A Study To Evaluate The Effect Of PF-04447943 On Qtc Interval In Healthy Adult Subjects

A Phase 1, Single-dose, Randomized, 4-treatment, 4-period Crossover, Placebo- And Positive-controlled, Double-blind (Open-label For Positive Control), Sponsor-open Study To Determine The Effect Of PF-04447943 On Qtc Interval In Healthy Adult Subjects

This is a study designed to ascertain the effect of PF-04447943 on QT interval in healthy adult subjects. This is conducted as part of standard drug development.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-04447943; Drug: Placebo; Drug: Moxifloxacin

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy female subjects of non childbearing potential and/or healthy male subjects, between the ages of 18 and 55 years.
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg.

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).
• History of cerebrovascular accident, transient ischemic attack (TIA), or traumatic brain injury.
• History of seizures or history or physical examination findings (eg localizing signs on neurologic examination) suggestive of structural central nervous system (CNS) abnormalities which may place patient at increased risk of seizures.
• History of orthostatic blood pressure changes or clinically significant orthostatic symptoms.
• Self reported history or risk factors for QT prolongation or torsades de pointes (eg, organic heart disease, congestive heart failure, hypokalemia, hypomagnesaemia, congenital long QT syndrome, myocardial ischemia or infarction), congenital deafness, family history of sudden death, and family history of long QT syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-04447943 low dose; 25 mg of PF-04447943	Drug: PF-04447943; Single oral dose of PF-04447943 administered as an extemporaneously prepared solution
Experimental: PF-04447943 high dose; 100 mg of PF-04447943	Drug: PF-04447943; Single oral dose of PF-04447943 administered as an extemporaneously prepared solution
Placebo Comparator: Placebo; Matching placebo for PF-04447943	Drug: Placebo; Single oral dose of matching placebo for PF-04447943 administered as an extemporaneously prepared solution
Active Comparator: Moxifloxacin; 400 mg of moxifloxacin	Drug: Moxifloxacin; Single oral dose of moxifloxacin administered as tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 0.5 Hour Post-Dose	Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.	0.5 hour post-dose
Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 1 Hour Post-Dose	Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.	1 hour post-dose
Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 2 Hours Post-Dose	Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.	2 hours post-dose
Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 3 Hours Post-Dose	Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.	3 hours post-dose
Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 4 Hours Post-Dose	Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.	4 hours post-dose
Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 8 Hours Post-Dose	Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.	8 hours post-dose
Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 12 Hours Post-Dose	Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.	12 hours post-dose
Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 24 Hours Post-Dose	Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.	24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo	Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across Moxifloxacin and placebo is reported in statistical analysis.	0.5, 1 , 2, 3, 4, 8, 12 and 24 hours post-dose
Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo	Least square mean of heart rate measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.	0.5, 1 , 2, 3, 4, 8, 12 and 24 hours post-dose
Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo	Least square mean of PR interval measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.	0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose
Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo	Least square mean of QRS interval measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.	0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state.	Baseline (Pre-dose) up to 28 days after last dose of study drug (56 days)
Number of Participants With Physical Examination Abnormalities	Full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Physical examination abnormalities were judged by the investigator.	Baseline (Pre-dose)
Number of Participants With Electrocardiogram (ECG) Abnormalities	Criteria for ECG abnormalities: maximum QTc corrected for heart rate using Bazett's formula (QTcB) and QTcF interval (450 to less than [<] 480 msec, 480 to <500 msec, greater than or equal to [>=] 500 msec; increase from baseline [IFB] >=30 msec and <60 msec, IFB >=60 msec). Baseline was defined as the average of the means obtained from the 3 sets of triplicate measurements taken at -1, -0.5 and 0 hours pre-dose on Day 1 within each intervention period.	Baseline up to 24 hours post-dose
Number of Participants With Vital Sign Abnormalities	Criteria for vital sign abnormalities: supine and standing pulse rate <40 bpm or greater than (>) 120 bpm, supine and standing systolic blood pressure (SBP) <90 millimeter of mercury (mmHg), supine and standing diastolic blood pressure (DBP) <50 mmHg, maximum (max.) increase from baseline (IFB) and decrease from baseline (DFB) in supine and standing SBP of >=30 mmHg, maximum IFB and DFB in supine and Standing DBP of >=20 mmHg.	Baseline (Pre-dose) up to 24 hours post-dose
Number of Participants With Laboratory Test Abnormalities	Hemoglobin(Hgb), hematocrit, red blood cell(RBC)<0.8*lower limit of normal(LLN), mean corpuscular(MC) Hgb, MC volume <0.9*LLN, >1.1*upper limit of normal(ULN), platelet<0.5*LLN,>1.75*ULN, lymphocyte, neutrophil<0.8*LLN, >1.2*ULN, basophil, eosinophil, monocyte>1.2*ULN, white blood cell(WBC)<0.6*LLN,>1.5*ULN, reticulocytes<0.5*LLN,>1.5*ULN; bilirubin>1.5*ULN, aspartate aminotransferase(AT), alanine AT, alkaline phosphatase>3.0*ULN, protein, albumin<0.8*LLN,>1.2*ULN; blood urea nitrogen, creatinine>1.3*ULN, uric acid>1.2*ULN; sodium<0.95*LLN,>1.05*ULN, potassium, chloride, calcium, bicarbonate<0.9*LLN,>1.1*ULN; glucose<0.6*LLN, >1.5*ULN, HbA1c>1.3*ULN, creatinine kinase>2*ULN; urine-specific gravity<1.003,>1.030, pH<4.5,>8, WBC, RBC>=20, bacteria>20, urobilinogen, glucose, ketone, protein, Hgb, nitrite, leukocyte esterase, bilirubin>=1; thyroid stimulating hormone<0.8*LLN,>1.2*ULN; cholesterol, triglycerides>1.3*ULN, high density lipoprotein cholesterol(DL-C) <0.8*LLN, low DL-C>1.2*ULN.	Baseline (Pre-dose) up to 24 hours post-dose
Maximum Plasma Concentration (Cmax) of PF-04447943		Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose
Time of Observed Maximum Plasma Concentration (Tmax) of PF-04447943		Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of PF-04447943	Area under the plasma concentration-time from time zero to time of last measurable concentration. Observed using the linear/log trapezoidal method.	Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2016
• Primary Completion (Actual): October 20, 2016
• Study Completion (Actual): October 20, 2016

Study Registration Dates

• First Submitted: May 25, 2016
• First Submitted That Met QC Criteria: May 25, 2016
• First Posted (Estimate): May 30, 2016

Study Record Updates

• Last Update Posted (Actual): December 28, 2018
• Last Update Submitted That Met QC Criteria: June 18, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: B0401018