A Study To Evaluate the Safety, Tolerability, And Pharmacokinetics Of PF-06266047 In Healthy Adult Subjects

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Placebo-controlled, Randomized, Subject- And Investigator-blind, Sponsor-open, Crossover Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Pf-06266047 After Administration Of Single Ascending Doses To Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02539550
• Other study ID #: B7481001
• Secondary ID: 2015-001796-52
• Status: Completed
• Phase: Phase 1
• First received: August 10, 2015
• Last updated: June 22, 2016
• Start date: August 2015
• Est. completion date: May 2016

Study information

• Verified date: June 2016
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of PF-06266047 after first-time administration to healthy adult subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Healthy female subjects of non-childbearing potential and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG or clinical laboratory tests. Female subjects of non-childbearing potential must meet at least one of the following criteria:

1. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state;

2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;

3. Have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations) will be considered to be of childbearing potential.

2. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).

3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

4. Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

5. Subject must be willing to avoid direct sunlight exposure or any high intensity ultraviolet light exposure, from the first day of dosing with study medication and until the follow-up visit; and to apply sun cream/lotion with a high sun protection factor, as appropriate.

Exclusion Criteria:

1. 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).

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

3. A positive urine drug screen.

4. History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening.

5. Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study medication (whichever is longer).

6. Screening supine blood pressure >140 mm Hg (systolic) or >90 mm Hg (diastolic), following at least 5 minutes of supine rest. If blood pressure (BP) is >140 mm Hg (systolic) or >90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three BP values should be used to determine the subject's eligibility.

7. Screening supine 12-lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility.

8. Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat, if deemed necessary:

• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic aminotransferase (SGOT) or alanine aminotransferase (ALT)/serum glutamic pyruvic aminotransferase (SGPT) >1.5 x upper limit of normal (ULN);

• Total bilirubin >1.5 x ULN; subjects with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is <ULN.

9. Pregnant female subjects; breastfeeding female subjects; 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 or longer based upon the compound's half-life characteristics.

10. 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 study medication. As an exception, acetaminophen/paracetamol may be used at doses of <1 g/day. Limited use of non-prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor. Herbal supplements and hormone replacement therapy must be discontinued at least 28 days prior to the first dose of study medication.

11. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing.

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

13. Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol.

14. 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.

15. Other 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.

16. Any subject considered at risk of suicide or self harm based on investigator judgement and/or the details of a risk assessment.

17. Use of tobacco or nicotine-containing products in excess of the equivalent of 5 cigarettes per day.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Placebo
Placebo
• PF-06266047
PF-06266047

Locations

Country	Name	City	State
Belgium	Pfizer Clinical Research Unit	Bruxelles

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events (AEs)	Number of participants with AEs occurring after first dose of study drug. Relatedness to study drug will be assessed by investigator.	Baseline up to 1 day of dosing	Yes
Primary	Number of subjects with standard safety laboratory test results of potential clinical significance	Number of subjects with standard safety laboratory test results of potential clinical significance (according to pre-defined criteria).	Baseline up to 1 day of dosing	Yes
Primary	Electrocardiogram (ECG)	Absolute values and changes from baseline for the ECG parameters	0, 1, 2, 4, 8, 12, 24, 48, and 72 hours post-dose	Yes
Primary	Orthostatic blood pressure and pulse rate	Absolute values and changes from baseline for blood pressure and pulse rate	0, 1, 2, 4, 8, 12, 24, 48, and 72 hours post-dose	Yes
Primary	Abnormal rhythms as observed on continuous cardiac telemetry	All abnormal rhythms will be reviewed by the study physician for the presence of rhythms of potential clinical concern. The time, duration and description of any clinically significant event will be recorded.	Baseline period of at least 2 hours and continuous tracing for at least 8 hours following single dose administration	Yes
Secondary	Maximum Observed Plasma Concentration (Cmax)	Maximum Observed Plasma Concentration (Cmax)	0, 0.5, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax)	Time to Reach Maximum Observed Plasma Concentration (Tmax)	0, 0.5, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	0, 0.5, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose	No
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]	AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).	0, 0.5, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose	No
Secondary	Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	0, 0.5, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose	No
Secondary	Apparent Oral Clearance (CL/F)	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	0, 0.5, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose	No
Secondary	Apparent Volume of Distribution (Vz/F)	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.	0, 0.5, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose	No

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