Clinical trial NCT04494269: A Study to Evaluate Pharmacokinetics and Safety of Tegoprazan in Subjects With Hepatic Impairment and Healthy Controls
Official title: An Open-label, Multi-center, Single-dose, Parallel-group Study to Evaluate Pharmacokinetics and Safety of Tegoprazan in Subjects With Hepatic Impairment and Healthy Controls
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hepatic Impairment
Healthy
Lead sponsor: HK inno.N Corporation
Sponsor class: INDUSTRY
First posted: 2020-07-31
Enrollment: 28
Sex: ALL
Minimum age (years): 19
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to compare the pharmacokinetic and safety of tegoprazan following single oral dose in subjects with hepatic impairment versus healthy control.

Detailed description: \[Pharmacokinetic Assessment\]

* Measurements

  - Tegoprazan and desmethyl tegoprazan (M1) in blood and urine
* Endpoints

  * Primary endpoints: AUClast and Cmax of tegoprazan and M1
  * Secondary endpoints: CL/F, t1/2, AUCinf, and fu of tegoprazan; CLrenal and Ae of tegoprazan and M1

\[Safety Assessment\]

* Adverse events (AEs)
* Clinical laboratory tests
* Vital sign
* Physical examination
* Electrocardiogram (ECG)

Eligibility criteria: \[Healthy Control Group\]

Inclusion Criteria:

* Subjects aged 19 to 70(inclusive) years at the time of signing the informed consent form.
* Subjects with a body weight of ≥ 50 kg and ≤ 90 kg at screening.
* Subjects with AST, ALT, and ALP levels of ≤ 1.5 × upper limit of the normal reference range (ULN) with total bilirubin \< 2 mg/dL and PT (INR) \< 1.7 at screening.
* Subjects who have no chronic disease or any congenital disease within the last 5 years and no pathological symptoms or findings as a result of an internal examination
* Subjects who provide voluntary written informed consent to study participation after being informed of detailed explanation and fully understanding study objectives, procedures and characteristics of the investigational product(IP).

Exclusion Criteria:

* Subjects who show symptoms of acute disease at the time of screening.
* Subjects with any clinically significant disease related to ongoing cardiovascular problem, respiratory system, kidney, endocrine system, hematologic, central nervous system, mental health disorder, or malignant tumor.
* Subjects with history or current evidence of gastrointestinal or hepatobiliary disease which may affect PK evaluation of the IP.
* Subjects with history or current evidence of clinically significant hypersensitivity to drugs containing any ingredient of proton pump inhibitors or potassium-competitive acid blockers and other drugs (such as aspirin and antibiotics).
* Subjects with systolic blood pressure (BP) of \< 90 mmHg or \> 160 mmHg, or diastolic BP of \< 50 mmHg or \> 100 mmHg at screening.
* Subjects who have received medication or food which may significantly affect absorption, distribution, metabolism, or elimination of study drug within 7 days prior to scheduled study treatment.
* Subjects who have participated in any other clinical study or bioequivalence study and received investigational agent within 180 days prior to scheduled study treatment.
* Subjects who have donated whole blood within 60 days prior to the scheduled study treatment, or has donated blood components or received transfusion within 30 days prior to scheduled study treatment.
* Subjects who are unable to use a medically acceptable contraceptive method throughout the study.
* Subjects who are determined ineligible for study participation by the investigator for other reasons.

\[Subjects with Hepatic Impairment\]

Inclusion Criteria:

* Subjects with chronic liver disease who meet any of the followings:

  * Chronic Hepatitis B;
  * Chronic Hepatitis C;
  * Alcoholic liver disease;
  * Non-alcoholic fatty liver disease; or
  * Liver fibrosis and cirrhosis.
* Subjects aged 19 to 70 years (inclusive) at the time of signing the informed consent form.
* Subjects with body weight of ≥ 50 kg and ≤ 90 kg with a BMI of ≥ 18.0 kg/m2 and ≤ 30 kg/m2 at screening.
* Subjects who meet any of following criteria:

  * AST, ALT, or ALP level \> 1.5 × ULN at screening;
  * Total bilirubin ≥ 2 mg/dL at screening; or
  * PT (INR) ≥ 1.7 at screening.
* Subjects who provide voluntary written informed consent to study participation after being informed of detailed explanation and fully understanding study objectives, procedures and characteristics of the IP.

Exclusion Criteria:

* Subjects who show symptoms of acute disease at the time of screening.
* Subjects with any clinically significant disease related to ongoing cardiovascular problem, respiratory system, kidney, endocrine system, hematologic, central nervous system, mental health disorder, or malignant tumor.
* Subjects with a history or current evidence of gastrointestinal disease which may affect PK evaluation for the IP.
* Subjects who have clinical changes to an estimated level that may affect PK evaluation of the study drug within 30 days prior to the scheduled dosing date.
* Changes in existing medications including dosage regimen within 30 days prior to the scheduled dosing date.
* Subjects with prior history or current evidence of clinically significant hypersensitivity to drugs containing any ingredient of proton pump inhibitors or potassium-competitive acid blockers and other drugs (such as aspirin and antibiotics).
* Systolic BP of \< 90 mmHg or \> 160 mmHg, or diastolic BP of \< 50 mmHg or \> 100 mmHg at screening.
* Any concomitant medications or foods which may significantly affect absorption, distribution, metabolism, or elimination of the study drug within 7 days prior to the scheduled dosing date.
* Subjects who have participated in any other clinical study or bioequivalence study and received investigational agent within 180 days prior to scheduled study treatment.
* Subjects who have donated whole blood within 60 days prior to the scheduled dosing date, or have donated blood components or received transfusion within 30 days prior to the scheduled dosing date.
* Subjects who are unable to use medically acceptable contraceptive methods throughout the study.
* Subjects who are determined to be ineligible for study participation by the investigator for other reasons.

Primary outcomes:
measure: Pharmacokinetic Assessment
timeFrame: Up to 48 hours
measure: Pharmacokinetic Assessment
timeFrame: Up to 48 hours
Secondary outcomes:
measure: Pharmacokinetic Assessment
timeFrame: Up to 48 hours
measure: Pharmacokinetic Assessment
timeFrame: Up to 48 hours
measure: Pharmacokinetic Assessment
timeFrame: Up to 48 hours
measure: Pharmacokinetic Assessment
timeFrame: Up to 48 hours
measure: Pharmacokinetic Assessment
timeFrame: Up to 48 hours
measure: Pharmacokinetic Assessment
timeFrame: Up to 48 hours
Other outcomes:
Locations:
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Medical Center
name: Jung-Ryul Kim, MD, PhD
role: STUDY_CHAIR
affiliation: Samsung Medical Center
name: Yang-Won Min, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gachon University Gil Medical Center
name: Dong-Seong Shin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHA Bundang Medical Center
name: Eon-Hye Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: