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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03159416




Registration number
NCT03159416
Ethics application status
Date submitted
16/05/2017
Date registered
18/05/2017
Date last updated
9/11/2018

Titles & IDs
Public title
A Study of Inclisiran in Participants With Renal Impairment Compared to Participants With Normal Renal Function (ORION-7)
Scientific 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)
Secondary ID [1] 0 0
MDCO-PCS-16-03
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Impairment 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Inclisiran

Experimental: Inclisiran (normal renal function) - Participants will receive a single dose of 300 milligram (mg) inclisiran administered by SC injection on Day 1. Normal renal function is defined as estimated creatinine clearance (CrCl) of =90 milliliter (mL)/minute (min).

Experimental: Inclisiran (mild renal impairment) - Participants will receive a single dose of 300 mg inclisiran administered by SC injection on Day 1. Mild renal impairment is defined as CrCl ranging from 60 to 89 mL/min.

Experimental: Inclisiran (moderate renal impairment) - Participants will receive a single dose of 300 mg inclisiran administered by SC injection on Day 1. Moderate renal impairment is defined as CrCl ranging from 30 to 59 mL/min.

Experimental: Inclisiran (severe renal impairment) - Participants will receive a single dose of 300 mg inclisiran administered by SC injection on Day 1. Severe renal impairment is defined as CrCl ranging from 15 to 29 mL/min.


Treatment: Drugs: Inclisiran
Inclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) Of Inclisiran - Measurement of effect of renal impairment on PK of inclisiran by assessment of Cmax. Serial blood samples will be collected for the analysis. PK parameters will be determined from the plasma concentration-time profiles using a noncompartmental approach.
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
Pharmacokinetics: Tmax And t1/2 Of Inclisiran - Measurement of effect of renal impairment on PK of inclisiran by assessment of time to reach maximum plasma concentration (Tmax) and time for inclisiran to reach half of its initial value (t1/2). Serial blood samples will be collected for the analysis. PK parameters will be determined from the plasma concentration-time profiles using a noncompartmental approach.
Timepoint [2] 0 0
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
Primary outcome [3] 0 0
Pharmacokinetics: AUC0-24, AUC0-48, And AUC0-inf Of Inclisiran - Measurement of effect of renal impairment on PK of inclisiran by assessment of area under the curve of the plasma concentration (AUC) from time 0 to 24 hours (AUC0-24), from time 0 to 48 hours (AUC0-48), and from time 0 extrapolated to infinity (AUC0-inf). Serial blood samples will be collected for the analysis. PK parameters will be determined from the plasma concentration-time profiles using a noncompartmental approach.
Timepoint [3] 0 0
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
Primary outcome [4] 0 0
Pharmacokinetics: Apparent Total Clearance (CL/F) Following SC Administration Of Inclisiran - Measurement of effect of renal impairment on PK of inclisiran by assessment of CL/F. Serial blood samples will be collected for the analysis. PK parameters will be determined from the plasma concentration-time profiles using a noncompartmental approach.
Timepoint [4] 0 0
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
Primary outcome [5] 0 0
Pharmacokinetics: Vd/F During The Terminal Elimination Phase Following SC Administration Of Inclisiran - Measurement of effect of renal impairment on PK of inclisiran by assessment of apparent volume of distribution (Vd/F) of inclisiran during the terminal elimination phase. Serial blood samples will be collected for the analysis. PK parameters will be determined from the plasma concentration-time profiles using a noncompartmental approach.
Timepoint [5] 0 0
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
Primary outcome [6] 0 0
Pharmacokinetics: Amount Excreted Unchanged In Urine (Ae) Of Inclisiran Over 48 Hours Post-Dose - Measurement of effect of renal impairment on PK of inclisiran by assessment of Ae of inclisiran. Pooled urine samples will be used for the analysis.
Timepoint [6] 0 0
0 up to 6 hours, 6 up to 12 hours, 12 up to 24 hours, and 24 up to 48 hour post-dose intervals
Primary outcome [7] 0 0
Pharmacokinetics: Fraction Excreted (Fe) Of Inclisiran - Measurement of effect of renal impairment on PK of inclisiran by assessment of the urinary recovery rate over a specific collection interval (Fe), calculated as 100*Ae/Dose. Pooled urine samples will be used for the analysis.
Timepoint [7] 0 0
0 up to 6 hours, 6 up to 12 hours, 12 up to 24 hours, and 24 up to 48 hour post-dose intervals
Primary outcome [8] 0 0
Pharmacokinetics: Renal Clearance (CLr) Of Inclisiran - Measurement of effect of renal impairment on PK of inclisiran by assessment of CLr, calculated as Ae/AUC0-48 plasma. CLr will be calculated if possible (for example, if the percent of unchanged drug excreted in urine exceeds 20%). Pooled urine samples will be used for the analysis.
Timepoint [8] 0 0
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 outcome [1] 0 0
Change From Baseline In Lipids And Lipoproteins At Day 60 - Pharmacodynamic effects of inclisiran on lipids and lipoproteins (total cholesterol, triglycerides, and high-density lipoprotein cholesterol, calculated and measured by beta-quant low-density lipoprotein cholesterol [LDL-C]) will be measured as a percentage of change from baseline. Lipids and lipoproteins will be measured at baseline, 4, 48, 96 (Day 4), and 168 (Day 7) hours, and Day 30 and Day 60.
Timepoint [1] 0 0
Baseline, Day 60
Secondary outcome [2] 0 0
Change From Baseline In PCSK9 At Day 60 - Pharmacodynamic effects of inclisiran on PCSK9 will be measured as a percentage of change from baseline. PCSK9 protein levels will be measured at baseline, 4, 48, 96 (Day 4), and 168 (Day 7) hours, and Day 30 and Day 60.
Timepoint [2] 0 0
Baseline, Day 60

Eligibility
Key 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
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
The Medicines Company
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03159416
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Richard Robson, PhD
Address 0 0
Christchurch Clinical Studies Trust
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications