Starting Dose for Escalation Sample Clauses

Starting Dose for Escalation. Physiologically based PK modeling of the existing adult exposure data obtained in the FTIH study E7438-G000-101 informed the selection of the starting dose for this pediatric study. Systemic exposure data in adults together with in vitro data on the absorption, distribution, metabolism, and elimination (ADME) of tazemetostat were used to build a PK model that accurately described the time-concentration data from adults. This model was then transformed accounting for known age and developmental changes in physiological parameters, such as organ size and blood flows, as well as biochemical factors, e.g., the maturation of drug metabolizing enzyme expression and activity, to derive a series of age-based pediatric models for the PK of tazemetostat. Tazemetostat doses that resulted in predicted AUC at steady-state (AUCss) within the range of values observed in adults were identified. For children 1 year to 18 years of age, the starting dose of 240 mg/m2/dose BID is predicted to result in 64% and 36% of the AUCss observed for adults at 800 mg/dose and 1600 mg/dose, respectively (based upon free base). For children 6 months to 1 year of age, the starting dose of 240 mg/m2/dose BID was predicted to result in 80% and 45% of the AUCss observed for adults at 800 mg/dose and 1600 mg/dose respectively. The 1600 mg/dose, which did not meet protocol-specified criteria for the MTD, is the highest dose level administered in the adult FTIH study, E7438-G000-101. Preliminary PK parameters from the 240 mg/m2 BID and 300 mg/m2 BID dose cohorts in Study EZH-102 were determined and are displayed in Table 2, which follows.
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Related to Starting Dose for Escalation

  • Starting Salary All bargaining-unit positions will be hired at a starting salary commensurate with their experience. It is expected that those salaries will typically be within 20% of employees within that unit at a similar rank and/or experience level. In exceptional cases, bargaining-unit positions may be hired at a salary above that range contingent on extraordinary experience and extramural funding.

  • Petition for Annual Conference Session The Local Church acknowledges that pursuant to the governing standing rules of the Annual Conference, petitions for consideration of the legislative body must be submitted to the Secretary of the Annual Conference on or before April 1 of the current Annual Conference year. The Annual Conference will make reasonable efforts to assist the Local Church in completing the required petition, which will include this Disaffiliation Agreement as an attachment thereto making it subject to public review. If the petition is not filed in a timely manner, the Parties will make good faith efforts under the standing rules of the Annual Conference to cooperate to bring the petition to the legislative floor for consideration by appropriate motions to suspend the standing rules for the purposes of considering the petition.

  • HOLIDAY COMPENSATION FOR TIME WORKED 110. Employees required by their respective appointing officers to work on any of the above specified or substitute holidays, excepting Fridays observed as holidays in lieu of holidays falling on Saturday, shall be paid extra compensation of one additional day's pay at time-and-one-half the usual rate in the amount of 12 hours pay for 8 hours worked or a proportionate amount for less than 8 hours worked provided, however, that at the employee's request and with the approval of the appointing officer, an employee may be granted compensatory time off in lieu of paid overtime pursuant to the provisions of Section III.E.2. 111. Executive, administrative and professional employees designated in the Annual Salary Ordinance with the "Z" symbol shall not receive extra compensation for holiday work but may be granted time off equivalent to the time worked at the rate of-one-and-one-half times for work on the holiday.

  • Regular Work Week The regular work week shall be any five (5) consecutive days, Sunday through Saturday, for a total regular work week of forty (40) working hours, subject to the applicable premiums where provided for in this Agreement. Notwithstanding the above, employees may volunteer to work schedules that fall outside of the regular work week of Sunday through Saturday and may do so, upon approval by the Company, and with no penalty cost to the Company, but with applicable premiums as provided for in this Agreement.

  • Salary Scale The salary scale applicable to Employees shall be set out hereinafter in the Wage Schedule.

  • Equal Pay for Equal Work The principle of equal pay for equal work shall apply, regardless of sex.

  • Preparation for Each Auction (a) Not later than 9:30 A.M. on each Auction Date for the Preferred Shares, the Auction Agent shall advise BD by telephone or other electronic means of communication acceptable to the parties of the Maximum Rate in effect on such Auction Date. (b) The Auction Agent from time to time may, but shall not be obligated to, request BD to provide it with a list of the respective customers BD believes are Beneficial Owners of shares of each series of Preferred Shares. BD shall comply with any such request, and the Auction Agent shall keep confidential any such information, including information received as to the identity of Bidders in any Auction, and shall not disclose any such information so provided to any Person other than a Fund; and such information shall not be used by the Auction Agent or its officers, employees, agents or representatives for any purpose other than such purposes as are described herein; provided, however, that the Auction Agent reserves the right and is authorized to disclose any such information if (a) it is ordered to do so by a court of competent jurisdiction or a regulatory body, judicial or quasi-judicial agency or authority having the authority to compel such disclosure, (b) it is advised by its counsel that its failure to do so would be unlawful or (c) failure to do so would expose the Auction Agent to loss, liability, claim, damage or expense for which it has not received indemnity or security satisfactory to it. In the event that the Auction Agent is required to disclose information in accordance with the foregoing sentence, it shall provide written notice of such requirement to BD as promptly as practicable. The Auction Agent shall, subject to the terms of the Auction Agency Agreement, transmit any list of customers BD believes are Beneficial Owners of shares of each series of Preferred Shares and information related thereto only to its officers, employees, agents or representatives who need to know such information for the purposes of acting in accordance with this Agreement, and the Auction Agent shall prevent the transmission of such information to others and shall cause its officers, employees, agents and representatives to abide by the foregoing confidentiality restrictions; provided, however, that the Auction Agent shall have no responsibility or liability for the actions of any of its officers, employees, agents or representatives after they have left the employ of the Auction Agent.

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  • Placement on the Salary Schedule Members of the bargaining unit shall be placed on the salary schedule at the step appropriate for training and creditable years of experience.

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