Two-part, Randomized, Placebo-controlled, Repeated Stepped Infusion Dose Study of the Pharmacodynamics of Doxapram when Co-administered with Opioids

Healthy male volunteers, aged 18-45 yr

1. Past history of the anxiety disorder including panic attack, obsessive compulsive dis-order, phobias restricting normal daily function, social anxiety, and/or paranoia.
2. Current diagnosis of psychiatric disease requiring daily medication, including con-trolled or uncontrolled schizophrenia, history of or treatment of panic disorder, or any other uncontrolled psychiatric condition.
3. History of alcohol abuse (more than an average of 2-drinks per day) within the past 2 years.
4. History of drug abuse. Drug abuse defined as the use of a drug for a non-therapeutic effect.
5. History of smoking within the past year or a history of more than 5 years of consis-tent daily smoking.
6. Failure of the drug of abuse or ethanol breath tests at screening or check-in.
7. Positive for HIV, or Hepatitis B or C at screening.
8. Blood donation within 30 days of screening or plasma donation within 7 days of screening.
9. Subjects with a history of bleeding disorders or coagulopathies.
10. History of dyspnea, asthma, tuberculosis, chronic obstructive pulmonary disease, sleep apnea or any other ventilatory / lung disease.
11. Administration of any investigational drug or implantation of investigational device, or participation in another trial, within 30 days of screening.
12. Inability to perform acceptable, quality spirometry, and FEV1 <80% of predicted for age, sex and height.
13. Subjects who, in the opinion of the investigator, will not be able to participate opti-mally in the study.
14. Any surgical or medical condition which might significantly alter the distribution, me-tabolism or excretion of any drug. The investigator should be guided by evidence of any of the following, and be discussed with the Independent Physician prior to en-rollment into the trial:;a. history of pancreatic injury or pancreatitis;
b. history or presence of liver disease or liver injury;
c. history or presence of impaired renal function as indicated by clinically
significant elevation in creatinine, BUN/urea, urinary albumin, or clinically
significant urinary cellular constituents ; or
d. history of urinary obstruction or difficulty in voiding.
15. Subject who has a history of any infectious disease within 4 weeks prior to drug ad-ministration that in the opinion of the investigator, affects the subject*s ability to par-ticipate in the trial.
16. Subjects who are part of the study staff personnel or family members of the study staff personnel.
17. Subjects who have demonstrated allergic reactions (e.g., food, drug, atopic reactions or asthmatic episodes) which, in the opinion of the investigator and Independent Physician, interfere with their ability to participate in the trial.
18. Subjects who have a history of malignancy.
19. Personal or family history of malignant hyperthermia.
20. Daily consumption of caffeine greater than 5 caffeinated beverages (e.g., coffee, tea, soft drinks).