First-In-Human Study Of Single And Multiple Ascending Doses Of PF-06751979

NCT02509117 | Completed Phase 1 Results

• 1 other identifier: B8271001
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 2

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.

Conditions

Healthy Subjects

Keywords

Alzheimer's disease

Outcome Measures

Primary Outcomes (11)

• 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. Treatment-emergent were events between first dose of study drug up to the follow up visit (up to 47 days in Part A, 29 days in Part B and C), that were absent before treatment or that worsened relative to pretreatment state.

  Part A: Baseline up to 47 days; Part B and C: Baseline up to 29 days

• Number of Participants With Abnormal Physical Examinations Findings

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

  Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

• Number of Participants With Abnormal Neurological Examinations Findings

  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 A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

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

  Baseline

• Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on 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, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any self-injurious behavior, at day 7 were reported.

  Day 7

• Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on 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, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any self-injurious behavior, at Day 14 were reported.

  Day 14

• Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on 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, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any self-injurious behavior, at Day 19 were reported.

  Day 19

• Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

  Criteria for clinically significant ECG abnormalities: maximum PR interval \>=300 milliseconds (msec) and maximum PR interval increase from baseline (IFB): percent change (Pctchg) \>=25 percent (%) for baseline value of \>200 msec and Pctchg\>=50% for baseline value of \<=200 msec for PR interval, maximum QRS interval \>=140 msec and a maximum IFB: Pctchg\>=50%, maximum QTCF interval (Fridericia's Correction) of 450 msec to \<480 msec, 480 msec to \<500 msec or \>=500 msec and a maximum change of \<=30 change \<60 or \>=60 msec from baseline.

  Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

• Number of Participants With Laboratory Abnormalities

  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 (PT); PT 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)

  Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

• Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

  Following parameters were analyzed for examination of vital signs: supine systolic and diastolic blood pressure, pulse rate and body temperature.

  Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

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

  Continuous cardiac telemetry was conducted in participants. All abnormal cardiac rhythms were recorded and reviewed by the study physician for the presence of rhythms of potential clinical concern. In this outcome measure, number of participants who had cardiac rhythms of potential clinical concern (based on physician's discretion) were reported.

  Day 1

Secondary Outcomes (38)

• Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979

  predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 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

  predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

• Part A: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979

  predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

• Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(dn) of PF-06751979

  predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

• Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)(Dn) of PF-06751979

  predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

Study Arms (5)

Single Ascending Dose Cross-over

EXPERIMENTAL

Single Ascending Dose in 4-way cross-over design (PF-06751979/Placebo).

Drug: PF-06751979 single ascending dose; Drug: Placebo single dose

Multiple Ascending Dose PF-06751979

EXPERIMENTAL

Multiple dose administration to Healthy Subjects in parallel cohorts(PF-06751979)

Drug: PF-06751979 multiple ascending dose

Multiple Ascending Dose Placebo

PLACEBO COMPARATOR

Multiple dose administration to Healthy Subjects in parallel cohorts(Placebo)

Drug: Placebo multiple dose; Drug: PF-06751979 multiple dose

Multiple Dose Elderly PF-06751979

EXPERIMENTAL

Multiple dose administration to Healthy Elderly Subjects (PF-06751979)

Drug: PF-06751979 multiple dose

Multiple Dose Elderly Placebo

PLACEBO COMPARATOR

Multiple dose administration to Healthy Elderly Subjects (Placebo)

Drug: Placebo multiple dose

Interventions

PF-06751979 single ascending dose DRUG

PF-06751979 administered as a single dose (solution/suspension) in cross-over fashion. Each subject may receive up to 4 study treatments (placebo and up to 3 doses of PF-06751979). The dose levels are 3 mg, 12 mg, 40 mg, 160 mg.

Single Ascending Dose Cross-over

Placebo single dose DRUG

Matched Placebo solution/suspension administered as single dose.

Single Ascending Dose Cross-over

PF-06751979 multiple ascending dose DRUG

PF-06751979 (solution/suspension) administered daily for 14 consecutive days to parallel cohorts. The dose levels are 5 mg, 15 mg, 50 mg.

Multiple Ascending Dose PF-06751979

Placebo multiple dose DRUG

Matched Placebo (solution/suspension)administered daily for 14 consecutive days.

Multiple Ascending Dose Placebo; Multiple Dose Elderly Placebo

PF-06751979 multiple dose DRUG

PF-06751979 (solution/suspension) administered daily for 14 consecutive days. The dose level is 50 mg.

Multiple Dose Elderly PF-06751979

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

California Clinical Trials Medical Group, Inc

Glendale, California, 91206, United States

Location

Glendale Adventist Medical Center

Glendale, California, 91206, United States

Location

Related Links

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

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquires@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2015
• First Posted: July 27, 2015
• Study Start: July 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: November 1, 2018
• Results First Posted: November 1, 2018

Record last verified: 2018-02

Locations

US (2)