Clinical trial NCT04798638: A Study to Assess the Effect of Food on the Pharmacokinetics of TY-9591 in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: TYK Medicines, Inc
Sponsor class: INDUSTRY
First posted: 2021-03-15
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Cmax of TY-9591 and its metabolites
timeFrame: 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.
measure: Cmax of Osimertinib and its metabolites
timeFrame: 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.
measure: AUC(0-72h) of TY-9591 and its metabolites
timeFrame: 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.
measure: AUC(0-72h) of Osimertinib and its metabolites
timeFrame: 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:
measure: Tmax of TY-9591 and its metabolites
timeFrame: 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.
measure: Tmax of Osimertinib and its metabolites
timeFrame: 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.
measure: T1/2 of TY-9591 and its metabolites
timeFrame: 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.
measure: T1/2 of Osimertinib and its metabolites
timeFrame: 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.
measure: λz of TY-9591 and its metabolites
timeFrame: 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.
measure: λz of Osimertinib and its metabolites
timeFrame: 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.
measure: AUC(0-168h) of TY-9591 and its metabolites
timeFrame: 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.
measure: AUC(0-168h) of Osimertinib and its metabolites
timeFrame: 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.
measure: AUC(0-t) of TY-9591 and its metabolites
timeFrame: 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.
measure: AUC(0-t) of Osimertinib and its metabolites
timeFrame: 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.
measure: AUC(0-∞) of TY-9591 and its metabolites
timeFrame: 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.
measure: AUC(0-∞) of Osimertinib and its metabolites
timeFrame: 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.
measure: CL/F of TY-9591
timeFrame: 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.
measure: CL/F of Osimertinib
timeFrame: 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.
measure: Vss/F of TY-9591
timeFrame: 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.
measure: Vss/F of Osimertinib
timeFrame: 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.
measure: Calculated for both Cmax and AUC of TY-9591
timeFrame: 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.
measure: Calculated for both Cmax and AUC of Osimertinib
timeFrame: 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.
measure: Safety variables
timeFrame: Assessments performed throughout the study period.
Other outcomes:
Locations:
city: Changsha
country: China
facility: Hunan Provincial Tumor Hospital
state: Hunan
Study officials:
affiliation: Hunan Provincial Tumor Hospital
name: Kunyan Li, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Hunan Provincial Tumor Hospital
name: Xue Chen, MD
role: PRINCIPAL_INVESTIGATOR
References: