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

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Non-Randomized, Open-Label Trial to Evaluate the Effect of Hepatic Impairment on the Single Dose Pharmacokinetics of Intravenous TAK-954

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03277274
• Other study ID #: TAK-954-1006
• Secondary ID: 2017-000714-37U1
• Status: Completed
• Phase: Phase 1
• Start date: November 9, 2017
• Est. completion date: September 10, 2018

Study information

• Verified date: August 2019
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: September 10, 2018
• Est. primary completion date: September 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Healthy Volunteers
• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• TAK-954
TAK-954 intravenous infusion.

Locations

Country	Name	City	State
Czechia	PRA CZ, s.r.o	Praha 7	Praha
Slovakia	Summit Center of Clinical Research	Bratislava

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

Czechia,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)		Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
Primary	AUClast: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Total and Free)		Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
Primary	AUC8: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-954 (Total and Free)		Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
Secondary	Number of Participants With Clinically Significant Physical Examination Findings		Up to 14 days after the last dose of study drug (Day 15)
Secondary	Number of Participants With Markedly Abnormal Electrocardiograms (ECGs)		Up to 14 days after the last dose of study drug (Day 15)
Secondary	Number of Participants With Markedly Abnormal Values of Vital Signs		Up to 14 days after the last dose of study drug (Day 15)
Secondary	Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values		Up to 14 days after the last dose of study drug (Day 15)
Secondary	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)		Baseline up to 30 days after last dose of study drug (Day 31)