Oral Cyanocobalamin (Eligen B12) Bioavailability Study

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Cyanocobalamin

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 mg Eligen® B12 (Cyanocobalamin/SNAC); 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; Other Names: B12, Eligen® B12, Cobalamin
Experimental: 5 mg Eligen® B12 (Cyanocobalamin/SNAC); 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; Other Names: B12, Eligen® B12, Cobalamin
Active Comparator: 5 mg Oral Cyanocobalamin; 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; Other Names: B12, Eligen® B12, Cobalamin
Active Comparator: 1 mg Intravenous Cyanocobalamin; 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; Other Names: B12, Eligen® B12, Cobalamin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Emisphere Technologies, Inc.
• Investigators: Principal Investigator: Sandra M. Connolly, MD, MDS Pharma Services

Publications and helpful links

General Publications

• Castelli MC, Wong DF, Friedman K, Riley MG. Pharmacokinetics of oral cyanocobalamin formulated with sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC): an open-label, randomized, single-dose, parallel-group study in healthy male subjects. Clin Ther. 2011 Jul;33(7):934-45. doi: 10.1016/j.clinthera.2011.05.088. Epub 2011 Jul 1.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion: December 7, 2022
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: March 8, 2011
• First Submitted That Met QC Criteria: March 8, 2011
• First Posted (Estimate): March 9, 2011

Study Record Updates

• Last Update Posted (Estimate): March 9, 2011
• Last Update Submitted That Met QC Criteria: March 8, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: Pharmacokinetics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Vitamin B 12; Hydroxocobalamin
• Other Study ID Numbers: EMIS 112-C-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No