Study to Assess In-home Use of Evolocumab (AMG 145) Using a Prefilled Syringe or a Prefilled Autoinjector/Pen

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01849497
• Collaborator: (none)
• Enrollment: 149
• Locations: 26
• Arms: 2
• Patients Per Site: 5.7

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 home-use using either a pre-filled syringe or autoinjector/pen.

Condition or Disease	Intervention/Treatment	Phase
Primary Hypercholesterolemia; Mixed Dyslipidemia	Biological: Evolocumab Pre-filled Syringe; Biological: Evolocumab AI/pen	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 149 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-center, 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 Prefilled Syringe or a Prefilled Autoinjector/Pen
• Actual Study Start Date: Apr 18, 2013
• Actual Primary Completion Date: Sep 2, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Evolocumab PFS Participants received evolocumab 140 mg every 2 weeks for 4 weeks (Day 1, Week 2, and Week 4) subcutaneously using a prefilled syringe (PFS). Participants self-administered evolocumab in the clinic on Day 1 under supervision and then self-administered in a home setting at Weeks 2 and 4.	Biological: Evolocumab Pre-filled Syringe; Evolocumab subcutaneous injection via a single use, disposable pre-filled syringe.; Other Names: AMG 145 Repatha
Experimental: Evolocumab AI/pen Participants received evolocumab 140 mg every 2 weeks for 4 weeks (Day 1, Week 2, and Week 4) subcutaneously using a prefilled autoinjector/pen (AI/pen). Participants self-administered evolocumab in the clinic on Day 1 under supervision and then self-administered in a home setting at Weeks 2 and 4.	Biological: Evolocumab AI/pen; Evolocumab subcutaneous injection via a handheld mechanical (spring-based) autoinjector/pen.; Other Names: AMG 145 Repatha

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Full Administration of Evolocumab at Both Weeks 2 and 4 [Week 2 and Week 4]

   Self-administration of evolocumab was assessed by a telephone interview at Weeks 2 and 4. Each participant was asked about all attempted injection(s) and if the injection was administered in part, full, or none at all.

Secondary Outcome Measures

1. Percent Change From Baseline in LDL-C at Week 6 [Baseline and Week 6]

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	Encino	California	United States	91436
2	Research Site	Thousand Oaks	California	United States	91360
3	Research Site	Ventura	California	United States	93003
4	Research Site	Westlake Village	California	United States	91361
5	Research Site	Miami	Florida	United States	33173
6	Research Site	Port Charlotte	Florida	United States	33952
7	Research Site	Atlanta	Georgia	United States	30328
8	Research Site	Atlanta	Georgia	United States	30342
9	Research Site	Hammond	Indiana	United States	46320
10	Research Site	Auburn	Maine	United States	04210
11	Research Site	Manlius	New York	United States	13104
12	Research Site	Syracuse	New York	United States	13210
13	Research Site	Cadiz	Ohio	United States	43907
14	Research Site	Marion	Ohio	United States	43302
15	Research Site	Hillsboro	Oregon	United States	97123
16	Research Site	Duncansville	Pennsylvania	United States	16635
17	Research Site	Lansdale	Pennsylvania	United States	19446
18	Research Site	Rapid City	South Dakota	United States	57701
19	Research Site	Jackson	Tennessee	United States	38305
20	Research Site	Dallas	Texas	United States	75231
21	Research Site	Houston	Texas	United States	77074
22	Research Site	London	Ontario	Canada	N5W 6A2
23	Research Site	Toronto	Ontario	Canada	M8V 3X8
24	Research Site	Toronto	Ontario	Canada	M9V 4B4
25	Research Site	Woodstock	Ontario	Canada	N4S 5P5
26	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

• Boccara F, Dent R, Ruilope L, Valensi P. Practical Considerations for the Use of Subcutaneous Treatment in the Management of Dyslipidaemia. Adv Ther. 2017 Aug;34(8):1876-1896. doi: 10.1007/s12325-017-0586-8. Epub 2017 Jul 17. Review.
• 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. Review.
• Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01849497
• Other Study ID Numbers: 20120348
• First Posted: May 8, 2013
• Last Update Posted: Nov 29, 2018
• Last Verified: Nov 1, 2018

• 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 18 April 2013 and last patient enrolled on 05 August 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 PFS	Evolocumab AI/Pen
Arm/Group Description	Participants received evolocumab 140 mg every 2 weeks for 4 weeks (Day 1, Week 2, and Week 4) subcutaneously using a prefilled syringe (PFS). Participants self-administered evolocumab in the clinic on Day 1 under supervision and then self-administered in a home setting at Weeks 2 and 4.	Participants received evolocumab 140 mg every 2 weeks for 4 weeks (Day 1, Week 2, and Week 4) subcutaneously using a prefilled autoinjector/pen (AI/pen). Participants self-administered evolocumab in the clinic on Day 1 under supervision and then self-administered in a home setting at Weeks 2 and 4.
Period Title: Overall Study
STARTED	75	74
Received Treatment	75	74
COMPLETED	74	70
NOT COMPLETED	1	4

Baseline Characteristics

Arm/Group Title	Evolocumab PFS	Evolocumab AI/Pen	Total
Arm/Group Description	Participants received evolocumab 140 mg every 2 weeks for 4 weeks (Day 1, Week 2, and Week 4) subcutaneously using a prefilled syringe (PFS).	Participants received evolocumab 140 mg every 2 weeks for 4 weeks (Day 1, Week 2, and Week 4) subcutaneously using a prefilled autoinjector/pen (AI/pen).	Total of all reporting groups
Overall Participants	75	74	149
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.2 (11.1)	60.6 (9.6)	60.9 (10.3)
Sex: Female, Male (Count of Participants)
Female	36 48%	26 35.1%	62 41.6%
Male	39 52%	48 64.9%	87 58.4%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 2.7%	7 9.5%	9 6%
Black or African American	11 14.7%	7 9.5%	18 12.1%
Native Hawaiian or Other Pacific Islander	0 0%	1 1.4%	1 0.7%
White	62 82.7%	58 78.4%	120 80.5%
Missing	0 0%	1 1.4%	1 0.7%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	9 12%	6 8.1%	15 10.1%
Not Hispanic or Latino	66 88%	68 91.9%	134 89.9%
Stratification Factor: LDL-C Level (participants) [Number]
< 130 mg/dL	56 74.7%	56 75.7%	112 75.2%
≥ 130 mg/dL	19 25.3%	18 24.3%	37 24.8%
LDL-C Concentration (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	116.9 (25.0)	118.1 (28.7)	117.5 (26.8)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Full Administration of Evolocumab at Both Weeks 2 and 4
Description	Self-administration of evolocumab was assessed by a telephone interview at Weeks 2 and 4. Each participant was asked about all attempted injection(s) and if the injection was administered in part, full, or none at all.
Time Frame	Week 2 and Week 4

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Evolocumab PFS	Evolocumab AI/Pen
Arm/Group Description	Participants received evolocumab 140 mg every 2 weeks for 4 weeks (Day 1, Week 2, and Week 4) subcutaneously using a prefilled syringe (PFS).	Participants received evolocumab 140 mg every 2 weeks for 4 weeks (Day 1, Week 2, and Week 4) subcutaneously using a prefilled autoinjector/pen (AI/pen).
Measure Participants	75	74
Number (95% Confidence Interval) [percentage of participants]	96.0 128%	89.2 120.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Evolocumab PFS, 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	-6.8
	Confidence Interval	(2-Sided) 95%; -16.3 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline in LDL-C at Week 6
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Evolocumab PFS	Evolocumab AI/Pen
Arm/Group Description	Participants received evolocumab 140 mg every 2 weeks for 4 weeks (Day 1, Week 2, and Week 4) subcutaneously using a prefilled syringe (PFS).	Participants received evolocumab 140 mg every 2 weeks for 4 weeks (Day 1, Week 2, and Week 4) subcutaneously using a prefilled autoinjector/pen (AI/pen).
Measure Participants	75	74
Least Squares Mean (Standard Error) [percent change]	-59.74 (2.57)	-63.43 (2.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Evolocumab PFS, 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	-3.70
	Confidence Interval	(2-Sided) 95%; -10.38 to 2.99
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.38
	Estimation Comments

Adverse Events

Time Frame	From first dose of study drug until 28 days after last study drug administration (up to 8 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 PFS		Evolocumab AI/Pen
Arm/Group Description	Participants received evolocumab 140 mg every 2 weeks for 4 weeks (Day 1, Week 2, and Week 4) subcutaneously using a prefilled syringe (PFS).		Participants received evolocumab 140 mg every 2 weeks for 4 weeks (Day 1, Week 2, and Week 4) subcutaneously using a prefilled autoinjector/pen (AI/pen).
All Cause Mortality
	Evolocumab PFS		Evolocumab AI/Pen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Evolocumab PFS		Evolocumab AI/Pen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/75 (4%)		2/74 (2.7%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	1/75 (1.3%)		0/74 (0%)
Hepatobiliary disorders
Cholecystitis	1/75 (1.3%)		0/74 (0%)
Cholelithiasis	1/75 (1.3%)		0/74 (0%)
Nervous system disorders
Cerebrovascular accident	0/75 (0%)		1/74 (1.4%)
Renal and urinary disorders
Glomerulonephritis minimal lesion	0/75 (0%)		1/74 (1.4%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/75 (1.3%)		0/74 (0%)
Other (Not Including Serious) Adverse Events
	Evolocumab PFS		Evolocumab AI/Pen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/75 (5.3%)		2/74 (2.7%)
Nervous system disorders
Headache	4/75 (5.3%)		2/74 (2.7%)

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.