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Also known as [14C]PF-05221304, PF-05221304 Monotherapy, experimental drug
PF-05221304 · 3 trials · 4 indications
Magnetic resonance imaging proton density fat fraction (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 = PDFFs for (Segment I + Segment II + Segment III + Segment IVa + Segment IVb + Segment V + Segment VI + Segment VII + Segment VIII) divided by total number of segments assessed.
MRI-PDFF utilized a gradient echo sequence with low flip angle (FA) to minimize T1 bias, corrected T2\* decay (due to iron overload) via modeling of the fat signal as a superposition of multiple frequency components from 5 different lipid types, and was applied in each of the 9 Couinaud segments. This technique improved fat quantification accuracy for the entire liver permitting quantification of small differences/changes following pharmacological intervention.
Cmax was observed directly from data.
AUCinf was calculated by AUClast + (Clast\*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
fu was the fraction of PF-05221304 unbound in plasma. fu was calculated based on the post-dialysis plasma concentrations, post-dialysis buffer concentrations, collected post-dialysis plasma and post-dialysis buffer sample volume (assuming no volume shift prior to and after dialysis), and the total plasma concentrations.
Cmax,u was calculated by fu\*Cmax.
AUCinf,u was calculated by fu\*AUCinf.
| Arm | Type | Description |
|---|---|---|
| Placebo | PLACEBO_COMPARATOR | Placebo (PF 05221304) BID Placebo (PF 06865571) BID |
| PF-05221304 Monotherapy | EXPERIMENTAL | 15 mg PF-05221304 BID Placebo (PF-06865571) BID |
| PF-06865571 Monotherapy | EXPERIMENTAL | Placebo (PF-05221304) BID 300 mg PF-06865571 BID |
| PF-05221304 and PF-06865571 Combination | EXPERIMENTAL | 15 mg PF-05221304 BID 300 mg PF-06865571 BID |
| PF-05221304 - 2 mg | ACTIVE_COMPARATOR | PF-05221304 - 2 mg, once-daily |
| PF-05221304 - 10 mg | ACTIVE_COMPARATOR | PF-05221304 - 10 mg, once-daily |
| PF-05221304 - 25 mg | ACTIVE_COMPARATOR | PF-05221304 - 25 mg, once-daily |
| PF-05221304 - 50 mg | ACTIVE_COMPARATOR | PF-05221304 - 50 mg, once-daily |
| Cohort 1_Without impairment | EXPERIMENTAL | Single, 25 mg dose of PF-05221304 |
| Cohort 2_Mild impairment | EXPERIMENTAL | Single, 25 mg dose of PF-05221304 |
| Cohort 3_Moderate impairment | EXPERIMENTAL | Single, 25 mg dose of PF-05221304 |
| Cohort 4_Severe impairment | EXPERIMENTAL | Single, 25 mg dose of PF-05221304 |
| Name | Type | Description |
|---|---|---|
| PF-05221304 Monotherapy | DRUG | Participants enrolled in this Arm will receive 15 mg dose of PF-05221304 (3 tablets of 5 mg each) and 3 tablets of Placebo for PF-06865571, each to be taken twice daily for 41 days and once on Day 42. |
| PF-06865571 Monotherapy | DRUG | Participants enrolled in this Arm will receive 300 mg dose of PF-06865571 (3 tablets of 100 mg each) and 3 tablets of Placebo for PF-05221304, all to be taken twice daily for 41 days and once on Day 42. |
| Placebo | DRUG | Participants enrolled in this Arm will receive 3 tablets for Placebo of PF-05221304 and 3 tablets of Placebo of PF-06865571, to be taken twice daily for 41 days and once on Day 42. |
| PF-05221304 and PF-06865571 Combination | DRUG | Participants enrolled in this Arm will receive 15 mg dose of PF-05221304 (3 tablets of 5 mg each) and 3 tablets of PF-06865571 (3 tablets of 100 mg each), each to be taken twice daily for 41 days and once on Day 42. |
| PF-05221304 | DRUG | PF-05221304, Experimental Drug |
Inclusion Criteria: * Male subjects or female subjects of non childbearing potential * Total body weight of \>50 kg (110 lbs) and a BMI greater than or equal to 25 kg/m2 * Medical diagnosis of Type 2 Diabetes Mellitus (T2DM) being treated with no more than 1 acceptable oral antidiabetic drug OR Sub...
PF-05221304 is an investigational small molecule developed by Pfizer, Inc. (ticker PFE) for liver-related conditions. It has been studied in nonalcoholic fatty liver disease (NAFLD) and in adults with varying degrees of hepatic impairment. It is an oral agent that has completed early-stage clinical testing and has not been approved for any indication.
PF-05221304 was studied as a treatment for nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis. Clinical trials enrolled adults with NAFLD to assess the drug alone and co-administered with PF-06865571. It remains investigational and is not approved for treating NAFLD or any other condition.
PF-05221304 is developed by Pfizer, Inc., which trades on the New York Stock Exchange under the ticker PFE. Pfizer sponsored the clinical trials evaluating the compound in nonalcoholic fatty liver disease and in patients with hepatic impairment.
PF-05221304 is in Phase 1 development, with completed Phase 1 and Phase 2 studies in its clinical program. It is investigational and has not been approved by the FDA or any other regulatory agency for any indication. All trials of the drug are listed as completed.
PF-05221304 has been evaluated in completed trials including NCT03248882, a Phase 2a dose-ranging study in NAFLD with 305 participants; NCT03776175, a Phase 2 study of PF-05221304 co-administered with PF-06865571 in adults with NAFLD; and NCT03309202, a Phase 1 study in subjects with varying degrees of hepatic impairment.
Yes. [14C]PF-05221304 is a carbon-14 labeled form of PF-05221304 used in research, and PF-05221304 Monotherapy refers to treatment with the compound alone. All of these names refer to the same Pfizer investigational small molecule studied in nonalcoholic fatty liver disease and hepatic impairment.