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

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ClinicalTrials.gov Identifier: NCT04798638
Recruitment Status : Recruiting
First Posted : March 15, 2021
Last Update Posted : August 17, 2021
Sponsor:
Information provided by (Responsible Party):
TYK Medicines, Inc

Study Description
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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.

Condition or disease Intervention/treatment Phase
Healthy Volunteers 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 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 Phase 1

Detailed Description:
This is a single center, randomized, open label, two phases study in healthy adult volunteers. The first phase is a two-sequence, two-period crossover trial. The volunteers will be randomly distributed into two groups and given either TY-9591 tablets or Osimertinib Mesylate tablets on a single fasting administration. In the second phase, all volunteers will be administrated TY-9591 tablets after a high fat meal. The washout between each treatment is no less than 21 days.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Studies to Compare the Pharmacokinetics of TY-9591 Tablets and Osimertinib Mesylate Tablets After a Single Fasting Administration and Determine the Effect of Food on the Pharmacokinetics of TY-9591 Tablets in Healthy Volunteers
Actual Study Start Date : May 1, 2021
Estimated Primary Completion Date : August 20, 2021
Estimated Study Completion Date : August 30, 2021

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm1: TY-9591 + Osimertinib + TY-9591
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
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.
Other Name: TY-9591

Drug: Osimertinib Mesylate Tablets under Fasted Condition - Arm1
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.
Other Name: AZD9291

Drug: TY-9591 Tablets after a High-fat Meal - Arm1
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.
Other Name: TY-9591
Experimental: Arm2: Osimertinib + TY-9591 + TY-9591
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
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.
Other Name: AZD9291

Drug: TY-9591 Tablets under Fasted Condition - Arm2
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.
Other Name: TY-9591

Drug: TY-9591 Tablets after a High-fat Meal - Arm2
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.
Other Name: TY-9591


Outcome Measures
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Primary Outcome Measures :
  1. Cmax of TY-9591 and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of TY-9591 and its metabolites (TY-9591-D1 (AZ5104) and TY-9591-D2) by assessment of the maximum plasma concentration.

  2. Cmax of Osimertinib and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of Osimertinib and its metabolites (AZ5104 and AZ7550) by assessment of the maximum plasma concentration.

  3. AUC(0-72h) of TY-9591 and its metabolites [ Time Frame: 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. ]
    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.

  4. AUC(0-72h) of Osimertinib and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of Osimertinib and its metabolites (AZ5104 and AZ7550) by assessment of area under the plasma concentration time curve from zero to 72 hours.


Secondary Outcome Measures :
  1. Tmax of TY-9591 and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of TY-9591 and its metabolites by assessment of time to Cmax.

  2. Tmax of Osimertinib and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of Osimertinib and its metabolites by assessment of time to Cmax.

  3. T1/2 of TY-9591 and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of TY-9591 and its metabolites by assessment of Terminal half life.

  4. T1/2 of Osimertinib and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of Osimertinib and its metabolites by assessment of Terminal half life.

  5. λz of TY-9591 and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of TY-9591 and its metabolites by assessment of Terminal rate constant.

  6. λz of Osimertinib and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of Osimertinib and its metabolites by assessment of Terminal rate constant.

  7. AUC(0-168h) of TY-9591 and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of TY-9591 and its metabolites by assessment of area under the plasma concentration time curve from zero to 168 hours.

  8. AUC(0-168h) of Osimertinib and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of Osimertinib and its metabolites by assessment of area under the plasma concentration time curve from zero to 168 hours.

  9. AUC(0-t) of TY-9591 and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of TY-9591 and its metabolites by assessment of area under the plasma concentration time curve from zero to appointed time.

  10. AUC(0-t) of Osimertinib and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of Osimertinib and its metabolites by assessment of area under the plasma concentration time curve from zero to appointed time.

  11. AUC(0-∞) of TY-9591 and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of TY-9591 and its metabolites by assessment of area under the plasma concentration time curve from zero to infinity.

  12. AUC(0-∞) of Osimertinib and its metabolites [ Time Frame: 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. ]
    Pharmacokinetics of Osimertinib and its metabolites by assessment of area under the plasma concentration time curve from zero to infinity.

  13. CL/F of TY-9591 [ Time Frame: 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. ]
    Pharmacokinetics of TY-9591 only by assessment of apparent plasma clearance.

  14. CL/F of Osimertinib [ Time Frame: 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. ]
    Pharmacokinetics of Osimertinib only by assessment of apparent plasma clearance.

  15. Vss/F of TY-9591 [ Time Frame: 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. ]
    Pharmacokinetics of TY-9591 only apparent volume of distribution.

  16. Vss/F of Osimertinib [ Time Frame: 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. ]
    Pharmacokinetics of Osimertinib only apparent volume of distribution.

  17. Calculated for both Cmax and AUC of TY-9591 [ Time Frame: 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. ]
    Pharmacokinetics of TY-9591 parent to metabolite ratio.

  18. Calculated for both Cmax and AUC of Osimertinib [ Time Frame: 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. ]
    Pharmacokinetics of Osimertinib parent to metabolite ratio.

  19. Safety variables [ Time Frame: Assessments performed throughout the study period. ]
    Adverse events, clinical symptoms, vital signs, ECG's, clinical laboratory safety tests, ect.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male must be ≥ 18 and ≤ 55 years of age.
  2. 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.
  3. 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.
  4. The participants have good communications with investigators, understand and comply with all requirements and fully understand and sign the informed consent form.
  5. 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.

Exclusion Criteria:

  1. The participants who smoked daily >5 sticks of cigarette 3 months prior to screening or cannot give up smoking during study.
  2. 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.
  3. 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.
  4. The participants have history of substance abuse and drug use within 6 months before screening.
  5. 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.
  6. 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.
  7. The participants who participated other clinical trials and took the investigational drug 3 months prior to first dose.
  8. 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.
  9. 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.
  10. 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.
  11. The participants who cannot comply with the roles of unified diet.
  12. The participants who have positive test result in HBsAg, antibodies against HCV (anti-HCV), Anti-HCV, Anti-HIV and TPPA.
  13. The participants who cannot tolerate blood collection through venipuncture.
  14. Any factors judged by investigator that the participants cannot meet.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04798638


Contacts
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Contact: Kunyan Li, Ph.D 13549680713 Ikunyan@163.com
Contact: Xue Chen, MD 13875993587 cx_shirley@163.com

Locations
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China, Hunan
Hunan Provincial Tumor Hospital Recruiting
Changsha, Hunan, China, 410006
Contact: Kunyan Li, Ph.D    13549680713    Ikunyan@163.com   
Sponsors and Collaborators
TYK Medicines, Inc
Investigators
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Principal Investigator: Kunyan Li, Ph.D Hunan Provincial Tumor Hospital
Principal Investigator: Xue Chen, MD Hunan Provincial Tumor Hospital
More Information
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Responsible Party: TYK Medicines, Inc
ClinicalTrials.gov Identifier: NCT04798638    
Other Study ID Numbers: TYKM1601102
First Posted: March 15, 2021    Key Record Dates
Last Update Posted: August 17, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Osimertinib
Complement Factor H
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
 Molecular Mechanisms of Pharmacological Action
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs