Study of Multiple Oral Doses of PF-06835919 in Healthy Adult Japanese Participants

Study Overview
=================
Brief Summary
-----------------
This is a Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of multiple oral doses of PF-06835919 in healthy adult Japanese participants. A total of approximately 8 healthy participants will be enrolled in this study. Participants will be randomized to 2 groups to receive PF-06835919 or placebo treatment with a randomization ratio of 3:1.

Official Title
-----------------
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF MULTIPLE ORAL DOSES OF PF-06835919 IN HEALTHY ADULT JAPANESE PARTICIPANTS

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: PF-06835919
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female participants must be 18 to 55 years of age, inclusive, at the time of signing the ICD. A Japanese participant is defined as having 4 biological Japanese grandparents who were born in Japan. Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiovascular tests. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. Exclusion Criteria: 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). Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, HBcAb or HCVAb. Hepatitis B vaccination (positive HBsAb) is allowed. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention (Refer to Section 6.5 for additional details). Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). A positive urine drug test. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest: If BP is ≥140 mm Hg (systolic) or ≥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 participant's eligibility. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTc interval >450 msec, complete LBBB, signs of an acute or indeterminate age myocardial infarction, ST T interval changes suggestive of myocardial ischemia, second or third degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is >450 msec, this interval should be rate corrected using the Fridericia method (QTcF) and the resulting QTcF should be used for decision making and reporting. 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 participant's eligibility. Computer interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants. Participants 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: AST or ALT level ≥1.25 × ULN; Total bilirubin level ≥1.5 × ULN; participants 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. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine). Use of tobacco- or nicotine-containing products in excess of the equivalent >5 cigarettes/day or 2 chews of tobacco per day. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase 1, randomized, double-blind, sponsor-open, placebo-controlled study in healthy adult Japanese participants.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06835919<br> | Drug: PF-06835919<br>* PF-06835919 300 mg repeated doses<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo repeated doses<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. | Baseline (Day 1) to follow-up (Day 42) | 
| Number of Participants With Clinical Laboratory Findings of Potential Clinical Importance | To determine if there were any clinically significant laboratory abnormalities, haematological (hemoglobin, hematocrit, red blood cell count, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes), clinical chemistry (blood urea nitrogen, glucose [fasting], calcium, sodium, potassium, chloride, bicarbonate, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein) and urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin) tests were assessed. Each parameter was evaluated against commonly used and widely accepted criteria. | Day 1 to Day 10 | 
| Number of Participants With ECG Data of Potential Clinical Concern | ECG endpoints (QTcF, PR and QRS) meeting the criteria of potential clinical concern were summarized by treatment using categories as defined: 1.maximum post-dose QTcF ≤450msec, 450 - ≤480msec, 480 - ≤500msec and >500msec; 2. PR max. ≥300ms; 3. QRS max. ≥140ms. | Day 1 to Day 10 | 
| Number of Participants/Subjects With Vital Signs Data of Potential Clinical Concern | Single supine blood pressure and pulse measurements meeting the criteria of potential clinical concern were summarized by treatment using categories as defined: 1. Systolic Blood Pressure (BP) min. <90mm Hg; 2. Diastolic BP min. <50mm Hg; 3. Supine pulse rate min. <40 bpm, max. >120 bpm. | From Study Day 1 up tp Study Day 10 | 
| Summary of Maximum Plasma Concentration (Cmax) of PF-06835919 on Day 1 and Day 7 | Cmax was defined as maximum observed plasma concentration. | Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 on Day 1 and Day 7 | 
| Summary of Area Under the Plasma Concentration-Time Curve Over Dosing Interval (AUCtau) of PF-06835919 on Day 1 and Day 7 | AUCtau was defined as area under the plasma concentration-time curve over dosing interval. | Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 on Day 1 and Day 7 | 
| Summary of Time for Maximum Observed Concentration (Tmax) of PF-06835919 on Day 1 and Day 7 | Tmax was defined as Time for maximum observed concentration of PF-06835919. | Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 on Day 1 and Day 7 | 
| Summary of Terminal Half-life (t1/2) of PF-06835919 on Day 7 | t1/2 was defined as terminal half-life. | Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 on Day 7 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NASH, KHK, PF-06835919, Japanese