Clinical trial NCT04323124: Study of Single and Multiple Ascending Doses of PF-07059013 in Healthy Adult Participants
Official title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, SINGLE AND MULTIPLE DOSE ESCALATION STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF-07059013 AND OPEN-LABEL ASSESSMENT OF FOOD AND FORMULATION ON PHARMACOKINETICS OF PF-07059013 IN HEALTHY ADULT PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-03-26
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) of single and multiple ascending oral doses of PF-07059013 in healthy adult participants. Additionally, effects of different formulations and food on parameters, including PK may be explored.


Eligibility criteria: Inclusion Criteria:

1. Male and female (of non-child bearing potential) participants must be 18 to 55 years of age, inclusive, at the time of signing the ICD.
2. Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, including blood pressure, pulse rate, respiratory rate and temperature measurement, standard 12 lead ECG, laboratory tests, and cardiac monitoring (in Part 1 only).
3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

   Weight:
4. BMI of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
5. 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

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. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
3. History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing at screening for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody (HCVAb). As an exception a positive HBsAb test due to hepatitis B vaccination is permissible.
4. 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.
5. 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.
6. 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).
7. A positive urine drug test at screening or admission.
8. A positive urine cotinine test at screening or admission in Part 1 and 2.
9. 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.
10. 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 left bundle branch block (LBBB), signs of an acute or indeterminate age myocardial infarction, ST T interval changes suggestive of myocardial ischemia, second or third degree atrioventricular (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 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.
11. 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 ≥1.5 × 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;
    * PT/INR \>1.2 × ULN;
    * aPTT ≥1.5 × ULN;
    * Hemoglobin \<11.0 g/dL;
    * Lactate \>1 x ULN.
12. For Part 2 only, participants with absolute reticulocyte count \>150,000/uL at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary.
13. 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).
14. Use of tobacco/nicotine containing products for Part 1 or 2, and use of more than 5 cigarettes/day for Part 3.
15. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
16. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
17. 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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Treatment-Related Adverse Event(s) (Treatment-Related TEAE)
timeFrame: Baseline up to Follow-Up (15 weeks in Part 1 and Part 3, and 10 weeks in Part 2)
measure: Number of Participants With Laboratory Test Findings of Potential Clinical Importance
timeFrame: Part 1: from Screening to Day 8; Part 2: from Screening to Day 21; Part 3: from Screening to Day 5.
measure: Number of Participants With Vital Signs Findings of Potential Clinical Importance
timeFrame: Part 1: from Screening to Day 8; Part 2: from Screening to Day 21; Part 3: from Screening to Day 5.
measure: Number of Participants With Electrocardiogram (ECG) Findings of Potential Clinical Importance
timeFrame: Part 1: from Screening to Day 8; Part 2: from Screening to Day 21; Part 3: from Screening to Day 5.
Secondary outcomes:
measure: PF-07059013 Blood and Plasma Maximum Observed Concentration (Cmax) of Part 1
timeFrame: 0, 0.5, 1, 2, 5, 8, 12, 24, 36, 48, 72 (period 2-4 only), 96 (period 2-4 only), and 168 hours post dose of each period.
measure: PF-07059013 Blood and Plasma Time for Cmax (Tmax) of Part 1
timeFrame: 0, 0.5, 1, 2, 5, 8, 12, 24, 36, 48, 72 (period 2-4 only), 96 (period 2-4 only), and 168 hours post dose of each period.
measure: PF-07059013 Blood and Plasma Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Part 1
timeFrame: 0, 0.5, 1, 2, 5, 8, 12, 24, 36, 48, 72 (period 2-4 only), 96 (period 2-4 only), and 168 hours post dose of each period.
measure: PF-07059013 Blood and Plasma Cmax of Part 2
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12 hours post dose on Day 1, 7, and 14.
measure: PF-07059013 Blood and Plasma Tmax of Part 2
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12 hours post dose on Day 1, 7, and 14.
measure: PF-07059013 Blood and Plasma Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of Part 2
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12 hours post dose on Day 1, 7, and 14.
measure: p20 and p50 (Partial Pressure of Oxygen at Which Hemoglobin is 20% or 50% Saturated With Oxygen) Change From Baseline in Part 1
timeFrame: Part 1: 0 and 8 hours post dose.
measure: p20 and p50 (Partial Pressure of Oxygen at Which Hemoglobin is 20% or 50% Saturated With Oxygen) Change From Baseline in Part 2
timeFrame: Part 2: 0 and 8 hours post dose on Day 1, 7 and 14, and on Day 2, 15, 18.
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit - Brussels
state: Bruxelles-capitale, Région DE
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: