臨床研究等提出・公開システム

An Open-label, Crossover Study to Compare Different Formulations and to Evaluate Effect of Food on Pharmacokinetics of TAS-116 in Patients with Advanced Solid Tumors

A phase I study of Taiho Pharmaceutical Co., Ltd.

30

In Cohort 1 [Pharmacokinetic (PK) study of different formulations], the median (range) age was 64.0 (38-74) years, 61.5% of patients were male, and 61.5% had an ECOG PS of 0. In Cohort 2 (food-effect study), the median (range) age was 59.0 (40-78) years, 52.9% were male, and 35.3% had an ECOG PS of 0. The most common tumor types were lung cancer (33.3%), followed by pancreatic cancer (26.7%) and rectum (13.3%) and biliary tract (6.7%) cancers.

In Cohort 1, 13 patients received the study drug Formulations A and B, and 12 patients were included in the PK evaluable population. In Cohort 2, 17 patients received Formulation A under fasting and fed conditions, and 16 patients were included in the PK evaluable population. All patients (n = 30) treated in the PK evaluation period proceeded to the consecutive administration period.

In the consecutive administration period, 83.3% (25/30) of patients experienced treatment-related adverse events (TRAEs), and 33.3% (10/30) had Grade 3 or higher TRAEs. TRAEs with an incidence of >=15% included diarrhea (53.3%), decreased appetite (23.3%), nausea (20.0%), and malaise (16.7%). Grade 3 or higher TRAEs with an incidence of >=10% were anemia (13.3%) and diarrhea (10.0%). No TRAEs led to death or treatment discontinuation.

In Cohort 1, maximum concentration (Cmax), area under the curve (AUC)last, and AUCinf geometric mean ratios for Formulations A and B (90% confidence interval [CI]) were 0.8078 (0.6569-0.9933), 0.7973 (0.6672-0.9529), and 0.8094 (0.6697-0.9782), respectively; 90% CIs were not within the bioequivalence range (0.80-1.25). In Cohort 2, mean Cmax, AUClast, and AUCinf were higher in fed vs fasting conditions.

Overall response rate, disease control rate, and median progression-free survival were 0%, 33%, and 1.5 months, respectively. Four patients had stable disease >=5 months.

Bioequivalence of the two formulations was unconfirmed. Systemic exposure of Formulation A was approximately 20% less than Formulation B. A high-fat/calorie meal increased the relative pharmacokinetics and bioavailability of a single 160-mg dose.

Aug. 06, 2022

https://link.springer.com/article/10.1007/s10637-022-01285-9

No

Data will not be shared according to the Sponsor policy on data sharing. Taiho policy on data sharing may be found at https://www.taiho.co.jp/en/science/policy/clinical_trial_information_disclosure_policy/index.html.

Taiho Pharmaceutical Co., Ltd.

toiawaseCD1@taiho.co.jp

Taiho Pharmaceutical Co., Ltd.

toiawase@taiho.co.jp

completed

Jan. 15, 2019

Interventional

Open-label, two-cohort, respective two-arms, randomized phase I study

treatment purpose

1

Key inclusion criteria
- Provided written informed consent
- Histologically or cytologically confirmed solid tumor.
- Has a lack of response to conventional therapy or no availability of generally acknowledged standard therapy
- Is able to take medications orally and to eat meals enough
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Women of childbearing potential must have a negative pregnancy test at baseline.

Key exclusion criteria
- Has gastrointestinal dysfunction (eg, history of gastrectomy, including a little gastrectomy) that may markedly interfere with the absorption of TAS-116
- Has a serious illness or medical condition
- Women who are pregnant, breastfeeding

Both

Solid tumor

investigational material(s)
Generic name etc : TAS-116 Formulation A
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : (Food-effect study) Formulation A of TAS-116 (160 mg/body) will be administered orally under fed or fasting conditions once per day at the 1st and the 2nd administration. (PK study of different formulations) Formulation A of TAS-116 (160 mg/body) will be administered orally under fasting conditions once per day at the 1st or the 2nd administration.

control material(s)
Generic name etc : TAS-116 Formulation B
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : (PK study of different formulations) Formulation B of TAS-116 (160 mg/body) will be administered orally under fasting conditions once per day at the 1st or the 2nd administration.

pharmacokinetics
PK parameter
Comparison of each PK parameter of TAS-116 (Cmax, AUClast, and AUCinf).

safety
efficacy
Safety, Efficacy
CTCAE Version 4.03 , RECIST Version 1.1

+81-11-706-7061

Nov. 20, 2018