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

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03277274
• Collaborator: (none)
• Enrollment: 25
• Locations: 2
• Arms: 4
• Actual Duration (Months): 10
• Patients Per Site: 12.5
• Patients Per Site Per Month: 1.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Impairment; Healthy Volunteers	Drug: TAK-954	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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
• Actual Study Start Date: Nov 9, 2017
• Actual Primary Completion Date: Sep 1, 2018
• Actual Study Completion Date: Sep 10, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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]

2. 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]

3. 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

1. Number of Participants With Clinically Significant Physical Examination Findings [Up to 14 days after the last dose of study drug (Day 15)]

2. Number of Participants With Markedly Abnormal Electrocardiograms (ECGs) [Up to 14 days after the last dose of study drug (Day 15)]

3. Number of Participants With Markedly Abnormal Values of Vital Signs [Up to 14 days after the last dose of study drug (Day 15)]

4. 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)]

5. 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)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRA CZ, s.r.o	Praha 7	Praha	Czechia	170 00
2	Summit Center of Clinical Research	Bratislava		Slovakia	83101

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Oct 6, 2017
• Statistical Analysis Plan - Sep 5, 2018

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03277274
• Other Study ID Numbers: TAK-954-1006; 2017-000714-37; U1111-1196-9190
• First Posted: Sep 11, 2017
• Last Update Posted: Sep 25, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug Therapy
• Additional relevant MeSH terms: Liver Diseases

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 2 investigative sites in Czech Republic and Slovakia from 09 November 2017 to 10 September 2018.
Pre-assignment Detail	Participants with normal hepatic function and hepatic impairment were enrolled in 1 of the groups:B(moderate), C(severe) or D(healthy) to receive TAK-954 0.2mg. Based on available safety and PK data from Group B, participants were enrolled in reduced study design and were not enrolled in GroupA(mild). Groups A-D are equal to Groups 1-4 in protocol.

Arm/Group Title	Healthy Participants: TAK-954 0.2 mg	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
Arm/Group Description	TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Period Title: Overall Study
STARTED	8	10	7
COMPLETED	8	10	7
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Healthy Participants: TAK-954 0.2 mg	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg	Total
Arm/Group Description	TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	Total of all reporting groups
Overall Participants	8	10	7	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.5 (9.46)	55.6 (12.25)	57.9 (12.88)	57.2 (11.21)
Sex: Female, Male (Count of Participants)
Female	3 37.5%	4 40%	1 14.3%	8 32%
Male	5 62.5%	6 60%	6 85.7%	17 68%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	8 100%	10 100%	7 100%	25 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	8 100%	10 100%	7 100%	25 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Czech Republic	3 37.5%	3 30%	2 28.6%	8 32%
Slovakia	5 62.5%	7 70%	5 71.4%	17 68%
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	89.95 (17.098)	86.77 (19.823)	87.19 (21.331)	87.90 (18.667)
Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	31.1 (3.18)	30.4 (5.02)	27.9 (6.18)	29.9 (4.87)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	169.8 (11.30)	168.0 (10.47)	176.1 (6.28)	170.8 (10.01)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) set consisted of all participants who were enrolled and received the correct dose of study drug and had at least 1 measurable plasma concentration or amount of drug in the urine for TAK-954.

Arm/Group Title	Healthy Participants: TAK-954 0.2 mg	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
Arm/Group Description	TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Measure Participants	8	8	7
TAK-954 (Total)	2.629 (19.1)	2.440 (25.3)	1.893 (35.4)
TAK-954 (Free)	0.1381 (15.6)	0.1799 (24.4)	0.1778 (23.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Participants: TAK-954 0.2 mg, Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg
	Comments
	Type of Statistical Test	Other
	Comments	TAK-954 (Total): An analysis of variance (ANOVA) were performed on log transformed Cmax (total TAK-954) to compare each hepatically impaired group with the normal hepatic function group.
Statistical Test of Hypothesis	p-Value	0.579
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Healthy Participants: TAK-954 0.2 mg, Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
	Comments
	Type of Statistical Test	Other
	Comments	TAK-954 (Total): An ANOVA were performed on log transformed Cmax (total TAK-954) to compare each hepatically impaired group with the normal hepatic function group.
Statistical Test of Hypothesis	p-Value	0.026
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Healthy Participants: TAK-954 0.2 mg, Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg
	Comments
	Type of Statistical Test	Other
	Comments	TAK-954 (Free): An ANOVA were performed on log transformed Cmax (Free TAK-954) to compare each hepatically impaired group with the normal hepatic function group.
Statistical Test of Hypothesis	p-Value	0.020
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Healthy Participants: TAK-954 0.2 mg, Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
	Comments
	Type of Statistical Test	Other
	Comments	TAK-954 (Free): An ANOVA were performed on log transformed Cmax (Free TAK-954) to compare each hepatically impaired group with the normal hepatic function group.
Statistical Test of Hypothesis	p-Value	0.031
	Comments
	Method	ANOVA
	Comments

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The PK set consisted of all participants who were enrolled and received the correct dose of study drug and had at least 1 measurable plasma concentration or amount of drug in the urine for TAK-954.

Arm/Group Title	Healthy Participants: TAK-954 0.2 mg	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
Arm/Group Description	TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Measure Participants	8	8	7
TAK-954 (Total)	28.57 (19.2)	23.57 (26.2)	20.19 (32.7)
TAK-954 (Free)	1.501 (12.0)	1.737 (23.0)	1.898 (19.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Participants: TAK-954 0.2 mg, Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg
	Comments
	Type of Statistical Test	Other
	Comments	TAK-954 (Total): An ANOVA were performed on log transformed AUClast (Total TAK-954) to compare each hepatically impaired group with the normal hepatic function group.
Statistical Test of Hypothesis	p-Value	0.151
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Healthy Participants: TAK-954 0.2 mg, Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
	Comments
	Type of Statistical Test	Other
	Comments	TAK-954 (Total): An ANOVA were performed on log transformed AUClast (Total TAK-954) to compare each hepatically impaired group with the normal hepatic function group.
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Healthy Participants: TAK-954 0.2 mg, Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg
	Comments
	Type of Statistical Test	Other
	Comments	TAK-954 (Free): An ANOVA were performed on log transformed AUClast (Free TAK-954) to compare each hepatically impaired group with the normal hepatic function group.
Statistical Test of Hypothesis	p-Value	0.129
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Healthy Participants: TAK-954 0.2 mg, Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
	Comments
	Type of Statistical Test	Other
	Comments	TAK-954 (Free): An ANOVA were performed on log transformed AUClast (Free TAK-954) to compare each hepatically impaired group with the normal hepatic function group.
Statistical Test of Hypothesis	p-Value	0.023
	Comments
	Method	ANOVA
	Comments

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The PK set consisted of all participants who were enrolled and received the correct dose of study drug and had at least 1 measurable plasma concentration or amount of drug in the urine for TAK-954.

Arm/Group Title	Healthy Participants: TAK-954 0.2 mg	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
Arm/Group Description	TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Measure Participants	8	8	7
TAK-954 (Total)	31.30 (20.1)	25.44 (27.1)	22.60 (34.3)
TAK-954 (Free)	1.643 (13.8)	1.875 (24.0)	2.122 (21.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Participants: TAK-954 0.2 mg, Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg
	Comments
	Type of Statistical Test	Other
	Comments	TAK-954 (Total): An ANOVA were performed on log transformed AUCinf (Total TAK-954) to compare each hepatically impaired group with the normal hepatic function group.
Statistical Test of Hypothesis	p-Value	0.138
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Healthy Participants: TAK-954 0.2 mg, Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
	Comments
	Type of Statistical Test	Other
	Comments	TAK-954 (Total): An ANOVA were performed on log transformed AUCinf (Total TAK-954) to compare each hepatically impaired group with the normal hepatic function group.
Statistical Test of Hypothesis	p-Value	0.029
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Healthy Participants: TAK-954 0.2 mg, Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg
	Comments
	Type of Statistical Test	Other
	Comments	TAK-954 (Free): An ANOVA were performed on log transformed AUCinf (Free TAK-954) to compare each hepatically impaired group with the normal hepatic function group.
Statistical Test of Hypothesis	p-Value	0.201
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Healthy Participants: TAK-954 0.2 mg, Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
	Comments
	Type of Statistical Test	Other
	Comments	TAK-954 (Free): An ANOVA were performed on log transformed AUCinf (Free TAK-954) to compare each hepatically impaired group with the normal hepatic function group.
Statistical Test of Hypothesis	p-Value	0.023
	Comments
	Method	ANOVA
	Comments

4. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

The safety set consisted of all participants who were enrolled and received the study drug.

Arm/Group Title	Healthy Participants: TAK-954 0.2 mg	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
Arm/Group Description	TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Measure Participants	8	10	7
Count of Participants [Participants]	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Electrocardiograms (ECGs)
Time Frame	Up to 14 days after the last dose of study drug (Day 15)

Outcome Measure Data

Analysis Population Description

The safety set consisted of all participants who were enrolled and received the study drug.

Arm/Group Title	Healthy Participants: TAK-954 0.2 mg	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
Arm/Group Description	TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Measure Participants	8	10	7
Count of Participants [Participants]	0 0%	0 0%	2 28.6%

6. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

The safety set consisted of all participants who were enrolled and received the study drug.

Arm/Group Title	Healthy Participants: TAK-954 0.2 mg	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
Arm/Group Description	TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Measure Participants	8	10	7
Count of Participants [Participants]	0 0%	1 10%	1 14.3%

7. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

The safety set consisted of all participants who were enrolled and received the study drug.

Arm/Group Title	Healthy Participants: TAK-954 0.2 mg	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
Arm/Group Description	TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Measure Participants	8	10	7
Count of Participants [Participants]	0 0%	0 0%	0 0%

8. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

The safety set consisted of all participants who were enrolled and received the study drug.

Arm/Group Title	Healthy Participants: TAK-954 0.2 mg	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
Arm/Group Description	TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Measure Participants	8	10	7
Count of Participants [Participants]	2 25%	3 30%	1 14.3%

Adverse Events

Time Frame	TEAEs are adverse events that started after the first dose of study drug and no more than 30 days (Day 31) after the last dose of study drug
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Healthy Participants: TAK-954 0.2 mg		Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg		Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
Arm/Group Description	TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.		TAK-954 0.2 mg, infusion, intravenously, once on Day 1.		TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
All Cause Mortality
	Healthy Participants: TAK-954 0.2 mg		Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg		Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)		0/7 (0%)
Serious Adverse Events
	Healthy Participants: TAK-954 0.2 mg		Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg		Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Participants: TAK-954 0.2 mg		Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg		Group C, Severe Hepatic Impairment: TAK-954 0.2 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		3/10 (30%)		1/7 (14.3%)
Gastrointestinal disorders
Diarrhoea	1/8 (12.5%)	1	2/10 (20%)	2	1/7 (14.3%)	1
Flatulence	0/8 (0%)	0	1/10 (10%)	1	0/7 (0%)	0
Nervous system disorders
Headache	1/8 (12.5%)	1	0/10 (0%)	0	0/7 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.