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Renal ImpairmentPhase 1NCT03159416

A Study of Inclisiran in Participants With Renal Impairment Compared to Participants With Normal Renal Function (ORION-7)

A Phase 1 study testing Inclisiran in people with Renal Impairment, run by The Medicines Company at 2 sites in New Zealand.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for
Renal Impairment
What is being tested?
Inclisiran
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
2 sitesNew Zealand
Study dates
22 Jun 2017to 24 Mar 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

2 sites in 1 country.

New Zealand2 sites

  • Auckland Clinical Studies Limited

    Auckland

  • Christchurch Clinical Studies Trust

    Christchurch

Other trials in New Zealand

About this study

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)

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.

Being tested
Inclisiran
Medical subject headings
Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • InclisiranDrug

    Also called ALN-PCSSC

    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.

Study groups in NCT03159416
Study groupRoleWhat they receive
Inclisiran (normal renal function)ExperimentalParticipants 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).
Receives: Drug: Inclisiran
Inclisiran (mild renal impairment)ExperimentalParticipants 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.
Receives: Drug: Inclisiran
Inclisiran (moderate renal impairment)ExperimentalParticipants 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.
Receives: Drug: Inclisiran
Inclisiran (severe renal impairment)ExperimentalParticipants 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.
Receives: Drug: Inclisiran

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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

  2. 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.

    Measured: 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

  3. 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.

    Measured: 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

  4. 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.

    Measured: 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

  5. 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.

    Measured: 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

  6. 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.

    Measured: 0 up to 6 hours, 6 up to 12 hours, 12 up to 24 hours, and 24 up to 48 hour post-dose intervals

  7. 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.

    Measured: 0 up to 6 hours, 6 up to 12 hours, 12 up to 24 hours, and 24 up to 48 hour post-dose intervals

  8. 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.

    Measured: 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 (2)

  1. 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.

    Measured: Baseline, Day 60

  2. 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.

    Measured: Baseline, Day 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2017
  2. Study start22 Jun 2017
  3. Primary completion24 Mar 2018
  4. Study completion24 Mar 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03159416
Sponsor's protocol ID
MDCO-PCS-16-03
Status last verified
Nov 2018
First submitted
16 May 2017
Last updated
9 Nov 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 31630870

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Inclisiran in people with Renal Impairment, run by The Medicines Company at 2 sites in New Zealand.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) Of Inclisiran (time frame: 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). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03159416, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2018.

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