Obesity, Overweight
Conditions
Keywords
PF-07081532
Brief summary
The purpose of this study is to compare the amount of PF-07081532 in blood after taking two different forms of PF-07081532. This study is seeking participants who are at least 18 years of age and are overweight and/or obese. All study participants will receive a total of 2 single doses of this study medication in either form. Form A consists of a PF-07081532 20 mg immediate release tablet and a PF-07081532 60 mg immediate release tablet. Form B consists of a PF-07081532 80 mg immediate release tablet. Each single dose will be separated by a minimum of 6 days. The amount of PF-07081532 in the blood for 4 days after taking each single dose will be compared between the two different formulations of PF-07081532. The total time that participants will take part in this study is about 70 days. The first visit is a screening visit to ensure that participants are appropriately qualified for the study. This will occur up to 28 days before the first single dose. Participants will be admitted into the clinic one day prior to the first single dose and will remain in the clinic for a total of 11 days. The study team will phone the participants 28 to 35 days after the last dose of study medication.
Interventions
DRUGFormulation A (PF-07081532 20 mg plus 60 mg)
Formulation A: administered as a 20 mg immediate release tablet and a 60 mg immediate release tablet
DRUGFormulation B (PF-07081532 80 mg)
Formulation B: administered as a 80 mg immediate release tablet
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
(open label)
Intervention model description
PF-07081532 80 mg will be provided in 2 different oral formulations (A and B). Formulation A will be administered as a PF-07081532 20 mg immediate release tablet and a 60 mg immediate release tablet. Formulation B will be administered as a PF-07081532 80 mg immediate release tablet. The overall design is a randomized, open-label, single dose, 2-period, 2-sequence, crossover study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male and female participants must be at least 18 years of age, inclusive, at the time of signing the ICD * Male and female participants who are healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and ECGs * Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures * A total body weight \>50 kg (110 lb) and BMI of 25.0 to \<34.9 kg/m2, inclusive, at the screening visit * Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and protocol
Exclusion criteria
* 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) * Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection) * History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed * Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2, or pancreatitis, or participants with suspected MTC per the investigator's judgement * Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study * Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention * In females, current use of hormone replacement therapy or oral/injectable contraceptives containing ethinyl estradiol * Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives (whichever is longer) preceding the first dose of study intervention used in this study. Investigational products which are strong CYP3A inducers or time-dependent inhibitors are prohibited within 14 days plus 5 half-lives or 30 days (whichever is longer) prior to the dose of study intervention * Known prior participation (ie, randomized and received at least 1 dose of investigational product) in a study involving PF-07081532 or known intolerance to a GLP-1R agonist * A positive urine drug test * Using a properly sized and calibrated BP cuff, screening supine BP ≥140 mm Hg (systolic) or 90 mm Hg (diastolic) following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility * Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF \>450 ms, complete LBBB, signs of an acute or indeterminate- age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third- degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT interval is \>450 ms, this interval should be rate-corrected using the Fridericia method only and the resulting QTcF should be used for decision making and reporting. If QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding a participant * Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary: * Aspartate aminotransferase or alanine aminotransferase level ≥1.25 × upper limit of normal (ULN); * Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN; * HbA1c ≥6.5%; * Fasting blood glucose ≥126 mg/dL (7 mmol/L); * Calcitonin \> ULN; * eGFR \<60 mL/min/1.73 m2 as calculated by the CKD-EPI equation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Parameter - Area Under the Concentration-Time Curve to Infinity (AUCinf) of PF-07081532 | Pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours post dose on Day 1 of Period 1 and Period 2 | AUCinf is the area under the concentration-time curve to infinity. AUCinf was calculated by AUClast + (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. |
| Pharmacokinetics Parameter - Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532 | Pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours post dose on Day 1 of Period 1 and Period 2 | AUClast is the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast was calculated by Linear/Log trapezoidal method. |
| Pharmacokinetics Parameter - Maximum Observed Concentration (Cmax) of PF-07081532 | Pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours post dose of Day 1 Period 1 and Period 2. | Cmax is the maximum observed concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All-Causality and Treatment-Related) | From the first dose up to 28 to 35 days after administration of the final dose of study intervention (maximum of 51 days) | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Treatment-emergent are events between first dose of study intervention and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
| Number of Participants Meeting Pre-Specified Criteria of Electrocardiogram (ECGs) | Baseline (Day 1) up to Period 2 Day 5 | The pre-specified criteria of ECG included: PR interval, aggregated: value \>=300 msec, %change \>= 25/50% msec; QRS duration, aggregated: value\>=200 msec, %changes \>= 25/50% msec; QTCF interval, aggregated: 450\<=value\<480 msec, 480\<=value\<500 msec, value\>=500 msec, 30\<=changes\<60msec, and changes\>=60msec. |
| Number of Participants With Laboratory Abnormalities | Baseline (Day 1) up to Period 2 Day 5 | Participants with laboratory abnormalities that met pre-specified criteria: Urate (millimole/Liter) \> 1.2\*ULN (upper limit of normal) and Monocytes/Leukocytes (%) \> 1.2\*ULN. |
| Number of Participants Meeting Pre-Specified Criteria of Vital Signs | Baseline (Day 1) up to Period 2 Day 5 | Pre-specified criteria of vital signs included: Systolic blood pressure (BP): minimum (min) \<90 mmHg, change from baseline (CfB) maximum (max) decrease or increase \>=30mmHg; Diastolic BP min \<50mmHg, CfB max decrease or increase \>=20mmHg; supine pulse rate: min \< 40 beats per minute (bpm), max \> 120 bpm. |
Countries
United States
Participant flow
Pre-assignment details
A total of 20 participants were enrolled and treated in the study. All 20 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| All Participants This group includes all participants who enrolled in this study and received at least 1 dose of study intervention. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 42.90 years STANDARD_DEVIATION 11.04 |
| Body Mass Index | 28.55 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 9 / 20 | 8 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Pharmacokinetics Parameter - Area Under the Concentration-Time Curve to Infinity (AUCinf) of PF-07081532
AUCinf is the area under the concentration-time curve to infinity. AUCinf was calculated by AUClast + (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.
Time frame: Pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours post dose on Day 1 of Period 1 and Period 2
Population: 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 participants who contributed to this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Formulation A | Pharmacokinetics Parameter - Area Under the Concentration-Time Curve to Infinity (AUCinf) of PF-07081532 | 179400 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 40 |
| Formulation B | Pharmacokinetics Parameter - Area Under the Concentration-Time Curve to Infinity (AUCinf) of PF-07081532 | 178300 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 49 |
Comparison: Natural log transformed AUCinf was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within the sequence as a random effect. The adjusted mean differences and 90% Confidence Intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CI for the ratios. Formulation A was the Reference treatment while Formulation B was the Test treatment.90% CI: [92.92, 102.08]
Primary
Pharmacokinetics Parameter - Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532
AUClast is the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast was calculated by Linear/Log trapezoidal method.
Time frame: Pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours post dose on Day 1 of Period 1 and Period 2
Population: 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 participants who contributed to this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Formulation A | Pharmacokinetics Parameter - Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532 | 171900 ng*hr/mL | Geometric Coefficient of Variation 38 |
| Formulation B | Pharmacokinetics Parameter - Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532 | 170400 ng*hr/mL | Geometric Coefficient of Variation 47 |
Comparison: Natural log transformed AUClast was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within the sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CI for the ratios. Formulation A was the Reference treatment while Formulation B was the Test treatment.90% CI: [92.77, 102.17]
Primary
Pharmacokinetics Parameter - Maximum Observed Concentration (Cmax) of PF-07081532
Cmax is the maximum observed concentration.
Time frame: Pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours post dose of Day 1 Period 1 and Period 2.
Population: 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 participants who contributed to this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Formulation A | Pharmacokinetics Parameter - Maximum Observed Concentration (Cmax) of PF-07081532 | 8072 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 29 |
| Formulation B | Pharmacokinetics Parameter - Maximum Observed Concentration (Cmax) of PF-07081532 | 7741 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
Comparison: Natural log transformed Cmax was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within the sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CI for the ratios. Formulation A was the Reference treatment while Formulation B was the Test treatment.90% CI: [81.4, 110.18]
Secondary
Number of Participants Meeting Pre-Specified Criteria of Electrocardiogram (ECGs)
The pre-specified criteria of ECG included: PR interval, aggregated: value \>=300 msec, %change \>= 25/50% msec; QRS duration, aggregated: value\>=200 msec, %changes \>= 25/50% msec; QTCF interval, aggregated: 450\<=value\<480 msec, 480\<=value\<500 msec, value\>=500 msec, 30\<=changes\<60msec, and changes\>=60msec.
Time frame: Baseline (Day 1) up to Period 2 Day 5
Population: All participants who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Formulation A | Number of Participants Meeting Pre-Specified Criteria of Electrocardiogram (ECGs) | 0 Participants |
| Formulation B | Number of Participants Meeting Pre-Specified Criteria of Electrocardiogram (ECGs) | 1 Participants |
Secondary
Number of Participants Meeting Pre-Specified Criteria of Vital Signs
Pre-specified criteria of vital signs included: Systolic blood pressure (BP): minimum (min) \<90 mmHg, change from baseline (CfB) maximum (max) decrease or increase \>=30mmHg; Diastolic BP min \<50mmHg, CfB max decrease or increase \>=20mmHg; supine pulse rate: min \< 40 beats per minute (bpm), max \> 120 bpm.
Time frame: Baseline (Day 1) up to Period 2 Day 5
Population: All participants who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Formulation A | Number of Participants Meeting Pre-Specified Criteria of Vital Signs | 0 Participants |
| Formulation B | Number of Participants Meeting Pre-Specified Criteria of Vital Signs | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities
Participants with laboratory abnormalities that met pre-specified criteria: Urate (millimole/Liter) \> 1.2\*ULN (upper limit of normal) and Monocytes/Leukocytes (%) \> 1.2\*ULN.
Time frame: Baseline (Day 1) up to Period 2 Day 5
Population: All participants who took at least 1 dose of study intervention. Here Number of Participants Analyzed signifies participants who contributed to this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Formulation A | Number of Participants With Laboratory Abnormalities | Monocytes/Leukocytes (%) > 1.2*ULN | 0 Participants |
| Formulation A | Number of Participants With Laboratory Abnormalities | Urate (mmol/L) > 1.2*ULN | 0 Participants |
| Formulation B | Number of Participants With Laboratory Abnormalities | Monocytes/Leukocytes (%) > 1.2*ULN | 1 Participants |
| Formulation B | Number of Participants With Laboratory Abnormalities | Urate (mmol/L) > 1.2*ULN | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All-Causality and Treatment-Related)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Treatment-emergent are events between first dose of study intervention and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From the first dose up to 28 to 35 days after administration of the final dose of study intervention (maximum of 51 days)
Population: All participants who take at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Formulation A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All-Causality and Treatment-Related) | All Causality TEAEs | 9 Participants |
| Formulation A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All-Causality and Treatment-Related) | Treatment-Related TEAEs | 9 Participants |
| Formulation A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All-Causality and Treatment-Related) | All-Causality Treatment-Emergent SAE | 0 Participants |
| Formulation A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All-Causality and Treatment-Related) | Treatment-Related Treatment-Emergent SAE | 0 Participants |
| Formulation B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All-Causality and Treatment-Related) | Treatment-Related Treatment-Emergent SAE | 0 Participants |
| Formulation B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All-Causality and Treatment-Related) | All Causality TEAEs | 8 Participants |
| Formulation B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All-Causality and Treatment-Related) | All-Causality Treatment-Emergent SAE | 0 Participants |
| Formulation B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All-Causality and Treatment-Related) | Treatment-Related TEAEs | 8 Participants |