Mixed Dyslipidemia, Primary Hypercholesterolemia
Conditions
Keywords
LDL-C, triglycerides, high cholesterol
Brief summary
The primary objective of this study was to assess users' ability to administer a full dose of evolocumab in a home-use setting using either an automated mini-doser (AMD) or autoinjector/pen (AI/pen).
Interventions
BIOLOGICALEvolocumab AMD
Evolocumab subcutaneous injection using a single use, disposable AMD containing 3.5 mL deliverable volume.
BIOLOGICALEvolocumab AI/pen
Evolocumab subcutaneous injection using a handheld mechanical (spring-based) prefilled AI/Pen, each containing 1.0 mL deliverable volume.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Fasting LDL-C at screening \> 85 mg/dL * Fasting triglycerides less than or equal to 400 mg/dL (4.5 mmol/L)
Exclusion criteria
* New York Heart Association (NYHA) III or IV heart failure * Uncontrolled cardiac arrhythmia * Uncontrolled hypertension * Type 1 diabetes or poorly controlled type 2 diabetes * Uncontrolled hypothyroidism or hyperthyroidism
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Full Administration of Evolocumab at Both Weeks 4 and 8 | Weeks 4 and 8 | Self-administration of evolocumab was assessed by a telephone interview at Weeks 4 and 8. Each participant was asked about all attempted injection(s) and if the injection was administered in part, full, or none at all. Results only include full administrations that occurred inside the prespecified visit window. |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
Countries
Canada, United States
Participant flow
Recruitment details
Eligible patients were men and women ≥ 18 and ≤ 80 years of age with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 85 mg/dL, fasting triglycerides ≤ 400 mg/dL and on a stable dose of a statin with or without ezetimibe for at least 4 weeks. The first patient enrolled on 11 July 2013 and the last patient enrolled on 20 September 2013.
Pre-assignment details
Randomization was stratified on the basis of screening LDL-C concentration (\< 130 mg/dL \[3.4 mmol/L\] or ≥ 130 mg/dL). Participants were trained by study site staff to prepare and self-administer the study drug.
Participants by arm
| Arm | Count |
|---|---|
| Evolocumab AMD Participants received evolocumab 420 mg once a month subcutaneously using an automated mini-doser (AMD) (one 3.5 mL injection) for 8 weeks (Day 1, Week 4, and Week 8). | 82 |
| Evolocumab AI/Pen Participants received evolocumab 420 mg once a month subcutaneously using an autoinjector/pen (AI/pen) (three 1.0 mL injections) for 8 weeks (Day 1, Week 4, and Week 8). | 82 |
| Total | 164 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 5 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Evolocumab AMD | Evolocumab AI/Pen | Total |
|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 10.5 | 59.2 years STANDARD_DEVIATION 10 | 59.7 years STANDARD_DEVIATION 10.2 |
| LDL-C Concentration | 115.3 mg/dL STANDARD_DEVIATION 27 | 117.3 mg/dL STANDARD_DEVIATION 23.9 | 116.3 mg/dL STANDARD_DEVIATION 25.4 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 4 participants | 3 participants | 7 participants |
| Race/Ethnicity, Customized Black or African American | 6 participants | 2 participants | 8 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 participants | 6 participants | 10 participants |
| Race/Ethnicity, Customized Mixed Race | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 78 participants | 76 participants | 154 participants |
| Race/Ethnicity, Customized Other | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized White | 69 participants | 75 participants | 144 participants |
| Sex: Female, Male Female | 39 Participants | 39 Participants | 78 Participants |
| Sex: Female, Male Male | 43 Participants | 43 Participants | 86 Participants |
| Stratification Factor: LDL-C Level < 130 mg/dL | 60 participants | 59 participants | 119 participants |
| Stratification Factor: LDL-C Level ≥ 130 mg/dL | 22 participants | 23 participants | 45 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 82 | 0 / 82 |
| serious Total, serious adverse events | 0 / 82 | 1 / 82 |
Outcome results
Primary
Percentage of Participants With Full Administration of Evolocumab at Both Weeks 4 and 8
Self-administration of evolocumab was assessed by a telephone interview at Weeks 4 and 8. Each participant was asked about all attempted injection(s) and if the injection was administered in part, full, or none at all. Results only include full administrations that occurred inside the prespecified visit window.
Time frame: Weeks 4 and 8
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evolocumab AMD | Percentage of Participants With Full Administration of Evolocumab at Both Weeks 4 and 8 | 93.9 Percentage of participants |
| Evolocumab AI/Pen | Percentage of Participants With Full Administration of Evolocumab at Both Weeks 4 and 8 | 91.5 Percentage of participants |
95% CI: [-11.2, 6.1]
Secondary
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Evolocumab AMD | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -67.9 percent change | Standard Error 2.4 |
| Evolocumab AI/Pen | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -64.5 percent change | Standard Error 2.4 |
95% CI: [-2.9, 9.7]