Omnitram Pharmacokinetic Study In Healthy Volunteers
Omnitram Pharmacokinetic Study In Healthy Volunteers
The purpose of this study is to compare the safety, pharmacokinetic properties (the
 absorption, distribution and excretion), and analgesic activity of Omnitram (10 mg tablets),
 Tramadol (Ultram, 50 mg tablet) following oral administration of 9 doses healthy subjects.
A Phase 1, single-center, randomized, double-blind, placebo-controlled, three-period
 cross-over study to compare the safety, steady-state oral pharmacokinetics, and clinical
 activity of overencapsulated: 20 mg Omnitram (2x10 mg tablets), 50 mg Tramadol (1x50 mg
 Ultram tablet), and placebo.

 Forty male subjects in normal health, 21 to 55 years of age, will be randomized to three
 parallel arms (N=~13 each) to ingest a total of 9 doses of Omnitram, Tramadol, or placebo in
 a first treatment segment (one dose every 6 hours). Around the 9th dose blood samples are
 collected to quantify plasma Tramadol and Metabolite 1 (M1) enantiomers. After the 9th dose,
 pain tolerance is assessed with a cold pressor test (ice cold water immersion). After the 7th
 dose abuse liability measures and pupil diameter will be assessed. Subjects will washout for
 7 days after the first treatment segment and second treatment segment.
Inclusion Criteria:

 1. Healthy male with normal vital signs: systolic blood pressure > 90 mm Hg and < 140 mm
 Hg; diastolic blood pressure > 50 mm Hg and < 90 mm Hg; pulse 50 to 100 beats per
 minute; respiratory rate 12 to 20 breathes per minute

 2. Between the ages of 21 and 55 years of age

 3. Able and willing to give informed consent

 4. Able to comply with all study procedures

 5. Have adequate hematologic function as evidenced by the following screening results:

 -  White Blood Cell (WBC) >3,500/mm3 and < 12,000/mm3;

 -  Platelet Count > 150,000/mm3 and < 540,000/mm3;

 -  Hemoglobin > 12.5 gm/dL and < 20.5 gm/dL.

 Have adequate liver function as evidenced by the following screening results:

 -  Aspartate transaminase (AST) ≤ 60 IU/L;

 -  Alanine transaminase (ALT) ≤ 83 IU;

 -  Alkaline Phosphatase ≤ 150 IU/L;

 -  Total Bilirubin ≤ 1.2 mg/dL;

 -  Prothrombin Time (PT) < 1.2 upper limit of normal (ULN); Partial Thromboplastin
 Time (PTT) < 1.2 ULN.

 6. Electrocardiogram (ECG) within normal limits as determined by the PI

 7. Have adequate renal function as evidenced by the following screening result:

 Glomerular filtration rate (GFR) calculated by Cockcroft-Gault formula >60 ml/min.

 Urinalysis demonstrating < +1 glucose, +1 ketones, and +1 protein

 8. Negative urine test for substances of abuse, including opiates, per clinical research
 unit (CRU) standards

 9. Negative serology tests for HIV, hepatitis B surface antigen and hepatitis C virus
 antibody

 10. Body Mass Index (BMI) 19.0 to 32 kg/m

 11. Cold pressor screening results as follows: 1) pain tolerance of > 20 seconds and <120
 seconds

 Exclusion Criteria:

 1. Oral temperature > 38°C or history of current illness

 2. History of seizures, epilepsy, or recognized increase risk of seizure (e.g., head
 trauma, metabolic disorders, alcohol or drug withdrawal)

 3. History of cirrhosis or laboratory evidence of liver disease

 4. Use of alcohol within 24 hours of day -1 until the end of the study; and grapefruit,
 grapefruit-related citrus fruits (e.g., Seville oranges, pomelos), or grapefruit juice
 or grapefruit-related juices, or other medication, within 7 days of study drug
 administration and until the end of the study

 5. History of previous anaphylaxis, severe allergic reaction to Tramadol, codeine, or
 other opioid drugs

 6. Use of monoamine oxidase (MAO) inhibitors (including linezolid), Serotonin Reuptake
 Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and prescription or over-the
 counter (OTC) medications known to induce or inhibit drug metabolism, including
 cytochrome P450 2D6 (CYP2D6), and other drugs that may affect the serotonergic
 neurotransmitter systems including, but not limited to, triptans, dextromethorphan,
 tricyclic antidepressants, bupropion, lithium, tramadol, dietary supplements such as
 tryptophan and St. John's Wort, and antipsychotics or other dopamine antagonists.
 These restrictions are to be maintained from 14 days before study day -1, until the
 subject completes the study

 7. Any other unstable acute or chronic disease that could interfere with the evaluation
 of the safety of the study drug as determined by the principal Investigator in
 dialogue with the Sponsor Medical Monitor

 8. Unlikely to comply with the study protocol

 9. Known or suspected alcohol or drug abuse within the past 6 months

 10. Received another investigational agent within 4 weeks of Day 0, or within five
 half-lives of Day 0, whichever is longer; or receiving any other investigational agent
 during this study

 11. Any concurrent disease or condition that in the opinion of the investigator impairs
 the subject's ability to complete the trial. Psychological, familial, sociological,
 geographical or medical conditions which, in the Investigator's opinion, could
 compromise compliance with the objectives and procedures of this protocol, or obscure
 interpretation of the trial data