Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Danuglipron
PF-06882961 · 11 trials · 7 indications
Percent change from baseline in body weight at end of treatment was reported in this outcome measure. Analysis was performed using MMRM with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, natural log-transformed baseline as a covariate and the (natural log-transformed baseline)-by-time interaction with time fitted as a repeated effect and participant as a random effect. Values were back-transformed from the log scale. Percent change = 100 multiply by \[\*\](back-transformed LS Mean minus \[-\] 1). Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Percent change from baseline in body weight at end of treatment was reported in this outcome measure. Analysis was performed using MMRM with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, natural log-transformed baseline as a covariate and the (natural log-transformed baseline)-by-time interaction with time fitted as a repeated effect and participant as a random effect. Values were back-transformed from the log scale. Percent change = 100\*(back-transformed LS Mean - 1). Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment. AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE. Assessments of AE intensity were defined as mild (easily tolerated, causing minimal discomfort and not interfering with daily activities), moderate (causing sufficient discomfort and interferes with normal daily activities) and severe (preventing normal daily activities).
HbA1c can be used as a diagnostic test for diabetes. The target HbA1c level for people with diabetes is usually less than 7%.
AUC24 is the area under the plasma concentration-time profile from time zero to the time 24 hours. The planned analysis was not considered reliable by the sponsor.
Cmax is the maximum observed plasma concentration over 24 hours. The planned analysis was not considered reliable by the sponsor.
AUC24 was measured on Day 21, 35, and 56 for dose 40 mg BID, 80 mg BID, and 120 mg BID, respectively. The planned analysis was not considered reliable by the sponsor.
Cmax,ss was measured on Day 21, 35, and 56 for dose 40 mg BID, 80 mg BID, and 120 mg BID, respectively. The planned analysis was not considered reliable by the sponsor.
Cmax was the maximum observed plasma concentration and was directly observed from data.
AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity.
AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration.
Fu was defined as fraction of unbound drug in plasma.
AUClast is area under the plasma concentration-time profile from time 0 to last quantifiable concentration.
AUClast is area under the plasma concentration-time profile from time 0 to last quantifiable concentration.
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. Treatment emergent AEs were events between first dose of study drug and approximately 4 weeks after last dose of study drug, that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and all non-serious AEs.
Leukocytes (10\^9/liter \[L\]) bilirubin (micromol/L), glucose (millimoles \[mmol\]/L), triacylglycerol lipase (microkatals \[microkat\]/L): greater than (\>) 1.5\*upper limit normal (ULN); activated partial thromboplastin time (s): 1.1\*ULN; HDL cholesterol (mmol/L), thyroid stimulating hormone (TSH) (milliunits \[mU\]/L): less than (\<) 0.8\*lower limit normal (LLN); LDL cholesterol (mmol/L), urate (mmol/L): \>1.2\*ULN; triglycerides: \>1.3\*ULN; aspartate aminotransferase (microkat/L), alanine aminotransferase (microkat/L), gamma glutamyl transferase (microkat/L): \>3.0\*ULN; cholesterol (mmol/L): \>1.3\*ULN; urine glucose, ketones urine protein, urine hemoglobin, urobilinogen, nitrite, leukocyte esterase: greater than or equal to (\>=) 1; granular casts, hyaline casts: \>1.
Supine systolic blood pressure (SBP) measured in millimeter of mercury (mmHg) had following categories: minimum of absolute SBP \<90 mmHg, maximum of SBP \>=30 mmHg decrease from baseline and maximum of SBP \>=30 mmHg increase from baseline. Supine diastolic blood pressure (DBP) measured in mmHg had following categories: minimum of absolute DBP \<50 mmHg, maximum of DBP \>20 mmHg decrease from baseline and maximum of DBP \>=20 mmHg increase from baseline. Supine pulse rate measured in beats per minute (BPM) had following categories: minimum of absolute supine pulse rate \<40 BPM and maximum of absolute supine pulse rate \>120 BPM. Baseline was defined as the time-matched value from the average of the triplicate recordings on Day -1.
PR interval had following categories: maximum absolute PR interval \>=300 milliseconds (msec); when baseline PR interval \>200 msec and maximum increase from baseline in PR interval \>=25 percent; when baseline PR interval less than or equal to (\<=) 200 msec and maximum increase from baseline in PR interval \>=50 percent. QRS interval had following categories: maximum absolute QRS interval \>=140 msec; maximum increase from baseline in QRS interval \>=50 percent. QTC interval with Frederica's correction (QTCF) had following categories: absolute QTCF interval \>450 msec to \<=480 msec; absolute QTCF interval \>480 msec to \<=500 msec; absolute QTCF interval \>500 msec; QTCF interval increase from baseline \>=30 msec to \<=60 msec; QTCF interval increase from baseline \>60 msec.
Treatment-related adverse event (AE) was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent.
Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, reticulocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time \[PT\], PT/international normalized ratio, reticulocytes); chemistry (indirect bilirubin, direct bilirubin, protein, albumin, blood urea nitrogen, creatinine, creatine kinase, urate, calcium, sodium, potassium, chloride, bicarbonate, urine urobilinogen); urinalysis (pH, urine glucose, urine ketones, urine protein, urine hemoglobin, nitrites, leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline casts, urine bilirubin).
Vital signs categorical summarization criteria: 1) supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) \<50 mmHg; 3) supine pulse rate \<40 or \>120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (\>=) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP \>= 20 mmHg.
ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (\>=) 300 millisecond (msec), b) \>=25% increase when baseline is \> 200 msec or \>=50% increase when baseline is less than or equal to (\<=) 200 msec. 2\. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) \>=140 msec, b) \>=50% increase from baseline. 3\. QTcF interval (QT corrected using the Fridericia formula): a) \>450 msec and \<=480 msec, b) \>480 msec and \<=500 msec, c) \>500 msec, d) \>30 msec and \<=60 msec increase from baseline, e) \>60 msec increase from baseline
| Arm | Type | Description |
|---|---|---|
| Placebo (Cohorts 1 and 2) | PLACEBO_COMPARATOR | - |
| PF-06882961 40 milligrams (mg) twice daily (BID), 1-week titration (Cohort 1) | EXPERIMENTAL | The dose will be titrated with 1 week of dosing at each step to reach the target dose of 40 mg BID. |
| PF-06882961 80 mg BID, 1-week titration (Cohort 1) | EXPERIMENTAL | The dose will be titrated with 1 week of dosing at each step to reach the target dose of 80 mg BID. |
| PF-06882961 120 mg BID, 1-week titration (Cohort 1) | EXPERIMENTAL | The dose will be titrated with 1 week of dosing at each step to reach the target dose of 120 mg BID. |
| PF-06882961 160 mg BID, 1-week titration (Cohort 1) | EXPERIMENTAL | The dose will be titrated with 1 week of dosing at each step to reach the target dose of 160 mg BID. |
| PF-06882961 200 mg BID, 1-week titration (Cohort 1) | EXPERIMENTAL | The dose will be titrated with 1 week of dosing at each step to reach the target dose of 200 mg BID. |
| PF-06882961 120 mg BID, 2-week titration (Cohorts 1 and 2) | EXPERIMENTAL | The dose will be titrated with 2 weeks of dosing at each step to reach the target dose of 120 mg BID. |
| PF-06882961 160 mg BID, 2-week titration (Cohorts 1 and 2) | EXPERIMENTAL | The dose will be titrated with 2 weeks of dosing at each step to reach the target dose of 160 mg BID. |
| PF-06882961 200 mg BID, 2-week titration (Cohorts 1 and 2) | EXPERIMENTAL | The dose will be titrated with 2 weeks of dosing at each step to reach the target dose of 200 mg BID. |
| Placebo (Cohort 3) | PLACEBO_COMPARATOR | - |
| PF-06882961 80 mg BID, 4-week titration (Cohort 3) | EXPERIMENTAL | The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 80 mg BID. |
| PF-06882961 140 mg BID, 4-week titration (Cohort 3) | EXPERIMENTAL | The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 140 mg BID. |
| PF-06882961 200 mg BID, 4-week titration (Cohort 3) | EXPERIMENTAL | The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 200 mg BID. |
| Arm 1-PF-06882961 starting dose of 5 milligram (mg) BID titrated to 120 mg in participants with T2DM | EXPERIMENTAL | The dose will be titrated over 12 weeks, starting with a dose of 5 mg BID to reach the target dose of 120 mg BID. Titration steps include: 5 mg BID, 10 mg BID, 20 mg BID, 40 mg BID, 60 mg BID, 80 mg BID, 100 mg BID and 120 mg BID |
| Arm 2-PF-06882961 starting dose of 10 mg BID titrated to 100 mg in participants with T2DM | EXPERIMENTAL | The dose will be titrated over 12 weeks, starting with a dose of 10 mg BID to reach the target dose of 120 mg BID. Titration steps include: 10 mg BID, 20 mg BID, 40 mg BID, 60 mg BID, 80 mg BID, 100 mg BID and 120 mg BID |
| Arm 3-PF-06882961 starting dose of 5 mg BID titrated to 80 mg in participants with T2DM | EXPERIMENTAL | The dose will be titrated over 12 weeks, starting with a dose of 5 mg BID to reach the target dose of 80 mg BID. Titration steps include: 5 mg BID, 10 mg BID, 20 mg BID, 40 mg BID, 60 mg BID and 80 mg BID |
| Arm 4-PF-06882961 starting dose of 10 mg BID titrated to 80 mg in participants with T2DM | EXPERIMENTAL | The dose will be titrated over 12 weeks, starting with a dose of 10 mg BID to reach the target dose of 80 mg BID. Titration steps include: 10 mg BID, 20 mg BID, 40 mg BID, 60 mg BID and 80 mg BID |
| Arm 5 - Placebo in subjects with T2DM and Obesity | PLACEBO_COMPARATOR | Matching Placebo tablets taken twice a day (BID) |
| Arm 6-PF-06882961 starting dose of 10 mg BID titrated to 200 mg in participants with T2DM | EXPERIMENTAL | The dose will be titrated over 12 weeks, starting with a dose of 10 mg BID to reach the target dose of 200 mg BID. Titration steps include: 10 mg BID, 20 mg BID, 40 mg BID, 60 mg BID, 80 mg BID, 100 mg BID and 120 mg BID,140 mg BID, 160 mg BID, 180 MG BID, 200 mg BID |
| Arm 7-PF-06882961 starting dose of 10 mg BID titrated to 200 mg in participants with Obesity | EXPERIMENTAL | The dose will be titrated over 12 weeks, starting with a dose of 10 mg BID to reach the target dose of 200 mg BID. Titration steps include: 10 mg BID, 20 mg BID, 40 mg BID, 60 mg BID, 80 mg BID, 100 mg BID and 120 mg BID,140 mg BID, 160 mg BID, 180 MG BID, 200 mg BID |
| Placebo | PLACEBO_COMPARATOR | - |
| PF-06882961 2.5 milligrams (mg) | EXPERIMENTAL | - |
| PF-06882961 10 mg | EXPERIMENTAL | - |
| PF-06882961 40 mg | EXPERIMENTAL | Participants will be titrated up to 2 weeks to reach desired dose level |
| PF-06882961 80 mg | EXPERIMENTAL | Participants will be titrated up to 4 weeks to reach desired dose level |
| PF-06882961 120 mg | EXPERIMENTAL | Participants will be titrated up to 6 weeks to reach desired dose level |
| Cohort 1 | EXPERIMENTAL | Participants will receive a single dose of atorvastatin and multiple oral doses of danuglipron with and without atorvastatin |
| Cohort 2 | EXPERIMENTAL | Participants will receive a single dose of rosuvastatin and multiple oral doses of danuglipron with and without rosuvastatin |
| Cohort 3 | EXPERIMENTAL | Participants will receive a single dose of atorvastatin and multiple oral doses of danuglipron with and without atorvastatin |
| Cohort 4 | EXPERIMENTAL | Participants will receive a single dose of rosuvastatin and multiple oral doses of danuglipron with and without rosuvastatin |
| Single Arm | EXPERIMENTAL | Participants will receive multiple doses of danuglipron |
| PF-06882961 | EXPERIMENTAL | Participants will be titrated up to 6 weeks of the 8-week dosing duration to reach desired dose level 120 mg |
| Healthy participants with normal renal function | EXPERIMENTAL | This arm includes participants with normal renal function who will receive an oral dose of PF-06882961 20 milligrams (mg) on Day 1 |
| Participants with T2DM with normal renal function | EXPERIMENTAL | This arm includes participants with Type 2 Diabetes Mellitus (T2DM) with normal renal function who will receive an oral dose of PF-06882961 20 mg on Day 1 |
| Participants with T2DM with mild renal impairment | EXPERIMENTAL | This arm includes participants with Type 2 Diabetes Mellitus (T2DM) with mild renal impairment who will receive an oral dose of PF-06882961 20 mg on Day 1 |
| Participants with T2DM with moderate renal impairment | EXPERIMENTAL | This arm includes participants with Type 2 Diabetes Mellitus (T2DM) with moderate renal impairment who will receive an oral dose of PF-06882961 20 mg on Day 1 |
| Participants with T2DM with severe renal impairment | EXPERIMENTAL | This arm includes participants with Type 2 Diabetes Mellitus (T2DM) with severe renal impairment who will receive an oral dose of PF-06882961 20 mg on Day 1 |
| Period 1 | OTHER | Participants will receive the following treatments in this sequence : (i)Rosuvastatin alone (one dose of 10 mg), (ii) Midazolam alone (one dose of 2mg), (iii) PF 06882961 alone (120 mg twice daily), (iv) PF 06882961 (120 mg twice daily) + Rosuvastatin (one dose of 10mg), (v) PF 06882961 (120 mg) + Midazolam (one dose of 2 mg), (vi) PF 06882961 (200 mg) alone, (vii) PF 06882961 (200 mg) + Rosuvastatin (one dose of 10 mg), (viii) PF 06882961 (200 mg)+ Midazolam (one dose of 2 mg) in the study. |
| Formulation A (Cohort 1) | ACTIVE_COMPARATOR | Following an overnight fast of at least 10 hours, subjects received PF-06882961 (Danuglipron) 100 mg immediate release tablet as formulation A at approximately 0800 hours (±2 hours). A minimum of 72 hours between the single 100 mg doses administered in each period was employed |
| Formulation B (Cohort 1) | EXPERIMENTAL | Following an overnight fast of at least 10 hours, subjects received PF-06882961 (Danuglipron) 100 mg immediate release tablet as formulation B at approximately 0800 hours (±2 hours). A minimum of 72 hours between the single 100 mg doses administered in each period was employed |
| Formulation C (Cohort 1) | EXPERIMENTAL | Following an overnight fast of at least 10 hours, subjects received PF-06882961 (Danuglipron) 100 mg immediate release tablet as formulation C at approximately 0800 hours (±2 hours). A minimum of 72 hours between the single 100 mg doses administered in each period was employed |
| Formulation D (Cohort 1) | EXPERIMENTAL | Following an overnight fast of at least 10 hours, subjects received PF-06882961 (Danuglipron) 100 mg immediate release tablet as formulation D at approximately 0800 hours (±2 hours). A minimum of 72 hours between the single 100 mg doses administered in each period was employed |
| Formulation A (Cohort 2) | ACTIVE_COMPARATOR | Following an overnight fast of at least 10 hours, subjects received PF-06882961 (Danuglipron) 100 mg immediate release tablet as formulation A at approximately 0800 hours (±2 hours). A minimum of 72 hours between the single 100 mg doses administered in each period was employed |
| Formulation E (Cohort 2) | EXPERIMENTAL | Following an overnight fast of at least 10 hours, subjects received PF-06882961 (Danuglipron) 100 mg immediate release tablet as formulation E at approximately 0800 hours (±2 hours). A minimum of 72 hours between the single 100 mg doses administered in each period was employed |
| PF-06882961 30 mg | EXPERIMENTAL | - |
| PF-06882961 100 mg | EXPERIMENTAL | - |
| PF-06882961 300 mg | EXPERIMENTAL | - |
| PF-06882961 600 mg | EXPERIMENTAL | - |
| PF-06882961 dose TBD Cohort 5 | EXPERIMENTAL | - |
| PF-06882961 dose TBD Cohort 6 | EXPERIMENTAL | - |
| PF-06882961 dose TBD Cohort 7 | EXPERIMENTAL | - |
| PF-06882961 dose TBD Cohort 8 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Placebo (Cohorts 1 and 2) | DRUG | 4 matching placebo tablets taken twice daily |
| PF-06882961 (Cohorts 1 and 2) | DRUG | Participants will be randomized to one of 5 active target dose levels (40, 80, 120, 160 or 200 mg BID) achieved through 1-week titration steps, or 3 active target dose levels (120, 160 or 200 mg BID) achieved through 2-week titration steps, taking 4 tablets twice daily |
| Placebo (Cohort 3) | DRUG | 2 matching placebo tablets taken twice daily |
| PF-06882961 (Cohort 3) | DRUG | Participants will be randomized to one of 3 active target dose levels (80, 140 or 200 mg BID) achieved through 4-week titration steps, taking 2 tablets twice daily. |
| PF-06882961 | DRUG | PF-68882961 will be provided as tablets twice a day (BID) |
| Placebo | OTHER | Placebo comparator will be provided as tablets twice daily for 12 weeks |
| Danuglipron | DRUG | Danuglipron oral tablets |
| Atorvastatin | DRUG | Atorvastatin oral tablets |
| Rosuvastatin | DRUG | Rosuvastatin oral tablets |
| PF-06882961 20 mg | DRUG | PF-06882961 20 mg single oral dose provided in tablet form administered in a fed state on Day 1 |
| Midazolam | DRUG | 2mg single dose |
| PF-06882961 100 mg | DRUG | PF-06882961 100 mg will be provided in 5 different oral formulations A, B, C, D, and E. Cohort 1 is a randomized, open-label, single dose, 4-period, 4-sequence, crossover design where the first 2 periods are cross-over (Formulations A and B) and the second 2 periods are crossover (Formulations C and D). Cohort 2 is a randomized, open-label, single dose, 2-period, 2 sequence, crossover design (Formulations A and E) |
Inclusion Criteria: * Participants with obesity, defined as a Body Mass Index greater than or equal to 30.0 kg/m2 * Stable body weight, defined as \<5 kg change (per participant report) for 90 days before visit 1 Exclusion Criteria: * Any condition possibly affecting drug absorption * Current or ...
PF-06882961 is an investigational oral small molecule being studied for type 2 diabetes mellitus, obesity, and overweight with obesity. It is in Phase 2 clinical development and has been evaluated in completed trials including a 628-participant Phase 2 study in adults with obesity and a 151-participant Phase 2 study in adults with type 2 diabetes and obesity.
PF-06882961 targets the GLP-1 receptor, a receptor involved in glucose-dependent insulin secretion and appetite regulation. It is an oral small molecule GLP-1 receptor agonist, distinguishing it from peptide-based GLP-1 therapies that typically require injection.
PF-06882961 is being developed by Pfizer, Inc., which trades on the New York Stock Exchange under the ticker PFE. Pfizer has sponsored the clinical program, including Phase 1 and Phase 2 trials in type 2 diabetes and obesity.
PF-06882961 is in Phase 2 clinical development. It is investigational and has not been approved by the FDA. Five completed trials have evaluated the drug, including two Phase 2 studies and three Phase 1 studies, with a total enrollment of 644 participants across the program.
PF-06882961 has been studied in five completed trials. These include NCT04707313, a Phase 2 obesity study with 628 participants; NCT04617275, a Phase 2 study in type 2 diabetes and obesity; NCT04889157, a Phase 1 study in Chinese adults with type 2 diabetes; NCT04621227, a Phase 1 drug interaction study; and NCT04617275.
PF-06882961 and PF-06865571 are distinct compounds. PF-06882961 has been studied alone and in a regimen described as PF-06882961/PF-06865571 followed by PF-06882961. Other listed identifiers such as PF-06882961 20 mg, 50 mg, and 100 mg refer to dose strengths of PF-06882961 used in trials.