Study of Single and Multiple Ascending Doses of PF-07059013 in Healthy Adult Participants

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

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.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: PF-07059013

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles-capitale, Région DE
    • Brussels, Bruxelles-capitale, Région DE, Belgium, B-1070
      • Pfizer Clinical Research Unit - Brussels

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; PF-07059013 assignment	Drug: PF-07059013; Participants will recieve PF-07059013
Placebo Comparator: Placebo; Placebo assignment	Drug: Placebo; Participants will recieve placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Treatment-Related Adverse Event(s) (Treatment-Related TEAE)	Adverse events (AEs): any untoward medical occurrence in a clinical investigation participant administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Treatment-related TEAEs were any untoward medical occurrence attributed to study intervention. Relatedness to study treatment was determined by the investigator. Duration of participation of Part 1 and Part 3, from the screening visit to the follow-up phone call, was approximately 15 weeks. Duration of participation of Part 2, from the screening visit to the follow-up phone call, was approximately 10 weeks.	Baseline up to Follow-Up (15 weeks in Part 1 and Part 3, and 10 weeks in Part 2)
Number of Participants With Laboratory Test Findings of Potential Clinical Importance	Protocol-required safety laboratory assessments included chemistry, hematology, and urinalysis (and microscopy, if needed). Each parameter was evaluated against commonly used and widely accepted criteria. Laboratory test with abnormalities are reported. Evaluation activities as: Part 1: At Screening, Day -1, and Day 1 (at 8 hours post dose), 2, 5, 8. Part 2: At Screening, Day -1, 1, 2, 4, 7, 10, 14, 18, 21. Part 3: At Screening, Day -1, 2, 5.	Part 1: from Screening to Day 8; Part 2: from Screening to Day 21; Part 3: from Screening to Day 5.
Number of Participants With Vital Signs Findings of Potential Clinical Importance	Vital sign data included supine blood pressure, pulse rate, orthostatic blood pressure and oral temperature. Vital signs with abnormalities are reported. Evaluation activities as: Part 1: Supine blood pressure and pulse rate: At Screening, 0, 0.5, 1, 2, 5, 8, 12, 24, 36, 48, 72, 96, and 168 hours post dose. Orthostatic blood pressure, respiratory rate and oral temperature: 0, 2, 8, and 24 hours post dose. Part 2: Supine blood pressure and pulse rate: At Screening, Day 1, 2, 4, 7, 10, 14, 15, 18, 21. Orthostatic blood pressure, respiratory rate and oral temperature: Day 1, 7, 14, 18. Part 3: Supine blood pressure and pulse rate: At Screening, 0, 2, 5, 8, 12, 24, 48, and 96 hours post dose. Respiratory rate and oral temperature: 0, 24 and 96 hours post dose.	Part 1: from Screening to Day 8; Part 2: from Screening to Day 21; Part 3: from Screening to Day 5.
Number of Participants With Electrocardiogram (ECG) Findings of Potential Clinical Importance	Clinical significance of 12-Lead ECG data was assessed by the investigator. ECG findings with abnormalities were reported. Evaluation activities as: Part 1: At Screening, 0, 0.5, 1, 2, 5, 8, 12, 24, 36, 48, 72, 96, and 168 hours post dose. Part 2: At Screening, Day 1, 2, 4, 7, 10, 14, 15, 18, 21. Part 3: At Screening, 0, 2, 5, 8, 12, 24, 48, and 96 hours post dose.	Part 1: from Screening to Day 8; Part 2: from Screening to Day 21; Part 3: from Screening to Day 5.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PF-07059013 Blood and Plasma Maximum Observed Concentration (Cmax) of Part 1	PF-07059013 Blood and Plasma Cmax for Part 1 was evaluated. For Part 1, in period 1, participants were given PF-07059013 100 mg SD and PF-07059013 250 mg SD, all with polymer; in period 2, participants were given PF-07059013 500 mg SD and PF-07059013 1000 mg SD, all with polymer; in period 3, participants were given PF-07059013 2000 mg SD and PF-07059013 3000 mg SD, all with polymer; in period 4, participants were given PF-07059013 2000 mg SD and PF-07059013 3000 mg SD, all without polymer.	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.
PF-07059013 Blood and Plasma Time for Cmax (Tmax) of Part 1	PF-07059013 Blood and Plasma Tmax for Part 1 was evaluated. For Part 1, in period 1, participants were given PF-07059013 100 mg SD and PF-07059013 250 mg SD, all with polymer; in period 2, participants were given PF-07059013 500 mg SD and PF-07059013 1000 mg SD, all with polymer; in period 3, participants were given PF-07059013 2000 mg SD and PF-07059013 3000 mg SD, all with polymer; in period 4, participants were given PF-07059013 2000 mg SD and PF-07059013 3000 mg SD, all without polymer.	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.
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	PF-07059013 Blood and Plasma AUClast of Part 1 was evaluated. For Part 1, in period 1, participants were given PF-07059013 100 mg SD and PF-07059013 250 mg SD, all with polymer; in period 2, participants were given PF-07059013 500 mg SD and PF-07059013 1000 mg SD, all with polymer; in period 3, participants were given PF-07059013 2000 mg SD and PF-07059013 3000 mg SD, all with polymer; in period 4, participants were given PF-07059013 2000 mg SD and PF-07059013 3000 mg SD, all without polymer.	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.
PF-07059013 Blood and Plasma Cmax of Part 2	PF-07059013 Blood and Plasma Cmax of Part 2 was evaluated.	0, 0.5, 1, 2, 4, 6, 8, 12 hours post dose on Day 1, 7, and 14.
PF-07059013 Blood and Plasma Tmax of Part 2	PF-07059013 Blood and Plasma Tmax of Part 2 was evaluated.	0, 0.5, 1, 2, 4, 6, 8, 12 hours post dose on Day 1, 7, and 14.
PF-07059013 Blood and Plasma Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of Part 2	PF-07059013 Blood and Plasma AUCtau (the Dosing Interval, Where Tau = 24 Hours for QD Dosing) for Part 2 was evaluated.	0, 0.5, 1, 2, 4, 6, 8, 12 hours post dose on Day 1, 7, and 14.
p20 and p50 (Partial Pressure of Oxygen at Which Hemoglobin is 20% or 50% Saturated With Oxygen) Change From Baseline in Part 1	p20 and p50 change from baseline in Part 1 was evaluated.	Part 1: 0 and 8 hours post dose.
p20 and p50 (Partial Pressure of Oxygen at Which Hemoglobin is 20% or 50% Saturated With Oxygen) Change From Baseline in Part 2	p20 and p50 change from baseline in Part 2 was evaluated.	Part 2: 0 and 8 hours post dose on Day 1, 7 and 14, and on Day 2, 15, 18.

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2020
• Primary Completion (Actual): October 21, 2021
• Study Completion (Actual): October 21, 2021

Study Registration Dates

• First Submitted: March 18, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: C4061001; 2019-004918-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No