Single and Multiple Ascending Oral Doses of Avenanthramide

NCT06101784 | Completed Phase 1 DMC

• 1 other identifier: PROJ1602
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Inflammation

Keywords

Healthy subjects; Single ascending dose; Multiple ascending dose; Natural product; Placebo controlled; First in human

Outcome Measures

Primary Outcomes (34)

• Incidence of Adverse Events (Safety and Tolerability)

  Incidence of AEs on active treatment compared to placebo

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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))

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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

  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

  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

  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

  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

  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

  from drug administration up to 24 hours after the last dose

• Change in vital signs (Safety and Tolerability)

  The change in pulse rate (pbm)

  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)

  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).

  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

  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

  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

  from drug administration up to 24 hours after the last dose

Secondary Outcomes (42)

• The change in Pharmacokinetics

  Up to 24 hours after the last dose

• The change in Pharmacokinetics

  Up to 24 hours after the last dose

• The change in Pharmacokinetics

  Up to 24 hours after the last dose

• The change in Pharmacokinetics

  Up to 24 hours after the last dose

• The change in Pharmacokinetics

  Up to 24 hours after the last dose

Study Arms (4)

Avenanthramide tablet single oral dose

ACTIVE COMPARATOR

adaptive dose levels

Drug: Avenanthramide

Placebo to match Avenanthramide tablet single oral dose

PLACEBO COMPARATOR

adaptive dose levels

Drug: Placebo

Avenanthramide tablet multiple oral dose

ACTIVE COMPARATOR

adaptive dose levels

Drug: Avenanthramide

Placebo to match Avenanthramide tablet multiple oral dose

PLACEBO COMPARATOR

adaptive dose levels

Drug: Placebo

Interventions

Avenanthramide DRUG

In each cohort 6 subjects will be assigned to the active treatment and 2 subjects will be assigned to the placebo.

Avenanthramide tablet multiple oral dose; Avenanthramide tablet single oral dose

Placebo DRUG

In each cohort 6 subjects will be assigned to the active treatment and 2 subjects will be assigned to the placebo.

Placebo to match Avenanthramide tablet multiple oral dose; Placebo to match Avenanthramide tablet single oral dose

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \. Male or female subjects;
• \. Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively, for subjects participating in Part A and Part B;
• \. Age 18-60 years;
• \. Willing to avoid rigorous physical activity 1 day prior to the first drug administration and during study participation;
• \. Willing to avoid oat consumption for 1 week prior to the first drug administration and during study participation;
• \. Non- or ex-smoker; an ex-smoker is defined as someone who completely stopped using nicotine products for at least 6 months prior to the first study drug administration;
• \. Non- or ex-consumer of cannabis; an ex-consumer of cannabis is defined as someone who stopped using cannabis derived products for at least 6 months prior to the first study drug administration;
• \. Have no clinically significant diseases captured in the medical history and no evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by the investigator;
• \. Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without clinical significance, as determined by the investigator;
• \. Provision of signed and dated informed consent form (ICF);
• \. Stated willingness to comply with all study procedures and availability for the duration of the study;
• \. A male subject meeting one of the following criteria:
• Subject is able to procreate and agrees to use one of the accepted contraceptive regimens and not donate sperm from the first study drug administration to at least 90 days after the last drug administration. An acceptable method of contraception includes one of the following:
• True abstinence from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject (not periodic abstinence)
• Male condom with spermicide or male condom with a vaginal spermicide (gel, foam, or suppository) If the subject has a partner of childbearing potential, he and/or his partner must agree to use two acceptable birth control methods.

You may not qualify if:

• \. Allergy to any ingredient of the Investigational Products, including excipients;
• \. Oat products consumption within 1-week prior the first drug administration;
• \. History of significant hypersensitivity to any excipients of the formulation, as well as severe hypersensitivity reactions (like angioedema) to any drug;
• \. Presence of significant gastrointestinal (GI) conditions that interfere with absorption;
• \. Presence of significant cardiovascular disease, gastrointestinal disease, kidney disease, or endocrine disease: including diabetes, and untreated thyroid disease, or rheumatoid arthritis;
• \. Diagnosis of Gilbert syndrome;
• \. Systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 95 mmHg at screening;
• \. Major trauma or surgery within 3 months of study participation;
• \. Presence of clinically significant ECG abnormalities at the screening, as defined by medical judgment;
• \. Any clinically significant illness in the 28 days prior to the first study drug administration;
• \. Any history of tuberculosis or proven contact with tuberculosis;
• \. Positive test result for alcohol and/or drugs of abuse at screening or prior to the first drug administration;
• \. Positive screening results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HbsAg (B) (hepatitis B)) or Hepatitis C Virus (HCV (C)) tests at screening;
• \. Active treatment for any type of cancer, except basal cell carcinoma, within 1 year prior to the first drug administration;
• \. Use of any prescription drugs (with the exception of contraceptive or hormone replacement therapy) in the 28 days prior to the first study drug administration;

Sponsors & Collaborators

• Montreal Heart Institute: lead
• Ceapro Inc.: collaborator
• The Montreal Health Innovations Coordinating Center (MHICC): collaborator

Study Sites (1)

Montreal Heart Institute

Montreal, Quebec, H1T 1N6, Canada

Location

MeSH Terms

Conditions

Inflammation

Interventions

avenanthramide-2C

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jean-Claude Tardif, MD

  Montreal Heart Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-Blind, Placebo-Controlled, Randomized, Adaptive, First-in-Human Study, Single and Multiple Ascending Oral Doses

Study Record Dates

• First Submitted: August 7, 2023
• First Posted: October 26, 2023
• Study Start: December 9, 2023
• Primary Completion: June 16, 2025
• Study Completion: June 16, 2025
• Last Updated: April 20, 2026

Record last verified: 2026-01

Locations

CA (1)