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

Takeda

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers; Renal Impairment

Treatments: Drug: TAK-954

Study type: Interventional

Funder types: Industry

Identifiers

NCT03296787

TAK-954-1007

2017-000715-16 (EudraCT Number)

U1111-1196-9206 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. 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).

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.

3. 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).

4. 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

1. 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.

2. 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.

3. 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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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32 participants in 5 patient groups

Group A TAK-954 0.2 mg: Healthy Participants

Experimental group

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.

Treatment:

Drug: TAK-954

Group B TAK-954 0.2 mg: Mild Renal Impairment

Experimental group

Description:

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

Treatment:

Drug: TAK-954

Group C TAK-954 0.2 mg: Moderate Renal Impairment

Experimental group

Description:

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

Treatment:

Drug: TAK-954

Group D TAK-954 0.2 mg: Severe Renal Impairment

Experimental group

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.

Treatment:

Drug: TAK-954

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

Experimental group

Description:

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.

Treatment:

Drug: TAK-954