This study will test the hypothesis that PF-06649751 with continuous co-administration of trimethobenzamide hydrochloride (TMB) with will be safe and well tolerated. Single doses of PF-06649751 will be tested in this study, starting at a low dose and escalating to a dose projected to be under the current limits for drug concentration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
9
Experimental Pfizer compound.
Trimethobenzamide Hydrochloride is indicated for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis.
Belgium Pfizer Clinical Research Unit
Brussels, Belgium
Pfizer Clinical Research Unit
Brussels, Belgium
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Counts of participants who have treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to PF-06649751 will be assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category will be counted once within the category.
Time frame: 0 - 4 weeks
Supine and standing vital sign measurements
Measurement of blood pressure and pulse rate.
Time frame: 0 - 4 weeks
Electrocardiogram (ECG)
Measurement of standard 12-lead ECG, single or triplicate
Time frame: 0 - 4 weeks
Number of Participants With Laboratory Test Values of Potential Clinical Importance
Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance.
Time frame: 0 - 4 weeks
Maximum Observed Plasma Concentration (Cmax)
Maximum plasma concentration
Time frame: Day 1
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Time frame: Day 1 - 5
Area Under the Curve From Time Zero to Extrapolated Infinite Time AUCinf
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. It is obtained from AUC (0 - t) plus AUC (t - inf).
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Time frame: Day 1 - 5
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Day 1
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Day 1 - 5
Apparent Oral Clearance (CL/F)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Day 1 - 5
Apparent Volume of Distribution (Vz/F)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Time frame: Day 1 - 5