Trial Outcomes & Findings for Drug-Drug Interaction Study Assessing Effect of Itraconazole on PF-07321332/Ritonavir in Healthy Participants (NCT NCT04962022)
NCT ID: NCT04962022
Last Updated: 2023-07-13
Results Overview
The Cmax of PF-07321332 in the study was observed directly from data.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
12 participants
Primary outcome timeframe
Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2.
Results posted on
2023-07-13
Participant Flow
This was a 2-period,fixed-sequence crossover study. A total of 12 participants were assigned to and received the treatment in period 1. One participant discontinued due to withdrawal. The remaining 11 participants completed Period 1 and continued to receive the treatment in Period 2 and all completed Period 2.
Participant milestones
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Period 1
STARTED
|
12
|
0
|
|
Period 1
COMPLETED
|
11
|
0
|
|
Period 1
NOT COMPLETED
|
1
|
0
|
|
Period 2
STARTED
|
0
|
11
|
|
Period 2
COMPLETED
|
0
|
11
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Period 1
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Drug-Drug Interaction Study Assessing Effect of Itraconazole on PF-07321332/Ritonavir in Healthy Participants
Baseline characteristics by cohort
| Measure |
Overall Study
n=12 Participants
All participants who received PF-07321332 (suspension)/ritonavir 300/100 mg, Itraconazole 200 mg and PF-07321332(suspension)/ritonavir 300/100 mg in Period 1 and 2, respectively.
|
|---|---|
|
Age, Customized
<18 years
|
0 Participants
n=99 Participants
|
|
Age, Customized
18-25 years
|
0 Participants
n=99 Participants
|
|
Age, Customized
26-35 years
|
5 Participants
n=99 Participants
|
|
Age, Customized
36-45 years
|
3 Participants
n=99 Participants
|
|
Age, Customized
>45 years
|
4 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2.Population: The analysis population included all participants who took at least 1 dose of study intervention and in whom at least 1 concentration value was reported.
The Cmax of PF-07321332 in the study was observed directly from data.
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Maximum Observed Concentration (Cmax) of PF-07321332
|
4678 ng/mL
Geometric Coefficient of Variation 17
|
5546 ng/mL
Geometric Coefficient of Variation 15
|
PRIMARY outcome
Timeframe: Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2.Population: The analysis population included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
The AUCtau of PF-07321332 was determined by Linear/Log trapezoidal method.
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Profile From Time Zero to Time Tau (τ), Where Tau=12-hour Dosing Interval(AUCtau) for PF-07321332
|
33350 ng*hr/mL
Geometric Coefficient of Variation 20
|
46290 ng*hr/mL
Geometric Coefficient of Variation 18
|
SECONDARY outcome
Timeframe: Screening up to Day 35Population: The analysis population included all participants who took at least 1 dose of study intervention. Participants was analyzed according to the product they actually received.
An Adverse event (AE) was any untoward medical occurrence in a participant. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth, was a suspected transmission via a Pfizer product of an infectious agent,pathogenic or non-pathogenic, was considered serious. The focus of AE summaries was on treatment-emergent AE (TEAE). An AE was considered TEAE if the event occurred during the on-treatment period.
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=12 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Participants with TEAEs
|
7 Participants
|
10 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Participants with serious TEAEs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Screening up to Day 9 of Period 2 or Early termination/discontinuation.Population: The analysis population included all participants who took at least 1 dose of study intervention.
Safety laboratory assessments included urinalysis, hematology, chemistry and other. All the safety laboratory samples were collected following at least a 4-hour fast.
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=12 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Monocytes/Leukocytes（%）> 1.2 ✖ ULN
|
1 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Bicarbonate(mEq/L) > 1.1 ✖ ULN
|
6 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Fibrinogen(mg/dl) > 1.25 ✖ Baseline
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Leukocyte Esterase >= 1
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Screening up to Day 9 of Period 2 or Early termination/discontinuation.Population: The analysis population included all participants who took at least 1 dose of study intervention.
Triplicate 12-lead ECG readings approximately 2 minutes apart were taken at each test. All ECG assessments were made after at least a 5-minute rest in a supine position and prior to any blood draws or vital sign measurements.
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=12 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings
PR interval, Aggregate (msec) Value >= 300
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings
PR interval, Aggregate (msec) %Change >= 25/50%
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings
QRS Duration, Aggregate (msec) Value >= 140
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings
QRS Duration, Aggregate (msec) %Change >= 50%
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings
QTcF interval, Aggregate (msec) 450 < Value < = 480
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings
QTcF interval, Aggregate (msec) 480 < Value < = 500
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings
QTcF interval, Aggregate (msec) Value > 500
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings
QTcF interval, Aggregate (msec) 30 < Change < = 60
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings
QTcF interval, Aggregate (msec) Change > 60
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Screening up to Day 9 of Period 2 or Early termination/discontinuation.Population: The analysis population included all participants who took at least 1 dose of study intervention.
Vital signs(systolic and diastolic blood pressure, and pulse rate) were measured with participants after having a rest for at least 5 minutes in a supine position. Vital signs assessment were performed after collection of ECGs and prior to collection of blood draws if scheduled at the same time.
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=12 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Change From Baseline in Vital Signs Data - Supine Systolic Blood Pressure
Period 1/Day 3 0 hour (H)
|
1.4 mmHg
Standard Deviation 9.84
|
—
|
|
Change From Baseline in Vital Signs Data - Supine Systolic Blood Pressure
Period 1/Day 3 1H 30min
|
1.5 mmHg
Standard Deviation 9.03
|
—
|
|
Change From Baseline in Vital Signs Data - Supine Systolic Blood Pressure
Period 2/Day 4 0H
|
—
|
2.6 mmHg
Standard Deviation 11.34
|
|
Change From Baseline in Vital Signs Data - Supine Systolic Blood Pressure
Period 2/Day6 0H
|
—
|
3.6 mmHg
Standard Deviation 8.43
|
|
Change From Baseline in Vital Signs Data - Supine Systolic Blood Pressure
Period 2/Day6 1H
|
—
|
5.5 mmHg
Standard Deviation 10.11
|
|
Change From Baseline in Vital Signs Data - Supine Systolic Blood Pressure
Period 2/Day6 1H 30min
|
—
|
5.3 mmHg
Standard Deviation 13.52
|
|
Change From Baseline in Vital Signs Data - Supine Systolic Blood Pressure
Period 2/Day6 72 H
|
—
|
6.4 mmHg
Standard Deviation 10.11
|
SECONDARY outcome
Timeframe: Screening up to Day 9 of Period 2 or Early termination/discontinuation.Population: The analysis population included all participants who took at least 1 dose of study intervention.
Vital signs(systolic and diastolic blood pressure, and pulse rate) were measured with participants after having a rest for at least 5 minutes in a supine position. Vital signs assessment were performed after collection of ECGs and prior to collection of blood draws if scheduled at the same time.
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=12 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Change From Baseline in Vital Signs Data - Supine Diastolic Blood Pressure
Period 1/Day 3 0H
|
-0.9 mmHg
Standard Deviation 4.97
|
—
|
|
Change From Baseline in Vital Signs Data - Supine Diastolic Blood Pressure
Period 1/Day 3 1H 30min
|
0.5 mmHg
Standard Deviation 4.74
|
—
|
|
Change From Baseline in Vital Signs Data - Supine Diastolic Blood Pressure
Period 2/Day 4 0H
|
—
|
4.1 mmHg
Standard Deviation 4.09
|
|
Change From Baseline in Vital Signs Data - Supine Diastolic Blood Pressure
Period 2/Day 6 0H
|
—
|
3.5 mmHg
Standard Deviation 4.44
|
|
Change From Baseline in Vital Signs Data - Supine Diastolic Blood Pressure
Period 2/Day 6 1H
|
—
|
4.9 mmHg
Standard Deviation 4.87
|
|
Change From Baseline in Vital Signs Data - Supine Diastolic Blood Pressure
Period 2/Day 6 1H 30min
|
—
|
4.2 mmHg
Standard Deviation 5.44
|
|
Change From Baseline in Vital Signs Data - Supine Diastolic Blood Pressure
Period 2/Day 6 72H
|
—
|
2.9 mmHg
Standard Deviation 6.28
|
SECONDARY outcome
Timeframe: Screening up to Day 9 of Period 2 or Early termination/discontinuation.Population: The analysis population included all participants who took at least 1 dose of study intervention.
Vital signs(systolic and diastolic blood pressure, and pulse rate) were measured with participants after having a rest for at least 5 minutes in a supine position. Vital signs assessment were performed after collection of ECGs and prior to collection of blood draws if scheduled at the same time.
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=12 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Change From Baseline in Vital Signs Data - Supine Pulse Rate
Period 1/Day 3 0 H
|
-0.5 beats per minute(bpm)
Standard Deviation 5.92
|
—
|
|
Change From Baseline in Vital Signs Data - Supine Pulse Rate
Period 1/Day 3 1 H 30 min
|
-3.1 beats per minute(bpm)
Standard Deviation 4.64
|
—
|
|
Change From Baseline in Vital Signs Data - Supine Pulse Rate
Period 2/Day 4 0 H
|
—
|
-2.4 beats per minute(bpm)
Standard Deviation 5.50
|
|
Change From Baseline in Vital Signs Data - Supine Pulse Rate
Period 2/Day 6 0 H
|
—
|
-2.5 beats per minute(bpm)
Standard Deviation 8.26
|
|
Change From Baseline in Vital Signs Data - Supine Pulse Rate
Period 2/Day 6 1 H
|
—
|
-0.8 beats per minute(bpm)
Standard Deviation 10.84
|
|
Change From Baseline in Vital Signs Data - Supine Pulse Rate
Period 2/Day 6 1 H 30 min
|
—
|
-2.1 beats per minute(bpm)
Standard Deviation 12.79
|
|
Change From Baseline in Vital Signs Data - Supine Pulse Rate
Period 2/Day 6 72 H
|
—
|
0.3 beats per minute(bpm)
Standard Deviation 9.96
|
SECONDARY outcome
Timeframe: Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2Population: The analysis population included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
PF-07321332 Tmax was observed directed from data
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Time for Cmax (Tmax) for PF-07321332
|
1.020 hours(hr)
Interval 0.5 to 2.08
|
1.700 hours(hr)
Interval 0.5 to 4.0
|
SECONDARY outcome
Timeframe: Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2Population: The analysis population included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, "Number of Participants analyzed" signifies number of participants evaluable for this outcome measure.
Terminal half-life was defined as the time measured for the plasma concentration of drug to decrease by one half.
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=10 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Terminal Half-life(t1/2) of PF-07321332
|
8.255 hours(hr)
Standard Deviation 1.9465
|
7.793 hours(hr)
Standard Deviation 0.89019
|
SECONDARY outcome
Timeframe: Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2.Population: The analysis population included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
AUClast of PF-07321332 was determined by Linear/Log trapezoidal method.
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration(AUClast) of PF-07321332
|
41840 ng*hr/mL
Geometric Coefficient of Variation 21
|
74430 ng*hr/mL
Geometric Coefficient of Variation 21
|
SECONDARY outcome
Timeframe: Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2.Population: The analysis population included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
CL/F was apparent clearance.
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
|
Apparent Clearance(CL/F) of PF-07321332
|
8.990 L/hr
Geometric Coefficient of Variation 20
|
6.478 L/hr
Geometric Coefficient of Variation 18
|
SECONDARY outcome
Timeframe: Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2.Population: The analysis population included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, "Number of Participants analyzed" signifies number of participants evaluable for this outcome measure.
Vz/F was apparent volume of distribution.
Outcome measures
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 Participants
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning of Period 1.
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Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=10 Participants
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
|
|---|---|---|
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Apparent Volume of Distribution (Vz/F) of PF-07321332
|
104.7 L
Geometric Coefficient of Variation 33
|
72.07 L
Geometric Coefficient of Variation 16
|
Adverse Events
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
n=12 participants at risk
Participants received PF-07321332/ritonavir 300/100 mg administered orally every 12 hours for a total of 5 doses, from Day 1 morning to Day 3 morning in Period 1.
|
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
n=11 participants at risk
Participants received itraconazole 200 mg orally once a day from Days 1 through 8 of Period 2, for a total of 8 doses; and PF-07321332/ritonavir 300/100 mg administered orally every 12 hours from Days 4 through 6 of Period 2, for a total of 5 doses.
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|---|---|---|
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Cardiac disorders
Atrioventricular block first degree
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
0.00%
0/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Abdominal distension
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
2/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
36.4%
4/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Abdominal pain lower
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
0.00%
0/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Anorectal discomfort
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Breath odour
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
27.3%
3/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Change of bowel habit
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
0.00%
0/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
18.2%
2/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
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Gastrointestinal disorders
Diarrhoea
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
54.5%
6/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
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Gastrointestinal disorders
Dry mouth
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
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Gastrointestinal disorders
Dyspepsia
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Flatulence
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
0.00%
0/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Gastrointestinal motility disorder
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
0.00%
0/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Nausea
|
16.7%
2/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
18.2%
2/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
0.00%
0/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Nervous system disorders
Dizziness
|
16.7%
2/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
0.00%
0/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Nervous system disorders
Dysgeusia
|
16.7%
2/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
27.3%
3/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Nervous system disorders
Headache
|
33.3%
4/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
27.3%
3/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
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Nervous system disorders
Restless legs syndrome
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
0.00%
0/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Renal and urinary disorders
Pollakiuria
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Reproductive system and breast disorders
Testicular pain
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
General disorders
Asthenia
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
18.2%
2/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
General disorders
Fatigue
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
18.2%
2/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
General disorders
Feeling hot
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
General disorders
Influenza like illness
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
General disorders
Injection site pain
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
General disorders
Vessel puncture site haematoma
|
8.3%
1/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
0.00%
0/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
|
Ear and labyrinth disorders
Ear discomfort
|
0.00%
0/12 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
|
9.1%
1/11 • From screening up to Day 35.
Serious adverse events(SAE) and non-serious AEs were recorded on the case report form.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place