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

Primary Purpose

Hepatic Impairment, Healthy Volunteers

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

TAK-954

About this trial

This is an interventional other trial for Hepatic Impairment focused on measuring Drug Therapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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).
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).
Healthy participants (Group 4).

Exclusion Criteria:

Participants who have:

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).
Have severe hepatic encephalopathy ([greater than] > Grade II Portal Systemic Encephalopathy Score) (Group 1 to 3).
Surgical porto-systemic shunts, including transjugular intrahepatic portosystemic shunt (Group 1 to 3).
A history of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 1 month prior to trial entry (Group 1 to 3).
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.
Severe/advanced ascites and/or pleural effusion which requires emptying and albumin supplementation, as judged by the investigator (Group 1 to 3).
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).
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).

Sites / Locations

PRA CZ, s.r.o
Summit Center of Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Group 1 Mild Hepatic Impairment: TAK-954 0.2 mg

Group 2 Moderate Hepatic Impairment: TAK-954 0.2 mg

Group 3 Severe Hepatic Impairment: TAK-954 0.2 mg

Group 4 Healthy Participants: TAK-954 0.2 mg

Arm Description

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

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

Outcomes

Primary Outcome Measures

Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)

AUClast: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Total and Free)

AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-954 (Total and Free)

Secondary Outcome Measures

Number of Participants With Clinically Significant Physical Examination Findings

Number of Participants With Markedly Abnormal Electrocardiograms (ECGs)

Number of Participants With Markedly Abnormal Values of Vital Signs

Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

Full Information

NCT ID

NCT03277274

First Posted

September 7, 2017

Last Updated

August 28, 2019

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT03277274

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

November 9, 2017 (Actual)

Primary Completion Date

September 1, 2018 (Actual)

Study Completion Date

September 10, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatic Impairment, Healthy Volunteers

Keywords

Drug Therapy

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1 Mild Hepatic Impairment: TAK-954 0.2 mg

Arm Type

Experimental

Arm Description

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

Arm Title

Group 2 Moderate Hepatic Impairment: TAK-954 0.2 mg

Arm Type

Experimental

Arm Description

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

Arm Title

Group 3 Severe Hepatic Impairment: TAK-954 0.2 mg

Arm Type

Experimental

Arm Description

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

Arm Title

Group 4 Healthy Participants: TAK-954 0.2 mg

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

TAK-954

Intervention Description

TAK-954 intravenous infusion.

Primary Outcome Measure Information:

Title

Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)

Time Frame

Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion

Title

AUClast: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Total and Free)

Time Frame

Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion

Title

AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-954 (Total and Free)

Time Frame

Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion

Secondary Outcome Measure Information:

Title

Number of Participants With Clinically Significant Physical Examination Findings

Time Frame

Up to 14 days after the last dose of study drug (Day 15)

Title

Number of Participants With Markedly Abnormal Electrocardiograms (ECGs)

Time Frame

Up to 14 days after the last dose of study drug (Day 15)

Title

Number of Participants With Markedly Abnormal Values of Vital Signs

Time Frame

Up to 14 days after the last dose of study drug (Day 15)

Title

Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values

Time Frame

Up to 14 days after the last dose of study drug (Day 15)

Title

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

Time Frame

Baseline up to 30 days after last dose of study drug (Day 31)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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). 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). Healthy participants (Group 4). Exclusion Criteria: Participants who have: 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). Have severe hepatic encephalopathy ([greater than] > Grade II Portal Systemic Encephalopathy Score) (Group 1 to 3). Surgical porto-systemic shunts, including transjugular intrahepatic portosystemic shunt (Group 1 to 3). A history of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 1 month prior to trial entry (Group 1 to 3). 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. Severe/advanced ascites and/or pleural effusion which requires emptying and albumin supplementation, as judged by the investigator (Group 1 to 3). 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). 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

Facility Name

PRA CZ, s.r.o

City

Praha 7

State/Province

Praha

ZIP/Postal Code

170 00

Country

Czechia

Facility Name

Summit Center of Clinical Research

City

Bratislava

ZIP/Postal Code

83101

Country

Slovakia

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Learn more about this trial

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

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