Clinical 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.

NCT02793232 | Completed Phase 1 Results

• 2 other identifiers: B82710042016-000325-39
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test the safety, tolerability and blood concentrations of single and multiple oral doses of PF-06751979 in health subjects and healthy elderly subjects. PF-06751979 is being developed for the treatment of Alzheimer's disease.

Conditions

Healthy Subjects

Keywords

Safety; Tolerability; Pharmacokinetics; 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 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.

  Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days

• Number of Participants With Abnormal Physical Examinations Findings

  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.

  Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 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 36 days; Part B and C: Baseline up to 49 days

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

  Day 7

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

  Day 14

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

  Day 19

• Number of Participants With Abnormal Electrocardiogram (ECG) Findings

  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: Baseline up to 36 days; Part B and C: Baseline up to 49 days

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

  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.

  Day 1

• Number of Participants With Vital Sign Abnormalities

  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.

  Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 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 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 36 days; Part B and C: Baseline up to 49 days

Secondary Outcomes (38)

• 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

• Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) 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: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) 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

Study Arms (3)

Single Ascending Dose Crossover

EXPERIMENTAL

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

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

Multiple Ascending Dose

EXPERIMENTAL

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

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

Multiple Dose Elderly

EXPERIMENTAL

Multiple dose administration to Healthy Elderly Subjects (PF-06751979). This cohort is optional.

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

Interventions

PF-06751979 single dose DRUG

PF-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).

Single Ascending Dose Crossover

Placebo single dose DRUG

Matched Placebo suspension administered as single dose

Single Ascending Dose Crossover

PF-06751979 multiple ascending dose DRUG

PF-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).

Multiple Ascending Dose

Placebo multiple ascending dose DRUG

Matched placebo suspension administered daily for 14 consecutive days.

Multiple Ascending Dose

PF-06751979 multiple dose DRUG

PF-06751979 suspension administered daily for 14 consecutive days. The planned dose level is 340 mg (this is subject to change based on emerging data).

Multiple Dose Elderly

Placebo multiple elderly dose DRUG

Multiple dose administration to Healthy Elderly Subjects (Placebo)

Multiple Dose Elderly

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 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 indicating that the subject or a legally acceptable representative has been informed of all pertinent aspects of the study.
• Additional criterion for subjects of Japanese descent who may be enrolled in Part B (multiple ascending dose cohorts in healthy subjects): Japanese subjects who have four Japanese grandparents born in Japan.

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 the 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 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 (1)

Pfizer Clinical Research Unit

Brussels, B-1070, Belgium

Location

Related Links

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

MeSH Terms

Conditions

Alzheimer Disease

Interventions

PF-06751979

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_Inquiries@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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2016
• First Posted: June 8, 2016
• Study Start: June 13, 2016
• Primary Completion: January 5, 2017
• Study Completion: January 5, 2017
• Last Updated: September 17, 2018
• Results First Posted: September 17, 2018

Record last verified: 2017-12

Locations

BE (1)