Healthy
Conditions
Brief summary
The purpose of this study is to estimate the oral bioavailability of 3 new formulations of PF-07817883 (test) relative to reference tablet formulation in healthy adult participants under fasted conditions. The study will also assess the safety and tolerability of test and reference tablet formulations in healthy adult participants.
Detailed description
This is a Phase 1, open-label, randomized, 4-period, 4-sequence crossover study in healthy adult participants evaluating the rBA of 3 new PF-07817883 test oral formulation(s) compared to PF-07817883 reference oral formulation. Approximately 12 participants will be enrolled in this study with approximately equal number of participants randomized to 1 of 4 sequences.
Interventions
DRUGDrug: PF-07817883
PF-07817883 tablet
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study.
Intervention model description
4 period 4 sequence crossover design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male and female participants aged 18 years or older, at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and standard 12-lead ECG. * BMI of 16 to 32 kg/m2; and a total body weight \>45 kg * Capable of giving signed informed consent.
Exclusion criteria
* Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior, laboratory abnormality, or other conditions and situations that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. * Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). 1. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). 2. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed. * Positive test result for SARS-CoV-2 infection at admission
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Observed Plasma Concentration (Cmax) of PF-07817883 | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hours post-dose on Day 1 of each treatment period |
| Area Under the Concentration-time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of PF-07817883 | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hours post-dose on Day 1 of each treatment period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From start of study treatment (Day 1) up to 28-35 days after last dose of study treatment (maximum up to 47 days) | An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. Treatment-emergent are events between first dose of study treatment and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
| Number of Participants With Laboratory Test Abnormalities | From start of study treatment (Day 1) up to last dose of study treatment (maximum up to 12 days) | Laboratory parameters included hematology (eosinophils/leukocytes \[%\] greater than \[\>\] 1.2\*upper limit of normal), and urinalysis (urine hemoglobin and leukocyte esterase greater than or equal \[\>=\] to 1). |
| Number of Participants With Clinically Significant Abnormality in Vital Signs | From start of study treatment (Day 1) up to last dose of study treatment (maximum up to 12 days) | Vital signs included diastolic blood pressure (DBP), systolic blood pressure (SBP) and pulse rate (PR) were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value less than (\<) 90 millimeters of mercury (mmHg), change from baseline greater than or equal to (\>=) 30 mmHg increase, change from baseline \>=30 mmHg decrease; DBP: value \<50 mmHg, change from baseline \>=20 mmHg increase, change from baseline \>=20 mmHg decrease; PR: value \<40 beats per minute (bpm), value greater than (\>) 120 bpm. |
| Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG) | From start of study treatment (Day 1) up to last dose of study treatment (maximum up to 12 days) | Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest. Criteria were PR interval (\>=300 millisecond \[msec\], percent \[%\] change from baseline \>=25 to 50%), QRS duration (\>=140 msec, %change from baseline \>=50%), corrected QT interval using Fridericia's formula (QTcF) (\>500 msec, %change from baseline \>60 msec, 450 msec\<value less than equal to \[\<=\] 480 msec, 480 msec\<value\<=500 msec, 30 msec\<=change\<=60 msec). |
Countries
Belgium
Participant flow
Recruitment details
A total of 12 participants were enrolled and randomized in this study to 1 of the 4 study treatment sequences.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence 1: A Then B Then C Then D Participants were randomized to receive a single oral dose of treatment A on Day 1 of Period 1; followed by a single oral dose of treatment B on Day 1 of Period 2; followed by a single oral dose of treatment C on Day 1 of Period 3; followed by a single oral dose of treatment D on Day 1 of Period 4. Between 2 doses of consecutive period there was a gap of at least 48 hours (2 days). A=PF-07817883 300 mg tablet reference formulation, B=PF-07817883 300 mg tablet test formulation 1, C=PF-07817883 300 mg tablet test formulation 2 and D=PF-07817883 300 mg tablet test formulation 3. All formulations were administered under fasting condition. | 3 |
| Treatment Sequence 2: B Then D Then A Then C Participants were randomized to receive a single oral dose of treatment B on Day 1 of Period 1; followed by a single oral dose of treatment D on Day 1 of Period 2; followed by a single oral dose of treatment A on Day 1 of Period 3; followed by a single oral dose of treatment C on Day 1 of Period 4. Between 2 doses of consecutive period there was a gap of at least 48 hours (2 days). A=PF-07817883 300 mg tablet reference formulation, B=PF-07817883 300 mg tablet test formulation 1, C=PF-07817883 300 mg tablet test formulation 2 and D=PF-07817883 300 mg tablet test formulation 3. All formulations were administered under fasting condition. | 3 |
| Treatment Sequence 3: C Then A Then D Then B Participants were randomized to receive a single oral dose of treatment C on Day 1 of Period 1; followed by a single oral dose of treatment A on Day 1 of Period 2; followed by a single oral dose of treatment D on Day 1 of Period 3; followed by a single oral dose of treatment B on Day 1 of Period 4. Between 2 doses of consecutive period there was a gap of at least 48 hours (2 days). A=PF-07817883 300 mg tablet reference formulation, B=PF-07817883 300 mg tablet test formulation 1, C=PF-07817883 300 mg tablet test formulation 2 and D=PF-07817883 300 mg tablet test formulation 3. All formulations were administered under fasting condition. | 3 |
| Treatment Sequence 4: D Then C Then B Then A Participants were randomized to receive a single oral dose of treatment D on Day 1 of Period 1; followed by a single oral dose of treatment C on Day 1 of Period 2; followed by a single oral dose of treatment B on Day 1 of Period 3; followed by a single oral dose of treatment A on Day 1 of Period 4. Between 2 doses of consecutive period there was a gap of at least 48 hours (2 days). A=PF-07817883 300 mg tablet reference formulation, B=PF-07817883 300 mg tablet test formulation 1, C=PF-07817883 300 mg tablet test formulation 2 and D=PF-07817883 300 mg tablet test formulation 3. All formulations were administered under fasting condition. | 3 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 1 (3 Days) | Adverse Event | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Treatment Sequence 1: A Then B Then C Then D | Treatment Sequence 2: B Then D Then A Then C | Treatment Sequence 3: C Then A Then D Then B | Treatment Sequence 4: D Then C Then B Then A | Total |
|---|---|---|---|---|---|
| Age, Continuous Mean (SD) | 58.7 Years STANDARD_DEVIATION 4.93 | 34.7 Years STANDARD_DEVIATION 3.06 | 41.3 Years STANDARD_DEVIATION 18.15 | 51.0 Years STANDARD_DEVIATION 21.28 | 46.4 Years STANDARD_DEVIATION 15.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 2 / 11 | 2 / 11 | 3 / 12 | 2 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 12 | 0 / 11 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of PF-07817883
Time frame: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hours post-dose on Day 1 of each treatment period
Population: PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest in at least 1 treatment period. Here, Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: PF-07817883 300 mg Reference Formulation | Area Under the Concentration-time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of PF-07817883 | 17660 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 35 |
| Treatment B: PF-07817883 300 mg Test Formulation 1 | Area Under the Concentration-time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of PF-07817883 | 18200 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 22 |
| Treatment C: PF-07817883 300 mg Test Formulation 2 | Area Under the Concentration-time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of PF-07817883 | 21040 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 36 |
| Treatment D: PF-07817883 300 mg Test Formulation 3 | Area Under the Concentration-time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of PF-07817883 | 21510 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 33 |
Comparison: Natural log transformed AUCinf for PF-07817883 were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect in Periods 1 to 4. The ratio (Test/Reference) and 90% CIs were expressed as percentages.90% CI: [91.09, 115.54]
Comparison: Natural log transformed AUCinf for PF-07817883 were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect in Periods 1 to 4. The ratio (Test/Reference) and 90% CIs were expressed as percentages.90% CI: [110.81, 141.17]
Comparison: Natural log transformed AUCinf for PF-07817883 were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect in Periods 1 to 4. The ratio (Test/Reference) and 90% CIs were expressed as percentages.90% CI: [108.65, 136.43]
Primary
Maximum Observed Plasma Concentration (Cmax) of PF-07817883
Time frame: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hours post-dose on Day 1 of each treatment period
Population: Pharmacokinetic (PK) parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: PF-07817883 300 mg Reference Formulation | Maximum Observed Plasma Concentration (Cmax) of PF-07817883 | 2308 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 39 |
| Treatment B: PF-07817883 300 mg Test Formulation 1 | Maximum Observed Plasma Concentration (Cmax) of PF-07817883 | 2579 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| Treatment C: PF-07817883 300 mg Test Formulation 2 | Maximum Observed Plasma Concentration (Cmax) of PF-07817883 | 4266 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| Treatment D: PF-07817883 300 mg Test Formulation 3 | Maximum Observed Plasma Concentration (Cmax) of PF-07817883 | 3566 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
Comparison: Natural log transformed Cmax for PF-07817883 were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect in Periods 1 to 4. The ratio (Test/Reference) and 90 percent (%) confidence intervals (CIs) were expressed as percentages.90% CI: [93.01, 135.22]
Comparison: Natural log transformed Cmax for PF-07817883 were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect in Periods 1 to 4. The ratio (Test/Reference) and 90% CIs were expressed as percentages.90% CI: [155.79, 225.35]
Comparison: Natural log transformed Cmax for PF-07817883 were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect in Periods 1 to 4. The ratio (Test/Reference) and 90% CIs were expressed as percentages.90% CI: [127.4, 185.21]
Secondary
Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG)
Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest. Criteria were PR interval (\>=300 millisecond \[msec\], percent \[%\] change from baseline \>=25 to 50%), QRS duration (\>=140 msec, %change from baseline \>=50%), corrected QT interval using Fridericia's formula (QTcF) (\>500 msec, %change from baseline \>60 msec, 450 msec\<value less than equal to \[\<=\] 480 msec, 480 msec\<value\<=500 msec, 30 msec\<=change\<=60 msec).
Time frame: From start of study treatment (Day 1) up to last dose of study treatment (maximum up to 12 days)
Population: Safety analysis set included all participants randomly assigned to study treatment and who took at least 1 dose of study treatment in at least one treatment period. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: PF-07817883 300 mg Reference Formulation | Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG) | 0 Participants |
| Treatment B: PF-07817883 300 mg Test Formulation 1 | Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG) | 0 Participants |
| Treatment C: PF-07817883 300 mg Test Formulation 2 | Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG) | 0 Participants |
| Treatment D: PF-07817883 300 mg Test Formulation 3 | Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG) | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormality in Vital Signs
Vital signs included diastolic blood pressure (DBP), systolic blood pressure (SBP) and pulse rate (PR) were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value less than (\<) 90 millimeters of mercury (mmHg), change from baseline greater than or equal to (\>=) 30 mmHg increase, change from baseline \>=30 mmHg decrease; DBP: value \<50 mmHg, change from baseline \>=20 mmHg increase, change from baseline \>=20 mmHg decrease; PR: value \<40 beats per minute (bpm), value greater than (\>) 120 bpm.
Time frame: From start of study treatment (Day 1) up to last dose of study treatment (maximum up to 12 days)
Population: Safety analysis set included all participants randomly assigned to study treatment and who took at least 1 dose of study treatment in at least one treatment period. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: PF-07817883 300 mg Reference Formulation | Number of Participants With Clinically Significant Abnormality in Vital Signs | 0 Participants |
| Treatment B: PF-07817883 300 mg Test Formulation 1 | Number of Participants With Clinically Significant Abnormality in Vital Signs | 0 Participants |
| Treatment C: PF-07817883 300 mg Test Formulation 2 | Number of Participants With Clinically Significant Abnormality in Vital Signs | 0 Participants |
| Treatment D: PF-07817883 300 mg Test Formulation 3 | Number of Participants With Clinically Significant Abnormality in Vital Signs | 0 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities
Laboratory parameters included hematology (eosinophils/leukocytes \[%\] greater than \[\>\] 1.2\*upper limit of normal), and urinalysis (urine hemoglobin and leukocyte esterase greater than or equal \[\>=\] to 1).
Time frame: From start of study treatment (Day 1) up to last dose of study treatment (maximum up to 12 days)
Population: Safety analysis set included all participants randomly assigned to study treatment and who took at least 1 dose of study treatment in at least one treatment period. Participants were analyzed according to the product they actually received. Here, Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: PF-07817883 300 mg Reference Formulation | Number of Participants With Laboratory Test Abnormalities | 1 Participants |
| Treatment B: PF-07817883 300 mg Test Formulation 1 | Number of Participants With Laboratory Test Abnormalities | 0 Participants |
| Treatment C: PF-07817883 300 mg Test Formulation 2 | Number of Participants With Laboratory Test Abnormalities | 1 Participants |
| Treatment D: PF-07817883 300 mg Test Formulation 3 | Number of Participants With Laboratory Test Abnormalities | 2 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. Treatment-emergent are events between first dose of study treatment and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From start of study treatment (Day 1) up to 28-35 days after last dose of study treatment (maximum up to 47 days)
Population: Safety analysis set included all participants randomly assigned to study treatment and who took at least 1 dose of study treatment in at least one treatment period. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: PF-07817883 300 mg Reference Formulation | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Treatment B: PF-07817883 300 mg Test Formulation 1 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Treatment C: PF-07817883 300 mg Test Formulation 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Treatment D: PF-07817883 300 mg Test Formulation 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |