Trial Outcomes & Findings for A Study to Learn About How Itraconazole Affects the Blood Level of Study Medicine (PF-07817883) in Healthy Adults. (NCT NCT05822440)

NCT ID: NCT05822440

Last Updated: 2024-10-04

Results Overview

Cmax was observed directly from data and measured in nanogram per milliliter (ng/mL).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

12 participants

Primary outcome timeframe

Period 1: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4

Results posted on

2024-10-04

Participant Flow

A total of 12 participants were enrolled in the study. Study had 2 treatment periods with fixed sequence.

Participant milestones

Participant milestones
Measure
PF-07817883
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
PF-07817883 + Itraconazole
Participants received itraconazole 200 mg orally once in a day (QD) from Day 1 to Day 7 of Period 2. On Day 4 of Period 2, participants received PF-07817883 300 mg as a single oral dose.
Treatment Period 1 (5 Days)
STARTED
12
0
Treatment Period 1 (5 Days)
COMPLETED
12
0
Treatment Period 1 (5 Days)
NOT COMPLETED
0
0
Treatment Period 2 (8 Days)
STARTED
0
12
Treatment Period 2 (8 Days)
COMPLETED
0
12
Treatment Period 2 (8 Days)
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Learn About How Itraconazole Affects the Blood Level of Study Medicine (PF-07817883) in Healthy Adults.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Participants
n=12 Participants
All participants who received PF-07817883 300 mg orally on Day 1 of Period 1 and on Day 4 of Period 2 along with itraconazole 200 mg QD orally from Day 1 to Day 7 of Period 2.
Age, Continuous
38.7 Years
STANDARD_DEVIATION 8.48 • n=5 Participants
Sex: Female, Male
Female
4 Participants
n=5 Participants
Sex: Female, Male
Male
8 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
10 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 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
6 Participants
n=5 Participants
Race (NIH/OMB)
White
4 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: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4

Population: Pharmacokinetic (PK) parameter set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.

Cmax was observed directly from data and measured in nanogram per milliliter (ng/mL).

Outcome measures

Outcome measures
Measure
PF-07817883
n=12 Participants
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
PF-07817883 + Itraconazole
n=11 Participants
Participants received itraconazole 200 mg orally once in a day (QD) from Day 1 to Day 7 of Period 2. On Day 4 of Period 2, participants received PF-07817883 300 mg as a single oral dose.
Itraconazole + PF-07817883
Participants received itraconazole 200 mg QD with PF-07817883 300 mg SD from coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the study.
Maximum Observed Concentration (Cmax) of PF-07817883
4030 ng/mL
Geometric Coefficient of Variation 28
4985 ng/mL
Geometric Coefficient of Variation 41

PRIMARY outcome

Timeframe: Period 1: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4

Population: PK parameter set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.

AUCinf was derived by AUClast + (Clast\*/kel). AUClast was area under the plasma concentration-time profile from time 0 to the time of Clast; 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 loglinear concentration-time curve. AUCinf was measured in nanogram\*hour per milliliter (ng\*hr/mL).

Outcome measures

Outcome measures
Measure
PF-07817883
n=12 Participants
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
PF-07817883 + Itraconazole
n=11 Participants
Participants received itraconazole 200 mg orally once in a day (QD) from Day 1 to Day 7 of Period 2. On Day 4 of Period 2, participants received PF-07817883 300 mg as a single oral dose.
Itraconazole + PF-07817883
Participants received itraconazole 200 mg QD with PF-07817883 300 mg SD from coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the study.
Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883
21720 ng*hr/mL
Geometric Coefficient of Variation 26
46400 ng*hr/mL
Geometric Coefficient of Variation 36

SECONDARY outcome

Timeframe: Day 1 of dosing up to 35 days post last dose of study intervention (maximum up to 48 days)

Population: Safety analysis set included all participants enrolled and took at least 1 dose of study intervention.

An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. 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 defect, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. TEAEs were events that occurred between first dose of study intervention and up to maximum of 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure
PF-07817883
n=12 Participants
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
PF-07817883 + Itraconazole
n=12 Participants
Participants received itraconazole 200 mg orally once in a day (QD) from Day 1 to Day 7 of Period 2. On Day 4 of Period 2, participants received PF-07817883 300 mg as a single oral dose.
Itraconazole + PF-07817883
n=12 Participants
Participants received itraconazole 200 mg QD with PF-07817883 300 mg SD from coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the study.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
1 Participants
3 Participants
2 Participants

SECONDARY outcome

Timeframe: Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)

Population: Safety analysis set included all participants enrolled and took at least 1 dose of study intervention.

Laboratory assessments included: hematology assessments included monocytes/leukocytes (percentage \[%\]) greater than (\>) 1.2\*upper limit of normal (ULN), urinalysis assessments included urine hemoglobin greater than or equal to (\>=) 1, low power field (LPF), urine bacteria \>20/LPF.

Outcome measures

Outcome measures
Measure
PF-07817883
n=12 Participants
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
PF-07817883 + Itraconazole
n=12 Participants
Participants received itraconazole 200 mg orally once in a day (QD) from Day 1 to Day 7 of Period 2. On Day 4 of Period 2, participants received PF-07817883 300 mg as a single oral dose.
Itraconazole + PF-07817883
Participants received itraconazole 200 mg QD with PF-07817883 300 mg SD from coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the study.
Number of Participants With Laboratory Test Abnormalities
0 Participants
3 Participants

SECONDARY outcome

Timeframe: Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)

Population: Safety analysis set included all participants enrolled and took at least 1 dose of study intervention.

Standard 12-lead ECGs was collected using an ECG system that automatically calculates the heart rate (HR) and measures PR interval, QT interval, QTcF, and QRS interval. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position. To ensure safety of the participants, a qualified individual at the investigator site made comparisons to baseline measurements. Pre-defined criteria was defined as 30 milliseconds (ms) less than (\<) change less than or equal to (\<=) 60 ms.

Outcome measures

Outcome measures
Measure
PF-07817883
n=12 Participants
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
PF-07817883 + Itraconazole
n=12 Participants
Participants received itraconazole 200 mg orally once in a day (QD) from Day 1 to Day 7 of Period 2. On Day 4 of Period 2, participants received PF-07817883 300 mg as a single oral dose.
Itraconazole + PF-07817883
Participants received itraconazole 200 mg QD with PF-07817883 300 mg SD from coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the study.
Number of Participants With Electrocardiogram (ECG) Findings Per Pre-defined Criteria
0 Participants
1 Participants

SECONDARY outcome

Timeframe: Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)

Population: Safety analysis set included all participants enrolled and took at least 1 dose of study intervention.

Vital signs included: supine diastolic blood pressure (DBP) measured in millimetre of mercury (mmHg) with criteria value as follows- Value \<50 mmHg, change\>= 20 mmHg increase, change \>= 20 mmHg decrease; supine pulse rate (PR) measured in beats per minute (bpm) with criteria values as follows- value \< 40 bpm, value \> 120 bpm; supine systolic blood pressure (SBP, mmHg) with criteria values as follows- value\< 90 mmHg, change \>= 30 mmHg increase, change \>=30 mmHg decrease. Vital signs (SBP BP, and pulse rate) were measured with participants after having a rest for at least 5 minutes in a supine position. Supine BP was measured with the participant's arm supported at the level of the heart and recorded to the nearest mmHg after approximately 5 minutes of rest. If timing of these measurements coincided with a blood collection, BP and PR were obtained prior to nominal time of blood collection. Only participants having at least 1 vital sign findings per pre-defined criteria are reported.

Outcome measures

Outcome measures
Measure
PF-07817883
n=12 Participants
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
PF-07817883 + Itraconazole
n=12 Participants
Participants received itraconazole 200 mg orally once in a day (QD) from Day 1 to Day 7 of Period 2. On Day 4 of Period 2, participants received PF-07817883 300 mg as a single oral dose.
Itraconazole + PF-07817883
Participants received itraconazole 200 mg QD with PF-07817883 300 mg SD from coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the study.
Number of Participants With Vital Signs Findings Per Pre-defined Criteria
0 Participants
1 Participants

SECONDARY outcome

Timeframe: Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)

Population: Safety analysis set included all participants enrolled and took at least 1 dose of study intervention.

A complete physical examination included, at a minimum, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. A brief physical examination included, at a minimum, assessments of general appearance, the respiratory and CV systems, and participant-reported symptoms. Physical examinations were conducted by a physician, trained physician's assistant, or nurse practitioner as acceptable according to local regulation. Clinical significance of physical examination abnormalities was judged by physicians.

Outcome measures

Outcome measures
Measure
PF-07817883
n=12 Participants
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
PF-07817883 + Itraconazole
n=12 Participants
Participants received itraconazole 200 mg orally once in a day (QD) from Day 1 to Day 7 of Period 2. On Day 4 of Period 2, participants received PF-07817883 300 mg as a single oral dose.
Itraconazole + PF-07817883
Participants received itraconazole 200 mg QD with PF-07817883 300 mg SD from coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the study.
Number of Participants With Clinically Significant Abnormalities in Physical Examination
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Period 1: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4

Population: PK parameter set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.

Tmax is the time taken (in hours) to reach the maximum serum drug concentration. Tmax was observed directly from data as time of first occurrence.

Outcome measures

Outcome measures
Measure
PF-07817883
n=12 Participants
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
PF-07817883 + Itraconazole
n=11 Participants
Participants received itraconazole 200 mg orally once in a day (QD) from Day 1 to Day 7 of Period 2. On Day 4 of Period 2, participants received PF-07817883 300 mg as a single oral dose.
Itraconazole + PF-07817883
Participants received itraconazole 200 mg QD with PF-07817883 300 mg SD from coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the study.
Time to Reach Cmax (Tmax) of PF-07817883
1.76 Hours
Interval 0.517 to 4.03
2.00 Hours
Interval 1.52 to 4.0

SECONDARY outcome

Timeframe: Period 1: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4

Population: PK parameter set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.

Terminal half-life was defined as the time measured for the plasma concentration of drug to decrease by one half. t1/2 was determined by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.

Outcome measures

Outcome measures
Measure
PF-07817883
n=12 Participants
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
PF-07817883 + Itraconazole
n=11 Participants
Participants received itraconazole 200 mg orally once in a day (QD) from Day 1 to Day 7 of Period 2. On Day 4 of Period 2, participants received PF-07817883 300 mg as a single oral dose.
Itraconazole + PF-07817883
Participants received itraconazole 200 mg QD with PF-07817883 300 mg SD from coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the study.
Terminal Phase Half-Life (t1/2) of PF-07817883
5.502 Hours
Standard Deviation 2.3703
10.92 Hours
Standard Deviation 8.3667

SECONDARY outcome

Timeframe: Period 1: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4

Population: PK parameter set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf).

Outcome measures

Outcome measures
Measure
PF-07817883
n=12 Participants
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
PF-07817883 + Itraconazole
n=11 Participants
Participants received itraconazole 200 mg orally once in a day (QD) from Day 1 to Day 7 of Period 2. On Day 4 of Period 2, participants received PF-07817883 300 mg as a single oral dose.
Itraconazole + PF-07817883
Participants received itraconazole 200 mg QD with PF-07817883 300 mg SD from coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the study.
Apparent Clearance (CL/F) of PF-07817883
13.81 Liter/Hours
Geometric Coefficient of Variation 26
6.469 Liter/Hours
Geometric Coefficient of Variation 36

SECONDARY outcome

Timeframe: Period 1: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4

Population: PK parameter set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Outcome measures

Outcome measures
Measure
PF-07817883
n=12 Participants
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
PF-07817883 + Itraconazole
n=11 Participants
Participants received itraconazole 200 mg orally once in a day (QD) from Day 1 to Day 7 of Period 2. On Day 4 of Period 2, participants received PF-07817883 300 mg as a single oral dose.
Itraconazole + PF-07817883
Participants received itraconazole 200 mg QD with PF-07817883 300 mg SD from coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the study.
Apparent Volume of Distribution (Vz/F) of PF-07817883
100.4 Liter
Geometric Coefficient of Variation 63
86.29 Liter
Geometric Coefficient of Variation 51

Adverse Events

PF-07817883

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Itraconazole

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Itraconazole + PF-07817883

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
PF-07817883
n=12 participants at risk
Participants received PF-07817883 300 milligrams (mg) as a single oral dose on Day 1 of Period 1.
Itraconazole
n=12 participants at risk
Participants received itraconazole 200 mg orally once in a day (QD) alone from first dose of itraconazole administered alone in Period 2 Day 1 up to just before coadministration of PF-07817883 in Period 2 Day 4.
Itraconazole + PF-07817883
n=12 participants at risk
Participants received itraconazole 200 mg QD with PF-07817883 300 mg SD from coadministration of PF-07817883 with itraconazole in Period 2 Day 4 through the end of the study.
Gastrointestinal disorders
Abdominal distension
8.3%
1/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
Gastrointestinal disorders
Diarrhoea
8.3%
1/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
8.3%
1/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
Gastrointestinal disorders
Mouth haemorrhage
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
8.3%
1/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
Gastrointestinal disorders
Nausea
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
8.3%
1/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
Gastrointestinal disorders
Vomiting
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
8.3%
1/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
8.3%
1/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
General disorders
Feeling hot
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
8.3%
1/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
Nervous system disorders
Dizziness
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
8.3%
1/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
8.3%
1/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
Skin and subcutaneous tissue disorders
Ingrown hair
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
0.00%
0/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)
8.3%
1/12 • Day 1 up to 35 days after last dose of study drug (maximum up to 48 days)

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Results disclosure agreements

  • Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
  • Publication restrictions are in place

Restriction type: OTHER