Back to results

A Study to Evaluate the Effect of Renal Impairment and Dialysis Treatment on the Pharmacokinetics (PK) of a Single Intravenous (IV) TAK-954

Primary Purpose

Renal 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 Renal Impairment focused on measuring Drug therapy

Eligibility Criteria

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

Inclusion Criteria:

All participants: Male and female participants (non-childbearing potential) who are aged 18 to 75 years, inclusive, with a body mass index (BMI) between 18 to 35 kilogram per square meter (kg/m^2).
Group A: As much as possible, the healthy participants with normal renal function (creatinine clearance [CLcr] greater than or equal to [>=] 90 milliliter per minute [mL/min]) should be comparable to participants with renal impairment with respect to median age and weight (approximately 50 percent [%] of healthy participants on each side of the median age and weight of currently enrolled renally-impaired participants grouped together), sex, and race. This will be decided by the investigators in discussion with Takeda.
Groups B to E: Participants who have stable RI, defined as no clinically significant change in disease status, as documented by the participant's most recent CLcr assessment; serum creatinine must not vary more than approximately 30% from Screening to Day -1 to confirm stable disease. Participants should also be in good health commensurate with their renal status.
- Group B: Participants with mild RI (CLcr 60 to less than [<] 90 mL/min).
- Group C: Participants with moderate RI (CLcr 30 to <60 mL/min).
- Group D: Participants with severe RI or ESRD but not requiring dialysis (CLcr <30 mL/min).
- Group E: Participants with ESRD requiring dialysis (<15 mL/min requiring hemodialysis at least 3 times/week, and having been on the same dialysis treatment regimen for at least 1 month before trial entry).
Participants should be on a stable drug regimen defined as not starting a new drug or changing dosage within 7 days or 5 half-lives (whichever is longer) before dosing with TAK-954.

Exclusion Criteria:

All participants:
- Are renal allograft recipients within 1 year of screening.
- Have a history of gastrointestinal (GI) motility disorder or intestinal obstruction.
- Have urinary incontinence without catheterization.
Group A: Participants who, in the discretion of the investigator, have a history of clinically significant endocrine, GI, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases will be excluded from the trial.
Groups B to E:
- Receive dialysis other than intermittent dialysis (except Group E).
- Have renal disease secondary to hepatic disease (hepatorenal syndrome).
- At the discretion of the investigators, have any significant hepatic, cardiac, or pulmonary disease or participants who are clinically nephrotic.

Sites / Locations

PRA CZ, s.r.o
Fakultni Nemocnice Hradec Kralove
PRA Magyarorszag Kft.
Szent Imre Egyetemi Oktatokorhaz Belgyogyazati Szakmak Matrix Intezet

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Group A TAK-954 0.2 mg: Healthy Participants

Group B TAK-954 0.2 mg: Mild Renal Impairment

Group C TAK-954 0.2 mg: Moderate Renal Impairment

Group D TAK-954 0.2 mg: Severe Renal Impairment

Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD)

Arm Description

Participants with normal renal function receive TAK-954 0.2 milligram (mg), infusion, intravenously in fasted state, once on Day 1 of a 6-day period.

Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.

Participants without hemodialysis or End-stage Renal Disease (ESRD) receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.

Participants with hemodialysis receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 4-day period followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 4-day period.

Outcomes

Primary Outcome Measures

Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)

Groups A, C and D; AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for TAK-954 (Free and Total)

Groups A, C and D; AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Free and Total)

Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total)

Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine

Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 1

Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2

Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine

Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 1

Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 2

Groups A, C and D; CLR: Renal Clearance for TAK-954

Group E; CLR: Renal Clearance for TAK-954 in Period 1

Group E; CLR: Renal Clearance for TAK-954 in Period 2

Group E; CLD: Clearance of Dialysate for TAK-954 in Period 2

Secondary Outcome Measures

Full Information

NCT ID

NCT03296787

First Posted

September 25, 2017

Last Updated

August 6, 2020

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT03296787

Brief Title

A Study to Evaluate the Effect of Renal Impairment and Dialysis Treatment on the Pharmacokinetics (PK) of a Single Intravenous (IV) TAK-954

Official Title

A Phase 1, Open-Label, Parallel Group Trial to Evaluate the Effect of Renal Impairment and Dialysis Treatment on the Pharmacokinetics of a Single Intravenous Dose of TAK-954

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Completed

Study Start Date

November 21, 2017 (Actual)

Primary Completion Date

August 9, 2019 (Actual)

Study Completion Date

August 9, 2019 (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

Yes

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 renal function on the PK of TAK-954 following single-dose IV administration and to investigate the impact of hemodialysis on the PK of single IV doses of TAK-954.

Detailed Description

The drug being tested in this study is called TAK-954. This study will evaluate the effect of varying degrees of renal function on the PK of TAK-954 following single-dose IV administration and to investigate the impact of hemodialysis on the PK of single IV doses of TAK-954. The study will enroll approximately up to 40 participants. Participants will be enrolled in one of the 5 treatment groups based on their renal impairment which will be determined based on Cockcroft and Gault (CG) equation as follows: Group A TAK-954 0.2 mg: Healthy Participants Group B TAK-954 0.2 mg: Mild Renal Impairment Group C TAK-954 0.2 mg: Moderate Renal Impairment Group D TAK-954 0.2 mg: Severe Renal Impairment or End-stage Renal Disease (ESRD) Without Hemodialysis Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD) With Hemodialysis All participants in groups A to D will receive a single dose of TAK-954 and two single doses in Group E. Enrollment in Group B (Mild) and Group E (ESRD requiring dialysis) will be based on assessment of safety and available PK data from Group C and Group D respectively. This multi-center trial will be conducted in Czech Republic and Hungary. The overall time to participate in this study is approximately 8 weeks. Participants in Groups A to D will remain confined to clinic for 3 days. For both treatments, participants in Group E requiring dialysis will remain confined to clinic for 3 days. All participants will make a final visit to the clinic 10-14 days after receiving their last dose for a follow-up assessment.

6. Conditions and Keywords

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

Renal Impairment, Healthy Volunteers

Keywords

Drug therapy

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group A TAK-954 0.2 mg: Healthy Participants

Arm Type

Experimental

Arm Description

Participants with normal renal function receive TAK-954 0.2 milligram (mg), infusion, intravenously in fasted state, once on Day 1 of a 6-day period.

Arm Title

Group B TAK-954 0.2 mg: Mild Renal Impairment

Arm Type

Experimental

Arm Description

Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.

Arm Title

Group C TAK-954 0.2 mg: Moderate Renal Impairment

Arm Type

Experimental

Arm Description

Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.

Arm Title

Group D TAK-954 0.2 mg: Severe Renal Impairment

Arm Type

Experimental

Arm Description

Participants without hemodialysis or End-stage Renal Disease (ESRD) receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.

Arm Title

Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

TAK-954

Intervention Description

TAK-954 intravenous infusion.

Primary Outcome Measure Information:

Title

Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)

Time Frame

Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion

Title

Groups A, C and D; AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for TAK-954 (Free and Total)

Time Frame

Day 1 pre-infusion and at multiple time points (up to 72 hours) post-infusion

Title

Groups A, C and D; AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Free and Total)

Time Frame

Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion

Title

Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total)

Time Frame

Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion

Title

Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine

Time Frame