Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Ritlecitinib · 13 trials · 11 indications
Difference in the percentage of participants with SALT score less than or equal to 20 between ritlecitinib 100 mg once-daily (QD) versus placebo
To evaluate the long-term safety and tolerability of ritlecitinib in adult and adolescent participants with non-segmental vitiligo
To evaluate the long-term safety and tolerability of ritlecitinib in adult and adolescent participants with non-segmental vitiligo
Proportion of participants achieving F-VASI75 (defined as at least 75% improvement in F-VASI from Baseline) and T-VASI50 (defined as at least 50% improvement in T-VASI from Baseline)
Proportion of participants achieving F-VASI75 (defined as at least 75% improvement in F-VASI from Baseline).
To evaluate the safety and tolerability of ritlecitinib in adult participants with non segmental vitiligo
Proportion of participants achieving F-VASI75 (defined as at least 75% improvement in F-VASI from Baseline) and T-VASI50 (defined as at least 50% improvement in T-VASI from Baseline)
Safety and tolerability of ritlecitinib in participants with nonsegmental vitiligo
The difference in proportion of responders based on HiSCR50 response at Week 16 in patients with HS treated with ritlecitinib versus placebo.
The time and gastrointestinal location where the HPMC capsule(s) disintegrate and disperse the drug formulation.
Gastric emptying metrics may include a) time of 1st GE; b) time(s) for GE 10%, 25%, 50%, 75%, 90% and complete gastric emptying time GE100%.
Small Intestine transit metrics may include time for 10%, 25%, 50%, 75%, 90% and 100% of the formulation to transit through the small intestine.
Arrival time at the colon (ATC) metrics may include a) time(s) for ATC 10%, 25%, 50%, 75%, 90% and 100%.
The residence time of the formulation in the three primary regions of the large intestine to include the ascending, transverse and descending colon.
Residence time of the formulation in the gastrointestinal tract.
AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point 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.
AUCinf was defined as area under the plasma-concentration time profile from time zero extrapolated to infinite time. AUCinf for ritlecitinib was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point 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.
Cmax was defined as maximum observed plasma concentration. Cmax for ritlecitinib was observed directly from data.
Linear-log trapezoidal method was used for evaluation. For the calculation of AUCtau, pre-dose concentration of Day 7 was used as an estimate for the concentration of 24 hours post-dose on Day 7.
Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data.
AUCinf was defined as area under the plasma concentration time profile from time 0 extrapolated to infinite time.
Target occupancy for janus kinase 3 (JAK3) in peripheral blood mononuclear cells (PBMCs) by ritlecitinib was investigated in human blood by chemical probe-based enrichment and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. % TO is calculated as \[(baseline value - value at specified time point)\*100/baseline value\], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.
Target occupancy for Bruton's tyrosine kinase (BTK) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as \[(baseline value - value at specified time point)\*100/baseline value\], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.
Target occupancy forIL 2 inducible T-cell kinase (ITK) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as \[(baseline value - value at specified time point)\*100/baseline value\], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.
Target occupancy for tyrosine kinase expressed in T cells (TXK) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as \[(baseline value - value at specified time point)\*100/baseline value\], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.
Target occupancy for tyrosine kinase expressed carcinoma (TEC) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as \[(baseline value - value at specified time point)\*100/baseline value\], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.
Target occupancy for bone marrow tyrosine kinase gene in chromosome X (BMX) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as \[(baseline value - value at specified time point) \*100/baseline value\], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.
Plasma AUCinf for ritlecitinib is reported. AUCinf was calculated as \[AUClast+(Clast\*/kel)\], where AUClast is the area under the plasma concentration-time profile from time 0 to the time of the Clast, Clast is the last quantifiable concentration, Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Plasma Cmax for ritlecitinib is reported.
| Arm | Type | Description |
|---|---|---|
| Ritlecitinib 100 mg | EXPERIMENTAL | Randomized to Ritlecitinib 100 mg QD for 48 weeks. In addition to the active Ritlecitinib 100 mg capsule, a placebo capsule matching the Ritlecitinib 50 mg capsule will be given in order to maintain the blind. |
| Ritlecitinib 50 mg | EXPERIMENTAL | Randomized to Ritlecitinib 50 mg QD for 24 weeks. Depending on response status at Week 24 (ie, whether the participant has a SALT score of less than or equal to 20), the participant may be re-randomized to Ritlecitinib 50 mg QD or Ritlecitinib 100 mg QD for another 24 weeks. In addition to the active Ritlecitinib 50 mg capsule, a placebo capsule matching the Ritlecitinib 100 mg capsule will be given in order to maintain the blind. |
| External Placebo | NO_INTERVENTION | This group will be constructed using participant-level data at Week 24 from placebo groups of the appropriately chosen Pfizer clinical studies of Ritlecitinib in participants with alopecia areata. This data will be used for comparison between each Ritlecitinib dose and placebo at Week 24. As this arm will utilize data from other studies, no participants will be randomized to receive only placebo in this study. |
| Synthetic Placebo | NO_INTERVENTION | This group will be constructed using participant-level data up to Week 36 from the placebo groups of the appropriately chosen Pfizer clinical studies of Ritlecitinib in participants with alopecia areata and a longitudinal model and extrapolation. This data will be used for comparison between Ritlecitinib 100 mg and placebo at Week 36. As this arm will utilize data from other studies, no participants will be randomized to receive only placebo in this study. |
| Arm 1 | EXPERIMENTAL | Participants who previously received 1 ritlecitinib 50 mg capsule QD orally from BL to Week 52 in Study B7981040. Ritlecitinib 50 mg or Ritlecitinib 100 mg or Placebo will be assigned. |
| Arm 2 | EXPERIMENTAL | Participants who previously received 1 placebo 50 mg capsule QD orally from BL to Week 52 in Study B7981040 Ritlecitinib 50 mg or Ritlecitinib 100 mg or Placebo will be assigned |
| Arm 1- Ritlecitinib 100 milligrams (mg) | EXPERIMENTAL | Randomized to Ritlecitinib 100 mg QD for 52 weeks before progressing into the up/down titration extension period, rerandomized according to responder status. |
| Arm 2- Ritlecitinib 50mg | EXPERIMENTAL | Randomized to Ritlecitinib 50 mg QD for 52 weeks before progressing into the up/down titration extension period, rerandomized according to responder status. |
| Arm 3- Placebo | PLACEBO_COMPARATOR | Randomized to Placebo QD for 52 weeks before progressing into the up/down titration extension period, rerandomized according to responder status. |
| Arm 4- Ritlecitinib 100mg | EXPERIMENTAL | Non-randomized open-label Ritlecitinib 100mg QD for 52 weeks. |
| Placebo | PLACEBO_COMPARATOR | Placebo (placebo arm; approximately 200 participants) |
| Study Intervention | EXPERIMENTAL | Participants will receive one oral dose once daily (QD), starting with a loading dose of ritlecitinib for 8 weeks, followed by maintenance for 8 weeks. |
| Arm 3 | PLACEBO_COMPARATOR | Randomized to placebos matching the Ritlecitinib 50 mg and Ritlecitinib 100 mg capsules will be given to maintain blind from Day 1 to Week 12 (Period A). From Week 12 to Week 24 (Period B), will be switched to Ritlecitinib 100 mg. In addition to the active Ritlecitinib 100 mg capsule, a placebo matching the Ritlecitinib 50 mg capsule will be given to maintain blind. |
| Treatment Sequence 1 | EXPERIMENTAL | Ritlecitinib 100 mg solution (fasted, Period 1), followed by ritlecitinib 100 mg MR capsule with 153Sm2O3 (fasted, Period 2), and followed by ritlecitinib 100 mg MR capsule with 153Sm2O3 (fed, Period 3). |
| Treatment Sequence 2 | EXPERIMENTAL | Ritlecitinib 100 mg solution (fasted, Period 1), followed by ritlecitinib 100 mg MR capsule with 153Sm2O3 (fed, Period 2), and followed by ritlecitinib 100 mg MR capsule with 153Sm2O3 (fasted, Period 3). |
| Treatment Sequence 3 | EXPERIMENTAL | Ritlecitinib 100 mg MR capsule 2 (fasted, Period 1), followed by ritlecitinib 100 mg solution (fasted, Period 2), followed by ritlecitinib 100 mg MR capsule 1 (fasted, Period 3), and followed by ritlecitinib 100 mg MR capsule 1 (fed, Period 4) |
| Treatment Sequence 4 | EXPERIMENTAL | Ritlecitinib 100 mg solution (fasted, Period 1), followed by ritlecitinib 100 mg MR capsule 1 (fasted, Period 2), followed by ritlecitinib 100 mg MR capsule 2 (fasted, Period 3), and followed by ritlecitinib 100 mg MR capsule 2 (fed, Period 4) |
| Treatment Sequence 5 | EXPERIMENTAL | Ritlecitinib 100 mg MR capsule 1 (fasted, Period 1), followed by ritlecitinib 100 mg MR capsule 2 (fasted, Period 2), followed by ritlecitinib 100 mg solution (fasted, Period 3), and followed by ritlecitinib 100 mg MR capsule 2 (fed, Period 4) |
| Treatment Sequence 6 | EXPERIMENTAL | Ritlecitinib 100 mg MR capsule 2 (fasted, Period 1), followed by ritlecitinib 100 mg solution (fasted, Period 2), followed by ritlecitinib 100 mg MR capsule 1 (fasted, Period 3), and followed by ritlecitinib 100 mg MR capsule 2 (fed, Period 4) |
| Treatment A | ACTIVE_COMPARATOR | ritlecitinib 1 x 30 milligram (mg) intact blend-in-capsule (BiC) in fasted state |
| Treatment B | ACTIVE_COMPARATOR | contents of ritlecitinib 1 x 30 mg intact BiC sprinkled on strawberry jam in fasted state |
| Treatment C | ACTIVE_COMPARATOR | contents of ritlecitinib 1 x 30 mg intact BiC sprinkled on yoghurt in fasted state |
| Treatment D | ACTIVE_COMPARATOR | contents of ritlecitinib 1 x 30 mg intact BiC sprinkled on applesauce in fasted state |
| Treatment E | ACTIVE_COMPARATOR | ritlecitinib 1 x 30 mg intact BiC given with high fat meal |
| Ritlecitinib 20 mg | EXPERIMENTAL | Participants will receive Ritlecitinib 20 mg by mouth once daily (QD). |
| Ritlecitinib and tolbutamide | EXPERIMENTAL | In Period 1, participants will be dosed with a single administration of tolbutamide 500 mg tablet on Day 1. Period 1 will be immediately followed by Period 2 with no washout. In Period 2, participants will be dosed with oral 200 mg ritlecitinib QD for 10 days followed by administration of a single dose of 500 mg tolbutamide oral tablet within approximately 5 minutes after administration of a 200 mg dose of ritlecitinib on the morning of Day 10. |
| Cohort 1 | EXPERIMENTAL | Subjects will be dosed with 50 mg Ritlecitinib on Day 1 and followed up till Day 3 |
| Cohort 2 | EXPERIMENTAL | Subjects will be dosed with 200 mg Ritlecitinib on Day 1 and followed up till Day 3 |
| Name | Type | Description |
|---|---|---|
| Ritlecitinib 100 mg | DRUG | 100 mg Capsule |
| Ritlecitinib 50 mg | DRUG | 50 mg Capsule |
| Placebo - 100 mg | DRUG | Capsule (to match Ritlecitinib 100 mg) |
| Placebo - 50 mg | DRUG | Capsule (to match Ritlecitinib 50 mg) |
| Ritlecitinib | DRUG | Ritlecitinib 50 mg capsule once daily |
| Placebo | DRUG | Matching capsule once daily |
| Ritlecitinib 20 mg | DRUG | orally administered, Ritlecitinib 20 mg once daily (QD) |
| Tolbutamide | DRUG | Tolbutamide 500 mg provided as one 500 mg oral tablet |
| Ritlecitinib 200 mg | DRUG | 200 mg single dose |
Inclusion Criteria: Age: 1. 18 years of age or older at screening. Adolescents (12 to \<18 years of age at screening) are also eligible for this study, but only if permitted by the local IRB/EC and local regulatory health authority (if applicable). Where these approvals have not been granted, only...