falls
country: Canada
state: Ontario
city: North York
country: Canada
facility: Entralogix Clinical Research
state: Ontario
city: Oshawa
country: Canada
facility: Taunton Health Centre
state: Ontario
city: Pickering
country: Canada
facility: Steeple Hill Medical centre
state: Ontario
city: Sudbury
country: Canada
facility: G.S. Cardiac Lab Medicine Professional Corp
state: Ontario
city: Toronto
country: Canada
facility: Entralogix Clinical Research
state: Ontario
city: Toronto
country: Canada
facility: Eric Silver Medicine Professional Corporation
state: Ontario
city: Vaudreuil Dorion
country: Canada
facility: Clinique Médicale des Trois Lacs
state: Ontario
city: Courcelette
country: Canada
facility: Clinique Medicale Valcartier
state: Quebec
city: Delson
country: Canada
facility: Clinique Reseau le Trait d'Union
state: Quebec
city: Dolbeau-Mistassini
country: Canada
facility: Clinique Medicale Mistassini
state: Quebec
city: Grand Mere
country: Canada
facility: GMF Grand Mere
state: Quebec
city: Grand-Mere
country: Canada
facility: Clinique medicale
state: Quebec
city: Joliette
country: Canada
facility: CRM Lanaudiere
state: Quebec
city: Montreal
country: Canada
facility: Applied Medical Information Research AMIR
state: Quebec
city: Rosemere
country: Canada
facility: Clinique Services Sante Rosemere
state: Quebec
city: Saint-Jerome
country: Canada
facility: Csss de St-Jerome
state: Quebec
city: Val d'Or
country: Canada
facility: CSSS Vallee De L'Or
state: Quebec
city: Westmount
country: Canada
facility: Applied Medical Information Research (AMIR)
state: Quebec
city: Quebec
country: Canada
facility: Centre de recherche A&E
city: Quebec
country: Canada
facility: Clinique des maladies lipidiques de Quebec Inc.
Study officials:
affiliation: Institut de Recherches Cliniques de Montreal
name: Robert Dufour, M.D.
role: PRINCIPAL_INVESTIGATOR
References: