A Phase 1 interventional study of PF-06282999 and Placebo in Healthy, sponsored by Pfizer. Terminated at 2 sites in United States. Open to participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-08-02.
Sponsored by Pfizer · Phase 1, Interventional, and Basic science
An endotoxin challenge will be administered to healthy subjects to induce production of inflammatory markers. An investigational drug or placebo will be administered prior to the endotoxin challenge to assess the effect of the investigational drug on the markers of inflammation. Safety and tolerability will also be assessed.
The trial was terminated on 25 March 2015 due to safety concerns regarding the administration of endotoxin and because of the uncertain availability of future endotoxin lots.
Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Drug: PF-06282999 · Drug: Placebo · Other: LPS
Drug: PF-06282999 · Drug: Placebo · Other: LPS
Tablet, 125 mg, TID, 3 days, 1 of 2 periods
Tablet, 0 mg, TID, 3 days, 1 of 2 periods
IV bolus, 4 ng/kg, 1 day, QD, 2 of 2 periods
Also known as: Endotoxin
Tablet, 500 mg, BID, 3 days, 1 of 2 periods
Tablet, 0 mg, BID, 3 days, 1 of 2 periods
IV bolus, 4 ng/kg, 1 day, QD, 2 of 2 periods
Also known as: Endotoxin
Peak Myeloperoxidase (MPO) Activity Following Inflammatory Stimulus
MPO is a heme-containing peroxidase enzyme produced in the bone marrow and stored in the azurophilic granules of neutrophils, where it constitutes up to 5% of the cellular protein. Since PF-06282999 is a mechanism-based inactivator of MPO, it is of interest to evaluate the level of MPO activity in order to investigate the inhibition activity of PF-06282999.
Time frame: Days 1, 3-5
MPO Activity (Area Under the Concentration-time Profile From 0.5 to 2 Hours [AUC0.5-2hrs]) Following Inflammatory Stimulus
MPO is a heme-containing peroxidase enzyme produced in the bone marrow and stored in the azurophilic granules of neutrophils, where it constitutes up to 5% of the cellular protein. Since PF-06282999 is a mechanism-based inactivator of MPO, it is of interest to evaluate the level of MPO activity in order to investigate the inhibition activity of PF-06282999.
Time frame: Days 1, 3-5
MPO Activity (Area Under the Concentration-time Profile From 0 to 2 Hours [AUC0-2hrs]) Following Inflammatory Stimulus
MPO is a heme-containing peroxidase enzyme produced in the bone marrow and stored in the azurophilic granules of neutrophils, where it constitutes up to 5% of the cellular protein. Since PF-06282999 is a mechanism-based inactivator of MPO, it is of interest to evaluate the level of MPO activity in order to investigate the inhibition activity of PF-06282999.
Time frame: Days 1, 3-5
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs
An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs comprised both SAEs and non-SAEs. 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. TEAEs were defined as newly occurring AEs or those worsening after first dose. Due to early termination of the study, only AE data from partial enrollment are reflected and comparisons between treatment arms should not be attempted.
Time frame: From Day 0 till approximately 7-10 days following the last dose of PF-06282999/Placebo in Period 2 (up to approximately 2 months)
Number of Participants With Laboratory Test Abnormalities
Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy). Due to early termination of the study, only laboratory data from partial enrollment are reflected and comparisons between treatment arms should not be attempted.
Time frame: Baseline up to 7-10 days following the last dose of PF-06282999/Placebo in Period 2
Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria
Categorical summarization criteria in vital signs included: sitting, supine, and standing systolic blood pressure (SBP) of less than (\<)90 millimeters of mercury (mm Hg) or change (increase \[inc\] or decrease \[dec\]) in sitting, supine and standing SBP of more than or equal to (\>=)30 mm Hg; supine, sitting, and standing diastolic blood pressure (DBP) of \<50 mm Hg or change (inc or dec) in sitting, supine, and standing DBP of \>=20 mm Hg; supine and sitting pulse rate (PR) of \<40 or more than (\>)120 beats per minute (bpm); and standing PR of \<40 or \>140 bpm. Due to early termination of the study, only vital signs data from partial enrollment are reflected and comparisons between treatment arms should not be attempted.
Time frame: Screening and Days 1-2, 4-5, and approximately 7-10 days following the last dose of PF-06282999/Placebo in Period 2 for orthostatic (orth) measurements; Day 3 for supine measurements
Number of Participants With Electrocardiogram (ECG) Values Meeting Categorical Summarization Criteria
Criteria for ECG (12-lead) values meeting categorical summarization criteria were: the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization (PR interval \>=300 milliseconds (msec) and increase from baseline \>=25/50%; time from the beginning of the ECG Q wave to the end of the S wave corresponding to ventricular depolarization (QRS) interval \>=140 msec and increase of \>=50%; the beginning of the Q wave to the end of the T wave corresponding to electrical systole (QT) interval \>=500 msec; QT corrected using the Fridericia formula (QTcF) of 450 to \<480 msec, 480 to \<500 msec, and \>=500 msec, or an increase of 30 to \<60 msec or \>=60 msec. Due to early termination of the study, only ECG data from partial enrollment are reflected and comparisons between treatment arms should not be attempted.
Time frame: Screening; Days 1-5 and approximately 7-10 days following the last dose of PF-06282999/Placebo in Period 2
Number of Participants With Abnormal Urinary Biomarker Values
Urinary biomarkers included albumin, neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin-C.
Time frame: Days 1-3 prior to dosing with PF-06282999/Placebo; and Days 4-5
Concentrations of TNF-alpha, IL-1 Beta, IL-6, IL-8, and hsCRP
The effect of multiple oral doses of PF-06282999 on inflammatory biomarkers was a secondary objective in this study. The biomarkers are tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and high-sensitivity C-reactive protein (hsCRP).
Time frame: Days 1, 3, and 4
Peak (AUC0.5-2hours and AUC0-2hours) of MPO Activity/MPO Mass
MPO is a heme-containing peroxidase enzyme produced in the bone marrow and stored in the azurophilic granules of neutrophils, where it constitutes up to 5% of the cellular protein. Since PF-06282999 is a mechanism-based inactivator of MPO, it is of interest to evaluate the level of MPO activity in order to investigate the inhibition activity of PF-06282999.
Time frame: Days 1, 3-5
Maximum Plasma Concentration (Cmax) of PF-06282999
Time frame: Day 3
Area Under the Concentration-time Profile From Time 0 to End of Dosing Interval, Tau (AUCtau) of PF-06282999
Time frame: Day 3
Time to Cmax (Tmax) of PF-06282999
Time frame: Day 3
| Milestone | PF-06282999 125 mg TID Followed by Placebo | Placebo Followed by PF-06282999 125 mg TID | PF-06282999 500 mg BID Followed by Placebo | Placebo Followed by PF-06282999 500 mg BID |
|---|---|---|---|---|
| Started | 6 | 8 | 5 | 4 |
| Received at least one dose of drug | 6 | 8 | 5 | 4 |
| Completed | 6 | 8 | 5 | 4 |
| Not completed | 0 | 0 | 0 | 0 |
| Milestone | PF-06282999 125 mg TID Followed by Placebo | Placebo Followed by PF-06282999 125 mg TID | PF-06282999 500 mg BID Followed by Placebo | Placebo Followed by PF-06282999 500 mg BID |
|---|---|---|---|---|
| Started | 6 | 8 | 5 | 4 |
| Completed | 4 | 4 | 3 | 2 |
| Not completed | 2 | 4 | 2 | 2 |
| Withdrew: Study terminated by sponsor | 1 | 3 | 2 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 | 0 | 0 |
| Withdrew: Did not meet entrance criteria | 1 | 0 | 0 | 0 |
| Withdrew: Adverse event | 0 | 0 | 0 | 1 |
| Milestone | PF-06282999 125 mg TID Followed by Placebo | Placebo Followed by PF-06282999 125 mg TID | PF-06282999 500 mg BID Followed by Placebo | Placebo Followed by PF-06282999 500 mg BID |
|---|---|---|---|---|
| Started | 4 | 4 | 3 | 2 |
| Completed | 4 | 4 | 1 | 0 |
| Not completed | 0 | 0 | 2 | 2 |
| Withdrew: Study terminated by sponsor | 0 | 0 | 2 | 2 |
MPO is a heme-containing peroxidase enzyme produced in the bone marrow and stored in the azurophilic granules of neutrophils, where it constitutes up to 5% of the cellular protein. Since PF-06282999 is a mechanism-based inactivator of MPO, it is of interest to evaluate the level of MPO activity in order to investigate the inhibition activity of PF-06282999.
No measurements were reported for this outcome.
MPO is a heme-containing peroxidase enzyme produced in the bone marrow and stored in the azurophilic granules of neutrophils, where it constitutes up to 5% of the cellular protein. Since PF-06282999 is a mechanism-based inactivator of MPO, it is of interest to evaluate the level of MPO activity in order to investigate the inhibition activity of PF-06282999.
No measurements were reported for this outcome.
MPO is a heme-containing peroxidase enzyme produced in the bone marrow and stored in the azurophilic granules of neutrophils, where it constitutes up to 5% of the cellular protein. Since PF-06282999 is a mechanism-based inactivator of MPO, it is of interest to evaluate the level of MPO activity in order to investigate the inhibition activity of PF-06282999.
No measurements were reported for this outcome.
An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs comprised both SAEs and non-SAEs. 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. TEAEs were defined as newly occurring AEs or those worsening after first dose. Due to early termination of the study, only AE data from partial enrollment are reflected and comparisons between treatment arms should not be attempted.
| participants | PF-06282999 125 mg TID | Placebo | PF-06282999 500 mg BID |
|---|---|---|---|
| Participants with TEAEs | 10 | 17 | 5 |
| Participants with SAEs | 0 | 0 | 0 |
| Participants discontinued permanently due to TEAEs | 0 | 1 | 0 |
Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy). Due to early termination of the study, only laboratory data from partial enrollment are reflected and comparisons between treatment arms should not be attempted.
| participants | PF-06282999 125 mg TID | Placebo | PF-06282999 500 mg BID |
|---|---|---|---|
| Number of Participants With Laboratory Test Abnormalities | 5 | 8 | 5 |
Categorical summarization criteria in vital signs included: sitting, supine, and standing systolic blood pressure (SBP) of less than (\<)90 millimeters of mercury (mm Hg) or change (increase \[inc\] or decrease \[dec\]) in sitting, supine and standing SBP of more than or equal to (\>=)30 mm Hg; supine, sitting, and standing diastolic blood pressure (DBP) of \<50 mm Hg or change (inc or dec) in sitting, supine, and standing DBP of \>=20 mm Hg; supine and sitting pulse rate (PR) of \<40 or more than (\>)120 beats per minute (bpm); and standing PR of \<40 or \>140 bpm. Due to early termination of the study, only vital signs data from partial enrollment are reflected and comparisons between treatment arms should not be attempted.
| participants | PF-06282999 125 mg TID | Placebo | PF-06282999 500 mg BID |
|---|---|---|---|
| Orthostatic SBP <90 mm Hg (n=0,1,0) | 0 | 0 | 0 |
| Orthostatic DBP <50 mm Hg (n=0,1,0) | 0 | 0 | 0 |
| Orthostatic PR <40 bpm (n=0,1,0) | 0 | 0 | 0 |
| Orthostatic supine SBP <90 mm Hg (n=10,18,7) | 0 | 0 | 0 |
| Orthostatic sitting SBP <90 mm Hg (n=1,0,0) | 0 | 0 | 0 |
| Orthostatic standing SBP <90 mm Hg (n=10,17,6) | 0 | 0 | 0 |
| Orthostatic supine DBP <50 mm Hg (n=10,18,7) | 0 | 0 | 0 |
| Orthostatic sitting DBP <50 mm Hg (n=1,0,0) | 0 | 0 | 0 |
| Orthostatic standing DBP <50 mm Hg (n=10,17,6) | 0 | 0 | 1 |
| Orthostatic supine PR <40 bpm (n=10,18,7) | 0 | 0 | 0 |
| Orthostatic supine PR >120 bpm (n=10,18,7) | 0 | 0 | 0 |
| Orthostatic sitting PR <40 bpm (n=1,0,0) | 0 | 0 | 0 |
| Orthostatic standing PR <40 bpm (n=10,17,6) | 0 | 0 | 0 |
| Orthostatic standing PR >140 bpm (n=10,17,6) | 0 | 0 | 0 |
| Supine SBP <90 mm Hg (n=10,17,5) | 0 | 2 | 0 |
| Supine DBP <50 mm Hg (n=10,17,5) | 1 | 2 | 1 |
| Supine PR <40 bpm (n=10,17,5) | 0 | 0 | 0 |
| Supine PR >120 bpm (n=10,17,5) | 1 | 4 | 0 |
| Increase in orth supine SBP >=30 mm Hg (n=10,18,7) | 1 | 0 | 0 |
| Inc in orth standing SBP >=30 mm Hg (n=10,17,6) | 0 | 0 | 0 |
| Inc in orth supine DBP >=20 mm Hg (n=10,18,7) | 0 | 0 | 0 |
| Inc in orth standing DBP >=20 mm Hg (n=10,17,6) | 0 | 0 | 0 |
| Inc in supine SBP >=30 mm Hg (n=10,17,5) | 0 | 4 | 1 |
| Inc in supine DBP >=20 mm Hg (n=10,17,5) | 1 | 3 | 0 |
| Dec in orth supine SBP >=30 mm Hg (n=10,18,7) | 0 | 1 | 0 |
| Dec in orth standing SBP >=30 mm Hg (n=10,17,6) | 0 | 2 | 0 |
| Dec in orth supine DBP >=20 mm Hg (n=10,18,7) | 1 | 0 | 1 |
| Dec in orth standing DBP >=20 mm Hg (n=10,17,6) | 0 | 1 | 1 |
| Dec in supine SBP >=30 mm Hg (n=10,17,5) | 1 | 1 | 1 |
| Dec in supine DBP >=20 mm Hg (n=10,17,5) | 1 | 4 | 2 |
Criteria for ECG (12-lead) values meeting categorical summarization criteria were: the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization (PR interval \>=300 milliseconds (msec) and increase from baseline \>=25/50%; time from the beginning of the ECG Q wave to the end of the S wave corresponding to ventricular depolarization (QRS) interval \>=140 msec and increase of \>=50%; the beginning of the Q wave to the end of the T wave corresponding to electrical systole (QT) interval \>=500 msec; QT corrected using the Fridericia formula (QTcF) of 450 to \<480 msec, 480 to \<500 msec, and \>=500 msec, or an increase of 30 to \<60 msec or \>=60 msec. Due to early termination of the study, only ECG data from partial enrollment are reflected and comparisons between treatment arms should not be attempted.
| participants | PF-06282999 125 mg TID | Placebo | PF-06282999 500 mg BID |
|---|---|---|---|
| PR interval >=300 msec | 0 | 0 | 0 |
| QRS >=140 msec | 0 | 0 | 0 |
| QT >=500 msec | 0 | 0 | 0 |
| QTcF 450 to <480 msec | 0 | 2 | 0 |
| QTcF 480 to <500 msec | 0 | 0 | 0 |
| QTcF >=500 msec | 0 | 2 | 0 |
| PR interval increase >=25/50% | 0 | 0 | 0 |
| QRS increase >=50% | 0 | 0 | 0 |
| QTcF increase 30 to <60 msec | 0 | 3 | 1 |
| QTcF increase >=60 msec | 1 | 2 | 0 |
Urinary biomarkers included albumin, neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin-C.
No measurements were reported for this outcome.
The effect of multiple oral doses of PF-06282999 on inflammatory biomarkers was a secondary objective in this study. The biomarkers are tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and high-sensitivity C-reactive protein (hsCRP).
No measurements were reported for this outcome.
MPO is a heme-containing peroxidase enzyme produced in the bone marrow and stored in the azurophilic granules of neutrophils, where it constitutes up to 5% of the cellular protein. Since PF-06282999 is a mechanism-based inactivator of MPO, it is of interest to evaluate the level of MPO activity in order to investigate the inhibition activity of PF-06282999.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Collected over Baseline through and including 28 calendar days after the last administration of the investigational product, up to approximately 2 months.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| PF-06282999 125 mg TID | — | 0/10 (0%) | 10/10 (100%) |
| Placebo | — | 0/19 (0%) | 17/19 (89.5%) |
| PF-06282999 500 mg BID | — | 0/7 (0%) | 5/7 (71.4%) |
| Event | PF-06282999 125 mg TID | Placebo | PF-06282999 500 mg BID |
|---|---|---|---|
| PyrexiaGeneral disorders | 10/10 | 13/19 | 3/7 |
| ChillsGeneral disorders | 8/10 | 11/19 | 3/7 |
| HeadacheNervous system disorders | 8/10 | 13/19 | 4/7 |
| TachycardiaCardiac disorders | 7/10 | 13/19 | 4/7 |
| MyalgiaMusculoskeletal and connective tissue disorders | 6/10 | 9/19 | 3/7 |
| NauseaGastrointestinal disorders | 3/10 | 5/19 | 3/7 |
| VomitingGastrointestinal disorders | 2/10 | 1/19 | 2/7 |
| Dermatitis contactSkin and subcutaneous tissue disorders | 1/10 | 3/19 | 0/7 |
| HypotensionVascular disorders | 0/10 | 3/19 | 1/7 |
| Body temperature increasedInvestigations | 0/10 | 0/19 | 1/7 |
All 23 participants who were randomized to study treatment and who received at least 1 dose of study drug were included in the baseline analysis.
| Age, Continuous(years) | All Participants |
|---|---|
| Mean | 32.2 ± 5.3 |
| Sex: Female, Male(Participants) | All Participants |
|---|---|
| Female | 0 |
| Male | 23 |
This study is terminated, as verified in Jun 2016. You cannot join it, but the record below documents what was studied.
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