Efficacy and Safety Study of Oral Eligen® B12 in Subjects With Low Serum Cobalamin

A 60-DAY, Open-label, Randomized Study to Evaluate the Efficacy and Safety of Eligen® B12 OR Intramuscularly Administered B12 in Subjects With Low Serum Cobalamin With a 30 Day Extension to 90 Days of Dosing

The purpose of this study is to compare the efficacy and safety profile of a new oral vitamin B12 formulation (Eligen® B12) with intramuscular B12 in restoring normal B12 (cobalamin) concentrations in subjects with low cobalamin levels (<350 pg/mL).

Study Overview

• Status: Completed
• Conditions: Vitamin B 12 Deficiency
• Intervention / Treatment: Other: Vitamin B12 (cyanocobalamin)

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Vitamin B12 deficiency defined as serum cobalamin below 350 pg/mL
• Age 60 or older; or age 18 or older with gastrointestinal abnormalities including but not limited to gastrointestinal surgery (e.g. gastrectomy, gastric bypass), ileal resection, gastric atrophy, Celiac disease, Crohn's disease, or prolonged use (>3 months) of proton pump inhibitor drugs, or on a restricted diet (such as vegetarian or vegan).
• General good health, as indicated by lack of significant findings in medical history, physical examination, clinical laboratory tests (chemistry, hematology and urinalysis), vital signs, ECG and normal kidney function as determined by estimated creatinine clearance computed with the Cockcroft and Gault formula

Exclusion Criteria:

• Current treatment from a health care provider to treat vitamin B12 deficiency and/or symptoms;
• Daily use of neutralizing antacids (e.g. Maalox®)
• Inability to ingest oral medication
• Clinically significant laboratory value at screening
• Hypersensitivity or allergic reaction to vitamin B12
• Participation in a clinical research study involving a new chemical entity within 30 days of the first study dose
• Folate levels below the reference range provided by the clinical laboratory.
• Renal insufficiency
• Vitamin B6 deficiency

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Eligen® B12; Eligen® B12 1000 μg oral tablet taken in the fasted state as a single tablet with 50 mL water. Each dose self-administered daily, for 90 days, after an overnight fast and 1 hour before the morning meal.	Other: Vitamin B12 (cyanocobalamin)
Active Comparator: IM B12; Commercially available 1000 μg cyanocobalamin administered IM as 1 mL from a vial containing 1000 μg/mL drug administered by study personnel, in the research clinic, in the morning, in the fasted state and at least 1 hour prior to the morning meal on study Days 1, 3, 7, 10, 14, 21, 30, 60 and 90.	Other: Vitamin B12 (cyanocobalamin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Cobalamin Normalization	The primary efficacy outcome compares the proportion of subjects in each treatment arm in whom cobalamin levels are normalized (i.e., cobalamin ≥ 350 ng/mL) following 60 days of treatment	61 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance of B12 Normalization	Maintenance of cobalamin normalization after 90 days of treatment	91 days
Time to Normalization	Time to normalization of cobalamin levels	90 days
Percent Change from Baseline in Cobalamin Levels After 60 and 90 days of Treatment	Change from baseline is defined as (X-B) where B is the baseline (pre-dose Day 1) measurement of cobalamin (pg/mL) and X is the measurement of cobalamin(pg/mL) at Day 61 or Day 91, as required. Percent change from baseline is defined as 100(X-B)/B.	91 days
Percent Change from Baseline in Methylmalonic Acid (MMA) Levels After 60 and 90 Days of Treatment	Change from baseline is defined as (X-B) where B is the baseline (pre-dose Day 1) measurement of MMA (ng/mL) and X is the measurement of MMA (ng/mL) at Day 61 or Day 91, as required. Percent change from baseline is defined as 100(X-B)/B	91 days
Percent Change from Baseline in Homocysteine Levels After 60 and 90 Days of Treatment	Change from baseline is defined as (X-B) where B is the baseline (pre-dose Day 1) measurement of homocysteine (umol/L) and X is the measurement of homocysteine (umol/L) at Day 61 or Day 91, as required. Percent change from baseline is defined as 100(X-B)/B	91 days
Number of Subjects with Adverse Events as a Measure of Safety and Tolerability	The safety and tolerability of Eligen® B12 and intramuscular B12 assessed by physical examination findings, clinical laboratory test results, vital signs, 12-lead ECG results and adverse event reporting.	91 days
Holo-trancobalamin (holo-TC) Normalization	The proportion of subjects who achieve normalization of holo-TC levels (≥ 40 pmol/L) on Days 61 and 91 as an exploratory endpoint	91 days
Holo-TC and Cobalamin Correlation	Holo-TC levels in relation to cobalamin levels on Days 61 and 91 as an exploratory endpoint	91 days

Collaborators and Investigators

• Sponsor: Emisphere Technologies, Inc.
• Investigators: Principal Investigator: Benno Roesch, MD, Frontage (formerly ABR), 241 Main Street, Hackensack, NJ 07601 USA; Principal Investigator: Nancy Allegar, MD, Alatae Medical LLC, 390 Amwell Road, Building 5, Hillsborough, NJ 08844 USA; Principal Investigator: Mitchell K. Spinnell, MD, Gastroenterology, 1555 Center Avenue, Fort Lee, NJ 07024 USA; Principal Investigator: Michael M. Rothkopf, MD, South Mountain Medical Consultants, 1500 Pleasant Valley Way, Suite 201, West Orange, NJ 07052 USA; Principal Investigator: Peter Varunok, MD, Gastroenterology Associates, 243 North Road, Suite 304, Poughkeepsie, NY 12601 USA

Publications and helpful links

General Publications

• Castelli MC, Friedman K, Sherry J, Brazzillo K, Genoble L, Bhargava P, Riley MG. Comparing the efficacy and tolerability of a new daily oral vitamin B12 formulation and intermittent intramuscular vitamin B12 in normalizing low cobalamin levels: a randomized, open-label, parallel-group study. Clin Ther. 2011 Mar;33(3):358-371.e2. doi: 10.1016/j.clinthera.2011.03.003.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: March 4, 2011
• First Submitted That Met QC Criteria: March 9, 2011
• First Posted (Estimate): March 11, 2011

Study Record Updates

• Last Update Posted (Estimate): March 11, 2011
• Last Update Submitted That Met QC Criteria: March 9, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: B12; cobalamin; homocysteine; MMA; holotranscobalamin; Eligen
• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin B Deficiency; Vitamin B 12 Deficiency; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Vitamin B 12; Hydroxocobalamin
• Other Study ID Numbers: EMIS-112-C-02