Efficacy and Safety Study of Oral Eligen® B12 in Subjects With Low Serum Cobalamin
Primary Purpose
Vitamin B 12 Deficiency
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Vitamin B12 (cyanocobalamin)
Sponsored by
About this trial
This is an interventional treatment trial for Vitamin B 12 Deficiency focused on measuring cobalamin, B12, homocysteine, MMA, holotranscobalamin, Eligen
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Oral Eligen® B12
IM B12
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Maintenance of B12 Normalization
Maintenance of cobalamin normalization after 90 days of treatment
Time to Normalization
Time to normalization of cobalamin levels
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.
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
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
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.
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
Holo-TC and Cobalamin Correlation
Holo-TC levels in relation to cobalamin levels on Days 61 and 91 as an exploratory endpoint
Full Information
NCT ID
NCT01312831
First Posted
March 4, 2011
Last Updated
March 9, 2011
Sponsor
Emisphere Technologies, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01312831
Brief Title
Efficacy and Safety Study of Oral Eligen® B12 in Subjects With Low Serum Cobalamin
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
December 2010 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Emisphere Technologies, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vitamin B 12 Deficiency
Keywords
cobalamin, B12, homocysteine, MMA, holotranscobalamin, Eligen
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Oral Eligen® B12
Arm Type
Experimental
Arm Description
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.
Arm Title
IM B12
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Vitamin B12 (cyanocobalamin)
Primary Outcome Measure Information:
Title
Serum Cobalamin Normalization
Description
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
Time Frame
61 days
Secondary Outcome Measure Information:
Title
Maintenance of B12 Normalization
Description
Maintenance of cobalamin normalization after 90 days of treatment
Time Frame
91 days
Title
Time to Normalization
Description
Time to normalization of cobalamin levels
Time Frame
90 days
Title
Percent Change from Baseline in Cobalamin Levels After 60 and 90 days of Treatment
Description
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.
Time Frame
91 days
Title
Percent Change from Baseline in Methylmalonic Acid (MMA) Levels After 60 and 90 Days of Treatment
Description
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
Time Frame
91 days
Title
Percent Change from Baseline in Homocysteine Levels After 60 and 90 Days of Treatment
Description
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
Time Frame
91 days
Title
Number of Subjects with Adverse Events as a Measure of Safety and Tolerability
Description
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.
Time Frame
91 days
Title
Holo-trancobalamin (holo-TC) Normalization
Description
The proportion of subjects who achieve normalization of holo-TC levels (≥ 40 pmol/L) on Days 61 and 91 as an exploratory endpoint
Time Frame
91 days
Title
Holo-TC and Cobalamin Correlation
Description
Holo-TC levels in relation to cobalamin levels on Days 61 and 91 as an exploratory endpoint
Time Frame
91 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benno Roesch, MD
Organizational Affiliation
Frontage (formerly ABR), 241 Main Street, Hackensack, NJ 07601 USA
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nancy Allegar, MD
Organizational Affiliation
Alatae Medical LLC, 390 Amwell Road, Building 5, Hillsborough, NJ 08844 USA
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mitchell K. Spinnell, MD
Organizational Affiliation
Gastroenterology, 1555 Center Avenue, Fort Lee, NJ 07024 USA
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael M. Rothkopf, MD
Organizational Affiliation
South Mountain Medical Consultants, 1500 Pleasant Valley Way, Suite 201, West Orange, NJ 07052 USA
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Peter Varunok, MD
Organizational Affiliation
Gastroenterology Associates, 243 North Road, Suite 304, Poughkeepsie, NY 12601 USA
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
21600388
Citation
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.
Results Reference
derived
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Efficacy and Safety Study of Oral Eligen® B12 in Subjects With Low Serum Cobalamin
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