Oral Cyanocobalamin (Eligen B12) Bioavailability Study

Study Overview
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Brief Summary
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The purpose of this study is to assess and compare the pharmacokinetics (PK) of cyanocobalamin after the oral administration of Eligen® B12 (cyanocobalamin/SNAC), oral cyanocobalamin alone (commercially-available formulation) and cyanocobalamin administered intravenously (IV) (also a commercially-available formulation) to healthy male subjects under fasting conditions. The safety and tolerability of oral Eligen® B12 (cyanocobalamin/SNAC) versus oral cyanocobalamin alone and versus IV cyanocobalamin are also assessed.

Official Title
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An Open-label, Single-Dose, Parallel-Group, Randomized Study of Comparative Bioavailability of B12 After Oral Administration of B2 Formulated With an Absorption Promoter (SNAC), Oral B12 Alone and IV B12 in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Cyanocobalamin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects aged 18 to 45 years. Signed ICF prior to any study-related procedures. Normal organ function including renal and hepatic function. Normal hematological function. Body weight between 60 and 100 kg and within 18 - 30 kg/m2 for body mass index (BMI). Normal ranges in vital signs, ECG, and laboratory tests. Normal ranges of serum B12, methylmalonic acid (MMA), and homocysteine. Exclusion Criteria: Current use (within 14 days) of acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) (i.e., aspirin or ibuprofen) Current use (within 14 days) of antibiotics, antacids, multivitamins, or nutritional supplements. Absolute platelet count below 100 x 109/L History or current diagnosis of any clinically significant disease of the liver, kidneys or GI system, or any abnormal condition that compromises the function of these systems and could result in the possibility of altered absorption, excess accumulation, or impairment of metabolism or excretion of the study product. History or current diagnosis of any clinically significant hematological, immunological, metabolic, cardiovascular, neurological, or GI abnormalities which that should, in the opinion of the Investigator exclude the subject from this study. Any other clinically significant laboratory value at Screening, which, in the opinion of the Investigator, suggested a condition that could have precluded the subject from entering this study. At risk of transmitting infection via blood samples e.g., producing a positive HIV test at screening or having participated in a high-risk activity for contracting HIV; producing a positive HBsAg test at screening; producing a positive hepatitis C antibody test at screening. Participation in a clinical research study involving a new chemical entity within 30 days of study entry. Significant loss or donation of blood within 56 days or plasma within 30 days prior to the initial dose in this study. Unsuitable for any reason to receive study product in the opinion of the Investigator. Alcohol consumption within the last 48 hours prior to study entry or anytime during the study. Positive urine alcohol test.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10 mg Eligen® B12 (Cyanocobalamin/SNAC)<br>A single oral dose of Eligen® B12, cyanocobalamin/SNAC (5 mg cyanocobalamin/100 mg SNAC) administered in the fasted state as 2 tablets taken with 50 mL of water resulting in a total dose of 10 mg cyanocobalamin and 200 mg SNAC. | Drug: Cyanocobalamin<br> <br> * Other names: B12, Eligen® B12, Cobalamin;|
| Experimental: 5 mg Eligen® B12 (Cyanocobalamin/SNAC)<br>A single oral dose of Eligen® B12, cyanocobalamin/SNAC (5 mg cyanocobalamin/100 mg SNAC) administered in the fasted state as a tablet taken with 50 mL of water resulting in a total dose of 5 mg cyanocobalamin and 100 mg SNAC. | Drug: Cyanocobalamin<br> <br> * Other names: B12, Eligen® B12, Cobalamin;|
| Active Comparator: 5 mg Oral Cyanocobalamin<br>A single oral dose of cyanocobalamin alone (5 mg cyanocobalamin, commercial: VITALABS, INC) administered in the fasted state as a tablet taken with 50 mL of water resulting in a total dose of 5 mg cyanocobalamin. | Drug: Cyanocobalamin<br> <br> * Other names: B12, Eligen® B12, Cobalamin;|
| Active Comparator: 1 mg Intravenous Cyanocobalamin<br>A single intravenous (IV) dose of cyanocobalamin (1 mg cyanocobalamin) administered in the fasted state. Each subject will receive a 1 mL IV injection of a 1 mg/mL (1000 μg/mL) solution resulting in a total dose of 1 mg cyanocobalamin. | Drug: Cyanocobalamin<br> <br> * Other names: B12, Eligen® B12, Cobalamin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Cobalamin Pharmacokinetics (PK) | Serum cobalamin evaluated via collection and processing of blood samples from predose through 24 hours. Pharmacokinetics to be determined by non-compartmental analysis using predose to 24 hour serum cyanocobalamin non-baseline-adjusted and baseline-adjusted concentration data. Serum cobalamin PK parameters to include: Cmax, tmax, AUClast, AUC∞, t1/2, and Kel and bioavailability (% F) of oral formulations. | pre-dose to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects with Adverse Events as a Measure of Safety and Tolerability | Safety evaluated through the monitoring of medical history findings, physical examination findings, concomitant medications, vital signs (including blood pressure, respiratory rate, heart rate, and temperature), laboratory tests (hematology, serum chemistry, and urinalysis values), ECGs, AEs, and serious adverse events (SAEs). | pre-dose to 24 (end-of-study) hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics