Dose Adjustment Criteria. If a subject refuses the initial treatment or retreatment, the investigator must report the visit number, visit date, target SK number(s) that the subject refused to allow treatment for and the reason for the refusal in the subject’s CRF. If the subject’s refusal is associated with an AE, the investigator must also report the event on the appropriate CRF. The subject must have the Visit 2 initial study medication treatment to all target SKs to remain in the study. The subject does not need to be removed from the study based solely on her/his refusal to have a study medication retreatment at Visit 5 or Visit 7. Visit Window N/A N/A N/A ± 1 day ± 1 day ± 1 day ± 1 day ± 1 day ± 7 days ± 7 days ± 7 days Informed Consent X Inclusion/ Exclusion1 X X Subject Identifier2 X Dermatological Medical History X Demographics X Xxxxxxxxxxx Skin Type Assessment3 X Vital Signs4 X X X X X X Prior Medications/Therapies5 X Target and Non-Target SK Identification6 X Physician’s Lesion Assessment7 X X X X X X X X SK Dimensions8 X X X X X X X X SK Photography9 X X10 X11 X X10 X X10 X X X X Study Medication Application12 X X X Subject Satisfaction Assessment13 X X X X X X Concomitant Therapies14 X X X X X X X X X X X Adverse Events15 X X X X X X X X X X 1Subject inclusion/exclusion criteria will be reassessed prior to enrollment during Visit 2. 2Investigational sites will assign a unique five-digit subject identifier to each subject at Visit 1, formatted as NN-NNN where the first 2 digits are the site number, and the final 3 digits are the subject number that must be assigned in ascending numerical order (using leading zeroes, as appropriate). This subject identifier will be used in all study documentation for the duration of the study. 3Each subject’s skin must be assessed during Visit 1 using the Xxxxxxxxxxx Skin Type Assessment. Refer to Table 6 for the scale. 4Vital signs [including temperature, pulse, respiratory rate, blood pressure, height and weight (Visit 1 only)] will be measured by a qualified staff member at Visit 1, Visit 2, Visit 5, Visit 7 Visit 10, and Visit 11. 5Prior medications/therapies will be collected for a time-period of 13 days prior to Visit 1. Refer to Section 8.4 for a list of permitted and restricted concomitant medications. 6The treating investigator will identify 3 target SKs and up to 4 non-target SKs. Two (2) target SKs must be on the face, and the additional 1 target SK must be on the neck or décolletage. The 4 non-target SKs may be located on ...
Dose Adjustment Criteria. The Safety Review Team will review safety parameters after the first subject in each cohort has completed Visit Day 7. The remaining 2 subjects in the cohort will receive the same dose if neither the safety criteria for adjusting or stopping doses (Section 4.4.1) nor the criteria for study termination (Section 4.5) preclude their treatment. When all subjects in the cohort have completed Visit Day 28, the Safety Review Team will again evaluate the safety parameters. If the safety criteria for adjusting or stopping doses and the criteria for study termination are not met, the first subject in the next cohort will receive the next higher RBM-007 dose level. The same treatment sequence and interval safety evaluations will be performed for each cohort.
Dose Adjustment Criteria. During the treatment period, participants will be able to receive IP as long as there are no dose limiting safety/tolerability concerns. Participants who cannot tolerate 50 mg will receive 40 mg for the remainder of the treatment period. If dose adjustment is deemed necessary by the investigator at any time during the treatment period, the participant will return to the site to return any remaining IP and for the adjusted dose to be dispensed. At the discretion of the investigator, participants who cannot tolerate the 40-mg dose will be discontinued from IP (refer to Section 8.4.1 for procedures for early IP discontinuation). Participants are encouraged to continue to come in for assessments following IP discontinuation.
Dose Adjustment Criteria. During the Treatment Period, subjects will be able to receive study drug as long as there are no dose-limiting safety/tolerability concerns. Subjects who cannot tolerate 30 mg QD will receive 20 mg QD for the remainder of the Treatment Period. Subjects who experience intolerable AEs at the 20 mg QD dose level may be discontinued from study treatment at the discretion of the Investigator. Dose adjustments will be made based on tolerability as assessed by occurrence of a severe AE or a moderate AE of special interest (sedation, somnolence, dizziness, euphoric mood, confusion, drowsiness, inebriation (feeling drunk), or fatigue) judged by the investigator to be related to study drug. If a dose adjustment is deemed necessary by the Investigator at any time during the treatment period, the subject will return to the site to return any remaining current dose and for the adjusted dose to be dispensed.
Dose Adjustment Criteria. 7.4.1. Safety Criteria for Adjustment or Stopping Doses
7.4.1.1. TSR-042 Immune-related Adverse Events of Interest and Guidelines for Management
1. If systemic steroids are used as a part of irAEI management, the total dose of daily steroids should be equal to or less than prednisone 10 mg at the time of resuming TSR-042. All treatment delays (including any missed doses) and discontinuations, and the reason for delays or discontinuation of TSR-042, should be recorded in the eCRF. Of note, if the attribution of an AE is not clear between TSR-042 and niraparib (examples might include diarrhea or aspartate aminotransferase or alanine aminotransferase elevation), both agents may be withheld and a discussion with the Sponsor’s Medical Monitor is recommended. Diarrhea/colitis 2 to 3 Restart dosing when toxicity resolves to Grade 0 to 1. 4 Permanently discontinue. AST, ALT, or increased bilirubin 2 (AST or ALT >3 and ≤5× ULN or total bilirubin >1.5 and ≤3× ULN) Restart dosing when toxicity resolves to Grade 0 to 1 (see exception below).a 3 or 4 Permanently discontinue (see exception below).a (AST or ALT >5× ULN or total bilirubin >3× ULN) T1DM or 3 or 4 hyperglycemia or Restart dosing in appropriately managed, clinically and hyperglycemia T1DM (associated with metabolically stable patients, insulin replacement therapy is metabolic acidosis or required. ketonuria) Immune-related encephalitis Any grade Permanently discontinue.
Dose Adjustment Criteria. LJPC-501 dose may be titrated to achieve an age-, size-, and disease-appropriate MAP, which should remain above baseline, but less than 90 mmHg. Throughout treatment, LJPC-501 dose may be decreased to a minimum of 1.25 ng/kg/min and increased to a maximum rate of 40 ng/kg/min. If MAP exceeds 90 mmHg, SOC vasopressors should be down-titrated first, then LJPC-501 should be down-titrated if MAP remains ≥ 90 mmHg. Any decision to increase the dose rate above 40 ng/kg/min must be made in consultation with Sponsor. With Sponsor approval, the dose rate may be increased to a maximum of 80 ng/kg/min. Dose titration guidelines are provided in Section 8.3.2.
6.6.1. Safety Criteria for Adjustment or Stopping Doses
