Trial Outcomes & Findings for A Study to Understand the Effect of Itraconazole on the Levels of a Study Medicine Called ARV-471 in Healthy Adults (NCT NCT05538312)
NCT ID: NCT05538312
Last Updated: 2024-09-23
Results Overview
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.
COMPLETED
PHASE1
12 participants
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
2024-09-23
Participant Flow
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.
Participant milestones
| Measure |
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.
|
|---|---|
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Period 1 (6 Days)
STARTED
|
12
|
|
Period 1 (6 Days)
COMPLETED
|
12
|
|
Period 1 (6 Days)
NOT COMPLETED
|
0
|
|
Period 2 (12 Days)
STARTED
|
12
|
|
Period 2 (12 Days)
COMPLETED
|
12
|
|
Period 2 (12 Days)
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Understand the Effect of Itraconazole on the Levels of a Study Medicine Called ARV-471 in Healthy Adults
Baseline characteristics by cohort
| Measure |
All Participants
n=12 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.
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|---|---|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
41.33 Years
STANDARD_DEVIATION 11.52 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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-dosePopulation: 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.
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.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of ARV-471
|
18960 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 23
|
32020 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 24
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: 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.
Cmax was defined as maximum plasma concentration. Cmax of ARV-471 was observed directly from data.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of ARV-471
|
517.9 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 22
|
788.2 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 19
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: 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.
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.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-Time Profile From Time 0 to 120 Hours (AUC120) of ARV-473
|
4734 ng*hr/mL
Geometric Coefficient of Variation 30
|
7668 ng*hr/mL
Geometric Coefficient of Variation 28
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: 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.
ARV-473 was the epimer of ARV-471. Cmax was defined as maximum plasma concentration. Cmax of ARV-473 was observed directly from data.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
Cmax of ARV-473
|
56.37 ng/mL
Geometric Coefficient of Variation 26
|
86.31 ng/mL
Geometric Coefficient of Variation 27
|
—
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
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.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
Area Under the Plasma Concentration Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of ARV-471
|
16730 ng*hr/mL
Geometric Coefficient of Variation 24
|
28710 ng*hr/mL
Geometric Coefficient of Variation 21
|
—
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
AUC120 was defined as area under the plasma concentrationtime profile from time zero to 120 hours. AUC120 was calculate by Linear/Log trapezoidal method.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
AUC120 of ARV-471
|
16730 ng*hr/mL
Geometric Coefficient of Variation 24
|
26400 ng*hr/mL
Geometric Coefficient of Variation 20
|
—
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
Time for Cmax of ARV-471 was observed directly from data as time of first occurrence.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
Time for Cmax (Tmax) of ARV-471
|
6.00 hour
Interval 2.0 to 8.0
|
6.00 hour
Interval 4.0 to 8.0
|
—
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
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.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
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|---|---|---|---|
|
Terminal Half-Life (t1/2) of ARV-471
|
42.64 hour
Standard Deviation 4.0800
|
61.57 hour
Standard Deviation 9.1196
|
—
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
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.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
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|---|---|---|---|
|
Apparent Clearance After Oral Dose (CL/F) of ARV-471
|
10.54 liter per hour (L/hr)
Geometric Coefficient of Variation 23
|
6.245 liter per hour (L/hr)
Geometric Coefficient of Variation 24
|
—
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
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.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
Apparent Volume of Distribution After Oral Dose (Vz/F) of ARV-471
|
645.6 liter (L)
Geometric Coefficient of Variation 29
|
549.5 liter (L)
Geometric Coefficient of Variation 20
|
—
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
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.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
AUClast of ARV-473
|
4734 ng*hr/mL
Geometric Coefficient of Variation 30
|
9129 ng*hr/mL
Geometric Coefficient of Variation 31
|
—
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
ARV-473 was the epimer of ARV-471. Time for Cmax of ARV-473 was observed directly from data as time of first occurrence.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
Tmax of ARV-473
|
24.0 hour
Interval 24.0 to 48.1
|
35.9 hour
Interval 12.0 to 47.8
|
—
|
SECONDARY outcome
Timeframe: From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days)Population: All participants enrolled and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Treatment-emergent SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Treatment-emergent AEs
|
2 Participants
|
3 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline (Period 1 Day -1) up to Period 2 Day 12 (19 days)Population: All participants enrolled and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
Number of Participants With Clinical Laboratory Abnormalities
|
4 Participants
|
1 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline (Period 1 Day 1) up to Period 2 Day 5 (11 days)Population: All participants enrolled and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline (Period 1 Day 1) up to Period 2 Day 12 (18 days)Population: All participants enrolled and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Period 1: ARV-471 200 mg
n=12 Participants
Participants received a single dose of ARV-471 200 mg on Period 1 Day 1.
|
Period 2: ARV-471 200 mg + Itraconazole 200 mg
n=12 Participants
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.
|
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.
|
|---|---|---|---|
|
Number of Participants With Electrocardiogram (ECG) Abnormalities
|
0 Participants
|
0 Participants
|
—
|
Adverse Events
ARV-471 200 mg
Itraconazole 200 mg
ARV-471 200 mg + Itraconazole 200 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
ARV-471 200 mg
n=12 participants at risk
Participants received a single dose of ARV-471 200 mg on Day 1 of Period 1.
|
Itraconazole 200 mg
n=12 participants at risk
Participants received itraconazole 200 mg once daily alone over a period of Days 1-4 in Period 2.
|
ARV-471 200 mg + Itraconazole 200 mg
n=12 participants at risk
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.
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|---|---|---|---|
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Gastrointestinal disorders
Abdominal pain
|
8.3%
1/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
8.3%
1/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
0.00%
0/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
|
Gastrointestinal disorders
Diarrhoea
|
8.3%
1/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
8.3%
1/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
8.3%
1/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
|
Gastrointestinal disorders
Gingival discomfort
|
0.00%
0/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
8.3%
1/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
0.00%
0/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
|
General disorders
Fatigue
|
0.00%
0/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
0.00%
0/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
8.3%
1/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
1/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
0.00%
0/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
0.00%
0/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
|
Nervous system disorders
Somnolence
|
0.00%
0/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
0.00%
0/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
8.3%
1/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
8.3%
1/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
0.00%
0/12 • From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place