Clinical trial NCT02509117: First-In-Human Study Of Single And Multiple Ascending Doses Of PF-06751979
Official title: A Phase 1, Randomized, Double-blind, Sponsor-open, Placebo Controlled First-in-human Trial To Evaluate The Safety,Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-06751979 After Oral Administration Of Single And Multiple Ascending Doses To Healthy Adult And Elderly Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Alzheimer's disease
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-07-27
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to evaluate the safety, tolerability, PK and PD of PF-06751979 following oral doses in healthy adult and healthy elderly subjects.


Eligibility criteria: Inclusion Criteria:

* Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 55 years or between the ages of 60 and 85 years, inclusive.
* Body Mass Index (BMI) of 17.5 to 32 kg/m2; and a total body weight \>50 kg (110 lbs) at Screening.
* Evidence of a personally signed and dated informed consent document indicating that the subject or a legally acceptable representative has been informed of all pertinent aspects of the study.

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).
* Male subjects with partners currently pregnant; male subjects able to father children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
* Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol.
* Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
* Any severe acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Part A: Baseline up to 47 days; Part B and C: Baseline up to 29 days
measure: Number of Participants With Abnormal Physical Examinations Findings
timeFrame: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
measure: Number of Participants With Abnormal Neurological Examinations Findings
timeFrame: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
measure: Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline
timeFrame: Baseline
measure: Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7
timeFrame: Day 7
measure: Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14
timeFrame: Day 14
measure: Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19
timeFrame: Day 19
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
timeFrame: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
measure: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
timeFrame: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
measure: Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry
timeFrame: Day 1
Secondary outcomes:
measure: Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
measure: Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
measure: Part A: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
measure: Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(dn) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
measure: Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)(Dn) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
measure: Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)(Dn) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
measure: Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
measure: Part A: Plasma Decay Half-Life (t1/2) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
measure: Part A: Apparent Oral Clearance (CL/F) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
measure: Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
measure: Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14
measure: Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part B: Apparent Oral Clearance (CL/F) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau)(Dn) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14
measure: Part B: Peak-to-Trough Ratio (PTR) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 7, 14
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 14
measure: Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 at Day 7, 14
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part B: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
measure: Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau)
timeFrame: 0-24 hours on Day 14
measure: Part B: Percentage of Dose of PF-06751979 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%)
timeFrame: 0-24 hours on Day 14
measure: Part B: Renal Clearance of PF-06751979
timeFrame: 0-24 hours on Day 14
measure: Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14
timeFrame: Baseline, Day 14
measure: Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
measure: Part C: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hour post dose on Day 14
measure: Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part C: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau)(Dn) of PF-06751979
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14
measure: Part C: Apparent Oral Clearance (CL/F) of PF-06751979 on Day 14
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part C: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 on Day 14
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part C: Peak-to-Trough Ratio (PTR) of PF-06751979 at Day 14
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
measure: Part C: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 14
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
measure: Part C: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF 06751979 at Day 14
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
measure: Part C: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
measure: Part C: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14
timeFrame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
Other outcomes:
Locations:
city: Glendale
country: United States
facility: California Clinical Trials Medical Group, Inc
state: California
city: Glendale
country: United States
facility: Glendale Adventist Medical Center
state: California
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: