Healthy SubjectsPhase 1NCT04189484
Pharmacodynamic Biomarkers to Support Biosimilar Development: PCSK9 Inhibitors
A Phase 1 study testing Evolocumab and Alirocumab in people with Healthy Subjects and Pharmacokinetics, run by Food and Drug Administration (FDA) at 1 site in United States.
Trial summary
This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and alirocumab across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects, Pharmacokinetics, Pharmacodynamics
- What is being tested?
- Evolocumab and Alirocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jan 2020to 7 Apr 2021
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subject signs an institutional review board (IRB)-approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization) before any study related procedures are performed.
- Subject is a healthy man or woman, 18 to 55 years of age, inclusive, who has a body mass index of 18.5 to 32 kg/m2, inclusive, at Screening.
- Subject has a LDL-C level >=100 and <=190 mg/dL inclusive, at Screening.
- Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12 lead electrocardiogram (ECG) results, and physical examination findings at Screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
- Subject must have a negative test result for alcohol and drugs of abuse at screening and Check-in (Day -1).
- Female subjects must be of non-childbearing potential or, if they are of childbearing potential, they must: 1) have been strictly abstinent for 1 month before Check in (Day -1) and agree to remain strictly abstinent for the duration of the study and for at least 1 month after the last application of study drug; OR 2) be practicing 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from at least 1 month before Check in (Day -1) until at least 1 month after the last application of study drug.
- Male subjects must agree to practice 1 highly effective method of birth control (as determined by the investigator or designee) from at least 1 month before Check in (Day-1) until at least 1 month after the last application of study drug.
- Subject is highly likely (as determined by the investigator) to comply with the protocol defined procedures as to complete the study.
Who cannot join
- Subject is taking cholesterol medication (e.g. statins).
- Subject is anemic (i.e., with hematocrit or hemoglobin less than the lower limit of normal) or has any chronic condition(s) that may impact blood sample collection.
- Subject has had previous exposure to the biologic evolocumab or alirocumab.
- Subject has a history of asthma.
- Subject has a history of anaphylaxis from environmental exposures such as peanuts or bee stings.
- Subject has an allergic history that includes urticaria, angioedema or respiratory coughing or bronchospasm.
Show all 27Show fewer
- Subject has a history of severe local reactions or generalized erythema from skin allergen testing.
- Subject has used any prescription or nonprescription drugs (including aspirin or NSAIDs and excluding oral contraceptives and acetaminophen) within 14 days or 5 half-lives (whichever is longer) or complementary and alternative medicines within 28 days before the first dose of study drug.
- Subjects are currently participating in another clinical study of an investigational drug or are have been treated with any investigational drug within 30 days or 5 half-lives (whichever is longer) of the compound.
- Subject has used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff) within 6 weeks of Screening.
- Subject has consumed alcohol, xanthine containing products (e.g., tea, coffee, chocolate, cola), caffeine, grapefruit, or grapefruit juice within 48 hours of dosing. Subjects must refrain from ingesting these throughout the study.
- Subject has any underlying disease or surgical or medical condition (e.g., cancer, human immunodeficiency virus [HIV], severe hepatic or renal impairment) that could put the subject at risk or would normally prevent participation in a clinical study. This includes subjects with any underlying medical conditions that put subjects at higher risk for coronavirus disease of 2019 (COVID-19) complications; per current Center for Disease Control and Prevention (CDC) recommendations this includes:
- People with chronic lung disease or moderate to severe asthma
- People who have serious heart conditions
- People who are immunocompromised
- Many conditions can cause a person to be immunocompromised, including cancer treatment, smoking, bone marrow or organ transplantation, immune deficiencies, poorly controlled HIV, and prolonged use of corticosteroids and other immune weakening medications
- People with severe obesity (BMI of 40 or higher)
- People with diabetes
- People with chronic kidney disease undergoing dialysis
- People with liver disease
- Subject has any signs or symptoms that are consistent with COVID-19. Per current CDC recommendations this includes subjects with the symptoms cough or shortness of breath or difficulty breathing, or at least two of the following symptoms: fever, chills, repeated shaking with chills, muscle pain, headache, sore throat or new loss of taste/smell. In addition, the subject has any other findings suggestive of COVID-19 risk in the opinion of the investigator.
- Subject tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by a molecular diagnostic test performed prior to admission.
- Subject has known or suspected allergies or sensitivities to any study drug.
- Subject has clinical laboratory test results (hematology, serum chemistry lipid panel and comprehensive metabolic panel) at Screening that are outside the reference ranges provided by the clinical laboratory and considered clinically significant by the investigator.
- Subject has a positive test result at Screening for human immunodeficiency virus (HIV) 1 or 2 antibody, hepatitis C virus load, hepatitis C virus antibodies, or hepatitis B surface antigen.
- Subject is unable or unwilling to undergo multiple venipunctures for blood sample collection because of poor tolerability or poor venous access.
- Female subjects are pregnant or lactating before enrollment in the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Spaulding Clinical Research
West Bend, Wisconsin, 53095
About this study
Official title: Pharmacodynamic Biomarkers to Support Biosimilar Development: Clinical Study 2: PCSK9 Inhibitors - Alirocumab and Evolocumab
This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and alirocumab across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies.
This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab and alirocumab ) or placebo.
Read the detailed description
This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and alirocumab, two monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies.
This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab or alirocumab) or placebo. Evolocumab doses are 21, 35, 70, and 140 mg. Reslizumab doses are 15, 25, 50, and 100 mg . Each arm will include 8 subjects (4 male and 4 female).
Subjects will be admitted for treatment on day -1 and receive a single dose of study drug or placebo on day 1. Depending on the treatment arm, subjects will remain in confinement for one week and continue follow-up through day 42, 56, or 84.
Blood samples (approximately 5 mL per sample) will be collected for determination of plasma concentrations for study drug. Additional blood samples will be collected for lipid analysis and determination of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) (5 mL per sample; pharmacodynamic measure) and exploratory proteomics analyses (5 mL per sample).
Safety evaluations will include adverse event (AE) monitoring, vital sign measurements, and physical examinations. All AEs reported by the subject or observed by the investigator or clinical research unit (CRU) staff will be recorded. Any AE reported after the informed consent is signed and before study drug application will be recorded as medical history.
- Conditions
- Healthy Subjects, Pharmacokinetics, Pharmacodynamics
- Being tested
- Evolocumab, Alirocumab, Placebo
- Keywords
- Pharmacokinetics, Pharmacodynamics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabBiological
Evolocumab 21 mg administered SC
EvolocumabBiological
Evolocumab 35 mg administered SC
EvolocumabBiological
Evolocumab 70 mg administered SC
EvolocumabBiological
Evolocumab 140 mg administered SC
AlirocumabBiological
Alirocumab 15 mg administered SC
AlirocumabBiological
Alirocumab 25 mg administered SC
AlirocumabBiological
Alirocumab 50 mg administered SC
AlirocumabBiological
Alirocumab 100 mg administered SC
PlaceboBiological
Placebo administered SC
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Evolocumab low dose | Experimental | Single dose of evolocumab 21 mg subcutaneous (SC) Receives: Biological: Evolocumab |
| Arm B: Evolocumab intermediate low dose | Experimental | Single dose of evolocumab 35 mg SC Receives: Biological: Evolocumab |
| Arm C: Evolocumab intermediate high dose | Experimental | Single dose of evolocumab 70 mg SC Receives: Biological: Evolocumab |
| Arm D: Evolocumab high dose | Experimental | Single dose of evolocumab 140 mg SC Receives: Biological: Evolocumab |
| Arm E: Alirocumab low dose | Experimental | Single dose of alirocumab 15 mg SC Receives: Biological: Alirocumab |
| Arm F: Alirocumab intermediate low dose | Experimental | Single dose of alirocumab 25 mg SC Receives: Biological: Alirocumab |
| Arm G: Alirocumab intermediate high dose | Experimental | Single dose of alirocumab 50 mg SC Receives: Biological: Alirocumab |
| Arm H: Alirocumab high dose | Experimental | Single dose of alirocumab 100 mg SC Receives: Biological: Alirocumab |
| Arm I: Placebo | Placebo comparator | Single dose of placebo SC Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline-adjusted Area Under Effect Curve (AUEC) for LDL-C for Evolocumab and Alirocumab
The values and variability of AUEC for LDL-C at low, intermediate-low, intermediate-high, and high doses of evolocumab and alirocumab. AUEC was calculated as the baseline-subtracted area under the LDL-C concentration-time curve expressed in units of mg/(dL*day). More negative AUEC values represent greater reductions in LDL-C exposure from baseline. The standard deviation is noted in parentheses. For each subject and dose, the maximum decrease from baseline LDL-C was determined using all sampled timepoints. AUEC values were log-transformed and an ANCOVA model was used to calculate geometric means and 90% confidence intervals for each treatment group.
Measured: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Maximum Change From Baseline for LDL-C for Evolocumab and Alirocumab
The values and variability of maximum change from baseline for LDL-C at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab
Measured: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Secondary outcomes (7)
Baseline-adjusted AUEC for Apolipoprotein B (ApoB) for Evolocumab and Alirocumab
The values and variability of AUEC for ApoB at low, intermediate-low, intermediate-high, and high doses of evolocumab and alirocumab. AUEC was calculated as the baseline-subtracted area under the ApoB concentration-time curve expressed in units of mg/(dL*day). More negative AUEC values represent greater reductions in ApoB exposure from baseline. The standard deviation is noted in parentheses. For each subject and dose, the maximum decrease from baseline ApoB was determined using all sampled timepoints. AUEC values were log-transformed and an ANCOVA model was used to calculate geometric means and 90% confidence intervals for each treatment group.
Measured: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Maximum Change From Baseline for apoB for Evolocumab and Alirocumab
The values and variability of maximal difference at a single time-point for ApoB at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab
Measured: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Maximum Concentration (Cmax) for Evolocumab and Alirocumab
The values and variability of Cmax at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab
Measured: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8,12, 24, hours post-dose; once on Day 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Area Under the Curve (AUC) for Evolocumab and Alirocumab
The values and variability of AUC at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab
Measured: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8,12, 24, hours post-dose; once on Day 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Dose-response Parameters (Slope) for LDL-C Area Under the Effect Curve Models for Evolocumab and Alirocumab
Model parameter (slope) for LDL-C area under the effect curve model: Mean slope value calculated after combining data from low, intermediate low, intermediate high, and high doses of evolocumab or alirocumab with placebo data. The units of measure for slope are mg/dL•day / (mg dose).
Measured: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Pharmacodynamic Model Parameter, Maximum Effect (Emax), for LDL-C Maximum Change From Baseline Models With Evolocumab and Alirocumab
Model parameter (Emax) for LDL-C maximum change from baseline curve models calculated after combining data from low, intermediate low, intermediate high, and high doses of evolocumab or alirocumab with placebo data.
Measured: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for LDL-C Maximum Change From Baseline Models With Evolocumab and Alirocumab
Model parameter (ED50) for LDL-C maximum change from baseline curve models calculated after combining data from low, intermediate low, intermediate high, and high doses of evolocumab or alirocumab with placebo data.
Measured: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2019
- Study start7 Jan 2020
- Primary completion7 Apr 2021
- Study completion7 Apr 2021
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.
- Other trials for Healthy SubjectsStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab or alirocumab) or placebo
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Food and Drug Administration (FDA)
- Sponsor type
- US federal agency
- Collaborators
- Spaulding Clinical Research LLC
- Responsible party
- Sponsor
- Investigators
- Colleen Nalepinski, MPAS, PA-C, Principal investigator, Spaulding Clinical Research LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04189484
- Sponsor's protocol ID
- SCR-007
- Status last verified
- Nov 2023
- First submitted
- 2 Dec 2019
- Last updated
- 22 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Plan is to make data from the study publicly available as a part of manuscript publication. In addition, the protocol and statistical analysis plan will be made available online at this site as well as any eventual publications.
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacodynamic Biomarkers to Support Biosimilar Development: Clinical Study 2: PCSK9 Inhibitors - Alirocumab and Evolocumab
- ClinicalTrials.gov ID
- NCT04189484
- Acronym / sponsor ID
- SCR-007
- Conditions
- Healthy Subjects, Pharmacokinetics, Pharmacodynamics
- Keywords
- Pharmacokinetics, Pharmacodynamics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Food and Drug Administration (FDA)US federal agency
- Collaborators
- Spaulding Clinical Research LLC
- Study start
- 7 Jan 2020 (actual)
- Primary completion
- 7 Apr 2021 (actual)
- Study completion
- 7 Apr 2021 (actual)
- First posted
- 6 Dec 2019 (actual)
- Results
- Posted 22 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and alirocumab across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies.
This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab and alirocumab ) or placebo.
Detailed description
This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and alirocumab, two monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies.
This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab or alirocumab) or placebo. Evolocumab doses are 21, 35, 70, and 140 mg. Reslizumab doses are 15, 25, 50, and 100 mg . Each arm will include 8 subjects (4 male and 4 female).
Subjects will be admitted for treatment on day -1 and receive a single dose of study drug or placebo on day 1. Depending on the treatment arm, subjects will remain in confinement for one week and continue follow-up through day 42, 56, or 84.
Blood samples (approximately 5 mL per sample) will be collected for determination of plasma concentrations for study drug. Additional blood samples will be collected for lipid analysis and determination of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) (5 mL per sample; pharmacodynamic measure) and exploratory proteomics analyses (5 mL per sample).
Safety evaluations will include adverse event (AE) monitoring, vital sign measurements, and physical examinations. All AEs reported by the subject or observed by the investigator or clinical research unit (CRU) staff will be recorded. Any AE reported after the informed consent is signed and before study drug application will be recorded as medical history.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 9
- Model description
- Subjects will be randomized to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab or alirocumab) or placebo
| Arm | Type | Receives |
|---|---|---|
| Arm A: Evolocumab low dose | Experimental | Biological: EvolocumabSingle dose of evolocumab 21 mg subcutaneous (SC) |
| Arm B: Evolocumab intermediate low dose | Experimental | Biological: EvolocumabSingle dose of evolocumab 35 mg SC |
| Arm C: Evolocumab intermediate high dose | Experimental | Biological: EvolocumabSingle dose of evolocumab 70 mg SC |
| Arm D: Evolocumab high dose | Experimental | Biological: EvolocumabSingle dose of evolocumab 140 mg SC |
| Arm E: Alirocumab low dose | Experimental | Biological: AlirocumabSingle dose of alirocumab 15 mg SC |
| Arm F: Alirocumab intermediate low dose | Experimental | Biological: AlirocumabSingle dose of alirocumab 25 mg SC |
| Arm G: Alirocumab intermediate high dose | Experimental | Biological: AlirocumabSingle dose of alirocumab 50 mg SC |
| Arm H: Alirocumab high dose | Experimental | Biological: AlirocumabSingle dose of alirocumab 100 mg SC |
| Arm I: Placebo | Placebo comparator | Biological: PlaceboSingle dose of placebo SC |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Subject signs an institutional review board (IRB)-approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization) before any study related procedures are performed.
- Subject is a healthy man or woman, 18 to 55 years of age, inclusive, who has a body mass index of 18.5 to 32 kg/m2, inclusive, at Screening.
- Subject has a LDL-C level >=100 and <=190 mg/dL inclusive, at Screening.
- Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12 lead electrocardiogram (ECG) results, and physical examination findings at Screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
- Subject must have a negative test result for alcohol and drugs of abuse at screening and Check-in (Day -1).
Key exclusion criteria (27 listed)
- Subject is taking cholesterol medication (e.g. statins).
- Subject is anemic (i.e., with hematocrit or hemoglobin less than the lower limit of normal) or has any chronic condition(s) that may impact blood sample collection.
- Subject has had previous exposure to the biologic evolocumab or alirocumab.
- Subject has a history of asthma.
- Subject has a history of anaphylaxis from environmental exposures such as peanuts or bee stings.
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 |
|---|---|---|
| EvolocumabEvolocumab 21 mg administered SC | Biological | Arm A: Evolocumab low dose |
| EvolocumabEvolocumab 35 mg administered SC | Biological | Arm B: Evolocumab intermediate low dose |
| EvolocumabEvolocumab 70 mg administered SC | Biological | Arm C: Evolocumab intermediate high dose |
| EvolocumabEvolocumab 140 mg administered SC | Biological | Arm D: Evolocumab high dose |
| AlirocumabAlirocumab 15 mg administered SC | Biological | Arm E: Alirocumab low dose |
| AlirocumabAlirocumab 25 mg administered SC | Biological | Arm F: Alirocumab intermediate low dose |
| AlirocumabAlirocumab 50 mg administered SC | Biological | Arm G: Alirocumab intermediate high dose |
| AlirocumabAlirocumab 100 mg administered SC | Biological | Arm H: Alirocumab high dose |
| PlaceboPlacebo administered SC | Biological | Arm I: Placebo |
Primary outcome
Baseline-adjusted Area Under Effect Curve (AUEC) for LDL-C for Evolocumab and Alirocumab
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
The values and variability of AUEC for LDL-C at low, intermediate-low, intermediate-high, and high doses of evolocumab and alirocumab. AUEC was calculated as the baseline-subtracted area under the LDL-C concentration-time curve expressed in units of mg/(dL*day). More negative AUEC values represent greater reductions in LDL-C exposure from baseline. The standard deviation is noted in parentheses. For each subject and dose, the maximum decrease from baseline LDL-C was determined using all sampled timepoints. AUEC values were log-transformed and an ANCOVA model was used to calculate geometric means and 90% confidence intervals for each treatment group.
Maximum Change From Baseline for LDL-C for Evolocumab and Alirocumab
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
The values and variability of maximum change from baseline for LDL-C at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab
7 secondary outcomes
Baseline-adjusted AUEC for Apolipoprotein B (ApoB) for Evolocumab and Alirocumab
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Maximum Change From Baseline for apoB for Evolocumab and Alirocumab
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Maximum Concentration (Cmax) for Evolocumab and Alirocumab
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8,12, 24, hours post-dose; once on Day 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Area Under the Curve (AUC) for Evolocumab and Alirocumab
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8,12, 24, hours post-dose; once on Day 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Dose-response Parameters (Slope) for LDL-C Area Under the Effect Curve Models for Evolocumab and Alirocumab
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Pharmacodynamic Model Parameter, Maximum Effect (Emax), for LDL-C Maximum Change From Baseline Models With Evolocumab and Alirocumab
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for LDL-C Maximum Change From Baseline Models With Evolocumab and Alirocumab
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Plan is to make data from the study publicly available as a part of manuscript publication. In addition, the protocol and statistical analysis plan will be made available online at this site as well as any eventual publications.
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Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
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.
Colleen Nalepinski, MPAS, PA-C principal investigator
Spaulding Clinical Research LLC
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 and Alirocumab in people with Healthy Subjects and Pharmacokinetics, run by Food and Drug Administration (FDA) 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 8 inclusion and 27 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 22 Apr 2024. 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. Some participants in this study may receive a placebo. 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 22 Apr 2024). 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?
Baseline-adjusted Area Under Effect Curve (AUEC) for LDL-C for Evolocumab and Alirocumab (time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.). 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?
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 22 Apr 2024.