Clinical trial NCT03312777 (phase 1, status: completed)
Conditions: pain
ICD codes: N50.82, R07.2, R07.82, R10.13, R10.33, R14.1, R52
Drugs: omnitram, tramadol, placebo
SMILES: COC1=CC=CC(=C1)[C@@]1(O)CCCC[C@@H]1CN(C)C, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          1. Healthy males and females with normal vital signs: systolic blood pressure > 90 mm Hg
             and < 140 mm Hg; diastolic blood pressure > 45 mm Hg and < 90 mm Hg; pulse 40 to 100
             beats per minute; respiratory rate 10 to 20 breathes per minute.

          2. Between the ages of 18 and 50 years of age.

          3. Able and willing to give informed consent

          4. Able to comply with all study procedures.

          5. If female, must not be of childbearing potential or must agree to use one or more of
             the following forms of contraception during screening and for 30 days following study
             drug administration: hormonal (e.g., oral, transdermal, intravaginal, implant or
             injection); double barrier (i.e., condom, diaphragm with spermicide); intrauterine
             device (IUD) or system (IUS); vasectomized partner (6 months minimum); abstinence; or
             bilateral tubal ligation.

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

             WBC >3,500/mm3 and < 12,000/mm3 Platelet Count > 150,000/mm3 and < 540,000/mm3
             Hemoglobin > 12.0 gm/dL and < 20.5 gm/dL

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

             AST (SGOT) ≤ 60 IU/L ALT (SGPT) men ≤ 83 IU/L women < 60 IU/L Alkaline Phosphatase ≤
             200 IU/L Total Bilirubin ≤ 1.2 mg/dL PT and PTT < 1.2 ULN

          7. Electrocardiogram (ECG) without clinically significant findings as determined by the
             PI.

          8. 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.

          9. Negative pregnancy test within 1 week of study day 1 (women of childbearing potential
             only).

         10. Negative urine test for substances of abuse, including opiates, per CRU standards.

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

         12. Body Mass Index (BMI) 18.0 to 32 kg/m.

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

         14. Cytochrome P450 2D6 (CYP2D6) genotype by Genelex consistent with intermediate
             metabolizer phenotype or normal metabolizer phenotype.

        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 paroxetine, tramadol,
             codeine, or other opioid drugs.

          6. Use of 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 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. Currently pregnant or breast feeding.

          9. Unlikely to comply with the study protocol.

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

         11. Received another investigational agent within 4 weeks of Day 1, or receiving any other
             investigational agent during this study.

         12. 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.