A Single Dose Study Of PF-06678552 In Healthy Subjects

• ClinicalTrials.gov Identifier: NCT01992614
• Recruitment Status: Completed
• First Posted: November 25, 2013
• Last Update Posted: March 28, 2014
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

PF-06678552 is a new compound proposed for the treatment of hypercholesteremia. The primary purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of PF-06678552 in healthy subjects.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: PF-06678552 or Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study To Assess The Safety, Tolerability, And Pharmacokinetics Of PF-06678552 After Fed And Fasted Administration Of Single Escalating Oral Doses In Healthy Subjects
• Study Start Date: December 2013
• Actual Primary Completion Date: March 2014
• Actual Study Completion Date: March 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; Single ascending doses of PF-06678552 or placebo to investigate the safety, tolerability, PK, and PD.	Drug: PF-06678552 or Placebo; PF-06678552 or placebo will be administered as an extemporaneously prepared solution once in each period.
Experimental: Cohort 2; Single ascending doses of PF-06678552 or placebo to investigate the safety, tolerability, PK, and PD.	Drug: PF-06678552 or Placebo; PF-06678552 or placebo will be administered as an extemporaneously prepared solution once in each period.
Experimental: Cohort 3; Single ascending doses of PF-06678552 or placebo to investigate the safety, tolerability, PK, and PD.	Drug: PF-06678552 or Placebo; PF-06678552 or placebo will be administered as an extemporaneously prepared solution once in each period.

Outcome Measures

Primary Outcome Measures :

1. Assessment of adverse events (AEs), clinical laboratory tests, vital signs (including blood pressure and pulse rate) and cardiac conduction intervals as assessed via 12-lead electrocardiogram (ECG). [ Time Frame: 0 to 72 hours post dose ]

Secondary Outcome Measures :

1. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06678552 [ Time Frame: 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ]
   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
2. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - infinity)] for PF-06678552 [ Time Frame: 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ]
   AUC (0 - infinity)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity).
3. Maximum Observed Plasma Concentration (Cmax) for for PF-06678552 [ Time Frame: 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ]
   Maximum Observed Plasma Concentration (Cmax)
4. Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06678552 [ Time Frame: 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ]
   Time to Reach Maximum Observed Plasma Concentration (Tmax)
5. Plasma Decay Half-Life (t1/2) for PF-06678552 [ Time Frame: 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ]
   Plasma Decay Half-Life (t1/2)
6. Apparent Oral Clearance (CL/F) for PF-06678552 [ Time Frame: 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ]
   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. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
7. Apparent Volume of Distribution (Vz/F) for PF-06678552 [ Time Frame: 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ]
   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.
8. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06644927 [ Time Frame: 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ]
   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
9. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - infinity)] for PF-06644927 [ Time Frame: 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ]
   AUC (0 - infinity)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity).
10. Maximum Observed Plasma Concentration (Cmax) for PF-06644927 [ Time Frame: 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ]
    Maximum Observed Plasma Concentration (Cmax)
11. Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06644927 [ Time Frame: 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ]
    Time to Reach Maximum Observed Plasma Concentration (Tmax)
12. Plasma Decay Half-Life (t1/2) for PF-06644927 [ Time Frame: 0, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ]
    Plasma Decay Half-Life (t1/2)
13. Amount of PF-06644927 excreted in the urine (Ae) [ Time Frame: 0-4, 4-12, and 12-24 hours post dose ]
    Amount of drug excreted in the urine is a measure of the degree that the kidneys filter drug from the blood to the urine.
14. Percent of PF-06678552 dose excreted in the urine as PF-06644927 (Ae%) [ Time Frame: 0-4, 4-12, and 12-24 hours post dose ]
    The percent of PF-06678552 dose excreted in the urine as PF-06644927 is calculated from the mass of dose excreted in the urine compared to the total dose of PF-06678552 and corrected for the relative weight of PF-06644927 to PF-06678552.
15. Renal Clearance (CLr) for PF-06644927 [ Time Frame: 0-4, 4-12, and 12-24 hours post dose ]
    Renal clearance is the measure of the rate of drug moving into the urine from blood

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy male and/or female subjects of non childbearing potential.
• Body Mass Index (BMI) of 18 to 30.5 kg/m2; and a total body weight >50 kg
• Low density lipoprotein cholesterol between 115 mg/dL and 190 mg/dL

Exclusion Criteria:

• 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 time of dosing)

Contacts and Locations

Locations

Belgium

Pfizer Investigational Site

Brussels, Belgium, B-1070

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01992614
• Other Study ID Numbers: B7611001
• First Posted: November 25, 2013
• Last Update Posted: March 28, 2014
• Last Verified: March 2014

Keywords provided by Pfizer:

Single Ascending Dose; healthy subjects; Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases