Trial Outcomes & Findings for A Study to Evaluate the Effect of Hepatic Impairment on the Single Dose Pharmacokinetics (PK) of Intravenous TAK-954 (NCT NCT03277274)

NCT ID: NCT03277274

Last Updated: 2019-09-25

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 25 participants
• Primary outcome timeframe: Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
• Results posted on: 2019-09-25

Participant Flow

Participants took part in the study at 2 investigative sites in Czech Republic and Slovakia from 09 November 2017 to 10 September 2018.

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.

Participant milestones

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

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

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

PRIMARY outcome

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

Population: 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.

Outcome measures

Measure	Healthy Participants: TAK-954 0.2 mg n=8 Participants TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg n=8 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg n=7 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free) TAK-954 (Total)	2.629 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 19.1	2.440 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 25.3	1.893 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 35.4
Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free) TAK-954 (Free)	0.1381 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 15.6	0.1799 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 24.4	0.1778 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 23.1

PRIMARY outcome

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

Population: 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.

Outcome measures

Measure	Healthy Participants: TAK-954 0.2 mg n=8 Participants TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg n=8 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg n=7 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
AUClast: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Total and Free) TAK-954 (Total)	28.57 hour*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 19.2	23.57 hour*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 26.2	20.19 hour*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 32.7
AUClast: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Total and Free) TAK-954 (Free)	1.501 hour*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 12.0	1.737 hour*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 23.0	1.898 hour*nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 19.3

PRIMARY outcome

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

Population: 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.

Outcome measures

Measure	Healthy Participants: TAK-954 0.2 mg n=8 Participants TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg n=8 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg n=7 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-954 (Total and Free) TAK-954 (Total)	31.30 h*ng/mL Geometric Coefficient of Variation 20.1	25.44 h*ng/mL Geometric Coefficient of Variation 27.1	22.60 h*ng/mL Geometric Coefficient of Variation 34.3
AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-954 (Total and Free) TAK-954 (Free)	1.643 h*ng/mL Geometric Coefficient of Variation 13.8	1.875 h*ng/mL Geometric Coefficient of Variation 24.0	2.122 h*ng/mL Geometric Coefficient of Variation 21.8

SECONDARY outcome

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

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

Outcome measures

Measure	Healthy Participants: TAK-954 0.2 mg n=8 Participants TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg n=10 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg n=7 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Number of Participants With Clinically Significant Physical Examination Findings	0 Participants	0 Participants	0 Participants

SECONDARY outcome

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

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

Outcome measures

Measure	Healthy Participants: TAK-954 0.2 mg n=8 Participants TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg n=10 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg n=7 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Number of Participants With Markedly Abnormal Electrocardiograms (ECGs)	0 Participants	0 Participants	2 Participants

SECONDARY outcome

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

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

Outcome measures

Measure	Healthy Participants: TAK-954 0.2 mg n=8 Participants TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg n=10 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg n=7 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Number of Participants With Markedly Abnormal Values of Vital Signs	0 Participants	1 Participants	1 Participants

SECONDARY outcome

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

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

Outcome measures

Measure	Healthy Participants: TAK-954 0.2 mg n=8 Participants TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg n=10 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg n=7 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values	0 Participants	0 Participants	0 Participants

SECONDARY outcome

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

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

Outcome measures

Measure	Healthy Participants: TAK-954 0.2 mg n=8 Participants TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg n=10 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg n=7 Participants TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	2 Participants	3 Participants	1 Participants

Adverse Events

Healthy Participants: TAK-954 0.2 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Group C, Severe Hepatic Impairment: TAK-954 0.2 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Healthy Participants: TAK-954 0.2 mg n=8 participants at risk TAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1.	Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg n=10 participants at risk TAK-954 0.2 mg, infusion, intravenously, once on Day 1.	Group C, Severe Hepatic Impairment: TAK-954 0.2 mg n=7 participants at risk TAK-954 0.2 mg, infusion, intravenously, once on Day 1.
Gastrointestinal disorders Diarrhoea	12.5% 1/8 • Number of events 1 • 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 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.	20.0% 2/10 • Number of events 2 • 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 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.	14.3% 1/7 • Number of events 1 • 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 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.
Gastrointestinal disorders Flatulence	0.00% 0/8 • 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 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.	10.0% 1/10 • Number of events 1 • 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 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.	0.00% 0/7 • 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 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.
Nervous system disorders Headache	12.5% 1/8 • Number of events 1 • 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 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.	0.00% 0/10 • 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 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.	0.00% 0/7 • 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 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.

Additional Information

Medical director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER