A Study to Assess the Effect of Food on the Pharmacokinetics of TY-9591 in Healthy Volunteers

NCT04798638 | Completed Phase 1

• 1 other identifier: TYKM1601102
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the pharmacokinetics of TY-9591 tablets and Osimertinib Mesylate tablets after a single fasting administration and the effect of food on the pharmacokinetics of TY-9591 tablets in healthy volunteers.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (4)

• Cmax of TY-9591 and its metabolites

  Pharmacokinetics of TY-9591 and its metabolites (TY-9591-D1 (AZ5104) and TY-9591-D2) by assessment of the maximum plasma concentration.

  Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose.

• Cmax of Osimertinib and its metabolites

  Pharmacokinetics of Osimertinib and its metabolites (AZ5104 and AZ7550) by assessment of the maximum plasma concentration.

  Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose.

• AUC(0-72h) of TY-9591 and its metabolites

  Pharmacokinetics of TY-9591 and its metabolites (TY-9591-D1 (AZ5104) and TY-9591-D2) by assessment of area under the plasma concentration time curve from zero to 72 hours.

  Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose.

• AUC(0-72h) of Osimertinib and its metabolites

  Pharmacokinetics of Osimertinib and its metabolites (AZ5104 and AZ7550) by assessment of area under the plasma concentration time curve from zero to 72 hours.

  Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose.

Secondary Outcomes (19)

• Tmax of TY-9591 and its metabolites

  Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose.

• Tmax of Osimertinib and its metabolites

  Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose.

• T1/2 of TY-9591 and its metabolites

  Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose.

• T1/2 of Osimertinib and its metabolites

  Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose.

• λz of TY-9591 and its metabolites

  Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose.

Study Arms (2)

Arm1: TY-9591 + Osimertinib + TY-9591

EXPERIMENTAL

Participants will receive TY-9591 tablets under fasted condition in period 1 , followed by Osimeritinib Mesylate tablet under fasted condition in period 2. In period 3, participants will receive TY-9591 tablet in fed state (high-fat meal). The washout will be no less than 21 days between each treatment.

Drug: TY-9591 Tablets under Fasted Condition - Arm1; Drug: Osimertinib Mesylate Tablets under Fasted Condition - Arm1; Drug: TY-9591 Tablets after a High-fat Meal - Arm1

Arm2: Osimertinib + TY-9591 + TY-9591

EXPERIMENTAL

Participants will receive Osimeritinib Mesylate tablet under fasted condition in period 1 , followed by TY-9591 tablets under fasted condition in period 2. In period 3, participants will receive TY-9591 tablet in fed state (high-fat meal). The washout will be no less than 21 days between each treatment.

Drug: Osimertinib Mesylate Tablets under Fasted Condition - Arm2; Drug: TY-9591 Tablets under Fasted Condition - Arm2; Drug: TY-9591 Tablets after a High-fat Meal - Arm2

Interventions

TY-9591 Tablets under Fasted Condition - Arm1 DRUG

Phase 1 (period 1) fasted from 10 hours prior to dosing with 80 mg TY-9591 tablet (p o, once) and 4 hours after dosing on day 1.

Also known as: TY-9591

Arm1: TY-9591 + Osimertinib + TY-9591

Osimertinib Mesylate Tablets under Fasted Condition - Arm1 DRUG

Phase 1 (period 2) fasted from 10 hours prior to dosing with 80 mg Osimertinib Mesylate Tablets (p o, once) and 4 hours after dosing on day 1.

Also known as: AZD9291

Arm1: TY-9591 + Osimertinib + TY-9591

TY-9591 Tablets after a High-fat Meal - Arm1 DRUG

Phase 2 (period 3) allocated high-fat meal prior to dosing with 80 mg TY-9591 tablet (p o, once) and 4 hours after dosing on day 1.

Also known as: TY-9591

Arm1: TY-9591 + Osimertinib + TY-9591

Osimertinib Mesylate Tablets under Fasted Condition - Arm2 DRUG

Phase 1 (period 1) fasted from 10 hours prior to dosing with 80 mg Osimertinib Mesylate Tablets (p o, once) and 4 hours after dosing on day 1.

Also known as: AZD9291

Arm2: Osimertinib + TY-9591 + TY-9591

TY-9591 Tablets under Fasted Condition - Arm2 DRUG

Phase 1 (period 2) fasted from 10 hours prior to dosing with 80 mg TY-9591 tablet (p o, once) and 4 hours after dosing on day 1.

Also known as: TY-9591

Arm2: Osimertinib + TY-9591 + TY-9591

TY-9591 Tablets after a High-fat Meal - Arm2 DRUG

Phase 2 (period 3) allocated high-fat meal prior to dosing with 80 mg TY-9591 tablet (p o, once) and 4 hours after dosing on day 1.

Also known as: TY-9591

Arm2: Osimertinib + TY-9591 + TY-9591

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male must be ≥ 18 and ≤ 55 years of age.
• Bodyweight of male must be ≥ 50.0 kg (bodyweight of female must be ≥ 45.0 kg), and the Body Mass Index must be ≥ 19.0 and ≤26.0 kg/m2.
• The participants must have no birthing plan and agree to take adequate non-drug contraceptive measures within 2 weeks before screening to 6 months after the last drug treatment.
• The participants have good communications with investigators, understand and comply with all requirements and fully understand and sign the informed consent form.
• The results of physical examination, vital signs, ECG, laboratory examination and other relevant examination should compliance with the clinical protocol, or they will be recognized as non-clinical signs (NCS) if beyond the regulated range.

You may not qualify if:

• The participants who smoked daily \>5 sticks of cigarette 3 months prior to screening or cannot give up smoking during study.
• The participants consumed more than 14 units of alcohol per week (1 unit = 360 ml beers/45 ml liquor containing 40% alcohol/150 ml grape wine) 3 months prior to screening period, positive results of alcohol breath test and the volunteers who cannot give up drinking during study.
• The participants who have overconsumption of tea, coffee, and the drink with caffeine (\> 8 cup one day, 1 cup=250 ml) daily 3 months prior to screening period.
• The participants have history of substance abuse and drug use within 6 months before screening.
• The participants have history of chronic disease and serious illness in nervous system, vascular system, blood and lymphatic system, immune system, urinary system, respiratory system, digestive system and other metabolic system, any conditions and illness threat to the health of participants, and the history of hereditary disease.
• The participants had a clinically significant disease, major surgery within 3 months before screening or plan surgery during the study period, and the surgery could affect drug absorption, distribution, metabolism, and excretion.
• The participants who participated other clinical trials and took the investigational drug 3 months prior to first dose.
• The participants who have blood donation or excessive bleeding (≥ 400 ml) 3 months prior to first dose, and planned to donate blood or receive blood transfusions.
• The participants who were taking any prescription medicine, any over-the-counter (OTC), traditional chinese medicine and health care products within 14 days prior to screening period; CYP3A4 inducers/inhibitors within 30 days prior to screening period.
• The participants who have eaten grapefruit, orange, mango, pitaya, chocolate, any caffeinated food or drink that affects the absorption, distribution, metabolism and excretion of the drug within 7 days before first dose.
• The participants who cannot comply with the roles of unified diet.
• The participants who have positive test result in HBsAg, antibodies against HCV (anti-HCV), Anti-HCV, Anti-HIV and TPPA.
• The participants who cannot tolerate blood collection through venipuncture.
• Any factors judged by investigator that the participants cannot meet.

Sponsors & Collaborators

• TYK Medicines, Inc: lead

Study Sites (1)

Hunan Provincial Tumor Hospital

Changsha, Hunan, 410006, China

Location

MeSH Terms

Interventions

osimertinib

Study Officials

• Kunyan Li, Ph.D

  Hunan Provincial Tumor Hospital

  PRINCIPAL INVESTIGATOR

• Xue Chen, MD

  Hunan Provincial Tumor Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 15, 2021
• Study Start: April 30, 2021
• Primary Completion: September 9, 2021
• Study Completion: September 9, 2021
• Last Updated: December 7, 2022

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)