A Study to Understand the Effect of a Study Medicine Called ARV-471 on Rosuvastatin in Healthy Adults

AN INTERVENTIONAL, PHASE 1, OPEN-LABEL, FIXED-SEQUENCE, 2-PERIOD STUDY TO EVALUATE THE EFFECT OF A SINGLE ORAL DOSE OF ARV-471 (PF-07850327) ON THE PHARMACOKINETICS OF ROSUVASTATIN IN HEALTHY PARTICIPANTS

The purpose of this study is to understand if ARV-471 affects how a BCRP substrate (rosuvastatin) gets into the body in healthy adults.

All participants in this study will receive one dose of rosuvastatin alone by mouth in Period 1. In Period 2, everyone will receive one dose of ARV-471 by mouth 90 min before one dose of rosuvastatin by mouth. The levels of rosuvastatin in Period 1 will be compared to the levels of rosuvastatin in Period 2 to determine if ARV-471 affects how rosuvastatin gets into the body differently in healthy adults.

All participants will stay at the study clinic for 10 days and 9 nights.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ARV-471; Drug: Rosuvastatin

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and/or female participants of non-childbearing potential must be 18 to 65 years of age, inclusive at the time of signing informed consent document.
• Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical exam, laboratory tests, vital sign and standard 12-lead ECGs.
• BMI of 17.5 to 32 kg/m2; and a total body weight ≥45 kg.

Exclusion Criteria:

• 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).
• Pregnant female participants; breastfeeding female participants; Male participants with partners currently pregnant; fertile male participants who have partners of childbearing potential and are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for 90 days after the last dose of investigational product.
• Participants with known history of hypersensitivity to statin medication, sensitivity to ARV-471 or rosuvastatin or any of the formulation components of ARV-471 or rosuvastatin.
• 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 that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• 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.
• History of use of tobacco or nicotine-containing products in excess of the equivalent of 5 cigarettes/day or 2 chews of tobacco/day.
• History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening.
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin with/without ARV-471; Rosuvastatin administered as a single dose in Period 1 and Period 2. ARV-471 administered as a single dose in Period 2.	Drug: ARV-471; Experimental; Other Names: PF-07850327; Drug: Rosuvastatin; Probe substrate; Other Names: CRESTOR®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of Rosuvastatin	Cmax was defined as maximum plasma concentration. Cmax of rosuvastatin was observed directly from data.	0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 hours post dose on Day 1 in Periods 1 and 2
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Rosuvastatin	AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast of rosuvastatin was determined using Linear/Log trapezoidal method.	0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 hours post dose on Day 1 in Periods 1 and 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship with the study intervention. SAE is defined as one of the following: is fatal or life threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant; requires inpatient hospitalization or prolongation of existing hospitalization. Treatment-emergent AE is defined as an AE with onset date occurring during the on-treatment period. AEs include all SAEs and non-SAEs.	From the first dose (Day 1) up to 35 days after the last dose (Day 6) of study intervention (up to 41 days)
Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality)	Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid, cystatinC); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); clinical chemistry (glucose); urinalysis (dipstick [decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, bilirubin], microscopy. Abnormality was determined at the investigator's discretion.	Baseline (Period 1 Day -1) up to Period 2 Day 4 (10 days)
Number of Participants With Electrocardiogram (ECG) Abnormalities	ECG abnormalities criteria include a) a postdose QTc corrected using Fridericia's formula (QTcF) increased by >60 millisecond (ms) from the baseline and the absolute QTcF value >450 ms; or b) an absolute QTcF value >500 ms for any scheduled ECG.	Baseline (Period 1 Day 1) up to Period 2 Day 4 (9 days)
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Vital signs (blood pressure and pulse rate) were obtained with participant following at least a 5-minute rest in a supine position. Clinical significance of vital signs was determined at the investigator's discretion.	Baseline (Period 1 Day 1) up to Period 2 Day 4 (9 days)

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Arvinas Estrogen Receptor, Inc.
• 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): December 9, 2022
• Primary Completion (Actual): February 9, 2023
• Study Completion (Actual): March 6, 2023

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: December 7, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Actual): July 26, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: C4891029

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