Bioavailability of Two Doses of cogniVida™ With One Dose of Rebaudioside A in Healthy Male Subjects

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to examine the bioavailability of cogniVida™ in 10 healthy male subjects after consumption of two different doses of cogniVida™ (50 mg and 100 mg) and to compare the plasma values with values obtained in subjects receiving rebaudioside A (303.68 mg). In addition, also safety and tolerability parameters 24 hours after ingestion of the study compounds will be determined. cogniVida™ is considered a dietary supplement, and therefore it is not an approved drug by the Food and Drug Administration (FDA). It is regulated like a food. The U.S. Food and Drug Administration does not strictly regulate herbs and dietary supplements. The investigators do not claim that this supplement is meant to treat any ailment.

Official Title
-----------------
An Open-label, Sequential Supplementation Study Comparing the Bioavailability of Two Doses of cogniVida™ With One Dose of Rebaudioside A in Healthy Male Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Dietary Supplement: cogniVida 50mg/day
* Dietary Supplement: cogniVida100mg/day
* Dietary Supplement: Rebaudioside-A 303.7mg/day


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Sex: Male, age 30 - 50 years Subject is willing to maintain his or her habitual diet and physical activity patterns throughout the study period. Subject has no health conditions that would prevent him/her from fulfilling the study requirements as judged by the Investigator on the basis of medical history and routine laboratory test results Subject has a body mass index (BMI) of ≥20.00 and <28.00 kg/m2 at screening. Subject is willing to refrain from consuming drinks containing grapefruit 7 days prior to test days. Subject is willing to refrain from consuming caffeine, caffeine-containing products and alcoholic drinks 24 h prior to test days and until the end of each assessment period. Subject is willing to refrain from vigorous physical activity 12 h prior to test days. Subject understands the study procedures and signs forms providing informed consent to participate in the study and authorization for release of relevant protected health information to the study Investigator. Exclusion Criteria: Subject has a positive drug screening of amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, methamphetamines, methadone, 3,4-methylenedioxymethamphetamine, opiates or tricyclic antidepressants at screening. Subjects has a positive blood alcohol and breath carbon monoxide test at screening. Subject has abnormal laboratory test results of clinical significance, including, but not limited to: Epidermal-Growth-Factor-Receptor (eGFR) <60mL/min/1.73m2, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥1.5X the upper limit of normal at screening. Subject has donated more than 300 mL of blood or has lost a significant amount of blood during the three months prior to screening. Anemia of any etiology defined as hemoglobin < 140g/L for males and < 123g/L for female Subject has uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) as defined by the average blood pressure measured at screening. Subject has a history or presence of cardiac, renal, hepatic, endocrine (including diabetes mellitus), pulmonary, biliary, gastrointestinal, pancreatic, or neurologic disorders. Subject has a history, in the judgment of the Investigator, of a psychological illness or condition such as to interfere with the subject's ability to understand the requirements of the study. Subject has a history or presence of cancer in the prior five years, except for non-melanoma skin cancer. Excessive habitual caffeine consumption (>300 mg caffeine/d or ≥ 3 cups of caffeinated coffee/d), following screening and throughout the study period. Use of antibiotics or signs of active systemic infection. Treatment visits will be rescheduled to allow the subject to wash off of the antibiotic for at least one month prior to any test visit. Use of dietary supplements containing any of the following: ginkgo biloba, St. John's wort, ginseng, gotu kola (Indian pennywort); daily doses of vitamin E (≥30 mg/d) or folic acid (≥400 ug/d); thiamine, riboflavin, and/or pyridoxine (≥2 mg/d); and eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)or a combination of EPA + DHA (≥500 mg/d) within 2 weeks prior to screening. Consumption of stevia extract (reb A / steviosides) sweetened products/drinks or stevia leaves within one month of the study. Subject has had exposure to any non-registered drug product within 30 days prior to the screening visit. Recent history of (within 12 months of screening visit) or strong potential for alcohol or substance abuse. Alcohol abuse is defined as >14 drinks per week (1 drink = 12 oz beer, 5 oz wine, or 1½ oz distilled spirits). Subject has a known allergy or sensitivity to study product or any ingredients of the study product or meals provided.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cogniVida™ 50 mg/day<br> | Dietary Supplement: cogniVida 50mg/day<br>* 2 capsules 25 mg (total 50 mg) cogniVida™ once a day<br>|
| Experimental: cogniVida™ 100 mg/day<br> | Dietary Supplement: cogniVida100mg/day<br>* 4 capsules 25 mg (total 100 mg) cogniVida™ once a day<br>|
| Active Comparator: Rebaudioside-A 303.7 mg/day<br> | Dietary Supplement: Rebaudioside-A 303.7mg/day<br>* 4 capsules 75.92 mg (total 303.68 mg) rebaudioside A once a day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Area under the Curve (AUC) (0-72 hours) being produced after cogniVida™ (50 and 100 mg) and rebaudioside A (303.68 mg) consumption | Blood sampling timepoints: cogniVida: 0 min, 15min, 30min, 45min, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 48, and 72h after dosing. RebA: 0 min, 30min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36, 48, and 72h after dosing | 0 - 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to plasma peak (Tmax) being produced after cogniVida™ (50 and 100 mg) and rebaudioside A (303.68 mg) consumption | Blood sampling timepoints: cogniVida: 0 min, 15min, 30min, 45min, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 48, and 72h after dosing. RebA: 0 min, 30min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36, 48, and 72h after dosing | 0 - 72 hours | 
| Plasma Peak Concentration (Cmax) being produced after cogniVida™ (50 and 100 mg) and rebaudioside A (303.68 mg) consumption | Blood sampling timepoints: cogniVida: 0 min, 15min, 30min, 45min, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 48, and 72h after dosing. RebA: 0 min, 30min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36, 48, and 72h after dosing | 0 - 72 hours | 
| Time to reach half of peak concentration in plasma T1/2 being produced after cogniVida™ (50 and 100 mg) and rebaudioside A (303.68 mg) consumption | Blood sampling timepoints: cogniVida: 0 min, 15min, 30min, 45min, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 48, and 72h after dosing. RebA: 0 min, 30min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36, 48, and 72h after dosing | 0 - 72 hours | 
| Vital signs | Vital signs as safety parameters being measured 24 h after each supplementation. | 24 hours after each supplementation | 
| White blood cell (WBC) count (Routine Haematology) | White blood cells will be counted as a routine haematology parameter to assess safety 24 h after each supplementation. | 24 hours after each supplementation | 
| Hemoglobin (Routine Haematology) | Hemoglobin will be measured as a routine haematology parameter to assess safety 24 h after each supplementation. | 24 hours after each supplementation | 
| Blood urea nitrogen (BUN) (Clinical Chemistry) | Blood urea nitrogen will be measured as a routine clinical chemistry parameter to assess safety 24 h after each supplementation. | 24 hours after each supplementation | 
| Cystatin-C (Clinical Chemistry) | Cystatin-C will be measured as a routine clinical chemistry parameter to assess safety 24 h after each supplementation. | 24 hours after each supplementation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pharmacokinetics, Safety