A Study to Understand How the Study Medicine Called ARV-471 is Processed in Healthy Adults

NCT05930925 | Completed Phase 1 FDA Drug

• 1 other identifier: C4891014
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to understand how the study medicine ARV-471 is processed in the body of healthy males and females who do not have the potential to have children. This study is seeking for participants who:

• are healthy males and females who do not have the potential to have children.
• are 18 years of age or older.
• weigh more than 110 pounds.

Conditions

Healthy

Outcome Measures

Primary Outcomes (18)

• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of ARV-471 and ARV-473 (an epimer of ARV-471)

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Maximum Observed Plasma Concentration (Cmax) of ARV-471 and ARV-473 (an epimer of ARV-471)

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of ARV-471 and ARV-473 (an epimer of ARV-471)

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of ARV-471 and ARV-473 (an epimer of ARV-471)

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Plasma Decay Half-Life (t1/2) of ARV-471 and ARV-473 (an epimer of ARV-471)

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Apparent Oral Clearance (CL/F) of ARV-471

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Apparent Volume of Distribution (Vz/F) of ARV-471

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Renal Clearance (CLr) of ARV-471 and ARV-473 (an epimer of ARV-471)

  Day 1 at intervals of 0-6 hours, 6-12 hours, 12-24 hours, and at each subsequent 24-hour interval starting on Day 2 until Day 12 or the discharge day

• Cumulative Amount of Drug Recovered Unchanged in Urine (Ae) of ARV-471 and ARV-473 (an epimer of ARV-471) and the Total Amounts Expressed as a Percent of Dose (Ae(%))

  Day 1 at intervals of 0-6 hours, 6-12 hours, 12-24 hours, and at each subsequent 24-hour interval starting on Day 2 until Day 12 or the discharge day

• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Total Radioactivity

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Total Radioactivity

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of Total Radioactivity

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Plasma Decay Half-Life (t1/2) of Total Radioactivity

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Apparent Oral Clearance (CL/F) of Total Radioactivity

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Apparent Volume of Distribution (Vz/F) of Total Radioactivity

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

• Cumulative recovery (%) of radioactivity in urine and feces

  Starting on Day 1 to Day 12 or the discharge day

• Metabolite identification/profiling in feces, plasma and urine

  Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose

Secondary Outcomes (5)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Time the participant provides informed consent through and including follow-up contact occurring 28 to 35 calendar days after the last administration of the study intervention.

• Number of Participants With Clinical Laboratory Abnormalities

  Baseline up to Day 12/Discharge

• Number of Participants With Electrocardiogram (ECG) Abnormalities

  Baseline up to Day 12/Discharge

• Number of Participants With Clinically Significant Change From Baseline in Vital Signs

  Baseline up to Day 12/Discharge

• Number of Participants With Abnormalities in Physical Examinations

  Baseline up to Day 12/Discharge

Study Arms (2)

[phenyl-14C]ARV-471

EXPERIMENTAL

\[phenyl-14C\]ARV-471 is administered as a single dose

Drug: [phenyl-14C]ARV-471

[oxoisoindolin-14C]ARV-471

EXPERIMENTAL

\[oxoisoindolin-14C\]ARV-471 is administered as a single dose

Drug: [oxoisoindolin-14C]ARV-471

Interventions

[phenyl-14C]ARV-471 DRUG

Participants will receive a single dose of \[phenyl-14C\]ARV-471 by mouth

[phenyl-14C]ARV-471

[oxoisoindolin-14C]ARV-471 DRUG

Participants will receive a single dose of \[oxoisoindolin-14C\]ARV-471 by mouth

[oxoisoindolin-14C]ARV-471

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening.
• Male and female participants of non-childbearing potential who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG monitoring.
• Total body weight \>50 kg (110 lb).
• An informed consent document signed and dated by the subject.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

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 clinically significant thromboembolic or cerebrovascular events.
• History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination 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 medications, including vitamins, dietary and herbal supplements are prohibited in this study. A washout of 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention is required, or a longer washout is required for those that fall into the categories below:
• Moderate/strong CYP3A inducers; these are prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention.
• Moderate/strong CYP3A inhibitors; these are prohibited within 14 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.
• Previous administration with an investigational product (drug or vaccine) 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.
• Renal impairment as defined by an eGFR in adults of \<60 mL/min.
• Hematuria as defined as \>1+ heme on urine dipstick.
• Proteinuria or Albuminuria as defined as \>1+ protein on urine dipstick OR positive dipstick for albumin OR Albumin/Cr ratio on spot urine (UA) \>30 mg/g.
• Standard 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF \>450 ms, 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).

Sponsors & Collaborators

• Pfizer: lead
• Arvinas Estrogen Receptor, Inc.: collaborator

Study Sites (1)

PPD Phase I Clinic

Austin, Texas, 78744, United States

Location

Related Links

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

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2023
• First Posted: July 5, 2023
• Study Start: June 12, 2023
• Primary Completion: July 27, 2023
• Study Completion: August 14, 2023
• Last Updated: September 13, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)