Phase 1
Completed N=32
A Study to Evaluate the Effect of Renal Impairment and Dialysis Treatment on the Pharmacokinetics (PK) of a Single Intravenous (IV) TAK-954
Renal impairment · Healthy Volunteers
Source: ClinicalTrials.gov NCT03296787 ↗
Enrolled (actual)
32
Serious AEs
0.0%
Results posted
Aug 2020
Primary outcomePrimary: Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free) — 2.623; 2.536; 2.660; 0.1270 nanogram per milliliter (ng/mL) — p=0.7265
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free) |
2.623; 2.536; 2.660; 0.1270; 0.1282; 0.1572 | 0.7265 |
| PRIMARY 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) |
22.25; 24.91; 28.62; 1.078; 1.259; 1.690 | 0.3600 |
| PRIMARY 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) |
24.39; 30.00; 34.28; 1.184; 1.516; 2.025 | 0.0998 |
| PRIMARY Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total) |
25.43; 34.90; 38.59; 1.234; 1.749; 2.320 | 0.0038 sig |
| PRIMARY Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine |
0.03797; 0.01763; 0.01190 | — |
| PRIMARY Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 1 |
0.0003489 | — |
| PRIMARY Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2 |
0.001240 | — |
| PRIMARY Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine |
19.00; 8.808; 5.953 | — |
| PRIMARY Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 1 |
0.1739 | — |
| PRIMARY Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 2 |
0.6190 | — |
| PRIMARY Groups A, C and D; CLR: Renal Clearance for TAK-954 |
2.629; 1.255; 0.6836 | — |
| PRIMARY Group E; CLR: Renal Clearance for TAK-954 in Period 1 |
0.03192 | — |
| PRIMARY Group E; CLR: Renal Clearance for TAK-954 in Period 2 |
0.08330 | — |
| PRIMARY Group E; CLD: Clearance of Dialysate for TAK-954 in Period 2 |
1.368 | — |
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT03296787). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.