Study to Assess in Home Use of Evolocumab (AMG 145) Administration Using Either an Automated Mini-doser or a Prefilled Autoinjector/Pen

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01879319
• Collaborator: (none)
• Enrollment: 164
• Locations: 27
• Arms: 2
• Duration (Months): 5
• Patients Per Site: 6.1
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Primary Hypercholesterolemia; Mixed Dyslipidemia	Biological: Evolocumab AMD; Biological: Evolocumab AI/pen	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 164 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized Study in Subjects With Primary Hypercholesterolemia or Mixed Dyslipidemia to Assess Subjects' Ability to Administer a Full Dose of Evolocumab (AMG 145) in Home-use, Using Either a 3.5 mL Personal Injector or a Prefilled Autoinjector/Pen.
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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). Participants self-administered evolocumab in the clinic on Day 1 under supervision and then self-administered in a home setting at Weeks 4 and 8.	Biological: Evolocumab AMD; Evolocumab subcutaneous injection using a single use, disposable AMD containing 3.5 mL deliverable volume.; Other Names: AMG 145 Repatha
Experimental: 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). Participants self-administered evolocumab in the clinic on Day 1 under supervision and then self-administered in a home setting at Weeks 4 and 8.	Biological: Evolocumab AI/pen; Evolocumab subcutaneous injection using a handheld mechanical (spring-based) prefilled AI/Pen, each containing 1.0 mL deliverable volume.; Other Names: AMG-145 Repatha

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Phoenix	Arizona	United States	85020
2	Research Site	Encino	California	United States	91436
3	Research Site	Thousand Oaks	California	United States	91360
4	Research Site	Tustin	California	United States	92780
5	Research Site	Ventura	California	United States	93003
6	Research Site	Port Charlotte	Florida	United States	33952
7	Research Site	Saint Augustine	Florida	United States	32086
8	Research Site	Atlanta	Georgia	United States	30328
9	Research Site	Atlanta	Georgia	United States	30342
10	Research Site	Gainesville	Georgia	United States	30501
11	Research Site	Lexington	Kentucky	United States	40504
12	Research Site	Lewiston	Maine	United States	04240
13	Research Site	Ayer	Massachusetts	United States	01432
14	Research Site	Manlius	New York	United States	13104
15	Research Site	Cadiz	Ohio	United States	43907
16	Research Site	Marion	Ohio	United States	43302
17	Research Site	Duncansville	Pennsylvania	United States	16635
18	Research Site	Lansdale	Pennsylvania	United States	19446
19	Research Site	Jackson	Tennessee	United States	38305
20	Research Site	Nashville	Tennessee	United States	37203
21	Research Site	Austin	Texas	United States	78731
22	Research Site	Dallas	Texas	United States	75231
23	Research Site	Burnaby	British Columbia	Canada	V5G 1T4
24	Research Site	London	Ontario	Canada	N5W 6A2
25	Research Site	Sarnia	Ontario	Canada	N7T 4X3
26	Research Site	Toronto	Ontario	Canada	M9V 4B4
27	Research Site	Pointe-Claire	Quebec	Canada	H9R 3J1

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01879319
• Other Study ID Numbers: 20120356
• First Posted: Jun 17, 2013
• Last Update Posted: Dec 23, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Amgen: LDL-C, triglycerides, high cholesterol
• Additional relevant MeSH terms: Hypercholesterolemia; Dyslipidemias; Evolocumab; Antibodies, Monoclonal

Study Results

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 Detail	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.

Arm/Group Title	Evolocumab AMD	Evolocumab AI/Pen
Arm/Group Description	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). Participants self-administered evolocumab in the clinic on Day 1 under supervision and then self-administered in a home setting at Weeks 4 and 8.	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). Participants self-administered evolocumab in the clinic on Day 1 under supervision and then self-administered in a home setting at Weeks 4 and 8.
Period Title: Overall Study
STARTED	82	82
Received Treatment	82	82
COMPLETED	80	77
NOT COMPLETED	2	5

Baseline Characteristics

Arm/Group Title	Evolocumab AMD	Evolocumab AI/Pen	Total
Arm/Group Description	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).	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).	Total of all reporting groups
Overall Participants	82	82	164
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.1 (10.5)	59.2 (10.0)	59.7 (10.2)
Sex: Female, Male (Count of Participants)
Female	39 47.6%	39 47.6%	78 47.6%
Male	43 52.4%	43 52.4%	86 52.4%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	1 1.2%	1 1.2%	2 1.2%
Asian	4 4.9%	3 3.7%	7 4.3%
Black or African American	6 7.3%	2 2.4%	8 4.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
White	69 84.1%	75 91.5%	144 87.8%
Other	2 2.4%	0 0%	2 1.2%
Mixed Race	0 0%	1 1.2%	1 0.6%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	4 4.9%	6 7.3%	10 6.1%
Not Hispanic or Latino	78 95.1%	76 92.7%	154 93.9%
Stratification Factor: LDL-C Level (participants) [Number]
< 130 mg/dL	60 73.2%	59 72%	119 72.6%
≥ 130 mg/dL	22 26.8%	23 28%	45 27.4%
LDL-C Concentration (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	115.3 (27.0)	117.3 (23.9)	116.3 (25.4)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Full Administration of Evolocumab at Both Weeks 4 and 8
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Evolocumab AMD	Evolocumab AI/Pen
Arm/Group Description	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).	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).
Measure Participants	82	82
Number (95% Confidence Interval) [Percentage of participants]	93.9 114.5%	91.5 111.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Evolocumab AMD, Evolocumab AI/Pen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -11.2 to 6.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time Frame	Baseline and Weeks 10 and 12

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Evolocumab AMD	Evolocumab AI/Pen
Arm/Group Description	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).	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).
Measure Participants	82	82
Least Squares Mean (Standard Error) [percent change]	-67.9 (2.4)	-64.5 (2.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Evolocumab AMD, Evolocumab AI/Pen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; -2.9 to 9.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.2
	Estimation Comments

Adverse Events

Time Frame	From first dose of study drug until 28 days after last study drug administration (up to 12 weeks)
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Evolocumab AMD		Evolocumab AI/Pen
Arm/Group Description	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).		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).
All Cause Mortality
	Evolocumab AMD		Evolocumab AI/Pen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Evolocumab AMD		Evolocumab AI/Pen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/82 (0%)		1/82 (1.2%)
Vascular disorders
Deep vein thrombosis	0/82 (0%)		1/82 (1.2%)
Other (Not Including Serious) Adverse Events
	Evolocumab AMD		Evolocumab AI/Pen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/82 (0%)		0/82 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.