A Study To Evaluate The Pharmacokinetics, Excretion, Mass Balance and Metabolism of PF-07265803

NCT05286281 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C4411010
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the pharmacokinetics, excretion, mass balance and metabolism of PF-07265803 (formerly known as ARRY-371797) in approximately 6 healthy adult male participants.

Conditions

Healthy

Keywords

LMNA-related DCM; Cardiomyopathy; Lamin Type A; Heart failure; ARRY-371797

Outcome Measures

Primary Outcomes (6)

• Total Recovery of Radioactivity in Urine, Expressed as Percentage of Total Radioactive Dose Administered

  Radioactivity excreted in urine was reported as the percentage of the administered radioactivity excreted at each time interval, cumulatively through that interval and the total percent of dose recovered in urine.

  Predose, in intervals of 0-6, 6-12, 12-24, 24-48, 48-72, 72-96 hours postdose on Day 1, and each subsequent 24 hours interval up to discharge (maximum 14 days)

• Total Recovery of Radioactivity in Feces, Expressed as Percentage of Total Radioactive Dose Administered

  Radioactivity excreted in feces was reported as the percentage of the administered radioactivity excreted at each time interval, cumulatively through that interval and the total percent of dose recovered in feces.

  Predose, in intervals of each 24 hours post dose on Day 1 up to discharge (maximum 14 days)

• Total Recovery of Radioactivity in Total Excretion (Urine + Feces), Expressed as Percentage of Total Radioactive Dose Administered

  Radioactivity excreted in urine and feces was reported as the percentage of the administered radioactivity excreted at each time interval, cumulatively through that interval and the total percent of dose recovered in urine and feces.

  Predose, in intervals of each 24 hours post dose on Day 1 up to discharge (maximum 14 days)

• Relative Abundance of PF-07265803 and Its Metabolites in Plasma, Expressed as Percentage of Radioactivity

  Plasma homogenates were extracted for total radioactivity, and processed samples were analyzed by HPLC with radiochemical detection for quantitation of \[14C\]PF-07265803-derived components and by HRMS for identification of PF-07265803 and metabolites after a single 400-mg (100 μCi) oral dose of \[14C\]PF-07265803. Relative abundance of the metabolites of \[14C\]PF-07265803 in plasma based on \[14C\] quantitation was reported, expressed as percentage of radioactivity. PF-07265803 and four metabolites identified/characterized in human plasma including PF-07327859, PF-07327890, PF -07327860, and des(dimethylamino)-dioxy-PF-07265803 (m/z 461) were presented below. The plasma analysis was done with a single master pool sample (individual participants pooled based on time and from these a single master pool of all participants in one tube) due to the low amount of radioactivity in the plasma, hence there would be no mean or standard deviation.

  Predose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24, 36, 48, 72, 96, 120 hours post dose on Day 1

• Relative Abundance of PF-07265803 and Its Metabolites in Urine, Expressed as Percentage of Radioactivity

  Urine homogenates were extracted for total radioactivity, and processed samples were analyzed by HPLC with radiochemical detection for quantitation of \[14C\]PF-07265803-derived components and by HRMS for identification of PF-07265803 and metabolites after a single 400-mg (100 μCi) oral dose of \[14C\]PF-07265803. In this outcome measure, relative abundance of the metabolites of \[14C\]PF-07265803 in urine based on \[14C\] quantitation was reported, expressed as percentage of radioactivity. PF-07265803 and four metabolites identified/characterized in human urine including PF-07327859, PF-07327890, PF-07327891, and des(dimethylamino)-dioxy-PF-07265803 (m/z 461) were presented below.

  Predose, in intervals of 0-6, 6-12, 12-24, 24-48, 48-72, 72-96 hours postdose on Day 1, and each subsequent 24 hours interval up to discharge (maximum 14 days)

• Relative Abundance of PF-07265803 and Its Metabolites in Feces, Expressed as Percentage of Radioactivity

  Fecal homogenates were extracted for total radioactivity, and processed samples were analyzed by HPLC with radiochemical detection for quantitation of \[14C\]PF-07265803-derived components and by HRMS for identification of PF-07265803 and metabolites after a single 400-mg (100 μCi) oral dose of \[14C\]PF-07265803. In this outcome measure, relative abundance of the metabolites of \[14C\]PF-07265803 in feces based on \[14C\] quantitation was reported, expressed as percentage of radioactivity. PF-07265803 and four metabolites identified/characterized in human urine including PF-07327859, PF-07327890, PF-07327891, and PF-07327860 were presented below.

  Predose, in intervals of each 24 hours post dose on Day 1 up to discharge (maximum 14 days)

Secondary Outcomes (16)

• Area Under the Plasma Concentration-Time Profile From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of Total Radioactivity of [14C]PF-07265803 in Plasma

  Predose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24, 36, 48, 72, 96, 120 hours post dose on Day 1

• Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Total Radioactivity of [14C]PF-07265803 in Plasma

  Predose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24, 36, 48, 72, 96, 120 hours post dose on Day 1

• Maximum Plasma Concentration (Cmax) of Total Radioactivity of [14C]PF-07265803 in Plasma

  Predose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24, 36, 48, 72, 96, 120 hours post dose on Day 1

• Time for Cmax (Tmax) of Total Radioactivity of [14C]PF-07265803 in Plasma

  Predose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24, 36, 48, 72, 96, 120 hours post dose on Day 1

• Terminal Elimination Half-life (t1/2) of Total Radioactivity of [14C]PF-07265803 in Plasma

  Predose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24, 36, 48, 72, 96, 120 hours post dose on Day 1

Study Arms (1)

PF-07265803

EXPERIMENTAL

PF-07265803 is a p38 inhibitor formulated for oral delivery.

Drug: PF-07265803

Interventions

PF-07265803 DRUG

PF-07265803 is a p38 inhibitor formulated for oral delivery.

PF-07265803

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Participants must be male and ≥18 years of age at the time of signing the ICD.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be male and ≥18 years of age at the time of signing the informed consent.
• Male participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and electrocardiogram (ECG) monitoring.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests , lifestyle considerations , and other study procedures.
• Body Mass Index of 18.0 to 32 kg/m2; and a total body weight \>50 kg (110 lb).
• Capable of giving signed informed consent, 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, gastric bypass, duodenotomy, colectomy, history of inflammatory bowel disease).
• History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed.
• Participants with a history of irregular bowel movements; e.g., less than 1 bowel movement per day, regular episodes of diarrhea or constipation, irritable bowel syndrome (IBS) or lactose intolerance.
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic (eg. Contact with positive case)\] 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 with the exception of moderate/potent CYP3A inducers which are prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention.
• Current use of any prohibited concomitant medication(s) or those unwilling/unable to use a permitted concomitant medication(s).
• 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 and baseline supine blood pressure (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.
• Screening and baseline standard 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTcF interval \>450 msec, atrial fibrillation, 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 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 QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF 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 a participant.
• 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:
• Aspartate aminotransferase (AST) or Alanine Aminotransferase (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.
• 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) 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).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Labcorp Clinical Research Unit

Madison, Wisconsin, 53704, United States

Location

Related Links

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

MeSH Terms

Conditions

Cardiomyopathies; Limb-girdle muscular dystrophy, type 1B; Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

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: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: March 18, 2022
• Study Start: March 31, 2022
• Primary Completion: May 26, 2022
• Study Completion: May 26, 2022
• Last Updated: March 29, 2024
• Results First Posted: March 29, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)