A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Food Effect of Orally Administered IPG11406 in Healthy Adult Participants

简要总结

详细描述

This is a phase 1, randomized, double-blind, placebo-controlled, single and multiple dose escalation study to evaluate the safety, tolerability, PK and food effect of orally administered IPG11406 in healthy adult participants. The study will involve two sequential parts: a single ascending dose (SAD) period (Part A) followed by a multiple ascending dose (MAD) period (Part B). Part A Dose escalation will start from 0.5 mg. Currently, the 6 dose cohorts are Cohort 1 (0.5 mg), Cohort 2 (2 mg), Cohort 3 (6 mg), Cohort 4 (20 mg), Cohort 5 (40 mg), Cohort 6 (80 mg). About 42 healthy adult participants are being sequentially enrolled in 6 cohorts. There are 6 participants in Cohort 1 to Cohort 3. In each cohort, 4 participants will receive IPG11406 and 2 participants will receive the placebo as per the randomization code. Approximately 8 participants will be enrolled in Cohort 4 to Cohort 6 respectively; in each cohort, 6 participants will receive IPG11406 and 2 participants will receive the placebo as per the randomization code. In each Cohort, 2 sentinel participants will be dosed at least 48 hours prior to the remaining participants. One sentinel will be dosed with IPG11406 and the other with a matching placebo. The remaining participants will be dosed only if no significant safety issues are identified in the sentinel participants. Doses and sampling intervals may be modified based on the PK and safety data that emerges throughout the study. One of the SAD (Cohort 5 is tentatively to be selected, it may be modified based on the decision of SMC meeting.) cohorts will be selected to assess the effect of food on the pharmacokinetic parameters and referred to as the food effect (FE) cohort. Participants in this cohort will be requested to return to the clinical site to receive a second dose of IPG11406 or placebo after the administration of a meal, upon completion of the 4-day safety follow up period after their first dose. The second dose of IPG11406 or placebo will be administered following a standardized high fat meal (total calories approximately 800 to 1000 calories, with approximately 50% of total calories from fat). Healthy participants will be screened within 28 days prior to dosing. Participants in the SAD cohorts (including FE cohort) will be admitted to the study site on Day -1 for a total of 6 days. Administration of a single dose of IPG11406 or the placebo will occur on Day 1 under fasted conditions (Following an overnight fast of at least 10 hours, subjects will receive a single dose of IPG11406 or placebo with 240 mL water. Water can be ingested as desired except for 1 hour pre-dose until one hour post dose.). Participants will be discharged on Day 5 following collection of samples for PK analyses and the completion of safety assessments. A follow-up visit will occur on Day 8. Participants in the FE cohort will be admitted to the study site for at least 10 days for the 2 administrations of IPG11406. A washout of ≥ 4 days will be included between investigational product (IP) administrations. Administration of a single dose of IPG11406 or placebo will occur on Day 1 under fasted condition, and Day 6 (anticipated) under postprandial condition. Following completion of all safety assessments and sampling for PK analyses, subjects will be discharged on Day 10 (anticipated) after the second dose. There will be a follow-up visit on Day 13 (anticipated) after the single dose administration in each period. Once the final participant in the cohort has completed the Day 5 assessments and been discharged, the Safety Monitoring Committee (SMC) will review cumulative blinded safety data (including follow-up visit data from preceding cohorts) and available PK data to determine the safety and tolerability of the study drug. If the dose level is determined to be safe and well-tolerated, the next dose cohort will be enrolled and randomized in preparation to receive the next dose level of IPG11406 or the placebo. Part B Three dose levels (10 mg, 20 mg and 40 mg) are anticipated to be evaluated in the MAD, once daily. There will be approximately 8 subjects per cohort, 6 subjects will receive IPG11406 and 2 subjects will receive placebo per the randomization code. For Cohort M1 (10 mg), the MAD phase will commence following the establishment of the safety and tolerability of Cohort 4 (20 mg) in the SAD. The SMC will evaluate the safety, tolerability and PK data obtained from the participants of cohort 4 in the SAD to determine if the Cohort M1 will be enrolled and randomized to receive the 10 mg multiple dose levels of IPG11406 or placebo. For Cohort M2 (20 mg), the SMC will evaluate the safety, tolerability and PK data obtained from the participants of cohort 5 (40 mg) in the SAD as well as the safety and PK data from Cohort M1 to determine if the Cohort M2 will be enrolled and randomized to receive the 20 mg multiple dose levels of IPG11406 or placebo. For Cohort M3 (40 mg), the SMC will evaluate the safety, tolerability and PK data obtained from the participants of cohort 6 (80 mg) in the SAD as well as the safety and PK data from Cohort M2 to determine if the Cohort M3 will be enrolled and randomized to receive the 40 mg multiple dose levels of IPG11406 or placebo. All subjects will be screened within 28 days prior to dosing and will be admitted to the study site on Day -1. Dosing will start on the morning of Day 1 and will continue over a 10-day period at each dose level. Blood draws will be collected for the assessment of PK parameters. Participants will be discharged on Day 14 following completion of all PK sample collection and safety assessments. There will be a follow-up visit 7 days after the last dose. Once the final participant in the cohort has completed the Day 14 assessments and been discharged, the SMC will review blinded cumulative safety data (including the follow-up visit data) and available PK data to determine the safety and tolerability of the study drug.

主要结局

次要结局

• Part A-Single ascending dose (SAD):Maximum Plasma Concentration (Cmax)(Up to 6-8 days)
• Part A-Single ascending dose (under food effect):Maximum Plasma Concentration (Cmax)(Up to 8 days)
• Part A-Single ascending dose (under food effect): Area under the plasma concentration versus time curve (AUC)(Up to 8 days)
• Part A-Single ascending dose (SAD): Area under the plasma concentration versus time curve (AUC)(Up to 8 days)
• Part B- Multiple ascending dose (MAD):: Maximum Plasma Concentration [Cmax(Up to 17 days)
• Pharmacokinetic Indicators: Maximum Plasma Concentration (Cmax)(Up to 10 days)
• Pharmacokinetic Indicators: Area Under the Plasma Concentration Versus Time Curve (AUC)(Up to 10 days)
• Pharmacokinetic Indicators:Time to Maximum Concentration (Tmax)(Up to 10 days)