The Nutritional Benefits of Metanx in Patients With Diabetic Peripheral Neuropathy (MEDIAN)

Inclusion Criteria:

- Be male or female between 25 and 80 years of age, inclusive, at the time of consent

- Have a diagnosis of diabetes mellitus Type 2 as defined by the American Diabetes
Association and on stable therapy as defined per the investigator's opinion for at
least 1 month before the Screening Visit.

- Have a diagnosis of DPN established at least 6 months but not greater than 7 years
prior to Screening

- If receiving DPN-related medication, doses must be stable for at least 6 weeks and
should be taking only one of the following medications compliant with Exclusion
Criterion 7:

- Alpha-2-delta ligand [e.g., pregabalin (Lyrica) or gabapentin (Neurontin)

- Anticonvulsant [e.g., carbamazepine, topiramate (Topamax), valproic acid
(Depakote) or lamotrigine (Lamictal)]

- Serotonin-norepinephrine Reuptake Inhibitor (SNRI) [e.g., duloxetine (Cymbalta)
or venlafaxine (Effexor)]

- Tricyclic antidepressant (TCA) [e.g., amitriptyline, nortriptyline, imipramine,
and desipramine (Norpramin, Pertofrane)]

- Have a score between 3 and 6, inclusive, on the Michigan Neuropathy Screening
Instrument (MNSI) Part b

- Have a minimum score of 6 on the NTSS-6 at Screening

- Have negative urinalysis for drugs of abuse, such as amphetamines, barbiturates,
cannabinoids, cocaine, or opiates

- Have a negative urine pregnancy test at Screening if female and of childbearing
potential

- If female, must be either of nonchildbearing potential (surgically sterile or 2 years
postmenopausal) or agree to use two methods of effective contraception such as
hormonal contraception, intrauterine device or other mechanical contraception device,
or condom plus spermicide during the subject's participation

- If male, must be surgically sterile or agree to use two methods of effective
contraception such as condom plus spermicide during the subject's participation

- Have the ability to understand the requirements of the study, have provided written
informed consent as evidenced by signature on an informed consent form (ICF) approved
by an institutional review board (IRB), and agree to abide by the study restrictions
and return to the site for the required assessments

- Have provided written authorization for use and disclosure of protected health
information

Exclusion Criteria:

- Be pregnant or lactating

- Have a history of amputation, skin ulceration, and/or active Charcot of either foot

- Have a history of previous surgery involving the spine or lower extremity, with
residual symptoms of pain or difficulty with movement

- Have Crohn's disease or a history of any type of bariatric surgery or any surgical
resection of all or part of the stomach, duodenum, jejunum, and/or ileum. (Previous
surgical resections of the colon that spared the stomach, duodenum, jejunum and ileum
are allowed.)

- Have a history of surgery or hospitalization within 2 months prior to Screening or
planned hospitalization at any time during the study

- Be taking systemic corticosteroids within 2 months prior to Screening, opiates or
tramadol hydrochloride within 6 weeks prior to Screening, and/or immunosuppressives,
or receiving radiotherapy within 6 months prior to Screening

- Be taking more than one anticonvulsant, serotonin-norepinephrine reuptake inhibitor
(SNRI), or tricyclic antidepressant (TCA)

- Have ongoing evidence of peripheral vascular disease, including greater than one
nonpalpable pulse on either foot, history of claudication, or history of lower
extremity vascular bypass surgery or angioplasty

- Have circulating glycated hemoglobin (HbA1c) exceeding 11% at Screening

- Have an estimated glomerular filtration rate (eGFR) less than or equal to 40 ml/min
using the Modification of Diet in Renal Disease (MDRD) formula at Screening or have
end-stage renal disorder requiring hemodialysis

- Have uncontrolled hypertension defined as sustained systolic blood pressure (SBP)
greater than 200 mmHg or diastolic blood pressure (DBP) greater than 110 mmHg at
screening

- Have lung disease (uncontrolled asthma or shortness of breath) within 2 months prior
to Screening

- Use of any of the following supplements within 6 weeks before Screening: evening
primrose oil, vitamin B12 injection, greater than 10 mg of vitamin B6, or greater
than 800 µg of folate

- Have previously failed two or more prior therapies for painful DPN

- Currently abusing alcohol or drugs or have a history of such abuse within the past 3
years. (Alcohol abuse is defined as more than 2 drink units per day for women and
more than 3 drink units per day for men. One drink unit is defined as 1.5 oz [45 mL]
of distilled spirits, 5 oz [150 mL] of wine, or 12 oz [360 mL] of beer.)

- Have any nondiabetic cause of peripheral neuropathy

- Have a history of documented lumbar nerve entrapment or symptoms suggestive of a
lumbar nerve entrapment

- Have a history of systemic lupus erythematosis, rheumatoid arthritis, Sjögren's
syndrome, or mixed connective tissue disease

- If receiving thyroid replacement therapy, should be on a stable dose for at least 6
weeks prior to Screening

- Have a history of a positive HIV test or active Hepatitis B or C infection.

- Have a history or presence of malignancy within 10 years prior to Screening except
for basal or squamous cell carcinoma of the skin. Records to be submitted to Pamlab
for review and approval to randomize.

- Have prior use of or intolerance to Metanx® or any of its active ingredients

- Have been dosed or used a medical device in another investigational trial within 60
days prior to Screening.

- Have any clinically significant existing medical, psychiatric, or nonmedical
condition that in the opinion of the investigator places the subject at undue risk,
prevents compliance with the study protocol, or potentially jeopardizes the quality
of the data to be generated