Relative Bioavailability Study and Food Effect Study of TT-00420 (Tinengotinib) Capsule and Tablet Formulations in Healthy Volunteers

NCT04705922 | Completed Phase 1 FDA Drug

• 1 other identifier: TT420HV1102
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, 3-way crossover randomized study in adult healthy volunteers to evaluate the relative bioavailability of TT-00420 tablet and capsule formulations and to evaluate food effect on the pharmacokinetics of TT-00420 tablet.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• Area under the curve (AUC0-∞) of TT-00420

  Blood samples will be collected at indicated time points for pharmacokinetic analysis of TT-00420.

  From pre-dose up to 240 hours post-dose each period (each period is 14 days)

• Area under the curve (AUC0-t) of TT-00420

  Blood samples will be collected at indicated time points for pharmacokinetic analysis of TT-00420.

  From pre-dose up to 240 hours post-dose each period (each period is 14 days)

• Maximum observed concentration (Cmax) of TT-00420

  Blood samples will be collected at indicated time points for pharmacokinetic analysis of TT-00420.

  From pre-dose up to 240 hours post-dose each period (each period is 14 days)

Secondary Outcomes (10)

• Number of participants with adverse events (AEs)

  From admission up to 10 days following discharge

• Incidence of abnormal physical examinations

  At baseline and from admission to discharge, up to 12 days per period (each period is 14 days)

• Incidence of abnormal clinical laboratory tests

  At baseline and from admission to discharge, up to 12 days per period (each period is 14 days)

• Incidence of abnormal vital signs

  At baseline and from admission to discharge, up to 12 days per period (each period is 14 days)

• Incidence of abnormal weight

  At baseline and from admission to discharge, up to 12 days per period (each period is 14 days)

Study Arms (3)

Sequence 1 [TT-00420 tablet, fed; TT-00420 tablet, fasted; TT-00420 capsule, fasted]

EXPERIMENTAL

Participants will receive a single dose of TT-00420 tablet under fed conditions, followed by a single dose of TT-00420 tablet under fasted conditions, followed by a single dose of TT-00420 capsule under fasted conditions. There will be at least a 14-day wash-out period between each dose.

Drug: TT-00420 Capsule; Drug: TT-00420 Tablet

Sequence 2 [TT-00420 tablet, fasted; TT-00420 capsule, fed; TT-00420 tablet, fed]

EXPERIMENTAL

Participants will receive a single dose of TT-00420 tablet under fasted conditions, followed by a single dose of TT-00420 capsule under fasted conditions, followed by a single dose of TT-00420 tablet under fed conditions. There will be at least a 14-day wash-out period between each dose.

Drug: TT-00420 Capsule; Drug: TT-00420 Tablet

Sequence 3 [TT-00420 capsule, fasted; TT-00420 tablet, fed; TT-00420 tablet, fasted]

EXPERIMENTAL

Participants will receive a single dose of TT-00420 capsule under fasted conditions, followed by a single dose of TT-00420 tablet under fed conditions, followed by a single dose of TT-00420 tablet under fasted conditions. There will be at least a 14-day wash-out period between each dose.

Drug: TT-00420 Capsule; Drug: TT-00420 Tablet

Interventions

TT-00420 Capsule DRUG

TT-00420 capsule formulation, administered orally

Sequence 1 [TT-00420 tablet, fed; TT-00420 tablet, fasted; TT-00420 capsule, fasted]; Sequence 2 [TT-00420 tablet, fasted; TT-00420 capsule, fed; TT-00420 tablet, fed]; Sequence 3 [TT-00420 capsule, fasted; TT-00420 tablet, fed; TT-00420 tablet, fasted]

TT-00420 Tablet DRUG

TT-00420 tablet formulation, administered orally

Sequence 1 [TT-00420 tablet, fed; TT-00420 tablet, fasted; TT-00420 capsule, fasted]; Sequence 2 [TT-00420 tablet, fasted; TT-00420 capsule, fed; TT-00420 tablet, fed]; Sequence 3 [TT-00420 capsule, fasted; TT-00420 tablet, fed; TT-00420 tablet, fasted]

Eligibility Criteria

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

You may qualify if:

• Male or female subjects between 18 and 64 years of age inclusive, at the time of signing the informed consent.
• Body mass index (BMI) between 18 and 32 kg/m2, inclusive, and weighs at least 50 kg.
• Healthy as determined by the investigator based on medical history, clinical laboratory results (serum chemistry, hematology, urinalysis, and serology), vital sign measurements, 12-lead electrocardiogram (ECG) results, and physical examination findings. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only, if per the investigator discretion, the investigator judges and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Male subjects must not donate sperm starting at Screening, throughout the study period and for at least 90 days after final study drug administration.
• Male subjects with female sexual partner(s) of reproductive potential may be enrolled if the male:
• is documented to be surgically sterile (i.e., successfully vasectomized), or
• agrees to use 2 methods of highly effective contraception and agree to refrain from sperm donation from the time of Screening through 90 days post-doseHighly effective includes male condom with spermicide PLUS an effective contraceptive for the female partner that includes: OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring or IUD
• If female, is of non-childbearing potential, meeting the following requirements:
• pre-menopausal with documentation of surgical sterilization (i.e., hysterectomy, bilateral tubal ligation, bilateral oophorectomy, or bilateral salpingectomy at least 3 months prior to study entry), or
• post-menopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and with follicle-stimulating hormone (FSH) level ≥ 40 mIU/mL at Screening
• Able to sign the informed consent and comply with the protocol.

You may not qualify if:

• Any history of clinically serious disease.
• Any active or unstable clinically significant medical condition as judged by the Investigator.
• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
• Hypersensitivity or allergy to any of the study drugs or drugs of similar chemical classes.
• Hypersensitivity or allergy for components of the prescribed meal
• Received any investigational drug within 30 days or 5 half-lives(whichever is longer, if known) before the study.
• Subject who has undergone major surgery ≤ 2 months before study drug administration.
• Impaired cardiac function including clinically significant arrhythmias or clinically significant abnormality in clinical test, including but not limited to any of the following at Screening and Admission, repeat testing is allowed for verification, at the discretion of the Investigator:
• Heart rate \< 45 beats per minute (bpm) or \> 90 bpm.
• Systolic blood pressure (SBP) \< 90 mmHg or \> 140 mmHg; diastolic blood pressure (DBP) \< 50 mmHg or \> 90 mmHg.
• Average of the 3 QT intervals corrected using Fridericia's formula (QTcF) \> 450 milliseconds.
• Troponin I at screening \> upper limit of normal (ULN).
• Second degree or higher Atrioventricular block on ECG.
• Subject who has a known history of, or a positive test result for, hepatitis B surface antigen (HBsAg), immunoglobulin M (IgM) antibody to hepatitis B core antibody (anti-HBc) (IgM anti-HBc), hepatitis C virus antibody (anti-HCV), or human immunodeficiency virus (HIV) types 1 or 2, or syphilis at Screening.
• Subject with a history of severe visual diseases; or visual changes including flushing lights, blurry vision, color changes, or other visual changes.

Sponsors & Collaborators

• TransThera Sciences (Nanjing), Inc.: lead

Study Sites (1)

Pharmaron CPC

Baltimore, Maryland, 21201, United States

Location

Study Officials

• Mohamed Al-Ibrahim

  Pharmaron CPC

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 12, 2021
• Study Start: December 29, 2020
• Primary Completion: March 7, 2021
• Study Completion: July 23, 2021
• Last Updated: January 3, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)