Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
PF-06648671 · 4 trials · 3 indications
Camx after single dose of 25 mg PF-06648671 in period 1 and period 2
Tmax following single doses of PF-06648671 in period 1 and period 2
AUCinf following single doses of PF-06648671 in period 1 and period 2
AUClast following single doses of PF-06648671 in period 1 and period 2
t1/2 following single doses of PF-06648671 in period 1 and period 2
CL/F following single doses of PF-06648671 in period 1 and period 2
Vz/F following single doses of PF-06648671 in period 1 and period 2
AUC24 on day 1, 7 and 14 in part 1, day 1 and 14 in part 2
t1/2 post last dose on Day 14
CL/F on day 14
Vz/F on day 14
PF-06648671 CSF concentration on day 1 and day 14 (cohort 3) or day 15 (cohorts 5, 6 and 8) prior to dosing in part 1
accumulation of PF-06648671 plasma AUC24 on day 7 and day 14 relative to day 1 in part 1, AUC on day 14 relative to day 1 in part 2
PF-06648671 plasma Cmax on day 7 and 14 relative to day 1 in part 1, day 14 to day 1 in part 2
percentage of parent drug recovered in urine over 24 hours on day 14 in part 1 and part 2
Renal clearance of PF-06648671 on day 14
CSF Abeta 40 and 42 concentration on day 14 (cohort 3) or on day 15 (cohorts 5, 6 and 8) prior to dosing compared to day 1 baseline
the AUC ratio of midazolam between day 14 in period 2 vs day 1 in period 1 in optional part 3
the Cmax ratio of midazolam between day 14 in period 2 vs day 1 in period 1 in optional part 3
Counts of participants who have TEAEs, defined as newly occuring or worsening after first dose. Relatedness to PF-06648671 will be assessed by the investigator (Yes/No). Participants with multiple occurences of an AE within a category will be counted once within the category
Measurement of blood pressure and pulse rate
Measurement of standard 12-lead ECG, single or triplicate
Pre-defined criteria were established for each lab test to identify potential clinical importance
| Arm | Type | Description |
|---|---|---|
| single cohort | EXPERIMENTAL | single dose of PF-06648671 in period 1 and 14-day dose of itraconazole plus single dose of PF-06648671 in period 2 |
| PF-06648671 High dose group | EXPERIMENTAL | subjects receive a single oral dose of PF-06648671 at 300 mg |
| PF-06648671 Low dose group | EXPERIMENTAL | Subjects receive a single oral dose of PF-06648671 lower than 300 mg dose |
| Placebo group | PLACEBO_COMPARATOR | Subjects receive matching placebo |
| PF-06648671 Low dose group (2) | EXPERIMENTAL | Optional arm. Subjects receive a single oral dose of PF-06648671 at second lower dose if 300 mg dose is not repeated in cohort 2 |
| Multiple Doses PF-06648671 (Cohort1) | EXPERIMENTAL | Healthy subjects receive 14-day repeated dose once a day at 4 mg of PF-06648671 or matching placebo |
| Multiple Doses PF-06648671 (cohort 2) | EXPERIMENTAL | Healthy subject receive 14-day repeated dose once a day at 12 mg of PF-06648671 or matching placebo |
| Multiple doses PF-06648671 (cohort 3) | EXPERIMENTAL | Healthy subject receive 14-day repeated dose once a day at 40 mg of PF-06648671 or matching placebo and CSF LP is collected at baseline and steady state predose on day 1 and 14 |
| Multiple Doses PF-06648671 (cohort 4) | EXPERIMENTAL | Healthy subject receive 14-day repeated dose once a day at 40 mg of PF-06648671 or matching placebo |
| Multiple Doses PF-06648671 (cohort 5) | EXPERIMENTAL | Healthy subject receive 14-day repeated dose once a day at 100 mg of PF-06648671 or matching placebo, CSF LP is collected at baseline 72 hours prior to day 1 dosing and at steady-state on Day 15, 24 hours after last dosing on day 14 |
| Multiple Doses in Healthy Elderly (cohort 7) | EXPERIMENTAL | Healthy Elderly subjects receive 14-day repeated dose once a day at MTD PF-06648671 defined in healthy adult subjects (part 1) |
| Multiple Doses PF-06648671 (cohort 8) | EXPERIMENTAL | Healthy subjects receive 14-day repeated dose once a day at 360 mg of PF-06648671 or matching placebo, CSF LP is collected at baseline 72 hours prior to day 1 dosing and at steady-state on Day 15, 24 hours post last dose |
| Midazolam DDI (optional cohort 9) | EXPERIMENTAL | Healthy Subjects receive single dose of 2 mg midazolam in period 1 followed by 14 days PF-06648671 once a day and coadministration of PF-06648671 and midazolam 2 mg in period 2 (Optional cohort) |
| Multiple Doses PF-06648671 (cohort 6) | EXPERIMENTAL | Healthy subject receive 14-day repeated dose once a day at 200 mg of PF-06648671 or matching placebo, CSF LP is collected at baseline 72 hours prior to day 1 dosing and at steady-state on Day 25, 24 hours after last dosing on day 14 |
| Single Ascending Doses Cohort 1 | EXPERIMENTAL | subjects receive 3 active doses and one placebo |
| Single Ascending Doses Cohort 2 | EXPERIMENTAL | subjects receive 3 doses and one placebo |
| Cohort 3 | EXPERIMENTAL | optional cohort |
| Name | Type | Description |
|---|---|---|
| PF-06648671 | DRUG | Subjects will receive a single dose of PF-06648671 25 mg oral suspension on day 1 in period 1 and a single dose on Day 4 in period 2. |
| Itraconazole | DRUG | Subjects will receive itraconazole 200 mg oral solution once a day for 14 days in period 2 |
| Placebo | DRUG | Placebo which will be dosed as oral suspension, single doses to match PF-06648671 |
| Midazolam | DRUG | commercial available oral solution of 2 mg midazolam as CYP3A probe substrate for drug interaction evaluation. Midazolam will be given as single dose with and without co-administration of PF-06648671 |
Inclusion Criteria: 1. Healthy male and/or female subjects of non childbearing potential between the ages of 18 and 55 years at the time of screening, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including...
PF-06648671 is an investigational small molecule being developed by Pfizer, Inc. (PFE). It is currently in Phase 1 clinical development. Studies have evaluated it in healthy subjects, including healthy adults and healthy elderly subjects, to assess its safety, pharmacokinetics, and pharmacodynamic effects.
PF-06648671 is being studied in healthy subjects, including healthy adults and healthy elderly subjects. The clinical trials focus on evaluating its safety, tolerability, pharmacokinetics, and pharmacodynamic effects, particularly its effect on beta-amyloid concentrations in cerebrospinal fluid. It is not approved for any disease indication.
PF-06648671 is developed by Pfizer, Inc., a biopharmaceutical company traded on the New York Stock Exchange under the ticker PFE.
PF-06648671 is in Phase 1 clinical development. All four clinical trials listed for the drug are Phase 1 studies and have been completed. The drug remains investigational and has not been approved by regulatory authorities.
PF-06648671 has been studied in four completed Phase 1 trials. These include NCT02316756, a single ascending dose study in healthy subjects in Belgium; NCT02407353, a study of its pharmacodynamic effects on beta-amyloid in cerebrospinal fluid in the United States; NCT02440100, a repeat-dose study in healthy adults and elderly subjects in Belgium; and NCT02883114, a drug interaction study with itraconazole in healthy adults in the United States.
A completed Phase 1 trial, NCT02407353, evaluated the pharmacodynamic effects of single oral doses of PF-06648671 on beta-amyloid (Aβ) concentrations in cerebrospinal fluid. The study enrolled 22 healthy subjects in the United States. Results from this trial have not been reported in the available data.