Vitamin B 12 Deficiency
Conditions
Keywords
cobalamin, B12, homocysteine, MMA, holotranscobalamin, Eligen
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).
Interventions
Sponsors
Emisphere Technologies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Cobalamin Normalization | 61 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
| Measure | Time frame | Description |
|---|---|---|
| Maintenance of B12 Normalization | 91 days | Maintenance of cobalamin normalization after 90 days of treatment |
| Time to Normalization | 90 days | Time to normalization of cobalamin levels |
| Percent Change from Baseline in Cobalamin Levels After 60 and 90 days of Treatment | 91 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 Treatment | 91 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 Treatment | 91 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 Tolerability | 91 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) Normalization | 91 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 Correlation | 91 days | Holo-TC levels in relation to cobalamin levels on Days 61 and 91 as an exploratory endpoint |
Outcome results
None listed