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This is a Phase 1, randomized, placebo-controlled, double-blind (investigator- and participant-blinded), sponsor-open study of PF-07081532. Study participants will receive the investigational product or placebo every day for 42 days.
The purpose of the study is to evaluate the safety, tolerability and pharmacokinetics (PK) of multiple oral doses of PF-07081532 in participants with inadequately controlled type 2 diabetes mellitus, on metformin and optionally in non-diabetic participants with obesity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-07081532 | Experimental | multiple dosing, once-daily for 42 days |
|
| Placebo | Placebo Comparator | multiple dosing, once-daily for 42 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-07081532 | Drug | Study Drug, once daily for 42 days |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (All Causalities) | An adverse event (AE) was any untoward medical occurrence in clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE (SAE) was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. A severe AE was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, limiting self-care activities of daily living. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period (starting after or on the first dose but before the last dose plus at least 28 days). AEs included all SAEs and non-SAEs. | Baseline up to at least 28 days after last dose of study intervention (77 days) |
| Number of Participants With Treatment-emergent Adverse Events (Treatment Related) | A treatment related adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study drug, considered related to the study drug (assessed by the investigator [Yes/No]). A serious AE (SAE) was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. A severe AE was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, limiting self-care activities of daily living. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period (starting after or on the first dose but before the last dose plus at least 28 days). AEs included all SAEs and non-SAEs. | Baseline up to at least 28 days after last dose of study intervention (77 days) |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-Time Profile From 0 to 24 Hours (AUC24) of PF-07081532 on Day 1 and Day 42 | AUC24 of PF-07081532 were determined by Linear/Log trapezoidal method on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively. |
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Inclusion Criteria:
Exclusion Criteria
Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, hepatic, psychiatric, neurological, dermatological, or allergic disease;
Medical history of T2DM (for non-diabetic obese participants, if enrolled);
Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes;
Evidence or history of clinically significant cardiovascular disease;
Any malignancy not considered cured;
Acute pancreatitis or history of chronic pancreatitis;
Acute gallbladder disease;
Any condition possibly affecting drug absorption;
Personal or family history of MTC or MEN2;
Medical or psychiatric condition that may increase the risk of study participation;
Any vaccination within the 1 week prior to admission to the CRU;
Previous administration with an investigational drug within 30 days or 5 half-lives preceding first dose;
Known prior participation in a trial involving PF-07081532;
A positive urine drug screen at screening or admission;
Positive testing at screening for HIV, HBsAg, HBcAb, HBsAb or HCVAb;
Positive COVID-19 test at screening or admission;
Supine BP ≥160 mm Hg (systolic) or ≥100 mm Hg (diastolic);
12-lead ECG clinically relevant abnormalities that may affect participant safety or interpretation of study results;
Participants with ANY of the following abnormalities in clinical laboratory tests: *AST or ALT level ≥1.5x ULN;
History of alcohol abuse, binge drinking and/or any illicit drug use or dependence within 6 months of Screening;
Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing;
History of sensitivity to heparin or heparin induced thrombocytopenia;
Known intolerance to any GLP-1R agonist.
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Qps-Mra, Llc | South Miami | Florida | 33143 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38751362 | Derived | Buckeridge C, Tsamandouras N, Carvajal-Gonzalez S, Brown LS, Hernandez-Illas M, Saxena AR. Once-daily oral small-molecule glucagon-like peptide-1 receptor agonist lotiglipron (PF-07081532) for type 2 diabetes and obesity: Two randomized, placebo-controlled, multiple-ascending-dose Phase 1 studies. Diabetes Obes Metab. 2024 Aug;26(8):3155-3166. doi: 10.1111/dom.15643. Epub 2024 May 16. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo (Type 2 Diabetes Mellitus [T2DM]) | Adult participants with T2DM inadequately controlled on metformin received matching placebo (number of placebo tablets were matched to the number of PF-07081532 tablets for 20 mg, 40, 60, or 80 mg) once daily (QD) for 6 weeks. |
| FG001 | PF-07081532 20-60 mg (T2DM) | Adult participants with T2DM inadequately controlled on metformin received PF-07081532 20 mg QD for 4 weeks and then 60 mg QD for 2 weeks. |
| FG002 | PF-07081532 40-80 mg (T2DM) | Adult participants with T2DM inadequately controlled on metformin received PF-07081532 40 mg QD for 4 weeks and then 80 mg QD for 2 weeks. |
| FG003 | Placebo (Obesity) | Adult participants with obesity, without T2DM received matching placebo (number of placebo tablets were matched to the number of PF-07081532 tablets for 20 mg or 60 mg) QD for 6 weeks. |
| FG004 | PF-07081532 20-60 mg (Obesity) | Adult participants with obesity, without T2DM received PF-07081532 20 mg QD for 4 weeks and then 60 mg QD for 2 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All participants enrolled and randomly assigned to study intervention.
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo (Type 2 Diabetes Mellitus [T2DM]) | Adult participants with T2DM inadequately controlled on metformin received matching placebo (number of placebo tablets were matched to the number of PF-07081532 tablets for 20 mg, 40, 60, or 80 mg) once daily (QD) for 6 weeks. |
| BG001 | PF-07081532 20-60 mg (T2DM) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-emergent Adverse Events (All Causalities) | An adverse event (AE) was any untoward medical occurrence in clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE (SAE) was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. A severe AE was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, limiting self-care activities of daily living. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period (starting after or on the first dose but before the last dose plus at least 28 days). AEs included all SAEs and non-SAEs. | All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | Baseline up to at least 28 days after last dose of study intervention (77 days) |
Baseline up to 77 days
The same event may appear as both an AE and an SAE. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo (Type 2 Diabetes Mellitus [T2DM]) | Adult participants with T2DM inadequately controlled on metformin received matching placebo (number of placebo tablets were matched to the number of PF-07081532 tablets for 20 mg, 40, 60, or 80 mg) once daily (QD) for 6 weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA v25.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 21, 2021 | Jun 13, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 29, 2022 | Jun 13, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| Drug |
Placebo, once daily for 42 days |
|
Following laboratory parameters analyzed for laboratory examination: hemoglobin (HGB); hematocrit; erythrocytes; erythrocytes (Ery.) mean corpuscular volume; Ery. mean corpuscular HGB; Ery. mean corpuscular HGB concentration; platelets; leukocytes; lymphocytes; neutrophils; basophils; eosinophils; monocytes; bilirubin; direct bilirubin; indirect bilirubin; aspartate aminotransferase; alanine aminotransferase; gamma glutamyl transferase; alkaline phosphatase; albumin; urea nitrogen; creatinine; urate; cholesterol; high density lipoprotein (HDL) cholesterol; sodium; potassium; chloride; calcium; bicarbonate; thyroxine; free; thyrotropin; creatine kinase; amylase; triacylglycerol lipase; triglycerides; pH; urine glucose; ketones; urine protein; urine hemoglobin; urobilinogen; urine bilirubin; nitrite; leukocyte esterase; urine erythrocytes; urine leukocytes; epithelial cells; casts; and bacteria. |
| Baseline up to 7-14 days after last dose of study drug (maximum: 56 days) |
| Number of Participants With Pre-specified Categorical Post-Baseline Vital Signs Data | Pre-specified categorical criteria included: supine systolic blood pressure (SBP) less than (<) 90 millimeters of mercury (mmHg), supine SBP increase from baseline greater or equal to (>=) 30 mmHg, supine SBP decrease from baseline >=30 mmHg, supine diastolic blood pressure (DBP) <50 mmHg, supine DBP increase from baseline >=20 mmHg, supine DBP decrease from baseline >=20 mmHg, supine pulse rate <40 beats per minutes (bpm), and supine pulse rate greater than (>) 120 bpm. 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. | Baseline up to 14 days after last dose of study intervention (maximum: 56 days) |
| Number of Participants With Pre-specified Categorical Post-Baseline Electrocardiogram (ECG) Data | Triplicate 12-lead ECGs were collected using an ECG machine that automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS complex. Pre-specified categorical criteria included: PR interval greater or equal to 300 msec, PR interval %Chg>=25/50% (%Chg>=25/50% denotes baseline >200 msec and >=25% increase or baseline less than or equal to [<=] 200 msec and >=50% increase), QRS interval >=140 msec, QRS interval increase from baseline >=50%, QT interval corrected using Fridericia's formula (QTcF) >450 msec and <=480 msec, QTcF >480 msec and <=500 msec, QTcF >500 msec, QTcF increase from baseline >30 msec and <=60 msec, and QTcF increase from baseline >60 msec. | Baseline up to 14 days after last dose of study intervention (maximum: 56 days) |
| Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42 |
| Maximum Observed Plasma Concentration (Cmax) of PF-07081532 on Day 1 and Day 42 | Cmax of PF-07081532 were observed directly from data from time 0 to 24 hours on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively. | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42 |
| Time to Reach Cmax (Tmax) of PF-07081532 on Day 1 and Day 42 | Tmax of PF-07081532 were observed directly from data as time of first occurrence on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively. | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42 |
| Terminal Half-life (t1/2) of PF-07081532 on Day 42 | t1/2 of PF-07081532 was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively. | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 42 |
| Withdrawal by Subject |
|
Adult participants with T2DM inadequately controlled on metformin received PF-07081532 20 mg QD for 4 weeks and then 60 mg QD for 2 weeks. |
| BG002 | PF-07081532 40-80 mg (T2DM) | Adult participants with T2DM inadequately controlled on metformin received PF-07081532 40 mg QD for 4 weeks and then 80 mg QD for 2 weeks. |
| BG003 | Placebo (Obesity) | Adult participants with obesity, without T2DM received matching placebo (number of placebo tablets were matched to the number of PF-07081532 tablets for 20 mg or 60 mg) QD for 6 weeks. |
| BG004 | PF-07081532 20-60 mg (Obesity) | Adult participants with obesity, without T2DM received PF-07081532 20 mg QD for 4 weeks and then 60 mg QD for 2 weeks. |
| BG005 | Total | Total of all reporting groups |
| Participant |
|
| Years |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Placebo (Type 2 Diabetes Mellitus [T2DM]) | Adult participants with T2DM inadequately controlled on metformin received matching placebo (number of placebo tablets were matched to the number of PF-07081532 tablets for 20 mg, 40, 60, or 80 mg) once daily (QD) for 6 weeks. |
| OG001 | PF-07081532 20-60 mg (T2DM) | Adult participants with T2DM inadequately controlled on metformin received PF-07081532 20 mg QD for 4 weeks and then 60 mg QD for 2 weeks. |
| OG002 | PF-07081532 40-80 mg (T2DM) | Adult participants with T2DM inadequately controlled on metformin received PF-07081532 40 mg QD for 4 weeks and then 80 mg QD for 2 weeks. |
| OG003 | Placebo (Obesity) | Adult participants with obesity, without T2DM received matching placebo (number of placebo tablets were matched to the number of PF-07081532 tablets for 20 mg or 60 mg) QD for 6 weeks. |
| OG004 | PF-07081532 20-60 mg (Obesity) | Adult participants with obesity, without T2DM received PF-07081532 20 mg QD for 4 weeks and then 60 mg QD for 2 weeks. |
|
|
| Primary | Number of Participants With Treatment-emergent Adverse Events (Treatment Related) | A treatment related adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study drug, considered related to the study drug (assessed by the investigator [Yes/No]). A serious AE (SAE) was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. A severe AE was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, limiting self-care activities of daily living. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period (starting after or on the first dose but before the last dose plus at least 28 days). AEs included all SAEs and non-SAEs. | All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | Baseline up to at least 28 days after last dose of study intervention (77 days) |
|
|
|
| Primary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Following laboratory parameters analyzed for laboratory examination: hemoglobin (HGB); hematocrit; erythrocytes; erythrocytes (Ery.) mean corpuscular volume; Ery. mean corpuscular HGB; Ery. mean corpuscular HGB concentration; platelets; leukocytes; lymphocytes; neutrophils; basophils; eosinophils; monocytes; bilirubin; direct bilirubin; indirect bilirubin; aspartate aminotransferase; alanine aminotransferase; gamma glutamyl transferase; alkaline phosphatase; albumin; urea nitrogen; creatinine; urate; cholesterol; high density lipoprotein (HDL) cholesterol; sodium; potassium; chloride; calcium; bicarbonate; thyroxine; free; thyrotropin; creatine kinase; amylase; triacylglycerol lipase; triglycerides; pH; urine glucose; ketones; urine protein; urine hemoglobin; urobilinogen; urine bilirubin; nitrite; leukocyte esterase; urine erythrocytes; urine leukocytes; epithelial cells; casts; and bacteria. | All participants randomly assigned to study intervention and who took at least 1 dose of study intervention and had at least 1 observation of the given laboratory test while on study treatment or during follow up. Here, "number analyzed" signifies number of participants evaluable for each category. | Posted | Count of Participants | Participants | Baseline up to 7-14 days after last dose of study drug (maximum: 56 days) |
|
|
|
| Primary | Number of Participants With Pre-specified Categorical Post-Baseline Vital Signs Data | Pre-specified categorical criteria included: supine systolic blood pressure (SBP) less than (<) 90 millimeters of mercury (mmHg), supine SBP increase from baseline greater or equal to (>=) 30 mmHg, supine SBP decrease from baseline >=30 mmHg, supine diastolic blood pressure (DBP) <50 mmHg, supine DBP increase from baseline >=20 mmHg, supine DBP decrease from baseline >=20 mmHg, supine pulse rate <40 beats per minutes (bpm), and supine pulse rate greater than (>) 120 bpm. 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. | All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | Baseline up to 14 days after last dose of study intervention (maximum: 56 days) |
|
|
|
| Primary | Number of Participants With Pre-specified Categorical Post-Baseline Electrocardiogram (ECG) Data | Triplicate 12-lead ECGs were collected using an ECG machine that automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS complex. Pre-specified categorical criteria included: PR interval greater or equal to 300 msec, PR interval %Chg>=25/50% (%Chg>=25/50% denotes baseline >200 msec and >=25% increase or baseline less than or equal to [<=] 200 msec and >=50% increase), QRS interval >=140 msec, QRS interval increase from baseline >=50%, QT interval corrected using Fridericia's formula (QTcF) >450 msec and <=480 msec, QTcF >480 msec and <=500 msec, QTcF >500 msec, QTcF increase from baseline >30 msec and <=60 msec, and QTcF increase from baseline >60 msec. | All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | Baseline up to 14 days after last dose of study intervention (maximum: 56 days) |
|
|
|
| Secondary | Area Under the Concentration-Time Profile From 0 to 24 Hours (AUC24) of PF-07081532 on Day 1 and Day 42 | AUC24 of PF-07081532 were determined by Linear/Log trapezoidal method on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively. | All randomized participants that received at least 1 dose of PF-07081532, have at least 1 of the PK parameters of interest calculated and contributed to the summary statistics. Data collection was not planned for the placebo arms (Placebo [T2DM] and Placebo [obesity]). | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*hr/mL) | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42 |
|
|
|
| Secondary | Maximum Observed Plasma Concentration (Cmax) of PF-07081532 on Day 1 and Day 42 | Cmax of PF-07081532 were observed directly from data from time 0 to 24 hours on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively. | All randomized participants that received at least 1 dose of PF-07081532, have at least 1 of the PK parameters of interest calculated and contributed to the summary statistics. Data collection was not planned for the placebo arms (Placebo [T2DM] and Placebo [obesity]). | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms per milliliter | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42 |
|
|
|
| Secondary | Time to Reach Cmax (Tmax) of PF-07081532 on Day 1 and Day 42 | Tmax of PF-07081532 were observed directly from data as time of first occurrence on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively. | All randomized participants that received at least 1 dose of PF-07081532, have at least 1 of the PK parameters of interest calculated and contributed to the summary statistics. Data collection was not planned for the placebo arms (Placebo [T2DM] and Placebo [obesity]). | Posted | Median | Full Range | Hours | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42 |
|
|
|
| Secondary | Terminal Half-life (t1/2) of PF-07081532 on Day 42 | t1/2 of PF-07081532 was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively. | All randomized participants that received at least 1 dose of PF-07081532, have at least 1 of the PK parameters of interest calculated and contributed to the summary statistics for t1/2. Data collection was not planned for the placebo arms (Placebo [T2DM] and Placebo [obesity]). | Posted | Mean | Standard Deviation | Hours | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 42 |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 5 |
| 6 |
| EG001 | PF-07081532 20-60 mg (T2DM) | Adult participants with T2DM inadequately controlled on metformin received PF-07081532 20 mg QD for 4 weeks and then 60 mg QD for 2 weeks. | 0 | 8 | 0 | 8 | 7 | 8 |
| EG002 | PF-07081532 40-80 mg (T2DM) | Adult participants with T2DM inadequately controlled on metformin received PF-07081532 40 mg QD for 4 weeks and then 80 mg QD for 2 weeks. | 0 | 9 | 0 | 9 | 6 | 9 |
| EG003 | Placebo (Obesity) | Adult participants with obesity, without T2DM received matching placebo (number of placebo tablets were matched to the number of PF-07081532 tablets for 20 mg or 60 mg) QD for 6 weeks. | 0 | 2 | 0 | 2 | 0 | 2 |
| EG004 | PF-07081532 20-60 mg (Obesity) | Adult participants with obesity, without T2DM received PF-07081532 20 mg QD for 4 weeks and then 60 mg QD for 2 weeks. | 0 | 9 | 0 | 9 | 7 | 9 |
| Constipation | Gastrointestinal disorders | MedDRA v25.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA v25.0 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA v25.0 | Non-systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA v25.0 | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA v25.0 | Non-systematic Assessment |
|
| Lip dry | Gastrointestinal disorders | MedDRA v25.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA v25.0 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA v25.0 | Non-systematic Assessment |
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| Early satiety | General disorders | MedDRA v25.0 | Non-systematic Assessment |
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| Hordeolum | Infections and infestations | MedDRA v25.0 | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA v25.0 | Non-systematic Assessment |
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| Rib fracture | Injury, poisoning and procedural complications | MedDRA v25.0 | Non-systematic Assessment |
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| Skin laceration | Injury, poisoning and procedural complications | MedDRA v25.0 | Non-systematic Assessment |
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| Hepatic enzyme increased | Investigations | MedDRA v25.0 | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA v25.0 | Non-systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA v25.0 | Non-systematic Assessment |
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| Costochondritis | Musculoskeletal and connective tissue disorders | MedDRA v25.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA v25.0 | Non-systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA v25.0 | Non-systematic Assessment |
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| Adjustment disorder with depressed mood | Psychiatric disorders | MedDRA v25.0 | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v25.0 | Non-systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA v25.0 | Non-systematic Assessment |
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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.
| D004700 | Endocrine System Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Participants with SAEs |
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| Participants with severe AEs |
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| Participants with AEs leading to permanent discontinuation from study |
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| Hematocrit (%) <0.8 x LLN |
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| Erythrocytes (10^6/mm^3) <0.8 x LLN |
|
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| Ery. Mean Corpuscular Volume (10^-15 liters [L]) <0.9 x LLN |
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| Ery. Mean Corpuscular Volume (10^-15 L) >1.1 x upper limit of normal (ULN) |
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| Ery. Mean Corpuscular HGB (picograms per cell [pg/cell]) <0.9 x LLN |
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| Ery. Mean Corpuscular HGB (pg/cell) >1.1 x ULN |
|
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| Ery. Mean Corpuscular HGB Concentration (g/dL) <0.9 x LLN |
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| Ery. Mean Corpuscular HGB Concentration (g/dL) >1.1 x ULN |
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| Platelets (10^3/mm^3) <0.5 x LLN |
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| Platelets (10^3/mm^3) >1.75 x ULN |
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| Leukocytes (10^3/mm^3) <0.6 x LLN |
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| Leukocytes (10^3/mm^3) >1.5 x ULN |
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| Lymphocytes (10^3/mm^3) <0.8 x LLN |
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| Lymphocytes (10^3/mm^3) >1.2 x ULN |
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| Neutrophils (10^3/mm^3) <0.8 x LLN |
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| Neutrophils (10^3/mm^3) >1.2 x ULN |
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| Basophils (10^3/mm^3) >1.2 x ULN |
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| Eosinophils (10^3/mm^3) >1.2 x ULN |
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| Monocytes (10^3/mm^3) >1.2 x ULN |
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| Bilirubin (milligrams per deciliter [mg/dL]) >1.5 x ULN |
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| Direct Bilirubin (mg/dL) >1.5 x ULN |
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| Indirect Bilirubin (mg/dL) >1.5 x ULN |
|
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| Aspartate Aminotransferase (units per liter [U/L]) >3.0 x ULN |
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| Alanine Aminotransferase (U/L) >3.0 x ULN |
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| Gamma Glutamyl Transferase (U/L) >3.0 x ULN |
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| Alkaline Phosphatase (U/L) >3.0 x ULN |
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| Albumin (g/dL) <0.8 x LLN |
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| Albumin (g/dL) >1.2 x ULN |
|
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| Urea Nitrogen (mg/dL) >1.3 x ULN |
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| Creatinine (mg/dL) >1.3 x ULN |
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| Urate (mg/dL) >1.2 x ULN |
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| Cholesterol (mg/dL) >1.3 x ULN |
|
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| High density lipoprotein (HDL) cholesterol (mg/dL) <32 |
|
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| Sodium (milliequivalents per liter [mEq/L]) <0.95 x LLN |
|
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| Sodium (milliequivalents per liter [mEq/L]) >1.05 x ULN |
|
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| Potassium (mEq/L) <0.9 x LLN |
|
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| Potassium (mEq/L) >1.1 x ULN |
|
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| Chloride (mEq/L) <0.9 x LLN |
|
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| Chloride (mEq/L) >1.1 x ULN |
|
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| Calcium (mg/dL) <0.9 x LLN |
|
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| Calcium (mg/dL) >1.1 x ULN |
|
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| Bicarbonate (mEq/L) <0.9 x LLN |
|
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| Bicarbonate (mEq/L) >1.1 x ULN |
|
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| Thyroxine, Free (nanograms per deciliter [ng/dL]) <0.8 x LLN |
|
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| Thyroxine, Free (ng/dL) >1.2 x ULN |
|
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| Thyrotropin (micro-international units per milliliter [uIU/mL]) <0.8 x LLN |
|
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| Thyrotropin (uIU/mL) >1.2 x ULN |
|
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| Creatine Kinase (U/L) >2.0 x ULN |
|
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| Amylase (U/L) >1.5 x ULN |
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| Triacylglycerol Lipase (U/L) >1.5 x ULN |
|
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| Triglycerides (mg/dL) >1.3 x ULN |
|
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| pH <4.5 |
|
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| pH >8 |
|
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| Urine glucose >=1 |
|
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| Ketones >=1 |
|
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| Urine Protein >=1 |
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| Urine hemoglobin >=1 |
|
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| Urobilinogen >=1 |
|
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| Urine Bilirubin >=1 |
|
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| Nitrite >=1 |
|
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| Leukocyte Esterase >=1 |
|
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| Urine Erythrocytes (per high power field [/HPF]) >=20 |
|
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| Urine Leukocytes (/HPF) >=20 |
|
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| Epithelial Cells (per low power field [/LPF]) >=6 |
|
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| Casts (/LPF) >1 |
|
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| Bacteria (/HPF) >20 |
|
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| Supine SBP increase from baseline >=30 mmHg |
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| Supine SBP decrease from baseline >=30 mmHg |
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| Supine DBP <50 mmHg |
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| Supine DBP increase from baseline >=20 mmHg |
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| Supine DBP decrease from baseline >=20 mmHg |
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| Pulse rate <40 bpm |
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| Pulse rate >120 bpm |
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| PR interval %Chg>=25/50% |
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| QRS interval >=140 msec |
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| QRS interval increase from baseline >=50% |
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| 450 ms< QTcF<=480 msec |
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| 480 ms< QTcF<=500 msec |
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| QTcF >500 msec |
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| 30 ms< QTcF increase from baseline <=60 msec |
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| QTcF increase from baseline >60 msec |
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| Study Day 42 |
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| Study Day 42 |
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| Study Day 42 |
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