Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03121664 | A Study To Estimate The Effects Of Itraconazole On Pharmacokinetics Of Pf-06649751 In Healthy Adult Subjects | PHASE1 | COMPLETED | 11 | — | — | Apr 7, 2017 | Sep 14, 2017 | Nov 6, 2017 | 1 | Belgium |
| NCT02262767 | A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of PF-06649751 Co-administered With Trimethobenzamide Hydrochloride in Healthy Subjects | PHASE1 | COMPLETED | 9 | — | — | Nov 1, 2014 | Dec 1, 2014 | Jan 14, 2015 | 2 | Belgium |
| NCT02066909 | A Study To Observe Safety And Blood Concentrations Of PF-06649751 During And Following The Oral Administration Of Multiple Doses Of PF-06649751 In Healthy Adult Western and Japanese Volunteers | PHASE1 | COMPLETED | 77 | — | — | Feb 1, 2014 | Apr 1, 2015 | Jun 24, 2015 | 1 | United States |
| NCT01981694 | A Phase I Trial to Investigate the Safety and Tolerability of PF-06649751 | PHASE1 | COMPLETED | 18 | — | — | Nov 1, 2013 | Feb 1, 2014 | Mar 26, 2014 | 1 | United States |
Maximum Observed Plasma Concentration
Area Under the Curve From Time Zero to the end of the dosing period
Counts of participants who have treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to PF-06649751 will be assessed by the investigator (Yes/No). Participants with multiple occurrences 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 laboratory test to define the values that would be identified as of potential clinical importance.
Maximum plasma concentration
Time for Cmax
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Minimum concentration pre-dose
Ratio of accumulation for AUCtau. Corrected for titrated doses.
Ratio of accumulation for Cmax. Corrected for titrated doses.
Peak-to-trough ratio at steady state
C-SSRS assessed whether participant experienced following: completed suicide (1), suicide attempt (2) (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3)("Yes" on "preparatory acts or behavior"), suicidal ideation (4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)("Yes" on "Has subject engaged in non-suicidal self-injurious behavior").
Calculated from urinary volumes and concentration
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).
Measurement of eye blink rate for a given dose at time of predicted maximum blood concentration of the compound
| Arm | Type | Description |
|---|---|---|
| Cohort 1 | EXPERIMENTAL | - |
| Single Ascending Doses Cohort 1 | EXPERIMENTAL | Single doses, given by oral solution, starting at 0.75 mg up to a possible maximum of 3.0 mg. The subject will have been fasted for 10 hours prior to the single dose. For each dosing period, 3 subjects will be given a placebo as a comparator while 6 are given active dose. The subjects will be given concomitant trimethobenzamide hydrochloride for the 3 weeks that the subject is in the CRU. For each of the three periods, subjects will be crossed-over from placebo or PF-06649751. Each PF-06649751 dose is separated by one week. |
| Single Ascending Doses Cohort 2 | EXPERIMENTAL | Single doses, given by oral solution, starting at 4.5 mg up to a possible maximum of 9.0 mg. The subject will have been fasted for 10 hours prior to the single dose. For each dosing period, 3 subjects will be given a placebo as a comparator while 6 are given active dose. The subjects will be given concomitant trimethobenzamide hydrochloride for the 3 weeks that the subject is in the CRU. For each of the three periods, subjects will be crossed-over from placebo or PF-06649751. Each PF-06649751 dose is separated by one week. |
| Cohort 2 | EXPERIMENTAL | Dosing in healthy Western subjects. |
| Cohort 3 | EXPERIMENTAL | Dosing in healthy Western subjects. |
| Cohort 4 | EXPERIMENTAL | Dosing in healthy Western subjects. |
| Cohort 5 | EXPERIMENTAL | Dosing in healthy Western subjects. |
| Cohort 6 | EXPERIMENTAL | Dosing in healthy Western subjects. |
| Cohort 7 | EXPERIMENTAL | Dosing in healthy Western subjects. |
| Optional Cohort 8 | EXPERIMENTAL | Dosing in healthy Western subjects. Cohort may not be conducted. |
| Cohort 9 | EXPERIMENTAL | Dosing in healthy Japanese subjects. |
| Single ascending doses | EXPERIMENTAL | - |
| Measurement of eye blink rate | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| PF06649751, Itraconazole | DRUG | PF-06649751 0.25 mg on Days 1,2,3 PF-06649751 0.5 mg on Days 4,5,6 PF-06649751 1 mg on Days 7 to Day 25 Itracoanzole 200 mg on Days 12 to Day 25 |
| PF-06649751 | DRUG | Experimental Pfizer compound. |
| Trimethobenzamide Hydrochloride | DRUG | Trimethobenzamide Hydrochloride is indicated for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis. |
| 0.15 mg PF-06649751 | DRUG | Oral dosing of 0.15 mg PF-06649751 extemporaneously-prepared solution given once-daily for 14 days. |
| 0.5 mg PF-06649751 | DRUG | Oral dosing of 0.5 mg PF-06649751 extemporaneously-prepared solution given once-daily for 14 days. |
| 1.5 mg PF-06649751 | DRUG | Oral dosing of tablets up to 1.5 mg PF-06649751 given once-daily for 14 days. |
| 1.5 mg PF-06649751 21 Days | DRUG | Oral dosing of tablets up to 1.5 mg PF-06649751 given once-daily for 21 days. |
| 3.0 mg PF-06649751 | DRUG | Oral dosing of tablets up to 3.0 mg PF-06649751 given once-daily for 28 days. |
| 5.0 mg PF-06649751 | DRUG | Oral dosing of tablets up to 5.0 mg PF-06649751 given once-daily for 28 days. |
| 8.0 mg PF-06649751 | DRUG | Oral dosing of tablets up to 8.0 mg PF-06649751 given once-daily for 28 days. |
| 1.5 mg PF-06649751 in healthy Japanese subjects | DRUG | Oral dosing of tablets up to 1.5 mg PF-06649751 given once-daily for 14 days given in healthy Japanese subjects. |
Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study: * Healthy female subjects of nonchildbearing potential and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive. * Female subject...