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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05652660
• Other study ID #: C4891029
• Status: Completed
• Phase: Phase 1
• Start date: December 9, 2022
• Est. completion date: March 6, 2023

Study information

• Verified date: March 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 6, 2023
• Est. primary completion date: March 6, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• ARV-471
Experimental
• Rosuvastatin
Probe substrate

Locations

Country	Name	City	State
United States	New Haven Clinical Research Unit	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Arvinas Estrogen Receptor, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed plasma concentration (Cmax) of rosuvastatin when rosuvastatin is administered alone		Period 1 - Day 1 pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 hours post-dose
Primary	Maximum observed plasma concentration (Cmax) of rosuvastatin when rosuvastatin is administered with ARV-471		Period 2 - Day 1 pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 hours post-dose
Primary	Area under the curve from time zero to extrapolated infinite time [AUC (0 - 8)] of rosuvastatin when rosuvastatin is administered alone	AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).	Period 1 - Day 1 pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 hours post-dose
Primary	Area under the curve from time zero to extrapolated infinite time [AUC (0 - 8)] of rosuvastatin when rosuvastatin is administered with ARV-471	AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).	Period 2 - Day 1 pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 hours post-dose
Secondary	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 drug without regard to possibility of causal relationship with the study treatment. 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.	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.
Secondary	Number of participants with clinical laboratory abnormalities	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.	Baseline up to Period 2 Day 4
Secondary	Number of participants with electrocardiogram (ECG) abnormalities	ECG abnormalities criteria include a) a postdose QTcF is increased by >60 ms from the baseline and is >450 ms; or b) an absolute QTcF value is >500 ms for any scheduled ECG.	Baseline up to Period 2 Day 4
Secondary	Number of participants with clinically significant change from baseline in vital signs	Blood pressure and pulse rate will be performed following at least a 5-minute rest in a supine position.	Baseline up to Period 2 Day 4

External Links

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