Clinical trial NCT03217604: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Doses of PF-06852231 in Healthy Subjects
Official title: A Phase 1, Randomized, Double-blind, Sponsor-open, Placebo-controlled, First-in-human Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Single Ascending Oral Doses Of Pf-06852231 Administered To Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: PF-06852231
Safety
Tolerability
Pharmacokinetics
First-in-human
Healthy subjects
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-07-14
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of single ascending doses of PF-06852231 after first-time administration to healthy adult subjects. The safety, tolerability, and pharmacokinetics of an active metabolite (PF-06892787) will also be evaluated in this study.


Eligibility criteria: Inclusion Criteria:

1. Healthy female subjects of non-childbearing potential and male subjects, who at the time of screening are between 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 electrocardiogram, or clinical laboratory tests.
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 scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
2. 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).
3. Screening supine BP greater than or equal to 140 mm Hg (systolic) or greater than or equal to 90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is greater than or equal to 140 mm Hg (systolic) or greater than or equal to 90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the subject's eligibility.
4. Screening supine 12-lead ECG demonstrating a corrected QT (QTc) interval \>450 msec or a QRS interval \>120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the subject's eligibility.
5. 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 test, if deemed necessary:

   * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level greater than or equal to 1.5x upper limit of normal (ULN);
   * Total bilirubin level greater than or equal to 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 less than or equal to ULN.
6. 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.
7. Unwilling or unable to comply with the criteria in the Lifestyle Requirements section of this protocol.
8. Other acute or chronic medical or psychiatric conditions

Primary outcomes:
measure: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
timeFrame: Baseline up to 14 days after last dose of study medication
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline up to 14 days after last dose of study medication
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: 0, 1, 2, 4, 8, 12, 24, 48, 72 hours(h) post-dose
measure: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings
timeFrame: 0, 1, 2, 4, 8, 12, 24, 48, 72 h post-dose
measure: Abnormal rhythms as observed continuous cardiac telemetry
timeFrame: 8 h post-dose
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) for PF-06852231
timeFrame: 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 h post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06852231
timeFrame: 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 h post-dose
measure: Area Under the Curve From Time Zero to Time of Last Measurable Plasma Concentration (AUClast) for PF-06852231
timeFrame: 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 h post-dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-06852231
timeFrame: 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 h post-dose
measure: Plasma Decay Half-Life (t1/2) of PF-06852231
timeFrame: 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 h post-dose
measure: Maximum Observed Plasma Concentration (Cmax) for PF-06892787 (metabolite of PF-06852231)
timeFrame: 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 h post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06892787 (metabolite of PF-06852231)
timeFrame: 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 h post-dose
measure: Area Under the Curve From Time Zero to Time of Last Measurable Plasma Concentration (AUClast) for PF-06892787 (metabolite of PF-06852231)
timeFrame: 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 h post-dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-06892787 (metabolite of PF-06852231)
timeFrame: 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 h post-dose
measure: Plasma Decay Half-Life (t1/2) of PF-06892787 (metabolite of PF-06852231)
timeFrame: 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 h post-dose
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: