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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-003282-38 | EudraCT Number |
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| Name | Class |
|---|---|
| Arvinas Estrogen Receptor, Inc. | INDUSTRY |
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The purpose of this study is to understand if a strong CYP3A4 inhibitor (itraconazole) affects how ARV-471 is processed and eliminated in healthy adults.
All participants in this study will receive one dose of ARV-471 alone by mouth in Period 1. In Period 2, everyone will receive itraconazole by mouth once a day for multiple days. Participants will also receive one dose of ARV-471 by mouth. The levels of ARV-471 in Period 1 will be compared to the levels of ARV-471 in Period 2 to determine if the CYP3A4 inhibitor affects how ARV-471 is processed differently in healthy adults.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| vepdegestrant with and without itraconazole | Experimental | vepdegestrant administered as a single dose in Period 1 and Period 2. Itraconazole administered once a day for 11 days in Period 2. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| vepdegestrant | Drug | Participants will receive a single dose of vepdegestrant by mouth in Period 1 and Period 2, with a washout period of at least 10 days between doses of vepdegestrant |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of ARV-471 | AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of ARV-471. AUCinf was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) of ARV-471 | Cmax was defined as maximum plasma concentration. Cmax of ARV-471 was observed directly from data. | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
| Area Under the Plasma Concentration-Time Profile From Time 0 to 120 Hours (AUC120) of ARV-473 | ARV-473 was the epimer of ARV-471. AUC120 was defined as area under the plasma concentrationtime profile from time zero to 120 hours. AUC120 was calculate by Linear/Log trapezoidal method. | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose |
| Cmax of ARV-473 | ARV-473 was the epimer of ARV-471. Cmax was defined as maximum plasma concentration. Cmax of ARV-473 was observed directly from data. | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of ARV-471 | AUClast was defined as area under the plasma concentrationtime profile from time zero to the time of the last quantifiable concentration (Clast). AUClast was calculated by Linear/Log trapezoidal method. | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
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Inclusion Criteria
Exclusion Criteria
Moderate/potent CYP3A inducers which are prohibited within 14 days plus 5 half-lives (whichever is longer) prior to the first dose of study intervention.
Moderate/potent CYP3A inhibitors which are prohibited within 14 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pfizer Clinical Research Unit - Brussels | Brussels | Bruxelles-capitale, Région de | B-1070 | Belgium |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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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.
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The study consisted of 2 periods in a single fixed sequence. A total of 12 participants were screened and enrolled into the study. All enrolled participants were treated and completed the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants | Participants received a single dose of ARV-471 (PF-07850327) 200 milligram (mg) on Period 1 Day 1. After completion of Period 1, participants received 200 mg itraconazole once daily on Period 2 Days 1-4 and 6-11. On Period 2 Day 5, participants received a single dose of Itraconazole 200 mg first, immediately followed by a single dose of ARV-471 200 mg. Following Period 1, a washout period of at least 10 days must occur between the 2 single doses of ARV-471. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 (6 Days) |
| |||||||||||||
| Period 2 (12 Days) |
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Baseline participants included all participants enrolled and who took at least 1 dose of study intervention.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | Participants received a single dose of ARV-471 (PF-07850327) 200 milligram (mg) on Period 1 Day 1. After completion of Period 1, participants received 200 mg itraconazole once daily on Period 2 Days 1-4 and 6-11. On Period 2 Day 5, participants received a single dose of Itraconazole 200 mg first, immediately followed by a single dose of ARV-471 200 mg. Following Period 1, a washout period of at least 10 days must occur between the 2 single doses of ARV-471. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of ARV-471 | AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of ARV-471. AUCinf was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. | Analysis population included all participants who received at least 1 dose of ARV-471 and/or itraconazole and had at least 1 of the ARV-471 or ARV-473 pharmacokinetic (PK) parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*hr/mL) | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
|
From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ARV-471 200 mg | Participants received a single dose of ARV-471 200 mg on Day 1 of Period 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
AUCinf for ARV-473 could only be reported for 2 of 12 participants in Period 1 (ARV-471 alone) and 6 of 12 participants in Period 2 (ARV-471 + itraconazole) based on protocol prespecified criteria, therefore was not used as the primary endpoint for ARV-473. Furthermore, AUC120, was selected as the primary endpoint for ARV-473 in lieu of AUClast to account for the difference in sampling intervals between Test Treatment (0-168 hours) and Reference Treatment (0-120 hours).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 12, 2023 | Apr 19, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 12, 2022 | Apr 19, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Itraconazole | Drug | Participants will receive itraconazole by mouth once a day for 11 days in Period 2. |
|
|
| AUC120 of ARV-471 | AUC120 was defined as area under the plasma concentrationtime profile from time zero to 120 hours. AUC120 was calculate by Linear/Log trapezoidal method. | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose |
| Time for Cmax (Tmax) of ARV-471 | Time for Cmax of ARV-471 was observed directly from data as time of first occurrence. | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
| Terminal Half-Life (t1/2) of ARV-471 | Terminal half-life (t1/2) was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
| Apparent Clearance After Oral Dose (CL/F) of ARV-471 | CL/F was defined as apparent oral clearance and calculated by dose/AUCinf. AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinite time. | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
| Apparent Volume of Distribution After Oral Dose (Vz/F) of ARV-471 | Vz/F was defined as apparent volume of distribution calculated by dose/(AUCinf * kel). AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinite time and kel was defined as the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
| AUClast of ARV-473 | ARV-473 was the epimer of ARV-471. AUClast was defined as area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast). AUClast was calculated by Linear/Log trapezoidal method. | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
| Tmax of ARV-473 | ARV-473 was the epimer of ARV-471. Time for Cmax of ARV-473 was observed directly from data as time of first occurrence. | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
| 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 of study intervention (up to 52 days) |
| 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, leukoesterase, urobilinogen, bilirubin], microscopy. Abnormality was determined at the investigator's discretion. | Baseline (Period 1 Day -1) up to Period 2 Day 12 (19 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 5 (11 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 12 (18 days) |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Period 1: ARV-471 200 mg |
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1. |
| OG001 | Period 2: ARV-471 200 mg + Itraconazole 200 mg | Participants received a single dose of Itraconazole 200 mg first, immediately followed by a single dose of ARV-471 200 mg on Period 2 Day 5. |
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) of ARV-471 | Cmax was defined as maximum plasma concentration. Cmax of ARV-471 was observed directly from data. | Analysis population included all participants who received at least 1 dose of ARV-471 and/or itraconazole and had at least 1 of the ARV-471 or ARV-473 PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
|
|
|
|
| Primary | Area Under the Plasma Concentration-Time Profile From Time 0 to 120 Hours (AUC120) of ARV-473 | ARV-473 was the epimer of ARV-471. AUC120 was defined as area under the plasma concentrationtime profile from time zero to 120 hours. AUC120 was calculate by Linear/Log trapezoidal method. | Analysis population included all participants who received at least 1 dose of ARV-471 and/or itraconazole and had at least 1 of the ARV-471 or ARV-473 PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose |
|
|
|
|
| Primary | Cmax of ARV-473 | ARV-473 was the epimer of ARV-471. Cmax was defined as maximum plasma concentration. Cmax of ARV-473 was observed directly from data. | Analysis population included all participants who received at least 1 dose of ARV-471 and/or itraconazole and had at least 1 of the ARV-471 or ARV-473 PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
|
|
|
|
| Secondary | Area Under the Plasma Concentration Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of ARV-471 | AUClast was defined as area under the plasma concentrationtime profile from time zero to the time of the last quantifiable concentration (Clast). AUClast was calculated by Linear/Log trapezoidal method. | Analysis population included all participants who received at least 1 dose of ARV-471 and/or itraconazole and had at least 1 of the ARV-471 or ARV-473 PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
|
|
|
|
| Secondary | AUC120 of ARV-471 | AUC120 was defined as area under the plasma concentrationtime profile from time zero to 120 hours. AUC120 was calculate by Linear/Log trapezoidal method. | Analysis population included all participants who received at least 1 dose of ARV-471 and/or itraconazole and had at least 1 of the ARV-471 or ARV-473 PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose |
|
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|
| Secondary | Time for Cmax (Tmax) of ARV-471 | Time for Cmax of ARV-471 was observed directly from data as time of first occurrence. | Analysis population included all participants who received at least 1 dose of ARV-471 and/or itraconazole and had at least 1 of the ARV-471 or ARV-473 PK parameters of primary interest. | Posted | Median | Full Range | hour | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
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| Secondary | Terminal Half-Life (t1/2) of ARV-471 | Terminal half-life (t1/2) was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. | Analysis population included all participants who received at least 1 dose of ARV-471 and/or itraconazole and had at least 1 of the ARV-471 or ARV-473 PK parameters of primary interest. | Posted | Mean | Standard Deviation | hour | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
|
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| Secondary | Apparent Clearance After Oral Dose (CL/F) of ARV-471 | CL/F was defined as apparent oral clearance and calculated by dose/AUCinf. AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinite time. | Analysis population included all participants who received at least 1 dose of ARV-471 and/or itraconazole and had at least 1 of the ARV-471 or ARV-473 PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour (L/hr) | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
|
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| Secondary | Apparent Volume of Distribution After Oral Dose (Vz/F) of ARV-471 | Vz/F was defined as apparent volume of distribution calculated by dose/(AUCinf * kel). AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinite time and kel was defined as the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. | Analysis population included all participants who received at least 1 dose of ARV-471 and/or itraconazole and had at least 1 of the ARV-471 or ARV-473 PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter (L) | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
|
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|
| Secondary | AUClast of ARV-473 | ARV-473 was the epimer of ARV-471. AUClast was defined as area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast). AUClast was calculated by Linear/Log trapezoidal method. | Analysis population included all participants who received at least 1 dose of ARV-471 and/or itraconazole and had at least 1 of the ARV-471 or ARV-473 PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
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|
|
| Secondary | Tmax of ARV-473 | ARV-473 was the epimer of ARV-471. Time for Cmax of ARV-473 was observed directly from data as time of first occurrence. | Analysis population included all participants who received at least 1 dose of ARV-471 and/or itraconazole and had at least 1 of the ARV-471 or ARV-473 PK parameters of primary interest. | Posted | Median | Full Range | hour | Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose |
|
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| 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 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. | All participants enrolled and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days) |
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| 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, leukoesterase, urobilinogen, bilirubin], microscopy. Abnormality was determined at the investigator's discretion. | All participants enrolled and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | Baseline (Period 1 Day -1) up to Period 2 Day 12 (19 days) |
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| Secondary | 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. | All participants enrolled and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | Baseline (Period 1 Day 1) up to Period 2 Day 5 (11 days) |
|
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| Secondary | 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. | All participants enrolled and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | Baseline (Period 1 Day 1) up to Period 2 Day 12 (18 days) |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 2 |
| 12 |
| EG001 | Itraconazole 200 mg | Participants received itraconazole 200 mg once daily alone over a period of Days 1-4 in Period 2. | 0 | 12 | 0 | 12 | 3 | 12 |
| EG002 | ARV-471 200 mg + Itraconazole 200 mg | Participants received a single dose of ARV-471 200 mg on Day 5 of Period 2 co-administered with itraconazole 200 mg once daily on Days 5-11 in Period 2. | 0 | 12 | 0 | 12 | 2 | 12 |
| Diarrhoea | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Gingival discomfort | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
Not provided
Not provided
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| D010879 |
| Piperazines |
Mixed Model |
Mixed Model |
Mixed Model |
Mixed Model |
Mixed Model |
Mixed Model |
|