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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04798638
• Other study ID #: TYKM1601102
• Status: Completed
• Phase: Phase 1
• Start date: April 30, 2021
• Est. completion date: September 9, 2021

Study information

• Verified date: August 2021
• Source: TYK Medicines, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 9, 2021
• Est. primary completion date: September 9, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

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.
• 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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
China	Hunan Provincial Tumor Hospital	Changsha	Hunan

Sponsors (1)

Lead Sponsor	Collaborator
TYK Medicines, Inc

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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	Tmax of TY-9591 and its metabolites	Pharmacokinetics of TY-9591 and its metabolites by assessment of time to Cmax.	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	Tmax of Osimertinib and its metabolites	Pharmacokinetics of Osimertinib and its metabolites by assessment of time to Cmax.	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	T1/2 of TY-9591 and its metabolites	Pharmacokinetics of TY-9591 and its metabolites by assessment of Terminal half life.	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	T1/2 of Osimertinib and its metabolites	Pharmacokinetics of Osimertinib and its metabolites by assessment of Terminal half life.	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	?z of TY-9591 and its metabolites	Pharmacokinetics of TY-9591 and its metabolites by assessment of Terminal rate constant.	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	?z of Osimertinib and its metabolites	Pharmacokinetics of Osimertinib and its metabolites by assessment of Terminal rate constant.	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	AUC(0-168h) of TY-9591 and its metabolites	Pharmacokinetics of TY-9591 and its metabolites by assessment of area under the plasma concentration time curve from zero to 168 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	AUC(0-168h) of Osimertinib and its metabolites	Pharmacokinetics of Osimertinib and its metabolites by assessment of area under the plasma concentration time curve from zero to 168 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	AUC(0-t) of TY-9591 and its metabolites	Pharmacokinetics of TY-9591 and its metabolites by assessment of area under the plasma concentration time curve from zero to appointed time.	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	AUC(0-t) of Osimertinib and its metabolites	Pharmacokinetics of Osimertinib and its metabolites by assessment of area under the plasma concentration time curve from zero to appointed time.	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	AUC(0-8) of TY-9591 and its metabolites	Pharmacokinetics of TY-9591 and its metabolites by assessment of area under the plasma concentration time curve from zero to infinity.	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	AUC(0-8) of Osimertinib and its metabolites	Pharmacokinetics of Osimertinib and its metabolites by assessment of area under the plasma concentration time curve from zero to infinity.	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	CL/F of TY-9591	Pharmacokinetics of TY-9591 only by assessment of apparent plasma clearance.	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	CL/F of Osimertinib	Pharmacokinetics of Osimertinib only by assessment of apparent plasma clearance.	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	Vss/F of TY-9591	Pharmacokinetics of TY-9591 only apparent volume of distribution.	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	Vss/F of Osimertinib	Pharmacokinetics of Osimertinib only apparent volume of distribution.	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	Calculated for both Cmax and AUC of TY-9591	Pharmacokinetics of TY-9591 parent to metabolite ratio.	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	Calculated for both Cmax and AUC of Osimertinib	Pharmacokinetics of Osimertinib parent to metabolite ratio.	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	Safety variables	Adverse events, clinical symptoms, vital signs, ECG's, clinical laboratory safety tests, ect.	Assessments performed throughout the study period.