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

Takeda

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment; Healthy Volunteers

Treatments: Drug: TAK-954

Study type: Interventional

Funder types: Industry

Identifiers

NCT03277274

TAK-954-1006

2017-000714-37 (EudraCT Number)

U1111-1196-9190 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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25 participants in 4 patient groups

Group 1 Mild Hepatic Impairment: TAK-954 0.2 mg

Experimental group

Description:

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

Treatment:

Drug: TAK-954

Group 2 Moderate Hepatic Impairment: TAK-954 0.2 mg

Experimental group

Description:

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

Treatment:

Drug: TAK-954

Group 3 Severe Hepatic Impairment: TAK-954 0.2 mg

Experimental group

Description:

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

Treatment:

Drug: TAK-954

Group 4 Healthy Participants: TAK-954 0.2 mg

Experimental group

Description:

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

Treatment:

Drug: TAK-954