A Study to See if a Combination of Vitamins That is Injected Into a Muscle is as Good and Safe as a Vitamin That is Taken by Mouth

Efficacy and Safety of a Parenterally Administered Fixed Vitamin Combination (Vitamin B6, B12 and Folic Acid) On Vitamin B12 Status and Methylation Capacity in Cobalamin Deficiency Compared to Oral Vitamin B12 Supplementation

Primary efficacy objective:

To investigate the effects of a parenterally vitamin B12 combination treatment versus an oral vitamin B12 mono therapy on the vitamin B12 status in female and male patients as determined by the change from baseline in serum vitamin B12 concentration after 4 weeks (28 days) of treatment.

Secondary efficacy objectives:

To evaluate the effects of a parenterally vitamin B12 combination versus an oral vitamin B12 mono therapy after 4 weeks of treatment on:

• Serum holotranscobalamin
• Serum homocysteine
• Serum methylmalonic acid
• Combined vitamin B12 markers (cB12)
• Serum folic acid
• Serum vitamin B6
• Serum S-adenosylmethione (SAM)
• Serum S-adenosylhomocysteine (SAH)
• SAM/SAH ratio
• WHO-5 Well-Being Index
• Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36)
• Visual analogue scale (VAS) EQ-5D.

Safety objectives:

To evaluate the safety and tolerability of oral vitamin B12 mono therapy versus intramuscular vitamin B12 combination.

Inclusion Criteria:

1. Provision of written informed consent to participate in the study (according to Order of the Ministry of Health of Ukraine No. 690 (with amendments)).
2. Female and male patients aged ≥18.
3. Vitamin B12 deficiency, defined as serum vitamin B12 < 350 pmol/L.
4. Female patients of childbearing potential (WOCBP) must be using two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc., with the exception of oral contraceptives), from the time of screening and for the duration of the study, through study completion and for 1 month following study completion. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Female patients who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF. All female patients of childbearing potential must have negative pregnancy test results at screening. An additional pregnancy test will be performed on Days 0, 28, 56.
5. Able to communicate well with the investigator and able to understand and comply with the requirements of the study.
6. Patients are otherwise in relatively good health as determined by past medical history, physical examination, vital signs, and laboratory tests at screening (V -1).

Exclusion Criteria:

1. Active or recent vitamin B12, folic acid, B6 intake (the subject must not receive vitamin B12, folic acid, B6 drugs or food supplements for at least 6 months).
2. Participation in a previous clinical study with vitamin B12 within the 6 months prior to screening.
3. Any contraindication to one of the study drugs.
4. Pregnant or nursing (lactating) women.
5. Donation or loss of 400 mL or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation.
6. Subjects with anemia (hemoglobin < 10 mg/dL) or significant neurological symptoms due to vitamin B12 deficiency.
7. Any diseases that prevent intrinsic-factor independent passive diffusion in the small intestine (e.g. ileum resection)
8. Current drug addiction and/or alcohol abuse as evidenced by patient history and/or as determined by the investigator at V-1.
9. Cognitive or behavioural abnormalities that could impair the capacity to give informed consent or carry out protocol-specified procedures.
10. Inability to take oral medication.
11. Inability or unwillingness to comply with the study protocol.
12. Previous (last 6 months) or current participation in another clinical study.
13. Other medical, neuropsychiatric, or social conditions that, in the opinion of the investigator, are likely to adversely affect the risk-benefit of study participation, interfere with study compliance, or confound the study results.
14. Subjects who are in a dependent relationship with the Investigator or the Sponsor.
15. Subjects unwilling to give written informed consent to saving and/or propagation of anonymised medical data