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

NCT04323124 | Terminated Phase 1 Results

• 2 other identifiers: C40610012019-004918-34
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• PF-07059013 Blood and Plasma Maximum Observed Concentration (Cmax) of Part 1

  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

  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

  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

  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

  0, 0.5, 1, 2, 4, 6, 8, 12 hours post dose on Day 1, 7, and 14.

Study Arms (2)

Treatment

EXPERIMENTAL

PF-07059013 assignment

Drug: PF-07059013

Placebo

PLACEBO COMPARATOR

Placebo assignment

Drug: Placebo

Interventions

PF-07059013 DRUG

Participants will recieve PF-07059013

Treatment

Placebo DRUG

Participants will recieve placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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).
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Weight:
• 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.

You may not qualify if:

• 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 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.
• 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.
• 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 at screening or admission.
• A positive urine cotinine test at screening or admission in Part 1 and 2.
• 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 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.
• 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;

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer Clinical Research Unit - Brussels

Brussels, Bruxelles-capitale, Région de, B-1070, Belgium

Location

Related Publications (1)

• Lee KC, Wan KX, Barricklow J, Lim CN, Clarke S, Potts D, Holmes K, Gonzalez P, Kavetska O. Using Mitra sampling to support first-in-human pharmacokinetic evaluations for PF-07059013. Bioanalysis. 2023 Sep;15(17):1083-1094. doi: 10.4155/bio-2023-0066. Epub 2023 Aug 16.

  PMID: 37584365 DERIVED

Related Links

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

Limitations and Caveats

After the completion of the Part 1 and Part 2, due to failure to demonstrate sufficient pharmacologic effect in relation to the study PK and pharmacodynamic (PD) objectives in healthy participants as defined in the study protocol, the study was terminated prematurely. The decision to terminate the study was made while Part 3 was in progress (5 participants enrolled).

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2020
• First Posted: March 26, 2020
• Study Start: July 17, 2020
• Primary Completion: October 21, 2021
• Study Completion: October 21, 2021
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)