Hepatic ImpairmentPhase 1NCT03277274
A Study to Evaluate the Effect of Hepatic Impairment on the Single Dose Pharmacokinetics (PK) of Intravenous TAK-954
A Phase 1 study testing TAK-954 in people with Hepatic Impairment and Healthy Volunteers, run by Takeda at 2 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment, Healthy Volunteers
- What is being tested?
- TAK-954
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 9 Nov 2017to 10 Sep 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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).
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
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.
Read the 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.
- Conditions
- Hepatic Impairment, Healthy Volunteers
- Being tested
- TAK-954
- Keywords
- Drug Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-954Drug
TAK-954 intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 Mild Hepatic Impairment: TAK-954 0.2 mg | Experimental | TAK-954 0.2 milligram (mg), intravenous, administered as 60-minute infusion, once on Day 1. Receives: Drug: TAK-954 |
| Group 2 Moderate Hepatic Impairment: TAK-954 0.2 mg | Experimental | TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1. Receives: Drug: TAK-954 |
| Group 3 Severe Hepatic Impairment: TAK-954 0.2 mg | Experimental | TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1. Receives: Drug: TAK-954 |
| Group 4 Healthy Participants: TAK-954 0.2 mg | Experimental | TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1. Receives: Drug: TAK-954 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)
Measured: 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)
Measured: 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)
Measured: Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
Secondary outcomes (5)
Number of Participants With Clinically Significant Physical Examination Findings
Measured: Up to 14 days after the last dose of study drug (Day 15)
Number of Participants With Markedly Abnormal Electrocardiograms (ECGs)
Measured: Up to 14 days after the last dose of study drug (Day 15)
Number of Participants With Markedly Abnormal Values of Vital Signs
Measured: 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
Measured: 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)
Measured: Baseline up to 30 days after last dose of study drug (Day 31)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2017
- Study start9 Nov 2017
- Primary completion1 Sep 2018
- Study completion10 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03277274
- Sponsor's protocol ID
- TAK-954-1006
- Other IDs
- 2017-000714-37, U1111-1196-9190, 2017
- Status last verified
- Aug 2019
- First submitted
- 7 Sep 2017
- Last updated
- 25 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03277274
- Acronym / sponsor ID
- TAK-954-1006
- Conditions
- Hepatic Impairment, Healthy Volunteers
- Keywords
- Drug Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 9 Nov 2017 (actual)
- Primary completion
- 1 Sep 2018 (actual)
- Study completion
- 10 Sep 2018 (actual)
- First posted
- 11 Sep 2017 (actual)
- Results
- Posted 25 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 Mild Hepatic Impairment: TAK-954 0.2 mg | Experimental | Drug: TAK-954TAK-954 0.2 milligram (mg), intravenous, administered as 60-minute infusion, once on Day 1. |
| Group 2 Moderate Hepatic Impairment: TAK-954 0.2 mg | Experimental | Drug: TAK-954TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1. |
| Group 3 Severe Hepatic Impairment: TAK-954 0.2 mg | Experimental | Drug: TAK-954TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1. |
| Group 4 Healthy Participants: TAK-954 0.2 mg | Experimental | Drug: TAK-954TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK-954TAK-954 intravenous infusion. | Drug | 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 |
Primary outcome
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
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
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
5 secondary outcomes
Number of Participants With Clinically Significant Physical Examination Findings
Time frame: Up to 14 days after the last dose of study drug (Day 15)
Number of Participants With Markedly Abnormal Electrocardiograms (ECGs)
Time frame: Up to 14 days after the last dose of study drug (Day 15)
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)
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Takeda
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAK-954 in people with Hepatic Impairment and Healthy Volunteers, run by Takeda at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Czechia, Slovakia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2019.