Healthy
Conditions
Brief summary
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.
Interventions
DRUGPF-04447943
Single oral dose of PF-04447943 administered as an extemporaneously prepared solution
DRUGPlacebo
Single oral dose of matching placebo for PF-04447943 administered as an extemporaneously prepared solution
DRUGMoxifloxacin
Single oral dose of moxifloxacin administered as tablet
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 1 Hour Post-Dose | 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. |
| Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 2 Hours Post-Dose | 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. |
| Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 3 Hours Post-Dose | 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. |
| Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 4 Hours Post-Dose | 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. |
| Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 8 Hours Post-Dose | 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. |
| Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 12 Hours Post-Dose | 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. |
| Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 24 Hours Post-Dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Laboratory Test Abnormalities | Baseline (Pre-dose) up to 24 hours post-dose | 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. |
| Maximum Plasma Concentration (Cmax) of PF-04447943 | Pre-dose (0 hour), 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) | Baseline (Pre-dose) up to 28 days after last dose of study drug (56 days) | 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. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) 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 from time zero to time of last measurable concentration. Observed using the linear/log trapezoidal method. |
| 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 | — |
| Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 0.5, 1 , 2, 3, 4, 8, 12 and 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 Moxifloxacin and placebo is reported in statistical analysis. |
| Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 0.5, 1 , 2, 3, 4, 8, 12 and 24 hours post-dose | 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. |
| Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose | 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. |
| Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose | 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. |
| Number of Participants With Physical Examination Abnormalities | Baseline (Pre-dose) | 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. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities | Baseline up to 24 hours post-dose | 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. |
| Number of Participants With Vital Sign Abnormalities | Baseline (Pre-dose) up to 24 hours post-dose | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study All participants who were randomized to receive Moxifloxacin first, placebo first, PF-04447943 100 mg first and PF-04447943 25 mg first in intervention period 1. | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Intervention Period 2 (1 Day) | Adverse Event | 0 | 1 | 0 | 0 |
| Intervention Period 2 (1 Day) | Family related obligations | 0 | 0 | 1 | 0 |
| Intervention Period 3 (1 Day) | Adverse Event | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 36.3 years STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 42 | 0 / 41 | 0 / 42 |
| other Total, other adverse events | 7 / 43 | 3 / 42 | 3 / 41 | 2 / 42 |
| serious Total, serious adverse events | 0 / 43 | 0 / 42 | 0 / 41 | 0 / 42 |
Outcome results
Primary
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.
Time frame: 0.5 hour post-dose
Population: Electrocardiogram (ECG) analysis population included all participants randomized and treated who had at least 1 post-dose ECG measurement in at least 1 period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | 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 | 404.09 Millisecond (Msec) | Standard Error 0.9544 |
| Placebo | 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 | 408.92 Millisecond (Msec) | Standard Error 0.9659 |
| Placebo | 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 | 404.38 Millisecond (Msec) | Standard Error 0.9653 |
Comparison: PF-04447943 25 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.819590% CI: [-2.38, 1.8]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.000490% CI: [2.44, 6.64]Repeated Measures Model
Primary
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.
Time frame: 12 hours post-dose
Population: ECG analysis population included all participants randomized and treated who had at least 1 post-dose ECG measurement in at least 1 period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 12 Hours Post-Dose | 399.83 Msec | Standard Error 0.9544 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 12 Hours Post-Dose | 399.38 Msec | Standard Error 0.9659 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 12 Hours Post-Dose | 401.99 Msec | Standard Error 0.9653 |
Comparison: PF-04447943 25 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.089390% CI: [-4.24, -0.07]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.041290% CI: [-4.71, -0.51]Repeated Measures Model
Primary
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.
Time frame: 1 hour post-dose
Population: ECG analysis population included all participants randomized and treated who had at least 1 post-dose ECG measurement in at least 1 period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 1 Hour Post-Dose | 404.23 Msec | Standard Error 0.9544 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 1 Hour Post-Dose | 409.14 Msec | Standard Error 0.965 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 1 Hour Post-Dose | 404.09 Msec | Standard Error 0.9653 |
Comparison: PF-04447943 25 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.914690% CI: [-1.95, 2.22]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: <0.000190% CI: [2.95, 7.14]Repeated Measures Model
Primary
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.
Time frame: 24 hours post-dose
Population: ECG analysis population included all participants randomized and treated who had at least 1 post-dose ECG measurement in at least 1 period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 24 Hours Post-Dose | 401.72 Msec | Standard Error 0.9544 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 24 Hours Post-Dose | 400.28 Msec | Standard Error 0.9659 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 24 Hours Post-Dose | 403.06 Msec | Standard Error 0.9653 |
Comparison: PF-04447943 25 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.289290% CI: [-3.43, 0.74]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.029490% CI: [-4.88, -0.68]Repeated Measures Model
Primary
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.
Time frame: 2 hours post-dose
Population: ECG analysis population included all participants randomized and treated who had at least 1 post-dose ECG measurement in at least 1 period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 2 Hours Post-Dose | 403.76 Msec | Standard Error 0.9544 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 2 Hours Post-Dose | 406.78 Msec | Standard Error 0.9659 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 2 Hours Post-Dose | 402.52 Msec | Standard Error 0.9653 |
Comparison: PF-04447943 25 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.327290% CI: [-0.84, 3.33]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.000990% CI: [2.16, 6.36]Repeated Measures Model
Primary
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.
Time frame: 3 hours post-dose
Population: ECG analysis population included all participants randomized and treated who had at least 1 post-dose ECG measurement in at least 1 period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 3 Hours Post-Dose | 403.95 Msec | Standard Error 0.9544 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 3 Hours Post-Dose | 406.69 Msec | Standard Error 0.9659 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 3 Hours Post-Dose | 404.43 Msec | Standard Error 0.9653 |
Comparison: PF-04447943 25 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.702490% CI: [-2.57, 1.6]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.076890% CI: [0.16, 4.36]Repeated Measures Model
Primary
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.
Time frame: 4 hours post-dose
Population: ECG analysis population included all participants randomized and treated who had at least 1 post-dose ECG measurement in at least 1 period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 4 Hours Post-Dose | 402.76 Msec | Standard Error 0.9544 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 4 Hours Post-Dose | 405.94 Msec | Standard Error 0.9659 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 4 Hours Post-Dose | 404.73 Msec | Standard Error 0.9653 |
Comparison: PF-04447943 25 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.120190% CI: [-4.06, 0.12]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.342490% CI: [-0.89, 3.31]Repeated Measures Model
Primary
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.
Time frame: 8 hours post-dose
Population: ECG analysis population included all participants randomized and treated who had at least 1 post-dose ECG measurement in at least 1 period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 8 Hours Post-Dose | 397.31 Msec | Standard Error 0.9544 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 8 Hours Post-Dose | 398.55 Msec | Standard Error 0.9659 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 8 Hours Post-Dose | 398.66 Msec | Standard Error 0.9653 |
Comparison: PF-04447943 25 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.28790% CI: [-3.44, 0.74]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.933490% CI: [-2.21, 1.99]Repeated Measures Model
Secondary
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.
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose
Population: PK parameter analysis population included all enrolled participants treated with PF-04447943 and who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of PF-04447943 | 1454 Nanogram*hour per milliliter | Geometric Coefficient of Variation 27 |
| Placebo | Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of PF-04447943 | 6277 Nanogram*hour per milliliter | Geometric Coefficient of Variation 24 |
Secondary
Maximum Plasma Concentration (Cmax) of PF-04447943
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose
Population: Pharmacokinetic (PK) parameter analysis population included all enrolled participants treated with PF-04447943 and who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | Maximum Plasma Concentration (Cmax) of PF-04447943 | 225.8 Nanogram per milliliter | Geometric Coefficient of Variation 19 |
| Placebo | Maximum Plasma Concentration (Cmax) of PF-04447943 | 947.3 Nanogram per milliliter | Geometric Coefficient of Variation 17 |
Secondary
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.
Time frame: Baseline up to 24 hours post-dose
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) | Dispersion |
|---|---|---|---|---|
| Moxifloxacin 400 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB Interval >=500 msec | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB Interval 480 to <500 msec | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB IFB (>= 30 to <60) msec | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF IFB (>=30 to <60) msec | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF Interval 480 to <500 msec | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF Interval >=500 msec | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB Interval 450 to <480 msec | 1 Participants | 27 |
| Moxifloxacin 400 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF IFB (>=60) msec | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF Interval 450 to <480 msec | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB IFB (>=60) msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB IFB (>= 30 to <60) msec | 1 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF Interval >=500 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB Interval 450 to <480 msec | 3 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB Interval >=500 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB IFB (>=60) msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF Interval 450 to <480 msec | 1 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF IFB (>=30 to <60) msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF Interval 480 to <500 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB Interval 480 to <500 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF IFB (>=60) msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF IFB (>=30 to <60) msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF Interval 480 to <500 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF Interval >=500 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF Interval 450 to <480 msec | 1 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF IFB (>=60) msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB Interval 480 to <500 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB Interval 450 to <480 msec | 1 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB Interval >=500 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB IFB (>= 30 to <60) msec | 2 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB IFB (>=60) msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF Interval >=500 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB Interval 450 to <480 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB Interval 480 to <500 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB IFB (>=60) msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF IFB (>=30 to <60) msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF IFB (>=60) msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB Interval >=500 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB IFB (>= 30 to <60) msec | 1 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF Interval 450 to <480 msec | 0 Participants | — |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF Interval 480 to <500 msec | 0 Participants | — |
Secondary
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.
Time frame: Baseline (Pre-dose) up to 24 hours post-dose
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | Number of Participants With Laboratory Test Abnormalities | 17 Participants | 27 |
| Placebo | Number of Participants With Laboratory Test Abnormalities | 12 Participants | — |
| Placebo | Number of Participants With Laboratory Test Abnormalities | 12 Participants | — |
| Placebo | Number of Participants With Laboratory Test Abnormalities | 18 Participants | — |
Secondary
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.
Time frame: Baseline (Pre-dose)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | Number of Participants With Physical Examination Abnormalities | 1 Participants | 27 |
| Placebo | Number of Participants With Physical Examination Abnormalities | 1 Participants | — |
| Placebo | Number of Participants With Physical Examination Abnormalities | 1 Participants | — |
| Placebo | Number of Participants With Physical Examination Abnormalities | 2 Participants | — |
Secondary
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.
Time frame: Baseline (Pre-dose) up to 28 days after last dose of study drug (56 days)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) | Dispersion |
|---|---|---|---|---|
| Moxifloxacin 400 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 11 Participants | 27 |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 9 Participants | — |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants | — |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants | — |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 8 Participants | — |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants | — |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 8 Participants | — |
Secondary
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.
Time frame: Baseline (Pre-dose) up to 24 hours post-dose
Population: Safety analysis set included all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) | Dispersion |
|---|---|---|---|---|
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Supine Pulse Rate: <40 bpm | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Standing SBP: <90 mmHg | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Standing DBP: <50 mmHg | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 Participants | 27 |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Supine Pulse Rate: >120 bpm | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Standing Pulse Rate: <40 bpm | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Standing Pulse Rate: >120 bpm | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Max. IFB in Supine SBP: >=30mmHg | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Max. IFB in StandingSBP:>=30 mmHg | 1 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Max. IFB in Supine DBP: >=20 mmHg | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Max. IFB in StandingDBP:>=20 mmHg | 2 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Max. DFB in Supine SBP:>=30 mmHg | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Max. DFB in StandingSBP:>=30 mmHg | 2 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Max. DFB in Supine DBP:>=20 mmHg | 0 Participants | — |
| Moxifloxacin 400 mg | Number of Participants With Vital Sign Abnormalities | Max. DFB in StandingDBP:>=20 mmHg | 2 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine Pulse Rate: >120 bpm | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. IFB in Supine SBP: >=30mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. DFB in StandingDBP:>=20 mmHg | 4 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. IFB in StandingDBP:>=20 mmHg | 2 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. DFB in Supine DBP:>=20 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. IFB in StandingSBP:>=30 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. IFB in Supine DBP: >=20 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine Pulse Rate: <40 bpm | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Standing Pulse Rate: <40 bpm | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Standing DBP: <50 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Standing SBP: <90 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. DFB in Supine SBP:>=30 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Standing Pulse Rate: >120 bpm | 1 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. DFB in StandingSBP:>=30 mmHg | 1 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine Pulse Rate: >120 bpm | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine Pulse Rate: <40 bpm | 1 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. DFB in StandingSBP:>=30 mmHg | 1 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Standing Pulse Rate: <40 bpm | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Standing Pulse Rate: >120 bpm | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. DFB in StandingDBP:>=20 mmHg | 1 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. IFB in Supine SBP: >=30mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. IFB in StandingSBP:>=30 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. DFB in Supine DBP:>=20 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. IFB in Supine DBP: >=20 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. IFB in StandingDBP:>=20 mmHg | 3 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Standing SBP: <90 mmHg | 2 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. DFB in Supine SBP:>=30 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 1 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Standing DBP: <50 mmHg | 1 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. DFB in StandingDBP:>=20 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Standing Pulse Rate: >120 bpm | 1 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. DFB in StandingSBP:>=30 mmHg | 3 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Standing Pulse Rate: <40 bpm | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. DFB in Supine SBP:>=30 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Standing SBP: <90 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine Pulse Rate: <40 bpm | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. IFB in StandingSBP:>=30 mmHg | 1 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Supine Pulse Rate: >120 bpm | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. IFB in Supine DBP: >=20 mmHg | 1 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. DFB in Supine DBP:>=20 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. IFB in Supine SBP: >=30mmHg | 2 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Standing DBP: <50 mmHg | 0 Participants | — |
| Placebo | Number of Participants With Vital Sign Abnormalities | Max. IFB in StandingDBP:>=20 mmHg | 1 Participants | — |
Secondary
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.
Time frame: 0.5, 1 , 2, 3, 4, 8, 12 and 24 hours post-dose
Population: ECG analysis population included all participants randomized and treated who had at least 1 post-dose ECG measurement in at least 1 period.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 0.5 Hour | 405.34 Msec | Standard Error 0.9765 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 1 Hour | 411.98 Msec | Standard Error 0.9765 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 2 Hours | 413.85 Msec | Standard Error 0.9765 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 3 Hours | 413.03 Msec | Standard Error 0.9765 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 4 Hours | 413.69 Msec | Standard Error 0.9765 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 8 Hours | 406.72 Msec | Standard Error 0.9765 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 12 Hours | 407.52 Msec | Standard Error 0.9765 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 24 Hours | 406.81 Msec | Standard Error 0.9765 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 24 Hours | 403.06 Msec | Standard Error 0.9653 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 0.5 Hour | 404.38 Msec | Standard Error 0.9653 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 4 Hours | 404.73 Msec | Standard Error 0.9653 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 1 Hour | 404.09 Msec | Standard Error 0.9653 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 12 Hours | 401.99 Msec | Standard Error 0.9653 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 2 Hours | 402.52 Msec | Standard Error 0.9653 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 8 Hours | 398.66 Msec | Standard Error 0.9653 |
| Placebo | Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for Moxifloxacin and Placebo | 3 Hours | 404.43 Msec | Standard Error 0.9653 |
Comparison: Moxifloxacin 400 mg versus Placebo, 0.5 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.45490% CI: [-1.15, 3.07]Repeated Measures Model
Comparison: Moxifloxacin 400 mg versus Placebo, 1 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: <0.000190% CI: [5.77, 9.99]Repeated Measures Model
Comparison: Moxifloxacin 400 mg versus Placebo, 2 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: <0.000190% CI: [9.22, 13.44]Repeated Measures Model
Comparison: Moxifloxacin 400 mg versus Placebo, 3 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: <0.000190% CI: [6.48, 10.7]Repeated Measures Model
Comparison: Moxifloxacin 400 mg versus Placebo, 4 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: <0.000190% CI: [6.85, 11.07]Repeated Measures Model
Comparison: Moxifloxacin 400 mg versus Placebo, 8 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: <0.000190% CI: [5.96, 10.18]Repeated Measures Model
Comparison: Moxifloxacin 400 mg versus Placebo, 12 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: <0.000190% CI: [3.42, 7.64]Repeated Measures Model
Comparison: Moxifloxacin 400 mg versus Placebo, 24 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.003690% CI: [1.64, 5.85]Repeated Measures Model
Secondary
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.
Time frame: 0.5, 1 , 2, 3, 4, 8, 12 and 24 hours post-dose
Population: ECG analysis population included all participants randomized and treated who had at least 1 post-dose ECG measurement in at least 1 period. This outcome measure was planned not to be analyzed for reporting group: Moxifloxacin 400 mg.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 0.5 Hour | 60.72 Beats per minute (bpm) | Standard Error 0.6831 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 1 Hour | 60.98 Beats per minute (bpm) | Standard Error 0.6831 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 2 Hours | 58.55 Beats per minute (bpm) | Standard Error 0.6831 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 3 Hours | 58.37 Beats per minute (bpm) | Standard Error 0.6831 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 4 Hours | 58.73 Beats per minute (bpm) | Standard Error 0.6831 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 8 Hours | 61.13 Beats per minute (bpm) | Standard Error 0.6831 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 12 Hours | 66.22 Beats per minute (bpm) | Standard Error 0.6831 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 24 Hours | 59.32 Beats per minute (bpm) | Standard Error 0.6831 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 2 Hours | 61.73 Beats per minute (bpm) | Standard Error 0.6911 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 12 Hours | 66.60 Beats per minute (bpm) | Standard Error 0.6911 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 3 Hours | 61.21 Beats per minute (bpm) | Standard Error 0.6911 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 4 Hours | 60.74 Beats per minute (bpm) | Standard Error 0.6911 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 8 Hours | 63.40 Beats per minute (bpm) | Standard Error 0.6911 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 0.5 Hour | 63.91 Beats per minute (bpm) | Standard Error 0.6911 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 1 Hour | 64.43 Beats per minute (bpm) | Standard Error 0.6911 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 24 Hours | 60.23 Beats per minute (bpm) | Standard Error 0.6911 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 2 Hours | 57.64 Beats per minute (bpm) | Standard Error 0.691 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 1 Hour | 58.60 Beats per minute (bpm) | Standard Error 0.691 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 0.5 Hour | 59.44 Beats per minute (bpm) | Standard Error 0.691 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 3 Hours | 58.68 Beats per minute (bpm) | Standard Error 0.691 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 12 Hours | 66.95 Beats per minute (bpm) | Standard Error 0.691 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 8 Hours | 61.95 Beats per minute (bpm) | Standard Error 0.691 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 4 Hours | 58.24 Beats per minute (bpm) | Standard Error 0.691 |
| Placebo | Time-Matched Mean Difference in Heart Rate for PF-04447943 and Placebo | 24 Hours | 62.35 Beats per minute (bpm) | Standard Error 0.691 |
Comparison: PF-04447943 25 mg versus Placebo, 0.5 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.1690% CI: [-0.22, 2.78]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 1 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.009290% CI: [0.88, 3.87]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 2 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.317490% CI: [-0.59, 2.41]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 3 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.734490% CI: [-1.81, 1.19]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 4 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.588190% CI: [-1, 1.99]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 8 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.36890% CI: [-2.32, 0.68]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 12 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.4290% CI: [-2.23, 0.76]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 24 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.000990% CI: [-4.53, -1.53]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 0.5 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: <0.000190% CI: [2.96, 5.97]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 1 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: <0.000190% CI: [4.32, 7.33]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 2 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: <0.000190% CI: [2.58, 5.59]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 3 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.005990% CI: [1.02, 4.03]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 4 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.006390% CI: [1, 4.01]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 8 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.113890% CI: [-0.06, 2.95]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 12 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.697690% CI: [-1.86, 1.15]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 24 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.020890% CI: [-3.62, -0.61]Repeated Measures Model
Secondary
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.
Time frame: 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose
Population: ECG analysis population included all participants randomized and treated who had at least 1 post-dose ECG measurement in at least 1 period. This outcome measure was planned not to be analyzed for reporting group: Moxifloxacin 400 mg.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Moxifloxacin 400 mg | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 0.5 Hour | 171.59 Msec | Standard Error 0.9261 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 1 Hour | 171.15 Msec | Standard Error 0.9261 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 2 Hours | 170.43 Msec | Standard Error 0.9261 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 3 Hours | 169.86 Msec | Standard Error 0.9261 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 4 Hours | 170.59 Msec | Standard Error 0.9261 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 8 Hours | 164.86 Msec | Standard Error 0.9261 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 12 Hours | 166.08 Msec | Standard Error 0.9261 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 24 Hours | 172.09 Msec | Standard Error 0.9261 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 2 Hours | 169.72 Msec | Standard Error 0.9361 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 12 Hours | 165.48 Msec | Standard Error 0.9361 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 3 Hours | 169.34 Msec | Standard Error 0.9361 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 4 Hours | 169.22 Msec | Standard Error 0.9361 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 8 Hours | 165.25 Msec | Standard Error 0.9361 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 0.5 Hour | 170.52 Msec | Standard Error 0.9361 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 1 Hour | 169.28 Msec | Standard Error 0.9361 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 24 Hours | 169.50 Msec | Standard Error 0.9361 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 2 Hours | 171.60 Msec | Standard Error 0.9358 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 1 Hour | 172.09 Msec | Standard Error 0.9358 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 0.5 Hour | 172.24 Msec | Standard Error 0.9358 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 3 Hours | 170.85 Msec | Standard Error 0.9358 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 12 Hours | 166.49 Msec | Standard Error 0.9358 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 8 Hours | 167.31 Msec | Standard Error 0.9358 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 4 Hours | 171.16 Msec | Standard Error 0.9358 |
| Placebo | Time-Matched Mean Difference in PR Interval for PF-04447943 and Placebo | 24 Hours | 171.57 Msec | Standard Error 0.9358 |
Comparison: PF-04447943 25 mg versus Placebo, 0.5 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.57690% CI: [-2.53, 1.25]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 1 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.412690% CI: [-2.83, 0.95]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 2 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.308590% CI: [-3.06, 0.72]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 3 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.388990% CI: [-2.88, 0.9]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 4 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.619290% CI: [-2.46, 1.32]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 8 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.033290% CI: [-4.34, -0.56]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 12 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.722490% CI: [-2.3, 1.48]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 24 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.650790% CI: [-1.37, 2.41]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 0.5 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.136690% CI: [-3.62, 0.18]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 1 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.015390% CI: [-4.71, -0.91]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 2 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.10490% CI: [-3.78, 0.02]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 3 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.192490% CI: [-3.41, 0.4]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 4 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.092890% CI: [-3.84, -0.04]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 8 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.074590% CI: [-3.96, -0.16]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 12 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.383690% CI: [-2.91, 0.9]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 24 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.073490% CI: [-3.97, -0.17]Repeated Measures Model
Secondary
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.
Time frame: 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose
Population: ECG analysis population included all participants randomized and treated who had at least 1 post-dose ECG measurement in at least 1 period. The outcome measure was planned not to be analyzed for reporting group: Moxifloxacin 400 mg.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Moxifloxacin 400 mg | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 1 Hour | 90.51 Msec | Standard Error 0.5481 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 2 Hours | 90.89 Msec | Standard Error 0.5481 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 3 Hours | 89.36 Msec | Standard Error 0.5481 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 4 Hours | 89.84 Msec | Standard Error 0.5481 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 8 Hours | 89.14 Msec | Standard Error 0.5481 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 12 Hours | 89.61 Msec | Standard Error 0.5481 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 24 Hours | 89.31 Msec | Standard Error 0.5481 |
| Moxifloxacin 400 mg | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 0.5 Hour | 90.76 Msec | Standard Error 0.5481 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 8 Hours | 88.22 Msec | Standard Error 0.5547 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 1 Hour | 89.18 Msec | Standard Error 0.5547 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 4 Hours | 88.95 Msec | Standard Error 0.5547 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 0.5 Hour | 89.28 Msec | Standard Error 0.5547 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 2 Hours | 89.14 Msec | Standard Error 0.5547 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 12 Hours | 89.09 Msec | Standard Error 0.5547 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 24 Hours | 88.61 Msec | Standard Error 0.5547 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 3 Hours | 89.31 Msec | Standard Error 0.5547 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 12 Hours | 89.58 Msec | Standard Error 0.5544 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 24 Hours | 89.23 Msec | Standard Error 0.5544 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 4 Hours | 91.02 Msec | Standard Error 0.5544 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 8 Hours | 88.94 Msec | Standard Error 0.5544 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 3 Hours | 89.39 Msec | Standard Error 0.5544 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 1 Hour | 90.37 Msec | Standard Error 0.5544 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 0.5 Hour | 89.96 Msec | Standard Error 0.5544 |
| Placebo | Time-Matched Mean Difference in QRS Interval for PF-04447943 and Placebo | 2 Hours | 89.88 Msec | Standard Error 0.5544 |
Comparison: PF-04447943 25 mg versus Placebo, 0.5 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.258890% CI: [-0.36, 1.96]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 1 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.846590% CI: [-1.03, 1.3]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 2 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.150290% CI: [-0.15, 2.18]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 3 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.9790% CI: [-1.19, 1.14]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 4 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.094790% CI: [-2.34, -0.02]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 8 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.775990% CI: [-0.96, 1.36]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 12 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.964990% CI: [-1.13, 1.19]Repeated Measures Model
Comparison: PF-04447943 25 mg versus Placebo, 24 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.903490% CI: [-1.08, 1.25]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 0.5 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.339190% CI: [-1.85, 0.49]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 1 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.094890% CI: [-2.35, -0.02]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 2 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.295990% CI: [-1.91, 0.43]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 3 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.916190% CI: [-1.24, 1.09]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 4 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.003690% CI: [-3.24, -0.91]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 8 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.306390% CI: [-1.89, 0.44]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 12 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.491890% CI: [-1.65, 0.68]Repeated Measures Model
Comparison: PF-04447943 100 mg versus Placebo, 24 Hour: P-value was derived from repeated measures model with sequence, period, time, treatment and time-by-treatment as fixed effects and participant within sequence as a random effect.p-value: 0.386290% CI: [-1.78, 0.55]Repeated Measures Model
Secondary
Time of Observed Maximum Plasma Concentration (Tmax) of PF-04447943
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose
Population: PK parameter analysis population included all enrolled participants treated with PF-04447943 and who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Moxifloxacin 400 mg | Time of Observed Maximum Plasma Concentration (Tmax) of PF-04447943 | 1.0 Hours | Full Range 27 |
| Placebo | Time of Observed Maximum Plasma Concentration (Tmax) of PF-04447943 | 1.02 Hours | — |