A Study to Evaluate the Pharmacokinetics,Safety and Tolerability of Y-2 Sublingual Tablet in Healthy Adult Subjects

A 2-Part, Randomized, Phase I Study to Evaluate the Pharmacokinetics,Safety and Tolerability of Y-2 Sublingual Tablet in Healthy Adult Subjects

This study will assess the safety, tolerability and pharmacokinetics(PK) of Y-2 sublingual tablet in healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Y-2 Sublingual Tablet; Drug: Y-2 Sublingual Tablet; Drug: Y-2 Sublingual Tablet; Drug: Y-2 Sublingual Tablet; Drug: Y-2 Sublingual Tablet; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiaoying Yang; Phone Number: +86 18611125488; Email: yangxiaoying@simceregroup.com

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Parexel International Los Angeles Early Phase Clinical Unit
      • Contact: David Han, MD; Phone Number: 818-254-1600; Email: david.han@cctrials.com
      • Principal Investigator: David Han, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Inclusion Criteria

  1. Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
  2. Body Mass Index (BMI) ≥ 18 and ≤ 30 kg/m2 and weight ≥ 50kg at screening.
  3. A condition of general good health, as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, vital signs, laboratory profile and a 12-lead electrocardiogram (ECG).

  4. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following condition applies:

     • Not a woman of childbearing potential (WOCBP) as defined in Appendix 1 Contraceptive Guidance, OR
     • A WOCBP who agrees to follow the contraceptive guidance in Appendix 1 Contraceptive Guidance from screening through at least 90 days after the last dose of study drug; a WOCBP must have a negative beta-human chorionic gonadotropin (β-hCG) test at screening and baseline prior to administration of investigational product.

Exclusion Criteria:

1. Subject has a history of any clinically significant cardiac, respiratory (including asthma, bronchospasm), renal, hepatic,gastrointestinal, psychiatric, neurologic, hematologic or rheumatic disease, or psychiatric disease or disorder, current acute or chronic infections, or other abnormality that may affect safety, or potentially influence the study results, judged by the investigator or designee.
2. Evidence or history of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma.
3. Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 90 days or 5 half-lives (whichever is longer) prior to Day 1.
4. Receipt of any investigational product within 30 days or 5 halflives (whichever is longer) prior to Day 1.
5. Will have vaccination with live virus, attenuated live virus, or any live viral components within the 30 days prior to Day 1 or is to receive these vaccines at any time during study period or within 90 days after last dose.
6. Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for approximately 90 days after the last dose of study drug.
7. Male subject who is considering fathering a child or donating sperm during the study or for approximately 90 days after the last dose of study drug.
8. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to enroll this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Y-2 sublingual tablet dose group 1	Drug: Y-2 Sublingual Tablet; Subjects will receive one Y-2 sublingual tablet sublingually once daily for Day1 and Day 19 and twice daily for Day 6 to Day 18.; Drug: Y-2 Sublingual Tablet; Subjects will receive two Y-2 sublingual tablets sublingually once daily for Day1 and Day 19 and twice daily for Day 6 to Day 18.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition A, Day 6 with condition B and Day 11 with condition C.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition B, Day 6 with condition C and Day 11 with condition A.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition C, Day 6 with condition A and Day 11 with condition B.
Experimental: Y-2 sublingual tablet dose Group 2	Drug: Y-2 Sublingual Tablet; Subjects will receive one Y-2 sublingual tablet sublingually once daily for Day1 and Day 19 and twice daily for Day 6 to Day 18.; Drug: Y-2 Sublingual Tablet; Subjects will receive two Y-2 sublingual tablets sublingually once daily for Day1 and Day 19 and twice daily for Day 6 to Day 18.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition A, Day 6 with condition B and Day 11 with condition C.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition B, Day 6 with condition C and Day 11 with condition A.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition C, Day 6 with condition A and Day 11 with condition B.
Experimental: Y-2 sublingual tablet dose Group 3	Drug: Y-2 Sublingual Tablet; Subjects will receive one Y-2 sublingual tablet sublingually once daily for Day1 and Day 19 and twice daily for Day 6 to Day 18.; Drug: Y-2 Sublingual Tablet; Subjects will receive two Y-2 sublingual tablets sublingually once daily for Day1 and Day 19 and twice daily for Day 6 to Day 18.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition A, Day 6 with condition B and Day 11 with condition C.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition B, Day 6 with condition C and Day 11 with condition A.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition C, Day 6 with condition A and Day 11 with condition B.
Experimental: Y-2 sublingual tablet dose Group 4	Drug: Y-2 Sublingual Tablet; Subjects will receive one Y-2 sublingual tablet sublingually once daily for Day1 and Day 19 and twice daily for Day 6 to Day 18.; Drug: Y-2 Sublingual Tablet; Subjects will receive two Y-2 sublingual tablets sublingually once daily for Day1 and Day 19 and twice daily for Day 6 to Day 18.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition A, Day 6 with condition B and Day 11 with condition C.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition B, Day 6 with condition C and Day 11 with condition A.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition C, Day 6 with condition A and Day 11 with condition B.
Experimental: Y-2 sublingual tablet dose Group 5	Drug: Y-2 Sublingual Tablet; Subjects will receive one Y-2 sublingual tablet sublingually once daily for Day1 and Day 19 and twice daily for Day 6 to Day 18.; Drug: Y-2 Sublingual Tablet; Subjects will receive two Y-2 sublingual tablets sublingually once daily for Day1 and Day 19 and twice daily for Day 6 to Day 18.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition A, Day 6 with condition B and Day 11 with condition C.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition B, Day 6 with condition C and Day 11 with condition A.; Drug: Y-2 Sublingual Tablet; Subjects will receive Y-2 sublingual tablet with 3 different conditions once daily for Day1 Day 6 and Day 11. Day 1 with condition C, Day 6 with condition A and Day 11 with condition B.
Placebo Comparator: Placebo; Certain subjects in group 1 and group 2 will receive placebo.	Drug: Placebo; Placebo, sublingually, single and multiple ascending dosing in group 1 and 2 subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events（Part 1)	To evaluate the safety and tolerability following single and multiple administrations of Y-2 sublingual tablet in healthy adult subjects in part 1.	Until follow-up（Day26）or early termination
Maximum concentration（Cmax）in Part 2 healthy adult subjects	To evaluate the effects of different administration conditions on the PK of edaravone and dexborneol in plasma following single administration of Y-2 sublingual tablet in healthy adult subjects in part 2.	Day1，Day2， Day6，Day7，Day11，Day12
Time for Cmax (Tmax) in Part 2 healthy adult subjects	To evaluate the effects of different administration conditions on the PK of edaravone and dexborneol in plasma following single administration of Y-2 sublingual tablet in healthy adult subjects in part 2.	Day1，Day2， Day6，Day7，Day11，Day12
Area under the curve (AUC) in Part 2 healthy adult subjects	To evaluate the effects of different administration conditions on the PK of edaravone and dexborneol in plasma following single administration of Y-2 sublingual tablet in healthy adult subjects in part 2.	Day1，Day2， Day6，Day7，Day11，Day12
Terminal elimination half-life（t1/2） in Part 2 healthy adult subjects	To evaluate the effects of different administration conditions on the PK of edaravone and dexborneol in plasma following single administration of Y-2 sublingual tablet in healthy adult subjects in part 2.	Day1，Day2， Day6，Day7，Day11，Day12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum concentration（Cmax）in Part 1 healthy adult subjects	To characterize the PK of edaravone and dexborneol in plasma following single and multiple administrations of Y-2 sublingual tablet in healthy adult subjects in part 1.	Day1，Day2，Day6 and Day18 to Day20
Time for Cmax (Tmax) in Part 1 healthy adult subjects	To characterize the PK of edaravone and dexborneol in plasma following single and multiple administrations of Y-2 sublingual tablet in healthy adult subjects in part 1.	Day1，Day2，Day6 and Day18 to Day20
Area under the curve (AUC) in Part 1 healthy adult subjects	To characterize the PK of edaravone and dexborneol in plasma following single and multiple administrations of Y-2 sublingual tablet in healthy adult subjects in part 1.	Day1，Day2，Day6 and Day18 to Day20
Terminal elimination half-lifet（1/2 ）in Part 1 healthy adult subjects	To characterize the PK of edaravone and dexborneol in plasma following single and multiple administrations of Y-2 sublingual tablet in healthy adult subjects in part 1.	Day1，Day2，Day6 and Day18 to Day20
Adverse Events（Part 2)	To evaluate the safety following different single administration conditions of Y-2 sublingual tablet in healthy adult subjects in part 2.	Until follow-up（Day18）or early termination

Collaborators and Investigators

• Sponsor: Simcere Pharmaceutical Co., Ltd
• Investigators: Principal Investigator: David Han, MD, Parexel

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2023
• Primary Completion (Actual): November 21, 2023
• Study Completion (Actual): December 5, 2023

Study Registration Dates

• First Submitted: June 27, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: SIM0308-Y-2-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No