Clinical trial NCT03159416: A Study of Inclisiran in Participants With Renal Impairment Compared to Participants With Normal Renal Function (ORION-7)
Official title: A Single-Dose, Open-Label, Parallel-Group Study to Assess the Pharmacokinetics of Inclisiran in Subjects With Renal Impairment Compared to Subjects With Normal Renal Function (ORION-7)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: The Medicines Company
Sponsor class: INDUSTRY
First posted: 2017-05-18
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a Phase I, single-dose, open-label trial to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of a single dose of inclisiran subcutaneous (SC) injection in participants with mild, moderate, and severe renal impairment compared to participants with normal renal function.


Eligibility criteria: Inclusion Criteria:

* Male and female participants 18 to 80 years of age
* Participants should be qualified for inclusion based upon estimated CrCl ranges for normal renal function group and mild, moderate, and severe renal impairment groups

Exclusion Criteria:

* Participants with acute renal disease and/or history of renal transplant
* Urinary incontinence without catheterization
* Participants requiring hemodialysis
* Participants with LDL-C \<60 mg/deciliter (dL) (or less than 1.55 millimoles/liter \[mmol/L\])
* Participants with Amyloid Kidney (if known by pathology)
* Participants with any significant hepatic, cardiac, or pulmonary disease or participants who are clinically nephritic

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) Of Inclisiran
timeFrame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose and Day 4, Day 7, Day 14, and Day 30 post-dose
measure: Pharmacokinetics: Tmax And t1/2 Of Inclisiran
timeFrame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose and Day 4, Day 7, Day 14, and Day 30 post dose
measure: Pharmacokinetics: AUC0-24, AUC0-48, And AUC0-inf Of Inclisiran
timeFrame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose and Day 4, Day 7, Day 14, and Day 30 post dose
measure: Pharmacokinetics: Apparent Total Clearance (CL/F) Following SC Administration Of Inclisiran
timeFrame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose and Day 4, Day 7, Day 14, and Day 30 post dose
measure: Pharmacokinetics: Vd/F During The Terminal Elimination Phase Following SC Administration Of Inclisiran
timeFrame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose and Day 4, Day 7, Day 14, and Day 30 post dose
measure: Pharmacokinetics: Amount Excreted Unchanged In Urine (Ae) Of Inclisiran Over 48 Hours Post-Dose
timeFrame: 0 up to 6 hours, 6 up to 12 hours, 12 up to 24 hours, and 24 up to 48 hour post-dose intervals
measure: Pharmacokinetics: Fraction Excreted (Fe) Of Inclisiran
timeFrame: 0 up to 6 hours, 6 up to 12 hours, 12 up to 24 hours, and 24 up to 48 hour post-dose intervals
measure: Pharmacokinetics: Renal Clearance (CLr) Of Inclisiran
timeFrame: 0 up to 6 hours, 6 up to 12 hours, 12 up to 24 hours, and 24 up to 48 hour post-dose intervals
Secondary outcomes:
measure: Change From Baseline In Lipids And Lipoproteins At Day 60
timeFrame: Baseline, Day 60
measure: Change From Baseline In PCSK9 At Day 60
timeFrame: Baseline, Day 60
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies Limited
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust
Study officials:
affiliation: Christchurch Clinical Studies Trust
name: Richard Robson, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wright RS, Collins MG, Stoekenbroek RM, Robson R, Wijngaard PLJ, Landmesser U, Leiter LA, Kastelein JJP, Ray KK, Kallend D. Effects of Renal Impairment on the Pharmacokinetics, Efficacy, and Safety of Inclisiran: An Analysis of the ORION-7 and ORION-1 Studies. Mayo Clin Proc. 2020 Jan;95(1):77-89. doi: 10.1016/j.mayocp.2019.08.021. Epub 2019 Oct 17.