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

Not Applicable
Completed
Conditions
Vitamin B 12 Deficiency
Interventions
Other: Vitamin B12 (cyanocobalamin)
Registration Number
NCT01312831
Lead Sponsor
Emisphere Technologies, Inc.
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
49
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Oral Eligen® B12Vitamin B12 (cyanocobalamin)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.
IM B12Vitamin B12 (cyanocobalamin)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.
Primary Outcome Measures
NameTimeMethod
Serum Cobalamin Normalization61 days

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
NameTimeMethod
Maintenance of B12 Normalization91 days

Maintenance of cobalamin normalization after 90 days of treatment

Time to Normalization90 days

Time to normalization of cobalamin levels

Percent Change from Baseline in Cobalamin Levels After 60 and 90 days of Treatment91 days

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 Treatment91 days

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 Treatment91 days

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 Tolerability91 days

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) Normalization91 days

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 Correlation91 days

Holo-TC levels in relation to cobalamin levels on Days 61 and 91 as an exploratory endpoint

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