Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
PF-06865571 · 8 trials · 10 indications
MRI-PDFF technique is an established method that enables quantification of fat content in the liver. It measures the fraction of mobile protons in the liver attributable to fat content and provides whole liver coverage so that fat content can be assessed across 8 Couinaud liver segments. Whole liver PDFF = the sum of PDFFs for (Segment I + Segment II + Segment III + Segment IVa + Segment IVb + Segment V + Segment VI + Segment VII + Segment VIII) divided by (number of segments assessed and no missing/mapping at Baseline, and on Week 6). If some segments did not have results reported at Baseline and/or Week 6, liver PDFF was to be calculated using data in segments that had data available at both Baseline visit and Week 6 visit. For this outcome measure (OM), baseline is defined as the assessment undertaken between Visit 3/Week -2 and Visit 4/Day 1.
NASH resolution: disappearance of ballooning (Nonalcoholic Fatty Liver Disease \[NAFLD\] Activity Score \[NAS\] ballooning score=0;0=no ballooning,1=few balloon cells,2=many cells with prominent ballooning; higher scores(HS)=more disease activity \[DA\]),residual/no lobular inflammation(NAS lobular inflammation score 0/1,0=no foci,1= \<2 foci, 2=2-4 foci,3= \>4 foci; HS=more DA),NAS steatosis score 0,1,2,3; 0= \<5% hepatocytes involved (HI),1=5-33% HI ,2= 34-66% HI, 3= \>66% HI; HS=more DA. No worsening of fibrosis: no change/decrease of at least 1 stage in Brunt-Kleiner scale (BKS) compared to baseline (CTB). Improvement in fibrosis by \>=1 stage: decrease of at least 1 stage in BKS CTB. No worsening of NASH: no change/increase in NAS for ballooning, inflammation, steatosis CTB. BDRM utilized to characterize dose response across BID treatment groups, estimate posterior mean proportion (\& 90% credible interval \[CI\], indicated as 'confidence interval' below) for placebo and each BID dose studied.
Resolution of NASH: disappearance of ballooning (NAS ballooning score= 0; where 0= no ballooning, 1= few balloon cells, 2= many cells with prominent ballooning; higher scores= more disease activity), residual or no lobular inflammation (NAS lobular inflammation score 0 or 1, where 0= no foci, 1= \<2 foci, 2= 2-4 foci, 3= \>4 foci; higher scores= more disease activity), NAS steatosis score 0, 1, 2, or 3, where 0= \<5% hepatocytes involved, 1= 5-33% hepatocytes involved, 2= 34-66% hepatocytes involved, 3= \>66% hepatocytes involved; higher scores= more disease activity. No worsening of fibrosis: no change or decrease of at least 1 stage in BKS compared to baseline. Improvement in fibrosis by \>=1 stage: decrease of at least 1 stage in BKS compared to baseline. No worsening of NASH: no change or increase in NAS for ballooning, inflammation, steatosis compared to baseline.
The total recovery of radioactivity in urine was listed and summarized using descriptive statistics. In this outcome measure, the percentages of dose excreted in urine in Period 1 and Period 2 were reported.
The total recovery of radioactivity in feces was listed and summarized using descriptive statistics. In this outcome measure, the percentages of dose excreted in feces in Period 1 and Period 2 were reported.
The total recovery of radioactivity in the combination of urine and feces was listed and summarized using descriptive statistics. In this outcome measure, the percentages of dose excreted in total excreta (urine + feces) in Period 1 and Period 2 were reported.
Plasma samples were analyzed for radiolabeled PF-06865571 and its metabolites. \[14C\]PF-06865571 and the major metabolites in plasma, after oral administration of 300 mg \[14C\]PF-06865571 were identified. In this outcome measure, relative abundance of radiolabeled PF-06865571 in plasma based on \[14C\] quantitation was reported. The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.
Plasma samples were analyzed for radiolabeled PF-06865571 and its metabolites. \[14C\]PF-06865571 and the major metabolites in plasma, after oral administration of 300 mg \[14C\]PF-06865571 were identified. In this outcome measure, relative abundance of the metabolites of \[14C\]PF-06865571 in plasma based on \[14C\] quantitation was reported. The metabolites included 487, 391, 412, 556, M6 (PF-07822633), M7 (PF-07911964), 584, M1 (PF-06878236), 426, M4 (PF-06887477), 600, M5 (PF-06885984) and M2 (PF-06868609). The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.
Urine samples were analyzed for radiolabeled PF-06865571 and its metabolites. \[14C\]PF-06865571 and the major metabolites in urine, after oral administration of 300 mg \[14C\]PF-06865571 were identified. In this outcome measure, relative abundance of radiolabeled PF-06865571 in urine based on \[14C\] quantitation was reported. The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.
Urine samples were analyzed for radiolabeled PF-06865571 and its metabolites. \[14C\]PF-06865571 and the major metabolites in urine, after oral administration of 300 mg \[14C\]PF-06865571 were identified. In this outcome measure, relative abundance of the metabolites of \[14C\]PF-06865571 in urine based on \[14C\] quantitation was reported. The metabolites included 487, 391, 412, 556, M6 (PF-07822633), M7 (PF-07911964), 584, M1 (PF-06878236), 426, M4 (PF-06887477), 600, M5 (PF-06885984) and M2 (PF-06868609). The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.
Fecal samples were analyzed for radiolabeled PF-06865571 and its metabolites. \[14C\]PF-06865571 and the major metabolites in feces, after oral administration of 300 mg \[14C\]PF-06865571 were identified. In this outcome measure, relative abundance of radiolabeled PF-06865571 in feces based on \[14C\] quantitation was reported. The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.
Fecal samples were analyzed for radiolabeled PF-06865571 and its metabolites. \[14C\]PF-06865571 and the major metabolites in feces, after oral administration of 300 mg \[14C\]PF-06865571 were identified. In this outcome measure, relative abundance of the metabolites of \[14C\]PF-06865571 in feces based on \[14C\] quantitation was reported. The metabolites included 487, 391, 412, 556, M6 (PF-07822633), M7 (PF-07911964), 584, M1 (PF-06878236), 426, M4 (PF-06887477), 600, M5 (PF-06885984) and M2 (PF-06868609). The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.
Cmax of PF-06865571 was observed directly from data.
AUClast of PF-06865571 was determined by linear/log trapezoidal method.
AUCinf = Area under the plasma concentration versus time curve (AUC) from time 0 (pre-dose) to extrapolated infinite time (0-inf).
Metformin Cmax in absence of PF-06865571
Metformin Cmax in presence of PF-06865571
Metformin AUCinf in absence of PF-06865571
Metformin AUCinf in presence of PF-06865571
MRI-PDFF is an established method that enables quantification of fat content in the liver. The value of whole liver fat as assessed by MRI-PDFF is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level.
Number of participants with reported adverse events
Number of participants with potentially clinically important laboratory test findings
Number of participants with potentially clinically important ECG findings
Number of participants with potentially clinically important vital sign measurements
| Arm | Type | Description |
|---|---|---|
| Placebo | PLACEBO_COMPARATOR | Participants will receive medication for 6 weeks |
| DGAT2i (25 mg BID) + ACCi (10 mg BID) | EXPERIMENTAL | Participants will receive medication for 6 weeks |
| DGAT2i (100 mg BID) + ACCi (10 mg BID) | EXPERIMENTAL | Participants will receive medication for 6 weeks |
| DGAT2i (300 mg QD) + ACCi (20 mg QD) | EXPERIMENTAL | Participants will receive medication for 6 weeks |
| DGAT2i (300 mg BID) + ACCi (10 mg BID) | EXPERIMENTAL | Participants will receive medication for 6 weeks |
| PF-06865571 25 milligrams (mg) twice daily (BID) | EXPERIMENTAL | participants will receive medication for 48 weeks |
| PF-06865571 75 mg BID | EXPERIMENTAL | participants will receive medication for 48 weeks |
| PF-06865571 150 mg BID | EXPERIMENTAL | participants will receive medication for 48 weeks |
| PF-06865571 300 mg BID | EXPERIMENTAL | participants will receive medication for 48 weeks |
| PF-06865571 (150 mg BID) + PF-05221304 (5 mg BID) | EXPERIMENTAL | participants will receive medication for 48 weeks |
| PF-06865771 (300 mg BID) + PF-05221304 (10 mg BID) | EXPERIMENTAL | participants will receive medication for 48 weeks |
| Study arm | EXPERIMENTAL | One arm of healthy male participants administered a single oral dose of \[14C\]PF-06865571; followed by a single dose of unlabeled PF-06865571, and IV administration of \[14C\]PF-06865571 three hours later. |
| PF-06865571 Moderate Hepatic Impairment | EXPERIMENTAL | This arm includes participants with moderate hepatic impairment who will receive an oral dose of PF-06865571 100 mg on Day 1 |
| PF-06865571 Severe Hepatic Impairment | EXPERIMENTAL | This arm includes participants with severe hepatic impairment who will receive an oral dose of PF-06865571 100 mg on Day 1 |
| PF-06865571 Mild Hepatic Impairment | EXPERIMENTAL | This arm includes participants with mild hepatic impairment who will receive an oral dose of PF-06865571 100 mg on Day 1 |
| PF-06865571 Healthy Participants | EXPERIMENTAL | This arm includes healthy participants who will receive an oral dose of PF-06865571 100 mg on Day 1 |
| Metformin Alone | EXPERIMENTAL | Metformin alone |
| Metformin + PF-06865571 | EXPERIMENTAL | Co-administer metformin and PF-06865571 |
| PF-06865571 100 mg | EXPERIMENTAL | - |
| PF-06865571 600 mg | EXPERIMENTAL | - |
| Cohort 1_90mg and Matching Placebo | EXPERIMENTAL | - |
| Cohort 2_300mg and Matching Placebo | EXPERIMENTAL | - |
| Cohort 3_900mg and Matching Placebo | EXPERIMENTAL | - |
| Cohort 4_1800mg and Matching Placebo | EXPERIMENTAL | - |
| Cohort 5_3000mg and Matching Placebo | EXPERIMENTAL | - |
| Optional Cohort 6_TBD mg and Matching Placebo | EXPERIMENTAL | - |
| Optional Cohort 7_TBD mg and Matching Placebo | EXPERIMENTAL | - |
| Cohort 1_Active and Matching Placebo | EXPERIMENTAL | - |
| Cohort 2_Active and Matching Placebo | EXPERIMENTAL | - |
| Cohort 3_Active and Matching Placebo | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| PF-06865571 | DRUG | Tablet |
| PF-05221304 | DRUG | Tablet |
| Placebo | DRUG | Tablet |
| Oral [14C]PF-06865571 | DRUG | Oral radiolabeled PF-06865571 |
| Oral PF-06865571 | DRUG | Oral PF-06865571 |
| IV [14C]PF-06865571 | DRUG | IV radiolabeled PF-06865571 |
| PF-06865571 100 mg | DRUG | PF-06865571 in 100 mg oral tablet will be administered on Day 1 |
| Metformin | DRUG | Metformin |
Inclusion Criteria: * BMI ≥25 and ≤ 40 kg/m2 * concomitant medical conditions associated with NAFLD Exclusion Criteria: * Evidence of other causes of liver disease such as Alcoholic steatohepatitis, (de)compensated cirrhosis, active viral hepatitis * Any condition possibly affecting drug absorpti...
PF-06865571 is an investigational small molecule being studied for nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and hepatic impairment. It is being developed by Pfizer, Inc. (PFE) and is currently in Phase 1 clinical development.
PF-06865571 is being developed by Pfizer, Inc., a biopharmaceutical company traded on the New York Stock Exchange under the ticker symbol PFE. The drug is an investigational small molecule in Phase 1 clinical development for liver-related conditions.
PF-06865571 is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Clinical trials have been completed to evaluate its safety, tolerability, and pharmacokinetics in healthy subjects and in individuals with hepatic impairment.
PF-06865571 has completed four Phase 1 clinical trials. These include NCT03092232, a single-dose safety and pharmacokinetics study in healthy subjects; NCT03593707, a drug-drug interaction study with metformin; NCT04091061, a study in subjects with hepatic impairment; and NCT04866225, an ADME study in healthy adult males.
The mechanism of action for PF-06865571 has not been disclosed in available clinical trial information. The drug is being studied for its effects in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, but its specific molecular target has not been publicly identified.