Evaluation of Evolocumab (AMG 145) Efficacy in Diabetic Adults With Hypercholesterolemia/Mixed Dyslipidemia

A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Evolocumab (AMG 145) on LDL-C in Subjects With Type 2 Diabetes Mellitus and Hypercholesterolemia/Mixed Dyslipidemia

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02739984

Acronym

BANTING

Enrollment

424

Registered

2016-04-15

Start date

2016-05-17

Completion date

2017-08-03

Last updated

2018-08-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypercholesterolemia, Mixed Dyslipidemia, Type 2 Diabetes

Keywords

diabetes, type 2 diabetes, high blood cholesterol, hypercholesterolemia, mixed dyslipidemia, high cholesterol, statin intolerant

Brief summary

The purpose of this study is to evaluate the effect of 12 weeks of subcutaneous evolocumab taken monthly compared with subcutaneous placebo taken monthly on low density lipoprotein cholesterol (LDL-C) in adults with type 2 diabetes mellitus and high blood cholesterol on a maximally tolerated oral dose of statin of at least moderate-intensity.

Detailed description

This study will enroll adults with type 2 diabetes mellitus and elevated LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) levels on a stable, maximally tolerated statin dose of at least moderate-intensity at signing of the informed consent; statin therapy must remain unchanged during screening and the remainder of the study.

Interventions

BIOLOGICALEvolocumab

Administered by subcutaneous injection with an automated mini doser

DRUGPlacebo to Evolocumab

Administered by subcutaneous injection with an automated mini doser

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Male or female ≥ 18 years * Type 2 Diabetes Mellitus * Hemoglobin A1c \< 10% * Stable diabetes therapy * Must be on maximally tolerated dose of statin of at least moderate Intensity * Fasting triglycerides ≤ 600 mg/dL * Not at LDL-C or Non-HDL-C goal.

Exclusion criteria

* Moderate to severe renal dysfunction * Uncontrolled hypertension * Persistent active liver disease or hepatic dysfunction * Has taken a cholesterylester transfer protein inhibitor in the last 12 months, * Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke within 3 months prior to randomization

Design outcomes

Primary

Measure	Time frame
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	Baseline and Weeks 10 and 12
Percent Change From Baseline in LDL-C at Week 12	Baseline and week 12

Secondary

Measure	Time frame
Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Non-HDL-C at Week 12	Baseline and week 12
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B at Week 12	Baseline and week 12
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Total Cholesterol at Week 12	Baseline and week 12
Percentage of Participants With Mean LDL-C at Weeks 10 and 12 Less Than 70 mg/dL (1.8 mmol/L)	Weeks 10 and 12
Percentage of Participants With LDL-C at Week 12 Less Than 70 mg/dL (1.8 mmol/L)	Week 12
Percentage of Participants With at Least a 50% Reduction From Baseline in Mean LDL-C at Weeks 10 and 12	Baseline and weeks 10 and 12
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Lipoprotein(a) at Week 12	Baseline and week 12
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12	Baseline and week 12
Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in HDL-C at Week 12	Baseline and week 12
Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in VLDL-C at Week 12	Baseline and week 12
Percentage of Participants With at Least a 50% Reduction From Baseline in LDL-C at Week 12	Baseline and Week 12
Change From Baseline in LDL-C at Week 12	Baseline and week 12

Countries

Belgium, Canada, Italy, Mexico, Poland, Spain, United States

Participant flow

Recruitment details

Of 853 patients screened, a total of 424 participants were randomized at 58 centers in Belgium, Canada, Italy, Mexico, Poland, Spain and the United States from 17 May 2016 to 05 May 2017.

Pre-assignment details

Participants received subcutaneous placebo during a 6-week screening period. Participants who completed the screening period and met final eligibility criteria were randomized in a 1:2 ratio to placebo or evolocumab. Randomization was stratified by low-density lipoprotein cholesterol (LDL-C) level (\> or \< 130 mg/dL).

Participants by arm

Arm	Count
Placebo Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	143
Evolocumab Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.	281
Total	424

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	0	1
Overall Study	Lost to Follow-up	3	0
Overall Study	Sponsor Decision	1	0
Overall Study	Withdrawal by Subject	1	1

Baseline characteristics

Characteristic	Placebo	Evolocumab	Total
Age, Continuous	62.3 years STANDARD_DEVIATION 8.5	62.5 years STANDARD_DEVIATION 8.5	62.5 years STANDARD_DEVIATION 8.5
Age, Customized 65 - < 85 years	57 Participants	122 Participants	179 Participants
Age, Customized < 65 years	86 Participants	159 Participants	245 Participants
Age, Customized ≥ 85 years	0 Participants	0 Participants	0 Participants
Apolipoprotein B Concentration	98.1 mg/dL STANDARD_DEVIATION 22.1	97.1 mg/dL STANDARD_DEVIATION 23.3	97.5 mg/dL STANDARD_DEVIATION 22.9
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants	54 Participants	78 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	119 Participants	227 Participants	346 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
High-density Lipoprotein Cholesterol (HDL-C) Concentraion	45.2 mg/dL STANDARD_DEVIATION 12.2	43.6 mg/dL STANDARD_DEVIATION 12.9	44.2 mg/dL STANDARD_DEVIATION 12.7
LDL-C Concentration	110.4 mg/dL STANDARD_DEVIATION 33	108.6 mg/dL STANDARD_DEVIATION 31	109.2 mg/dL STANDARD_DEVIATION 31.6
Lipoprotein(a) Concentration	99.4 nmol/L STANDARD_DEVIATION 122.8	88.0 nmol/L STANDARD_DEVIATION 111.5	91.8 nmol/L STANDARD_DEVIATION 115.4
Non-High-density Lipoprotein Cholesterol (non-HDL-C) Concentration	145.5 mg/dL STANDARD_DEVIATION 33.9	144.6 mg/dL STANDARD_DEVIATION 34.9	144.9 mg/dL STANDARD_DEVIATION 34.5
Race/Ethnicity, Customized American Indian or Alaska Native	7 Participants	8 Participants	15 Participants
Race/Ethnicity, Customized Asian	2 Participants	4 Participants	6 Participants
Race/Ethnicity, Customized Black (or African American)	32 Participants	41 Participants	73 Participants
Race/Ethnicity, Customized Multiple	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants	2 Participants	2 Participants
Race/Ethnicity, Customized Other	0 Participants	2 Participants	2 Participants
Race/Ethnicity, Customized White	102 Participants	223 Participants	325 Participants
Sex: Female, Male Female	65 Participants	121 Participants	186 Participants
Sex: Female, Male Male	78 Participants	160 Participants	238 Participants
Stratification Factor: Low-density Lipoprotein Cholesterol (LDL-C) Level < 130 mg/dL	108 Participants	213 Participants	321 Participants
Stratification Factor: Low-density Lipoprotein Cholesterol (LDL-C) Level ≥ 130 mg/dL	35 Participants	68 Participants	103 Participants
Total Cholesterol Concentration	190.7 mg/dL STANDARD_DEVIATION 35	188.2 mg/dL STANDARD_DEVIATION 36.8	189.1 mg/dL STANDARD_DEVIATION 36.2
Triglycerides Concentration	177.3 mg/dL STANDARD_DEVIATION 89.2	184.2 mg/dL STANDARD_DEVIATION 102.2	181.9 mg/dL STANDARD_DEVIATION 98
Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration	33.6 mg/dL STANDARD_DEVIATION 14.3	34.8 mg/dL STANDARD_DEVIATION 15.4	34.4 mg/dL STANDARD_DEVIATION 15

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 141	1 / 280
other Total, other adverse events	19 / 141	37 / 280
serious Total, serious adverse events	2 / 141	14 / 280