Effects of Trigonelline Monohydrate on NAD+ Metabolism, Pharmacokinetics, Safety, and Tolerability in Healthy Adults

Inclusion Criteria:

• Adults who are 40 to 70 years of age (inclusive) at the time of signing the informed consent.

• Are able to consume study product capsules whole without chewing.

• Have suitable veins for repeated venipuncture.

• Non-smokers (including nicotine vaping) and have not used any nicotine products (patches, gums, etc.) for > 3 months prior to Visit 2. Non-smoker is defined as someone who does not habitually/regularly use products containing nicotine and willing to abstain for 14 days before Visit 2 until the last procedure.

• In otherwise good general health, as deemed by the investigator (based on a review of medical history, vital signs, laboratory safety tests, and physical examination if performed at screening).

• Have a BMI between 18.5 to 29.9 kg/m2 (inclusive) and weigh no less than 50.0 kg.

• Have maintained consistent dietary habits, including medication and supplement intake, and lifestyle for the last 3 months before screening and agree to maintain them throughout the study (unless required per the restrictions).

• Agree to follow the restrictions on concomitant treatments.

• Agree to follow the restrictions on lifestyle.

• Agree to use acceptable contraceptive methods.

• Willing and able to agree to the requirements of this study, be willing to give voluntary consent, and carry out all study-related procedures.

• Willing and able to comply with the protocol, including:

  1. Agree to consume the standardized meals provided at the site during Visit 2
  2. Agree to fast overnight, i.e., no food or liquids except for water for a minimum 8 hours prior to applicable visits

Exclusion Criteria:

• Individuals of CBP who are pregnant, intending to breastfeed, or intending to conceive at the time of consent and during the study, or demonstrate a positive pregnancy test.
• Have a known sensitivity, intolerability, or allergy to any of the standardized meals/snacks, study products, their excipients, or to any known allergens that may be present due to potential cross-contamination during manufacturing or processing.
• Have positive screening tests for drugs or cotinine screening.
• Have positive alcohol breath test at screening.
• Have high BP (≥140 systolic or ≥90 diastolic mmHg).
• Have clinically significant abnormal vital signs that in the opinion of the investigator may be of a concern for the study or participant safety.
• Have clinically significant abnormal safety laboratory assessment values in the opinion of the investigator at screening.
• Have current symptoms, or symptoms within the past 7 days of baseline, of an acute infection (e.g., fever, respiratory symptoms such as persistent cough or difficulty breathing), that may influence study outcomes as assessed by the investigator.
• Have Type I or II diabetes, thyroid disease, or non-stable asthma or chronic obstructive pulmonary disease (COPD).
• Reports a clinically significant illness during the 28 days before the first dose of study product.
• Have any abnormality, obstruction, or disorder of the gastrointestinal tract that may preclude swallowing (e.g., dysphagia) or impair gastrointestinal motility, digestion, or absorption (e.g., known intestinal malabsorption, celiac disease, inflammatory bowel disease [including Crohn's disease or ulcerative colitis], chronic pancreatitis, or steatorrhea).
• Have any history of gastrointestinal surgery or anatomical abnormality that, in the opinion of the investigator, may affect the oral absorption of the study product.
• Have current or a history of hematological disorders (e.g., sickle cell anemia or thalassemia), cerebrovascular disease, heart/cardiovascular disease (e.g., coronary artery disease, heart failure, stroke, peripheral vascular disease), renal disease (dialysis or renal failure), hepatic impairment/disease, neurological disorders (e.g., dementia or Parkinson's disease), immune disorders and/or immunocompromised (i.e., HIV/AIDS).
• Have a history of cancer (except localized skin cancer without metastases or in situ cervical cancer), unless recovery occurred more than 5 years before the screening visit.
• Are receiving treatments for or have been hospitalized in the last 12 months for psychiatric disorders (e.g., depression, bipolar disorder, schizophrenia, etc.) that may affect the participant's capability to carry out all procedures of the study at the investigator's discretion.
• Major surgery in 3 months prior to screening or planned major surgery during the study.
• Currently consumes, on average, more than 2 standard alcoholic beverages a day where one standard drink is defined as approximately as 330 mL (12 oz) of beer (~5% alcohol), 150 mL (5 oz) of wine (~12% alcohol), 40 mL (1.5 oz) of distilled spirits (e.g., vodka, whiskey, gin; ~40% alcohol).
• Have a history of alcohol or substance abuse in the 12 months prior to screening (including having been hospitalized for such in an in-patient or out-patient intervention program) or use that in the opinion of the investigator may be of a concern for the study.
• Reports a significant blood loss or blood donation totaling between 101 mL to 449 mL of blood within 30 days prior to baseline or a blood donation of more than 450 mL within 56 days prior to baseline.
• Reports donating plasma (e.g., plasmapheresis) within 15 days prior to baseline.
• Current enrolment or past participation in another study with any product(s) with at least one active ingredient within 30 days before first dose of study product or longer, if the previous test product is deemed by the investigator to have lasting effects that might influence the eligibility criteria or outcomes of current study.
• Living in the same household as another currently/previously enrolled participant in the present study.
• Any other medical condition/situation or use of medications/supplements/therapies that, in the opinion of the investigator, may adversely affect the participant's ability to participate in the study or its measures or pose a significant risk to the participant.