A Study to Evaluate the Effect of Hepatic Impairment on the Single Dose Pharmacokinetics (PK) of Intravenous TAK-954

NCT ID: NCT03277274

Last Updated: 2019-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-09
• Study Completion Date: 2018-09-10

Brief Summary

The purpose of this study is to evaluate the effect of varying degrees of hepatic function on the single dose PK of IV TAK-954.

Detailed Description

The drug being tested in this study is called TAK-954. This study will evaluate the safety and tolerability of single intravenous doses of TAK-954 in participants with varying degrees of hepatic function.

The study will enroll approximately up to 32 participants. Participants will be enrolled in one of the 4 treatment groups based on their degree of hepatic impairment which will be determined based on Child-Pugh Score as follow:

• Group 1 TAK-954 0.2 mg: Mild Hepatic Impairment (Child Pugh Class A)
• Group 2 TAK-954 0.2 mg: Moderate Hepatic Impairment (Child Pugh Class B)
• Group 3 TAK-954 0.2 mg: Severe Hepatic Impairment (Child Pugh Class C)
• Group 4 TAK-954 0.2 mg: Healthy Participants

The Child-Pugh classification will assess the severity of 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy grade) on a scale of 1 (none) to 3 (moderate). Total hepatic impairment score ranges from 5 (mild) to 15 (severe) where higher score indicates more severity.

All participants will receive a single dose of TAK-954 0.2 mg on Day 1.

This study may have a full study design, where Group 1 to Group 4 will enroll approximately 8 participants in each group or a reduced study design, where no participants will be enrolled in Group 1 and approximately 8 participants will be enrolled in Group 2 to Group 4.

This multi-center trial will be conducted in Czech Republic and Slovakia. The overall time to participate in this study is approximately 7 weeks. Participants will remain confined to the clinic for 4 days, with 2 further out-patient visits, and will make a final visit to the clinic 10-14 days after receiving their last dose of TAK-954 for a follow-up assessment.

Conditions

Hepatic Impairment; Healthy Volunteers

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Group 1 Mild Hepatic Impairment: TAK-954 0.2 mg

TAK-954 0.2 milligram (mg), intravenous, administered as 60-minute infusion, once on Day 1.

Group Type: EXPERIMENTAL

TAK-954

Intervention Type: DRUG

TAK-954 intravenous infusion.

Group 2 Moderate Hepatic Impairment: TAK-954 0.2 mg

TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.

Group Type: EXPERIMENTAL

TAK-954

Intervention Type: DRUG

TAK-954 intravenous infusion.

Group 3 Severe Hepatic Impairment: TAK-954 0.2 mg

TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.

Group Type: EXPERIMENTAL

TAK-954

Intervention Type: DRUG

TAK-954 intravenous infusion.

Group 4 Healthy Participants: TAK-954 0.2 mg

TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.

Group Type: EXPERIMENTAL

TAK-954

Intervention Type: DRUG

TAK-954 intravenous infusion.

Interventions

TAK-954

TAK-954 intravenous infusion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male and female participants (non-childbearing potential), with a body mass index (BMI) between 18 to 35 kilogram per square meter (kg/m^2) (All participants).

2. Participants with hepatic impairment who are medically stable as determined by the investigator, based on medical history and clinical evaluations including physical examinations, clinical laboratory tests, vital sign measurements, and 12-lead ECGs performed at the Screening Visit and at check-in on Day -1 (Group 1 to 3).

3. Healthy participants (Group 4).

Exclusion Criteria

Participants who have:

1. A history of hepatic carcinoma, hepatorenal syndrome, or presence of a liver mass by ultrasound, CT or MRI, or acute liver disease caused by an infection or drug toxicity (Group 1 to 3).

2. Have severe hepatic encephalopathy ([greater than] > Grade II Portal Systemic Encephalopathy Score) (Group 1 to 3).

3. Surgical porto-systemic shunts, including transjugular intrahepatic portosystemic shunt (Group 1 to 3).

4. A history of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 1 month prior to trial entry (Group 1 to 3).

5. Bilirubin levels above 5 times the upper limit of normal (ULN) at screening or Day -1 for Groups 1 and 2, there is no limit for Group 3.

6. Severe/advanced ascites and/or pleural effusion which requires emptying and albumin supplementation, as judged by the investigator (Group 1 to 3).

7. Renal creatinine clearance (CLcr) less than or equal to (<=) 50 milliliter per minute (mL/min), calculated using the Cockcroft-Gault equation from the serum creatinine measurement taken at screening (Group 1 to 3).

8. Who have a history of clinically significant endocrine, gastrointestinal (GI) (including motility disorder and intestinal obstruction), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases will be excluded from the trial (Group 4).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

PRA CZ, s.r.o

Prague, Prague, Czechia

Summit Center of Clinical Research

Bratislava, , Slovakia

Countries

Czechia; Slovakia

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-000714-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1196-9190

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-954-1006

Identifier Type: -

Identifier Source: org_study_id