HyperlipidemiaPhase 1NCT02275156

Estimation Study to Assess the Effect of Severe Renal Impairment and End-stage Renal Disease Hemodialysis on the Pharmacokinetics of Evolocumab

A Phase 1 study testing Evolocumab in people with Hyperlipidemia and Mixed Dyslipidemia, run by Amgen at 1 site in United States.

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

The primary objective of this study was to evaluate the pharmacokinetics of evolocumab after a single 140 mg subcutaneous (SC) dose in aduts with normal renal function or severe renal impairment or end-stage renal disease (ESRD) receiving hemodialysis. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Hyperlipidemia, Mixed Dyslipidemia
What is being tested?: Evolocumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 1 siteUnited States
Study dates: 19 Aug 2014to 19 Dec 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Body mass index (BMI) of ≥ 18 and ≤ 35 kg/m² at screening.
Subjects will have low-density lipoprotein cholesterol (LDL-C) of 70-190 mg/dL (inclusive) and on statin therapy.
Other inclusion criteria may apply.

Who cannot join

Subject with current or prior history of statin intolerance
Subject has previously received Evolocumab (AMG 145) or any other investigational therapy directed against PCSK9
Known substance abuse (eg, alcohol, licit or illicit drugs) within 12 months of day -1
Testing positive for alcohol and/or drugs-of-abuse at screening, day -1, or day 1 (alcohol only)
History of hypersensitivity or allergic reaction to mammalian-derived drug preparations
Known sensitivity to any of the active substances or their excipients to be administered during dosing, eg, carboxymethylcellulose
Other exclusion criteria may apply.

Trial locations and contacts

1 site in 1 country.

United States1 site

Research Site
Denver, Colorado, 80230

Other trials in United States

About this study

Official title: Phase 1, Open-label, Single-dose Study of Evolocumab (AMG 145) Administered Subcutaneously to Subjects With Normal Renal Function or Severe Renal Impairment or End Stage Renal Disease Receiving Hemodialysis

Conditions: Hyperlipidemia, Mixed Dyslipidemia
Being tested: Evolocumab
Keywords: Subjects with normal renal function or severe renal impairment (RI) or end stage renal disease (ESRD) receiving hemodialysis
Medical subject headings: Hyperlipidemias, Renal Insufficiency, Kidney Failure, Chronic

What participants receive

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

EvolocumabBiological
Also called AMG 145, Repatha
Administered by subcutaneous injection

Study groups in NCT02275156
Study group	Role	What they receive
Evolocumab	Experimental	Participants received a single 140 mg dose of evolocumab subcutaneously on Day 1. Receives: Biological: Evolocumab

What is being measured

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

Maximum Observed Serum Concentration (Cmax) of Evolocumab
Serum concentrations of evolocumab were measured by a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) of the assay was 800 ng/mL.
Measured: Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) for Evolocumab
Measured: Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose

Secondary outcomes (5)

Number of Participants With Adverse Events
The severity of each adverse event was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria:
- fatal;
- life threatening (places the participant at immediate risk of death);
- requires in patient hospitalization or prolongation of existing hospitalization;
- results in persistent or significant disability/incapacity;
- congenital anomaly/birth defect;
- other medically important serious event.
The investigator assessed whether each adverse event was possibly related to the study drug.
Measured: From the first dose of study drug up until Day 57
Number of Participants With Clinically Relevant Vital Sign or Clinical Laboratory Changes
The investigator reviewed vital signs and laboratory test results and determined whether an abnormal value in an individual participant represented a clinically significant change from the participant's baseline values.
Measured: 57 days
Number of Participants With Anti-evolocumab Antibodies
Blood samples were tested using an electrochemiluminescence-based bridging immunoassay to detect antibodies capable of binding to evolocumab.
Measured: 57 days
Area Under the Effect Curve From Baseline to Day 57 (AUECday1-57) for Low-density Lipoprotein Cholesterol (LDL-C)
The derived log-transformed AUECday1-57 for direct LDL-C was analyzed using a mixed-effect analysis of variance model. Log-transformed baseline LDL-C was the covariate.
Measured: 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
Mean Percent Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)
Serum PCSK9 concentrations were determined using a qualified ELISA. The LLOQ of the assay was 15 ng/mL.
Log-transformed baseline PCSK9 was included in the model as a covariate and participant as a random effect.
Measured: Baseline and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose

Timeline

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

19 Aug 201419 Dec 2014

First posted27 Oct 2014 (estimated)
Study start19 Aug 2014
Primary completion19 Dec 2014
Study completion19 Dec 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for HyperlipidemiaStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02275156
Sponsor's protocol ID: 20140213
Status last verified: Nov 2022
First submitted: 15 Jul 2014
Last updated: 7 Nov 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.
PubMed 29353350
Lee E, Gibbs JP, Emery MG, Block G, Wasserman SM, Hamilton L, Kasichayanula S, Hanafin P, Somaratne R, Egbuna O. Influence of Renal Function on Evolocumab Exposure, Pharmacodynamics, and Safety. Clin Pharmacol Drug Dev. 2019 Apr;8(3):281-289. doi: 10.1002/cpdd.650. Epub 2019 Jan 24.
PubMed 30676701

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Hyperlipidemia trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1, Open-label, Single-dose Study of Evolocumab (AMG 145) Administered Subcutaneously to Subjects With Normal Renal Function or Severe Renal Impairment or End Stage Renal Disease Receiving Hemodialysis
ClinicalTrials.gov ID: NCT02275156
Acronym / sponsor ID: 20140213
Conditions: Hyperlipidemia, Mixed Dyslipidemia
Keywords: Subjects with normal renal function or severe renal impairment (RI) or end stage renal disease (ESRD) receiving hemodialysis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 19 Aug 2014 (actual)
Primary completion: 19 Dec 2014 (actual)
Study completion: 19 Dec 2014 (actual)
First posted: 27 Oct 2014 (estimated)
Results: Posted 29 Jan 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Evolocumab	Experimental	Biological: EvolocumabParticipants received a single 140 mg dose of evolocumab subcutaneously on Day 1.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Body mass index (BMI) of ≥ 18 and ≤ 35 kg/m² at screening.
Subjects will have low-density lipoprotein cholesterol (LDL-C) of 70-190 mg/dL (inclusive) and on statin therapy.
Other inclusion criteria may apply.

Key exclusion criteria (7 listed)

Subject with current or prior history of statin intolerance
Subject has previously received Evolocumab (AMG 145) or any other investigational therapy directed against PCSK9
Known substance abuse (eg, alcohol, licit or illicit drugs) within 12 months of day -1
Testing positive for alcohol and/or drugs-of-abuse at screening, day -1, or day 1 (alcohol only)
History of hypersensitivity or allergic reaction to mammalian-derived drug preparations

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EvolocumabAlso: AMG 145, RepathaAdministered by subcutaneous injection	Biological	Evolocumab

Primary outcome

Maximum Observed Serum Concentration (Cmax) of Evolocumab
Time frame: Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
Serum concentrations of evolocumab were measured by a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) of the assay was 800 ng/mL.
Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) for Evolocumab
Time frame: Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose

5 secondary outcomes

Number of Participants With Adverse Events
Time frame: From the first dose of study drug up until Day 57
Number of Participants With Clinically Relevant Vital Sign or Clinical Laboratory Changes
Time frame: 57 days
Number of Participants With Anti-evolocumab Antibodies
Time frame: 57 days
Area Under the Effect Curve From Baseline to Day 57 (AUECday1-57) for Low-density Lipoprotein Cholesterol (LDL-C)
Time frame: 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
Mean Percent Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)
Time frame: Baseline and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose

Results and safety

Results posted to the registry on 29 Jan 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Normal Renal Function	6	6
Severe Renal Impairment	6	6
End Stage Renal Disease	6	6

Primary outcome: Maximum Observed Serum Concentration (Cmax) of Evolocumab

Time frame: Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose. Mean (Standard Deviation). Unit: μg/mL

Measure	Normal Renal Function n = 6	Severe Renal Impairment n = 6	End Stage Renal Disease n = 6
Value	21.3 (9.00)	15.1 (8.86)	11.7 (7.20)

Population analysed: Pharmacokinetic (PK) analysis set (all participants for whom at least 1 PK parameter could be adequately estimated)

Primary outcome: Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) for Evolocumab

Time frame: Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose. Mean (Standard Deviation). Unit: day*μg/mL

Measure	Normal Renal Function n = 6	Severe Renal Impairment n = 6	End Stage Renal Disease n = 6
Value	185 (92.5)	141 (109)	102 (80.1)

Population analysed: PK analysis set

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of study drug up until Day 57. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Evolocumab 140 mg - Normal Renal Function	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Evolocumab 140 mg - Severe RI	1 of 6 (16.7%)	1 of 6 (16.7%)	Not reported
Evolocumab 140 mg - ESRD Requiring Hemodialysis	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
Evolocumab 140 mg - Total	1 of 18 (5.6%)	4 of 18 (22.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 29353350Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.
Background: PubMed 30676701Lee E, Gibbs JP, Emery MG, Block G, Wasserman SM, Hamilton L, Kasichayanula S, Hanafin P, Somaratne R, Egbuna O. Influence of Renal Function on Evolocumab Exposure, Pharmacodynamics, and Safety. Clin Pharmacol Drug Dev. 2019 Apr;8(3):281-289. doi: 10.1002/cpdd.650. Epub 2019 Jan 24.
AmgenTrials clinical trials websiteLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Evolocumab in people with Hyperlipidemia and Mixed Dyslipidemia, run by Amgen at 1 site in United States.

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 3 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 7 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Yes. Results are posted in the registry (first posted 29 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Maximum Observed Serum Concentration (Cmax) of Evolocumab (time frame: Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose). The study lists 2 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 NCT02275156, which also lists 2 linked publications.

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 7 Nov 2022.