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

Healthy Clinical Trial

Official title:

A Phase 1, Double Blind, Sponsor Open, Randomized, Placebo Controlled, Single Ascending Dose Study To Investigate The Safety, Tolerability, And Pharmacokinetics Of Pf 06649751 Co-administered With Trimethobenzamide Hydrochloride In Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02262767
• Other study ID #: B7601007
• Secondary ID: 2014-003631-19
• Status: Completed
• Phase: Phase 1
• First received: October 9, 2014
• Last updated: January 13, 2015
• Start date: November 2014
• Est. completion date: December 2014

Study information

• Verified date: January 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

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

Locations

Country	Name	City	State
Belgium	Belgium Pfizer Clinical Research Unit	Brussels
Belgium	Pfizer Clinical Research Unit	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	0 - 4 weeks	Yes
Primary	Supine and standing vital sign measurements	Measurement of blood pressure and pulse rate.	0 - 4 weeks	Yes
Primary	Electrocardiogram (ECG)	Measurement of standard 12-lead ECG, single or triplicate	0 - 4 weeks	Yes
Primary	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.	0 - 4 weeks	Yes
Secondary	Maximum Observed Plasma Concentration (Cmax)	Maximum plasma concentration	Day 1	No
Secondary	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).	Day 1 - 5	No
Secondary	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).	Day 1 - 5	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax)		Day 1	No
Secondary	Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Day 1 - 5	No
Secondary	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.	Day 1 - 5	No
Secondary	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.	Day 1 - 5	No