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

Healthy Volunteers Clinical Trial

Official title:

A PHASE 1, DOUBLE-BLIND (3RD PARTY OPEN), RANDOMIZED, PLACEBO-CONTROLLED, DOSE ESCALATION STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF REPEAT ORAL DOSES OF PF-06372865 IN HEALTHY ADULT SUBJECTS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03351751
• Other study ID #: B7431011
• Status: Completed
• Phase: Phase 1
• Start date: November 8, 2017
• Est. completion date: February 28, 2018

Study information

• Verified date: May 2019
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: February 28, 2018
• Est. primary completion date: February 28, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Healthy female subjects of non-childbearing potential and/or male subjects between the ages of 18 and 55 years

2. Body mass index of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb)

3. 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)

4. For optional Japanese subjects only: Japanese subjects currently residing in the United States who have 4 biologic Japanese grandparents born in Japan

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease

2. Subjects with history of sleep apnea

3. Any condition possibly affecting drug absorption (eg, gastrectomy)

4. Positive urine drug test

5. History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males

6. Treatment with an investigational drug within 30 days or 5 half-lives of the first dose of PF-06372865 (whichever is longer)

7. 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

8. Screening supine 12-lead ECG demonstrating a corrected QT (QTc) interval >450 msec or a QRS interval >120 msec

9. 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

10. 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

11. Male subjects whose partners are currently pregnant

12. 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

13. Use of herbal supplements or hormone replacement therapy within 28 days prior to the first dose of PF-06372865

14. Blood donation of approximately 1 pint (500 mL) or more within 60 days prior to dosing

15. History of sensitivity to heparin or heparin-induced thrombocytopenia

16. History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody

17. Other acute or chronic medical or psychiatric condition including recent or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or PF-06372865 administration or may interfere with the interpretation of study results

18. Subjects with active suicidal ideations or suicidal behavior within 5 years prior to screening

19. Subjects with history of cyclic neutropenia.

20. Subjects with known history of hypersensitivity to benzodiazepines, or for whom benzodiazepines would be contraindicated

21. Subjects who have previously been exposed to, or participated in a study with, PF-06372865

22. Subjects with folate deficiency

23. Subjects who have had an X-ray within 4 weeks prior to screening

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Placebo
Placebo
• PF-06372865
PF-06372865

Locations

Country	Name	City	State
United States	Pfizer New Haven Clinical Research Unit	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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

External Links

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