A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Repeat Doses of PF-06372865 in Healthy Subjects

NCT03351751 | Completed Phase 1 FDA Drug

• 1 other identifier: B7431011
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple repeat oral doses of PF-06372865 in healthy adult subjects.

Conditions

Healthy Volunteers

Keywords

PF-06372865; Safety; Tolerability; Pharmacokinetics; Multiple dose; Healthy subjects

Outcome Measures

Primary Outcomes (11)

• Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)

  Treatment-related AEs are any untoward medical occurrences attributed to study drug in a participant who received study drug. A serious adverse events (SAE) is 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 are events between first dose of study drug and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to study drug is assessed by the investigator. Participants with multiple occurrences of an AE within a category are counted once within the category.

  Baseline up to 28-35 days after last dose of study medication

• Change From Baseline in Vital Signs

  Measurement of systolic and diastolic blood pressure and pulse rate

  0, 1, 2, 4, 8, and 12 hours post-dose on Days 1 and 21; also 0 and 2 hours post-dose on Days 4, 8, 11, 14, and 17

• Change From Baseline in Electrocardiogram (ECG) Parameters

  Measurement of the following ECG parameters: QT interval, QTcF, PR interval, RR interval, QRS interval, and heart rate.

  0, 1, 2, 4, 8, and 12 hours post-dose on Days 1 and 21; also 0 and 2 hours post-dose on Days 4, 8, 11, 14, and 17

• Number of Participants With Clinical Laboratory Abnormalities

  Lab tests include: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid albumin, total protein, folate); urinalysis (decimal logarithm of reciprocal of hydrogen ion activity \[pH\], glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy); other (follicle stimulating hormone, urine drug screening, hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, human immunodeficiency virus).

  Baseline up to 7-10 days after last dose of study medication

• Maximum Observed Plasma Concentration (Cmax) for PF-06372865 on Day 1

  Maximum observed plasma concentration

  0, 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06372865 on Day 1

  Time to reach maximum observed plasma concentration

  0, 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose

• Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for PF-06372865 on Day 1

  Area under the concentration curve from time 0 to end of the dosing interval. The dosing interval is 12 hours.

  0, 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose

• Maximum Observed Plasma Concentration (Cmax) for PF-06372865 on Day 21

  Maximum observed plasma concentration

  0, 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06372865 on Day 21

  Time to reach maximum observed plasma concentration

  0, 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose

• Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for PF-06372865 on Day 21

  Area under the concentration curve from time 0 to end of the dosing interval. The dosing interval is 12 hours.

  0, 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose

• Plasma Half-Life (t1/2)

  Time for the plasma concentration to decrease by one half.

  0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Day 21

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Subjects receiving placebo

Drug: Placebo

PF-06372865

EXPERIMENTAL

Subjects receiving PF-06372865

Drug: PF-06372865

Interventions

Placebo DRUG

Placebo

Placebo

PF-06372865 DRUG

PF-06372865

PF-06372865

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy female subjects of non-childbearing potential and/or male subjects between the ages of 18 and 55 years
• Body mass index of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb)
• Subjects who are willing and able to comply with all study procedures (including being able to swallow up to 8 tablets/dose or 16 tablets/day)
• For optional Japanese subjects only: Japanese subjects currently residing in the United States who have 4 biologic 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
• Subjects with history of sleep apnea
• Any condition possibly affecting drug absorption (eg, gastrectomy)
• Positive urine drug test
• History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males
• Treatment with an investigational drug within 30 days or 5 half-lives of the first dose of PF-06372865 (whichever is longer)
• Clinically significant orthostatic hypotension at screening or screening supine BP \>=140 mm Hg (systolic) or \>=90 mm Hg (diastolic), following at least 5 minutes of supine rest
• Screening supine 12-lead ECG demonstrating a corrected QT (QTc) interval \>450 msec or a QRS interval \>120 msec
• Subjects with any of the following abnormalities in clinical laboratory tests at screening: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level \>=1.5x upper limit of normal (ULN); total bilirubin level \>=1.5x ULN; subjects with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is \<=ULN
• Fertile male subjects who are unwilling or unable to use a highly effective method of contraception for the duration of the study and for at least 60 days after the last dose of PF-06372865
• Male subjects whose partners are currently pregnant
• Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of PF-06372865
• Use of herbal supplements or hormone replacement therapy within 28 days prior to the first dose of PF-06372865
• Blood donation of approximately 1 pint (500 mL) or more within 60 days prior to dosing
• History of sensitivity to heparin or heparin-induced thrombocytopenia

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

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

Interventions

PF-06372865

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2017
• First Posted: November 24, 2017
• Study Start: November 8, 2017
• Primary Completion: February 28, 2018
• Study Completion: February 28, 2018
• Last Updated: June 3, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)