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

NCT02262767 | Completed Phase 1

• 2 other identifiers: B76010072014-003631-19
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Healthy

Keywords

Phase 1, Randomized, Double Blind, Placebo-Controlled, Single-Dose Escalation, Safety, Tolerability, Pharmacokinetic, PF-06649751, Trimethobenzamide

Outcome Measures

Primary Outcomes (4)

• 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

• Supine and standing vital sign measurements

  Measurement of blood pressure and pulse rate.

  0 - 4 weeks

• Electrocardiogram (ECG)

  Measurement of standard 12-lead ECG, single or triplicate

  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.

  0 - 4 weeks

Secondary Outcomes (7)

• Maximum Observed Plasma Concentration (Cmax)

  Day 1

• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)

  Day 1 - 5

• Area Under the Curve From Time Zero to Extrapolated Infinite Time AUCinf

  Day 1 - 5

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  Day 1

• Plasma Decay Half-Life (t1/2)

  Day 1 - 5

Study Arms (2)

Single Ascending Doses Cohort 1

EXPERIMENTAL

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.

Drug: PF-06649751; Drug: Trimethobenzamide Hydrochloride

Single Ascending Doses Cohort 2

EXPERIMENTAL

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.

Drug: PF-06649751; Drug: Trimethobenzamide Hydrochloride

Interventions

PF-06649751 DRUG

Experimental Pfizer compound.

Single Ascending Doses Cohort 1; Single Ascending Doses Cohort 2

Trimethobenzamide Hydrochloride DRUG

Trimethobenzamide Hydrochloride is indicated for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis.

Also known as: Tigan

Single Ascending Doses Cohort 1; Single Ascending Doses Cohort 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

Belgium Pfizer Clinical Research Unit

Brussels, 1070, Belgium

Location

Pfizer Clinical Research Unit

Brussels, B-1070, Belgium

Location

MeSH Terms

Interventions

trimethobenzamide

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

• Constantino Kantaridis, MD

  Pfizer

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2014
• First Posted: October 13, 2014
• Study Start: November 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 14, 2015

Record last verified: 2015-01

Locations

BE (2)