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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Hepatic Impairment
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Praha
    • Praha 7, Praha, Czechia, 170 00
      • PRA CZ, s.r.o
• Slovakia
  • Bratislava, Slovakia, 83101
    • Summit Center of Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: TAK-954; TAK-954 intravenous infusion.
Experimental: 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.	Drug: TAK-954; TAK-954 intravenous infusion.
Experimental: 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.	Drug: TAK-954; TAK-954 intravenous infusion.
Experimental: Group 4 Healthy Participants: TAK-954 0.2 mg; TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.	Drug: TAK-954; TAK-954 intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
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
AUC∞: 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 Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Clinically Significant Physical Examination Findings	Up to 14 days after the last dose of study drug (Day 15)
Number of Participants With Markedly Abnormal Electrocardiograms (ECGs)	Up to 14 days after the last dose of study drug (Day 15)
Number of Participants With Markedly Abnormal Values of Vital Signs	Up to 14 days after the last dose of study drug (Day 15)
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)
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)

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2017
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): September 10, 2018

Study Registration Dates

• First Submitted: September 7, 2017
• First Submitted That Met QC Criteria: September 7, 2017
• First Posted (Actual): September 11, 2017

Study Record Updates

• Last Update Posted (Actual): September 25, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: TAK-954-1006; 2017-000714-37 (EudraCT Number); U1111-1196-9190 (Registry Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No