A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of PF-06649751 Co-administered With Trimethobenzamide Hydrochloride in Healthy Subjects

• Drug: PF-06649751
  Experimental Pfizer compound.
• Drug: Trimethobenzamide Hydrochloride
  Trimethobenzamide Hydrochloride is indicated for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis.
  Other Name: Tigan

• Experimental: Single Ascending Doses Cohort 1
  Single doses, given by oral solution, starting at 0.75 mg up to a possible maximum of 3.0 mg. The subject will have been fasted for 10 hours prior to the single dose. For each dosing period, 3 subjects will be given a placebo as a comparator while 6 are given active dose. The subjects will be given concomitant trimethobenzamide hydrochloride for the 3 weeks that the subject is in the CRU. For each of the three periods, subjects will be crossed-over from placebo or PF-06649751. Each PF-06649751 dose is separated by one week.
  Interventions:

  • Drug: PF-06649751
  • Drug: Trimethobenzamide Hydrochloride
• Experimental: Single Ascending Doses Cohort 2
  Single doses, given by oral solution, starting at 4.5 mg up to a possible maximum of 9.0 mg. The subject will have been fasted for 10 hours prior to the single dose. For each dosing period, 3 subjects will be given a placebo as a comparator while 6 are given active dose. The subjects will be given concomitant trimethobenzamide hydrochloride for the 3 weeks that the subject is in the CRU. For each of the three periods, subjects will be crossed-over from placebo or PF-06649751. Each PF-06649751 dose is separated by one week.
  Interventions:

  • Drug: PF-06649751
  • Drug: Trimethobenzamide Hydrochloride

Inclusion Criteria:

• Healthy male and/or female subjects of non childbearing potential between the ages of 18 and 55 years, inclusive.
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study medication (whichever is longer).
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.