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PF-06751979 single dose

Phase 1

Healthy Subjects | Small molecule | Other |Pfizer, Inc.|Last Updated: Sep 17, 2018

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindCONTROLLEDBiomarker
Total Trials1
Total Enrollment46
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02793232Clinical Trial In Healthy Volunteers And Health Elderly Volunteers To Evaluate The Safety, Tolerability And Blood Concentration After Single And Multiple Escalating Oral Doses Of PF-06751979.PHASE1 COMPLETED 46Jun 13, 2016Jan 5, 2017Sep 17, 20181 Belgium
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Study Endpoints
Primary Endpoints
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 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. Treatment emergent were events between first dose of study drug and up to the follow up visit (up to 36 days in Part A, 49 days in Part B and C), that were absent before treatment or that worsened relative to pretreatment state.

Number of Participants With Abnormal Physical Examinations Findings
Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days

Full physical examination included head, ears, eyes, nose, mouth, skin, heart, lung, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Abnormality in physical examinations was based on investigator's discretion.

Number of Participants With Abnormal Neurological Examinations Findings
Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days

The neurological examination included the assessment of higher cortical function, the cranial nerves, motor function, deep tendon reflexes, sensory exam, and coordination and gait. Abnormality in neurological examinations was based on investigator's discretion.

Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline
Baseline

C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome measure, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any non-suicidal self-injurious behavior, at baseline were reported.

Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 7
Day 7

C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome measure, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any non-suicidal self-injurious behavior, at Day 7 were reported.

Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 14
Day 14

C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome measure, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any non-suicidal self-injurious behavior, at Day 14 were reported.

Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 19
Day 19

C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome measure, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any non-suicidal self-injurious behavior, at Day 19 were reported.

Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days

Criteria for abnormal values of ECG parameters: maximum pulse rate (PR) interval greater than or equal to (\>=)300 milliseconds (msec); maximum PR interval increase from baseline (IFB): \>=25 percent (%) when baseline was greater than (\>)200 msec; or \>=50 % when baseline was greater than (\>)200 msec, maximum QRS interval \>=140 msec and QRS interval IFB: \>=50%. QT interval using Fridericia's correction (QTcF) ranges from 450 msec to maximum less than (\<)480 msec, less than or equal to (\<=) 480 msec to maximum \<500 msec and maximum \>=500 msec, maximum QTcF interval IFB range from \<=30 to \<60 msec and maximum \>=60 msec. Only categories which included at least 1 participant with abnormality are reported in this outcome measure.

Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry
Day 1

In all Periods of Part A, continuous cardiac monitoring was maintained for 8 hours (or longer if considered clinically necessary by the investigator) following dose administration on Day 1. All abnormal cardiac rhythms were recorded and reviewed by the study physician for the presence of rhythms of potential clinical concern.

Number of Participants With Vital Sign Abnormalities
Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days

Criteria for vital signs abnormalities: systolic blood pressure (SBP) \<90 millimeter of mercury (mmHg), diastolic blood pressure (DBP) \<50 mmHg, supine pulse rate \<40 beats per minute (bpm). Maximum IFB in Supine SBP \>=30 mmHg, Maximum decrease from baseline (DFB) in Supine SBP \>=30 mmHg, maximum DFB in Supine DBP \>=20 mmHg.

Number of Participants With Laboratory Abnormalities
Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days

Abnormalities criteria:hematology(hemoglobin; hematocrit; RBC\<0.8\*lower limit of normal \[LLN\]; platelets\<0.5\*LLN,\>1.75\*upper limit of normal \[ULN\]; WBC\<0.6\*LLN,\>1.5\*ULN; lymphocytes; neutrophils; basophils; eosinophils; monocytes\<0.8\*LLN,\>1.2\*ULN; coagulation(prothrombin ratio\>1.1\*ULN), liver(bilirubin\>1.5\*ULN; aspartate aminotransferase; alanine aminotransferase; alkaline phosphatase; gamma GT\>0.3\*ULN; protein; albumin\<0.8\*LLN,\>1.2\*ULN); renal(blood urea nitrogen, creatinine\>1.3\*ULN; uric acid\>1.2\*ULN); electrolytes(sodium\<0.95\*LLN,\>1.05\*ULN; potassium; chloride; calcium; bicarbonate\<0.9\*LLN,\>1.1\*ULN), chemistry(glucose\<0.6\*LLN,\>1.5\* ULN); urinalysis(pH \<4.5,\>8; glucose, ketones, protein, blood, urobilinogen, nitrite, bilirubin, leukocyte, esterase\>1; WBC; bacteria\>=20, epithelial cells\>=6; granular casts, hyaline casts, red cell casts, white cell casts\>1; lipids(cholesterol\[C\], LDL-C\>1.3\*ULN; HDL-C\<0.8\*LLN, triglycerides\>1.3\*ULN); hormones(T4, T3, T4, TSH\<0.8\*LLN,\>1.2\*ULN).

Secondary Endpoints
Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979
pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Part A: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979
pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelCROSSOVER
PurposeBASIC_SCIENCE
Treatment Arms
ArmTypeDescription
Single Ascending Dose CrossoverEXPERIMENTALSingle Ascending Dose in 4-way cross-over design (PF-06751979/Placebo).
Multiple Ascending DoseEXPERIMENTALMultiple dose administration to Healthy Subjects in parallel cohorts (PF-06751979).
Multiple Dose ElderlyEXPERIMENTALMultiple dose administration to Healthy Elderly Subjects (PF-06751979). This cohort is optional.
Interventions
NameTypeDescription
PF-06751979 single doseDRUGPF-06751979 administered as a single dose suspension in cross-over fashion. Each subject may receive up to 4 study treatments (placebo and up to 3 doses of PF 06751979). The planned dose levels are 200 mg, 400 mg, 700 mg, 200 mg fed (these doses are subject to change based on emerging data).
Placebo single doseDRUGMatched Placebo suspension administered as single dose
PF-06751979 multiple ascending doseDRUGPF-06751979 suspension administered daily for 14 consecutive days to parallel cohorts. The planned dose levels are mg, 100 mg, 200 mg, 340 mg (these are subject to change based on emerging data).
Placebo multiple ascending doseDRUGMatched placebo suspension administered daily for 14 consecutive days.
PF-06751979 multiple doseDRUGPF-06751979 suspension administered daily for 14 consecutive days. The planned dose level is 340 mg (this is subject to change based on emerging data).
Placebo multiple elderly doseDRUGMultiple dose administration to Healthy Elderly Subjects (Placebo)
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Eligibility Criteria
Age Range18 Years — 85 Years
SexALL
Healthy VolunteersYes
Study Sites1

Inclusion Criteria: * Healthy female subjects of non childbearing potential and male subjects. * Body Mass Index (BMI) of 17.5 to 30.5 kg/m2 (32 kg/m2 for healthy elderly); and a total body weight \>50 kg (110 lbs) at Screening. * Evidence of a personally signed and dated informed consent document ...

Countries:Belgium
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