Avenanthramides (AVA) are di-phenolic compounds found only in oats and are of interest due to suggested bioactivities, including antioxidant and anti-inflammatory effects in vitro and in vivo. Published data suggests that polyphenols can work as modifiers of signal transduction pathways to elicit their beneficial effects. These natural compounds express anti-inflammatory activity by modulation of pro-inflammatory gene expression such as cyclo-oxygenase, lipoxygenase, nitric oxide synthases and several pivotal cytokines, mainly by acting through nuclear factor-kappa B and mitogen-activated protein kinase signaling. The biomarkers of inflammation in blood, i.e., pro-inflammatory cytokines, chemokines, as well as other inflammatory markers (i.e., high sensitivity C-reactive protein) are of particular interest. Primary Objectives: * To assess the safety and tolerability of single ascending oral doses of avenanthramide in healthy subjects. * To assess the safety and tolerability of multiple ascending oral doses of avenanthramide in healthy subjects and subjects with elevated waist circumference and low-grade inflammation. Secondary Objectives: * To determine the pharmacokinetics of avenanthramide following single ascending oral doses in healthy subjects. * To compare the pharmacokinetics of avenanthramide following single oral dose in healthy subjects under fasting and fed conditions. * To determine the pharmacokinetics of avenanthramide following multiple ascending oral doses in healthy subjects. * To determine the pharmacokinetics of avenanthramide following multiple ascending oral doses in subjects with elevated waist circumference and low-grade inflammation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
96
In each cohort 6 subjects will be assigned to the active treatment and 2 subjects will be assigned to the placebo.
In each cohort 6 subjects will be assigned to the active treatment and 2 subjects will be assigned to the placebo.
Montreal Heart Institute
Montreal, Quebec, Canada
RECRUITINGIncidence of Adverse Events (Safety and Tolerability)
Incidence of AEs on active treatment compared to placebo
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (general biochemistry)
The change in serum laboratory parameters : Alanine aminotransferase (IU/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (general biochemistry)
The change in serum laboratory parameters : Aspartate aminotransferase (IU/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (general biochemistry)
The change in serum laboratory parameters : Total bilirubin (umol/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (general biochemistry)
The change in serum laboratory parameters : Direct bilirubin (umol/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (general biochemistry)
The change in serum laboratory parameters :Indirect bilirubin (umol/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (general biochemistry)
The change in serum laboratory parameters : Serum urea (mmol/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (general biochemistry)
The change in serum laboratory parameters : Serum creatinine (umol/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (general biochemistry)
The change in serum laboratory parameters : eGFR (mL/min/1.73 mE2)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (general biochemistry)
The change in serum laboratory parameters : Blood urea nitrogen (mg/dL)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (general biochemistry)
The change in serum laboratory parameters : Fasting glucose (mmol/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (general biochemistry)
The change in serum laboratory parameters : Fasting plasma insulin (pmol/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (general biochemistry)
The change in serum laboratory parameters : Total cholesterol (mmol/L))
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (hematology)
The change in serum laboratory parameters: (Leucocytes (10E9/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (hematology)
The change in serum laboratory parameters: Erythrocytes (10E12/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (hematology)
The change in serum laboratory parameters: Platelets count (10E9/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (hematology)
The change in serum laboratory parameters: Hemoglobin (g/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (hematology)
The change in serum laboratory parameters: Hematocrit (L/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (hematology)
The change in serum laboratory parameters: Mean corpuscular volume (fL)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (hematology)
The change in serum laboratory parameters: Mean corpuscular hemoglobin (pg)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (hematology)
The change in serum laboratory parameters: Mean corpuscular hemoglobin concentration (g/L)
Time frame: from drug administration up to 24 hours after the last dose
Change in laboratory parameters (hematology)
The change in serum laboratory parameters: Mean platelet volume (fL)
Time frame: from drug administration up to 24 hours after the last dose
Change in physical examination (Safety and Tolerability)
The change in review of body systems: head and neck
Time frame: from drug administration up to 24 hours after the last dose
Change in physical examination (Safety and Tolerability)
The change in review of body systems: cardiovascular
Time frame: from drug administration up to 24 hours after the last dose
Change in physical examination (Safety and Tolerability)
The change in review of body systems: respiratory
Time frame: from drug administration up to 24 hours after the last dose
Change in physical examination (Safety and Tolerability)
The change in review of body systems: abdomen
Time frame: from drug administration up to 24 hours after the last dose
Change in physical examination (Safety and Tolerability)
The change in review of body systems: brief neurological appearance
Time frame: from drug administration up to 24 hours after the last dose
Change in physical examination (Safety and Tolerability)
The change in review of body systems: brief general appearance
Time frame: from drug administration up to 24 hours after the last dose
Change in vital signs (Safety and Tolerability)
The change in pulse rate (pbm)
Time frame: from drug administration up to 24 hours after the last dose
Change in vital signs (Safety and Tolerability)
The change in blood pressure (mm Hg)
Time frame: from drug administration up to 24 hours after the last dose
Change in vital signs (Safety and Tolerability)
The change in body temperature (degrees Celsius).
Time frame: from drug administration up to 24 hours after the last dose
Change in ECG parameters (Safety and Tolerability)
The change in ECG parameters: PR interval
Time frame: from drug administration up to 24 hours after the last dose
Change in ECG parameters (Safety and Tolerability)
The change in ECG parameters: QRS interval
Time frame: from drug administration up to 24 hours after the last dose
Change in ECG parameters (Safety and Tolerability)
The change in ECG parameters: QT interval
Time frame: from drug administration up to 24 hours after the last dose
The change in Pharmacokinetics
Part A (Single Ascending Dose \[SAD\]) Plasma Day 1 (and Day 8 on the food-effect cohort): Cmax
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part A (Single Ascending Dose \[SAD\]) Plasma Day 1 (and Day 8 on the food-effect cohort): Tmax
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part A (Single Ascending Dose \[SAD\]) Plasma Day 1 (and Day 8 for food effect only): AUC0-T
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part A (Single Ascending Dose \[SAD\]) Plasma Day 1 (and Day 8 for food effect only): AUC0-∞,
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part A (Single Ascending Dose \[SAD\]) Plasma Day 1 (and Day 8 for food effect only): AUC 0-T/∞
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part A (Single Ascending Dose \[SAD\]) Plasma Day 1 (and Day 8 for food effect only): λz
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part A (Single Ascending Dose \[SAD\]) Plasma Day 1 (and Day 8 for food effect only): T1/2
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part A (Single Ascending Dose \[SAD\]) Plasma Day 1 (and Day 8 for food effect only): CL/F\*
Time frame: Up to 24 hours after the last dose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
The change in Pharmacokinetics
Part A (Single Ascending Dose \[SAD\]) Plasma Day 1 (and Day 8 for food effect only): VD/F\*
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part A (Single Ascending Dose \[SAD\]): Urine Day 1 (and Day 8 on the food-effect cohort): Ae \*for parent drug only:
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part A (Single Ascending Dose \[SAD\]): Urine Day 1 (and Day 8 on the food-effect cohort): Fe\* \*for parent drug only:
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part A (Single Ascending Dose \[SAD\]): Urine Day 1 (and Day 8 on the food-effect cohort): Clr\* \*for parent drug only:
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Plasma Day 1: Cmax
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Plasma Day 1: Tmax
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Plasma Day 1: AUC0-12
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Plasma Days 2 (prior to AM and PM dose), and 3 (prior to AM dose): Ctrough
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Plasma Day 3: Cmax
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Plasma Day 3: Tmax
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Plasma Day 3: Cmin
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Plasma Day 3: AUC0-24
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Plasma Day 3: AUCtau
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Plasma Day 3: T1/2
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Plasma Day 3: Rac(Cmax)
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Plasma Day 3: Rac(AUC)
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Urine Day 1 (12hrs), Day 3 (12hrs and 24hrs): Ae \* for parent drug only
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Urine Day 1 (12hrs), Day 3 (12hrs and 24hrs): Fe\* \* for parent drug only
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part B (Multiple Ascending Dose \[MAD\]) in healthy subjects: Urine Day 1 (12hrs), Day 3 (12hrs and 24hrs): Clr\* \* for parent drug only
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Plasma Day 1: Cmax
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Plasma Day 1: Tmax
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Plasma Day 1: AUC0-12
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Plasma Days 8, 15, 22 and 29 (prior to AM dose): Ctrough
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Plasma Day 29 : Cmax
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Plasma Day 29 : Tmax
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Plasma Day 29 : Cmin
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Plasma Day 29 : AUC0-24
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Plasma Day 29 : AUCtau
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Plasma Day 29 : T1/2
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Plasma Day 29 : Rac(Cmax)
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Plasma Day 29 : Rac(AUC)
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Urine Day 1 (12hrs) and Day 29 (12hrs and 24hrs). Ae
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Urine Day 1 (12hrs) and Day 29 (12hrs and 24hrs). Fe\*
Time frame: Up to 24 hours after the last dose
The change in Pharmacokinetics
Part C (MAD in subjects with elevated waist circumference and low-grade inflammation): Urine Day 1 (12hrs) and Day 29 (12hrs and 24hrs). Clr\*
Time frame: Up to 24 hours after the last dose