A Pilot Study to Evaluate the Lipid Effects of TRIA-662

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Cortria Corporation
Sponsor:
Collaborator:
Montreal Heart Institute
Information provided by (Responsible Party):
Cortria Corporation
ClinicalTrials.gov Identifier:
NCT02008084
First received: December 6, 2013
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

The purpose of this pilot study is to learn what study factors are important in designing a large, full-scale study of the effects of TRIA-662 on serum triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) levels. In this study, patients will first enter a Single-blind, dietary-controlled baseline period and receive 1000 mg placebo or active drug three times daily with meals (i.e., breakfast, lunch, and dinner) for 6 weeks. If the qualify to continue, they will then receive up to 2000 mg of active or placebo drug for an additional 14 weeks. Active drug will be given to 48 patients and placebo drug will be given to 16 patients. However, neither the patients not the clinic staff will know which patients are on active or placebo drug until the end of the study.


Condition Intervention Phase
Hypertriglyceridemia
Mixed Hyperlipidemia
Drug: TRIA-662
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Forced Dose-escalation, Multi-center Pilot Study to Evaluate the Lipid Regulating Effects of TRIA-662 (1-methylnicotinamide Chloride)

Resource links provided by NLM:


Further study details as provided by Cortria Corporation:

Primary Outcome Measures:
  • Recruitment Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The number of patients randomized per site per month during the study

  • Compliance to investigational product [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The proportion of randomized patients receiving the investigational product as per protocol.

  • Completion rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The proportion of randomized patients completing the 14-week follow-up.


Secondary Outcome Measures:
  • Effect on serum high-density lipoprotein cholesterol (HDL-C) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in serum HDL-C.

  • Variability of serum triglycerides [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The standard deviation of the change from baseline to end of study in serum triglycerides.

  • Effect on fasting glucose [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in fasting glucose.

  • Effect on C-reactive protein [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in C-reactive protein.

  • Effect on interleukin-6 (IL-6) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in IL-6.

  • Effect on total cholesterol (TC) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in TC

  • Effect on low-density lipoprotein cholesterol (LDL-C) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in LDL-C

  • Effect on very low-density lipoprotein cholesterol (VLDL-C) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in (VLDL-C),

  • Effect on total apolipoprotein B (apoB) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in apoB

  • Effect on total apolipoprotein A1 (apoA1) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in apoA1

  • Effect on lipoprotein (a) [Lp(a)] [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in Lp(a)

  • Effect on non-high density lipoprotein cholesterol (non-HDL-C) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in non-HDL-C

  • Effect on TG/HDL-C ratio [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in TG/HDL-C ratio

  • Effect on tumor necrosis factor - alpha (TNF-α) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The difference between groups in change from baseline to end of study in TNF-α


Estimated Enrollment: 64
Study Start Date: December 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: TRIA-662 single-blind baseline
Baseline, 6-week, dietary lead-in period
Drug: TRIA-662
Following Baseline randomized to active TRIA-662 2 x 500 mg tablets, three times daily with meals for 2 weeks and then active TRIA-662 2 x 1000 mg tablets, three times daily with meals for 12 weeks.
Drug: Placebo
Following Baseline randomized to placebo TRIA-662 2 x 500 mg tablets, three times daily with meals for 2 weeks and then placebo TRIA-662 2 x 1000 mg tablets, three times daily with meals for 12 weeks.
Experimental: TRIA-662
Following successful completion of the Baseline randomized to active drug
Drug: TRIA-662
Following Baseline randomized to active TRIA-662 2 x 500 mg tablets, three times daily with meals for 2 weeks and then active TRIA-662 2 x 1000 mg tablets, three times daily with meals for 12 weeks.
Placebo Comparator: Placebo
Following successful completion of the Baseline randomized to placebo drug
Drug: Placebo
Following Baseline randomized to placebo TRIA-662 2 x 500 mg tablets, three times daily with meals for 2 weeks and then placebo TRIA-662 2 x 1000 mg tablets, three times daily with meals for 12 weeks.

Detailed Description:

The primary objective of this pilot study is to assess the feasibility of a large,full-scale study that would evaluate the regulating effects of TRIA-662 on serum triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) levels. In this study, patients will first enter a Single-blind, dietary-controlled baseline period and receive 1000 mg placebo or active drug three times daily with meals (i.e., breakfast, lunch, and dinner) for 6 weeks. Upon completion of the 6-week dietary-controlled baseline period, subjects meeting all inclusion and no exclusion criteria will be randomized to the double-blind treatment period. In the double-blind treatment period patients will be randomized such that at least 48 subjects will be randomized to TRIA-662 and at least 16 patients will be randomized to placebo (3:1 ratio). The forced-dose titration will be achieved as follows: Weeks 1 - 2: Two 500 mg tablets three times daily with meals (total daily dose 3000 mg); Weeks 3 - 14: Two 1000 mg tablets three times daily with meals (total daily dose 6000 mg).

Investigational product will be administered three times daily with meals (i.e., breakfast, lunch, and dinner). Down titration to 3000 mg daily (two 500 mg tablets, three times daily) is allowed in the event that a patient cannot tolerate the 6000 mg daily treatment for the stipulated period. Under this scenario, the down-titrated patient will remain on the tolerated dose for the remainder of the study. Lipid and ancillary exploratory parameters will be evaluated during the baseline period, upon randomization and throughout the active treatment period. Throughout the study, patients must adhere to a heart-healthy diet, abstain from/minimize ethyl alcohol intake and control any other variables that may alter serum lipid levels (e.g., exercise, weight loss programs, drugs including over the counter agents preparations that may alter serum lipid levels. Safety and tolerability will be assessed throughout the trial through the evaluation of physical exams, electrocardiograms (ECGs), routine hematology and blood chemistry testing, vital signs and adverse events.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Women of childbearing potential must have a negative serum pregnancy test at screening

    Women are considered not of childbearing potential if they:

    1. have had a hysterectomy or tubal ligation prior to Visit 1.
    2. are postmenopausal (12 months no menses or menopausal follicle stimulating hormone level) Women of childbearing potential must agree to use an effective method of birth control throughout the study. Acceptable means of birth control include: implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, male or female condoms with spermicide, abstinence, or a sterile sexual partner.
  2. Patients who at Weeks -4 and -2 demonstrate LDL-C at the following levels at which drug therapy is not indicated according to ATP III guidelines and Framingham risk score:

    < 190 mg/dL (< 4.91 mmol/L) patients with 0 - 1 risk factor < 160 mg/dL (< 4.14 mmol/L) patients with ≥ 2 risk factors & 10 yr risk < 10% < 130 mg/dL (< 3.36 mmol/L) patients with ≥ 2 risk factors & 10 yr risk 10-20% < 100 mg/dL (< 2.59 mmol/L) patients with Type 2 diabetes & 10-yr risk > 20%

    Risk factors:

    • Cigarette smoking defined as any cigarette smoking in the past month.
    • Blood Pressure ≥ 140/90 mmHg (see exclusion #9) or on allowed medication
    • HDL-C < 40 mg/dL (1.03 mmol/L).
    • clinical CHD/sudden death in first degree male relative < 55 yr or first degree female relative < 65 yrs
    • men ≥ 45 years; women ≥ 55 years
  3. at Weeks -4 and -2 demonstrate mean serum triglycerides ≥ 200 mg/dL (2.26 mmol/L) but =< 500 mg/dL (5.65 mmol/L) at Weeks -4 and -2 and having lower level within 25% of upper level (higher value minus lower value)/higher value < 0.25).
  4. at Weeks -4 and -2 demonstrate serum HDL-C < 40 mg/dL (1.03 mmol/L) for men and < 50 mg/dL (1.29 mmol/L) for women.
  5. willing to maintain a stable diet and physical activity level throughout the study
  6. willing and able to sign the information and consent form and follow the protocol including availability for all visits/telephone follow-up for approximately 24 weeks.

Exclusion Criteria:

  1. pregnant, planning to become pregnancy during the study, or nursing
  2. clinically significant electrocardiographic abnormalities at Visit 1 or 4
  3. body mass index > 45 kg/m2 at Visit 1
  4. weight change of > 5% of initial body weight between Visit 1 and 4
  5. poorly controlled diabetes defined as a hemoglobin A1c > 9.5% at Visit 1
  6. evidence of hepatic disease (ALT or AST greater than 2.0 upper limit of normal (ULN), bilirubin > 1.5 ULN, or cirrhosis) at visit 1
  7. renal dysfunction defined as glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 at Visit 1
  8. hypothyroidism that is not treated or not stable for at least 6 months prior to Visit 1
  9. poorly controlled hypertension defined as a mean systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 100 mmHg at Visit 1. In individuals with end-organ damage, mean systolic blood pressure > 140 mmHg and mean diastolic blood pressure > 90 mmHg at Visit 1
  10. severe hypotension defined as systolic blood pressure =< 90 mm Hg or diastolic blood pressure =< 60 mm Hg AND symptomatic
  11. active peptic ulcer
  12. known intolerance or allergy to niacin (nicotinic acid), niacinamide (nicotinamide), or any of the tablet ingredients: 1-methylnicotinamide chloride, microcrystalline cellulose, povidone, silicified microcrystalline cellulose, crospovidone, anhydrous dibasic calcium phosphate, hydroxypropyl cellulose, magnesium stearate (vegetable origin), polyvinyl alcohol, titanium dioxide, talc, polyethylene glycol, methacrylic acid copolymer, and sodium bicarbonate.
  13. any known history of coronary artery disease, cerebrovascular disease or peripheral arterial disease
  14. Use after screening to the conclusion of the study of any of the following lipid modifying medications/supplements:

    1. Niacin (nicotinic acid) or niacinamide (nicotinamide)
    2. Fibrates/fibric acid derivatives like fenofibrate, gemfibrozil, clofibrate
    3. Bile acid sequestrants like cholestyramine, colesevelam, colestipol
    4. HMG-CoA reductase inhibitors (statins) including atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, simvastatin, rosuvastatin
    5. Ezetimibe
    6. Omega-3 fatty acids
    7. Supplements containing flaxseed, tryptophan, fish oil, or algal oil.
    8. Sterol/stanol products
    9. Red yeast rice supplements or soy isoflavone supplements.
    10. Dietary fiber supplements including > 2 teaspoonfuls of Metamucil® or psyllium containing supplements per day.
    11. Other natural health products or prescription agents judged by the investigator to have the potential to alter serum lipid levels in an individual subject.
  15. history of angina or myocardial infarction
  16. hyperuricemia or with a history of gouty arthritis
  17. known nephritic syndrome or >3 g protein/day in urine at Visit 1
  18. known familial lipoprotein lipase deficiency, apo CII deficiency, or familial dysbetalipoproteinemia.
  19. requirement for peritoneal dialysis or hemodialysis for renal insufficiency.
  20. history of malignancy, except patients who have been disease-free for > 5 yrs, or resected basal or squamous cell skin carcinoma or cervical carcinoma in situ.
  21. history of bariatric surgery.
  22. history of pancreatitis, except secondary to cholelithiasis.
  23. anticipation of major surgery during the study.
  24. treatment with weight loss drugs or programs during the trial.
  25. treatment with HIV-protease inhibitors, cyclophosphamide or isotretinoin.
  26. treatment with tamoxifen, estrogens, or progestins that have not been stable for > 4 week prior to screening at Visit 1
  27. routine or anticipated use of all systemic corticosteroids at Visit 1. Local, topical, inhaled, or nasal corticosteroids are permitted
  28. blood donation of > pint (0.5 L) within 30 days prior to screening, or plasma donation within 7 days prior to screening at Visit 1
  29. consumption of > 14 alcoholic drinks per week (1 drink = 12 oz beer, 5 oz wine, or 1.5 oz hard liquor) at Visit 1.
  30. history of drug abuse at Visit 1
  31. participation in another clinical trial within 30 days of signing the information and consent form.
  32. non-compliant to single blind investigational product (< 80% investigational product) or diet as per local judgment between Visit 1 and 4.
  33. Any condition or therapy that the investigator believes might pose a risk or make participation in the study not in the patient's best interest.
  34. Poor mental function or any reason to expect difficulty complying with the requirements of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02008084

Contacts
Contact: Tania Discenza, P.Dt. 514 461 1300 ext 2144 tania.discenza@mhicc.org

Locations
Canada, Alberta
Dr. Senaratne Professional Corporation Recruiting
Edmonton, Alberta, Canada, T6K 4C1
Contact: Manohara Senaratne, MD    780-735-7074    Manohara.Senaratne@albertahealthservices.ca   
Principal Investigator: Manohara Senaratne, MD         
The Bailey Clinic Recruiting
Red Deer, Alberta, Canada, T4N 6V7
Contact: Gordon Bailey, MD    403-343-8972    grbailey@thebaileyclinic.com   
Principal Investigator: Gordon Bailey, MD         
Canada, British Columbia
Manna Research Vancouver Recruiting
Vancouver, British Columbia, Canada, V6J 1S3
Contact: Melanie Mason, MD    604 336 8438      
Principal Investigator: Melanie Mason, MD         
Canada, New Brunswick
GA Research Associates, Ltd Recruiting
Moncton, New Brunswick, Canada, E1G 1A7
Contact: Ronald Bourgeois, MD    506 852 9865      
Principal Investigator: Ronald Bourgeois, MD         
Canada, Newfoundland and Labrador
Commonwealth Medical Clinic Recruiting
Mount Pearl, Newfoundland and Labrador, Canada, A1N 1W7
Contact: Dennis O'Keefe, MD    709-364-4992    dennis.okeefe@nfld.net   
Principal Investigator: Dennis O'Keefe, MD         
Canada, Ontario
KMH Cardiology & Diagnostics Centre Recruiting
Kitchener, Ontario, Canada, N2M 5N4
Contact: James Johnston, MD    905-855-1860    jjohnston@kmhlabs.com   
Principal Investigator: James Johnston, MD         
Aging, Rehabilitation & Geriatric Care, Lawson Health Research Institute-St Joseph's Health Care, Parkwood Recruiting
London, Ontario, Canada, N6C 5J1
Contact: Robert Petrella, MD    519-685-4292 ext #42075    petrella@uwo.ca   
Principal Investigator: Robert Petrella, MD         
Manna Research Inc. Recruiting
Toronto, Ontario, Canada, M9W 4L6
Contact: Azhar Toma, MD    416 740 2895      
Principal Investigator: Azhar Toma, MD         
Canada, Quebec
Rhodin Recherche Recruiting
Drummondville, Quebec, Canada, J2B 7T1
Contact: Benoit Gervais, MD    819 474 7477      
Principal Investigator: Benoit Gervais, MD         
Montreal Heart Institute Recruiting
Montreal, Quebec, Canada, H1T 1C8
Contact: Tania Discenza, P.Dt.    514 461 1300 ext 2144    tania.discenza@mhicc.org   
Principal Investigator: Jean-Claude Tardif, MD         
CardioVasc HR Recruiting
St-Jean sur Richelieu, Quebec, Canada, J3A 1C3
Contact: Daniel Savard, MD    450-376-6090    dr_savard@hotmail.com   
Principal Investigator: Daniel Savard, MD         
Centre de santé et de services sociaux du Sud de Lanaudière - Centre Hospitalier Pierre Le Gardeur Recruiting
Terrebonne, Quebec, Canada, J6V 2H2
Contact: Gilbert Gosselin, MD    (450) 654-7525 ext 11104    g.gosselin@videotron.ca   
Principal Investigator: Gilbert Gosselin, MD         
Centre de santé et de services sociaux de Trois-Rivières Recruiting
Trois-Rivières, Quebec, Canada, G8Z 3R9
Contact: Pascal Pelletier, MD    (819) 697-3333 ext x68421    pascal_pelletier_chrtr@ssss.gouv.qc.ca   
Principal Investigator: Pascal Pelletier, MD         
Canada
Clinique des Maladies Lipidiques de Quebec, Inc. Recruiting
Quebec, Canada, G1V 4M6
Contact: Jean Bergeron, MD    418 654 2162      
Principal Investigator: Jean Bergeron, MD         
Sponsors and Collaborators
Cortria Corporation
Montreal Heart Institute
Investigators
Principal Investigator: Jean-Claude Tardif, MD Montreal Heart Institute
  More Information

No publications provided

Responsible Party: Cortria Corporation
ClinicalTrials.gov Identifier: NCT02008084     History of Changes
Other Study ID Numbers: PNAI-MNA-03
Study First Received: December 6, 2013
Last Updated: April 25, 2014
Health Authority: Canada: Health Canada

Keywords provided by Cortria Corporation:
hypertriglyceridemia
mixed hyperlipidemia

Additional relevant MeSH terms:
Hyperlipidemia, Familial Combined
Hyperlipidemias
Hyperlipoproteinemia Type V
Hypertriglyceridemia
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias

ClinicalTrials.gov processed this record on August 26, 2014