Clinical trial NCT03492697: A Single Dose Crossover Study In Healthy Subjects To Evaluate Different Formulations Of PF-06882961
Official title: A Phase 1, Open-label Study In Healthy Subjects To Evaluate The Pharmacokinetics Of Pf-06882961 Following Single Oral Administration Of Immediate Release Tablets And An Immediate Release Oral Solution In The Fed State, And Controlled Release Tablets In The Fed And Fasted States
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-04-10
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This open label study will evaluate the pharmacokinetics (PK) following single oral doses of different formulations of PF-06882961, including controlled release (CR) tablets at 2 release rates (long and short duration), an immediate release (IR) oral solution, and IR tablets, in healthy adult subjects.


Eligibility criteria: Inclusion Criteria:

* Healthy female subjects of nonchildbearing potential and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive
* Body mass index (BMI) within 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb)
* Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study

Exclusion Criteria:

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal (including pancreatitis), cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
* Any condition possibly affecting drug absorption (eg, gastrectomy).
* A positive urine drug test.
* History of regular alcohol consumption exceeding 7 drinks/week for female subjects or 14 drinks/week for male subjects within 6 months before screening.
* Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of investigational product (whichever is longer).
* Subjects who have previously participated in prior studies with PF 06882961 as the investigational product.
* 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 QTc interval \>450 msec or a QRS interval \>120 msec.
* Aspartate aminotransferase (AST) level \>= 1.25 × upper limit of normal (ULN);
* Alanine aminotransferase (ALT) level \>= 1.25 × ULN;
* Total bilirubin level \>=1.5 × ULN;
* TSH \> ULN;
* HbA1c \>=6.5%.
* Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in the protocol for at least 28 days after the last dose of investigational product.
* 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 investigational product
* Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
* History of sensitivity to heparin or heparin induced thrombocytopenia.
* History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb).
* Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2), or subjects with suspected MTC per the investigator's judgement.
* Unwilling or unable to comply with the criteria in the Lifestyle Requirements section of the protocol.
* Subjects who are investigator 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, including their family members, directly involved in the conduct of the study.
* Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) for PF-06882961
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose in each period
measure: Time to Maximum Observed Plasma Concentration (Tmax) for PF-06882961
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose in each period
measure: Area under the curve from time zero to last quantifiable concentration for PF-06882961 (AUClast)
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose in each period
measure: Area under the curve from time zero to extrapolated infinite time for PF-06882961 (AUCinf), as data permit
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose in each period
measure: Observed Plasma Concentration for PF-06882961 at 24 hours post-dose (C24)
timeFrame: 24 hours post dose in each period
measure: Plasma Decay Half-Life (t1/2) for PF-06882961, as data permit
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose in each period
measure: Apparent clearance (CL/F) for PF-06882961, as data permit
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose in each period
measure: Peak-to-trough (PTR) ratio for PF-06882961
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose in each period
Secondary outcomes:
measure: Number of subjects with treatment-emergent adverse events (AEs)
timeFrame: Baseline to at least 28 days after last dose
measure: AUClast for PF-06882961 for CR tablet (long) and IR tablet in fed state
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose
measure: AUCinf for PF-06882961 for CR tablet (long) and IR tablet in fed state, as data permit
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose
measure: Cmax for PF-06882961 for CR tablet (long) and IR tablet in fed state
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose
measure: AUClast for PF-06882961 for CR tablet (long) in fed and fasted states
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose
measure: AUCinf for PF-06882961 for CR tablet (long) in fed and fasted states, as data permit
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose
measure: Cmax for PF-06882961 for CR tablet (long) in fed and fasted states
timeFrame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 24, 28, 32, 36 and 48 hours post dose
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Pfizer New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: