The Safety of a Hypolipidemic Agent in Healthy Normal Volunteers

Study Overview
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Brief Summary
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The primary objective of the study is to assess the blood profile of the N-methylnicotinamide (MNA) following administration of TRIA-662 (N-methylnicotinamide Chloride). The secondary objectives of the study are to characterize the safety and tolerability of TRIA-662 and to assess any potential gender-related differences in the plasma profile of MNA. Changes in serum lipid parameters with particular reference to triglycerides, lipoprotein lipase, and blood pressure effects will also be noted.

Detailed Description
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A total of 20 subjects volunteers (10 male and 10 female) will receive the following treatments administered in a randomized fashion with 2 embedded placebo dosages in each group (8 active Males and 8 active females with 2 placebo males and females): DRUG (Low Dose): Single therapeutic dose of MNA administered as a 90 mg oral dose DRUG (High Dose): Single therapeutic dose of MNA administered as a 270 mg oral dose PLACEBO: Placebo for MNA administered as an identically appearing oral dose Each treatment period will consist of a 3-day two-night confinement cycle with admission on day 1, treatment on day 1 with a single dose of active or placebo with discharge 24 hours following the last assessment the next morning. A washout period of 5 days will separate each treatment period. Standard biochemical and clinical baseline medical background and physical examination will occur at screening and at Day -1 to assess/confirm entry criteria. During each treatment period, serial plasma samples (n=12) for MNA assay will be collected on the treatment day. Safety assessments, including vitals signs (blood pressure, pulse rate, respiration rate, and oral body temperature), will be performed at screening, at baseline, and at 4 times throughout each treatment period. Physical examinations and standard clinical laboratory tests (hematology, serum chemistry, and urinalysis) will be obtained at screening, and at admission for each treatment period, and prior to subject's final discharge from the study. The Lunch meals on the dosing day will be identical in each subject on each occasion. The pharmacokinetic and safety assessments will be performed at specified times prior to and after study MNA administration.

Official Title
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A Randomized Placebo Controlled Double Blind Two Period Cross-Over Study to Assess the Safety and Pharmacokinetics and Pharmacodynamics of Oral Dosages of TRIA-662 (A Hypolipidemic Agent) in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: TRIA-662
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Good health (based on medical history, physical examination, electrocardiogram, and clinical laboratory tests) Non-smokers (refrained from any tobacco usage, including smokeless tobacco, nicotine patches, etc., for 6 months prior to the Screening visit) Between 18 and 50 years old (inclusive) Body weight within 20% of the desirable weight for adults at the Screening visit Able to execute informed written consent (informed consent must be obtained for all subjects before enrollment in the study. Willingness to abstain from alcohol and xanthine-containing food and beverages for the duration of each treatment period Willingness to remain in the clinic for the inpatient portions of the study Female subjects must be non-pregnant and either surgically sterile, postmenopausal for a least 1 year, or using an acceptable method of contraception defined as an oral, implanted, or transdermal contraceptive plus one of the following barrier methods: diaphragm with spermicidal cream/jelly or use of a condom by sexual partner. Exclusion Criteria: Currently abusing drugs or alcohol or with a history of drug or alcohol abuse within the past two years Unwilling or unable to comply with the protocol or reside in the study unit during the study period or to cooperate fully with the principal investigator and site personnel Has used any 1) prescription medication within 14 days prior to treatment in either treatment period or 2), or any over-the-counter (OTC) medication, herbal preparations, and/or vitamins within 48 hours prior to the start of study MNA administration on either treatment period of this study. Has a clinically abnormal ECG Has a serum potassium, sodium, calcium, or magnesium level that is not within normal limits or has other vital signs or clinical laboratory values at the screening visit that are deemed by the principal investigator to make the subject an inappropriate candidate for the study Has taken any other investigational drug during the 30 days prior to screening visit Has donated or lost more than a unit of blood within 30 days prior to screening visit History of renal, hepatic, gastrointestinal, cardiovascular, or hematologic disease Serious mental or physical illness within the past year Has any condition(s) that in the investigator's opinion would: a) warrant exclusion from the study or b) prevent the subject from completing the study Have a positive test for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody at screening Be a female subject with a positive serum pregnancy test or who is breast-feeding at screening Be unable to understand verbal and/or written English or any other language in which a certified translation of the informed consent is available Has a history of hypersensitivity or allergic reaction to Niacin or Nicotinamide Has had prior exposure to MNA Has a Mental capacity that is limited to the extent that the subject cannot provide legal consent or understand information regarding the side effects or tolerance of the study drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: TRIA-662 Placebo<br>Single dose of nine placebo capsules matching TRIA-662 drug capsules | Drug: Placebo<br>* Double-blind placebo<br>* Other names: Dummy;|
| Experimental: TRIA-662 Low Dose<br>Single-dose of TRIA-662 administered as three 30 mg TRIA-662 capsules and six matching placebo capsules | Drug: TRIA-662<br>* 1-MNA Chloride<br>* Other names: 1-MNA Chloride;|
| Experimental: TRIA-662 High Dose<br>Single dose of TRIA-662 administered as nine 30mg TRIA-662 capsules | Drug: TRIA-662<br>* 1-MNA Chloride<br>* Other names: 1-MNA Chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MNA Maximum plasma concentration (Cmax). | 5 mL venous blood samples will be collected by venipuncture at the specified times. These blood samples will be properly processed and analyzed for concentration of MNA and metabolites. The concentration data will undergo typical pharmacokinetic data analysis to arrive at the primary endpoints. | 0, 1, 2, 3, 4, 5, 8, 12, 18, 24 hours after dose. | 
| Time to plasma MNA Cmax | 5 mL venous blood samples will be collected by venipuncture at the specified times. These blood samples will be properly processed and analyzed for concentration of MNA and metabolites. The concentration data will undergo typical pharmacokinetic data analysis to arrive at the primary endpoints. | 0, 1, 2, 3, 4, 5, 8, 12, 18, 24 hours after dose. | 
| Area under the plasma MNA concentration curve | 5 mL venous blood samples will be collected by venipuncture at the specified times. These blood samples will be properly processed and analyzed for concentration of MNA and metabolites. The concentration data will undergo typical pharmacokinetic data analysis to arrive at the primary endpoints. | 0, 1, 2, 3, 4, 5, 8, 12, 18, 24 hours after dose. |