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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
Emisphere Technologies, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

    First Posted
    March 4, 2011
    Last Updated
    March 9, 2011
    Sponsor
    Emisphere Technologies, Inc.
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    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

    Learn more about this trial

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

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