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A Research Study Looking at How NNC0385-0434 Tablets Work to Lower Blood Cholesterol in People With Heart Disease or a High Risk of Heart Disease

Primary Purpose

Atherosclerotic Cardiovascular Disease

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
NNC0385-0434 A 15 mg
NNC0385-0434 A 40 mg
Placebo I A (for NNC0385-0434 A 15 mg)
NNC0385-0434 A 100 mg
Placebo I A (for NNC0385-0434 A 40 mg)
Placebo II A (for NNC0385-0434 A 100 mg)
Evolocumab 140 mg/mL, Repatha®
Sponsored by
Novo Nordisk A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atherosclerotic Cardiovascular Disease

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Males or females of non-childbearing potential.

  • Established atherosclerotic cardiovascular disease (ASCVD) (criteria a) or ASCVD risk (criteria b):

    1. Age 40 years or older at the time of signing informed consent and history of ASCVD
    2. Age above 50 years at the time of signing informed consent and with ASCVD risk
  • Serum LDL-C above or equal to 1.8 mmol/L (above or equal to 70 mg/dL) as measured by the central laboratory at screening.
  • Japanese participants: Serum LDL-C above or equal to 2.6 mmol/L (above or equal to 100 mg/dL) for participants of 40 years of age or older and with a history of coronary heart disease, and serum LDL-C above or equal to 3.1 mmol/L (above or equal to 120 mg/dL) for all other Japanese participants
  • Participants must be on maximally tolerated dose of statins.
  • Participants not receiving statin must have documented evidence of intolerance to all doses of at least two different statins.

Exclusion Criteria:

  • Treatment with PCSK9i therapy (alirocumab or evolocumab within 90 days prior to screening) or PCSK9 siRNA therapy (inclisiran within 12 months prior to screening).
  • Fasting triglyceride above 4.52 mmol/L (above 400 mg/dL) as measured by the central laboratory at screening.
  • Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
  • Renal impairment with eGFR less than 30 ml/min/1.73 m2 as measured by the central laboratory at screening

Sites / Locations

  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Active Comparator

Arm Label

Oral NNC0385-0434 15 mg once-daily (OD)

Oral placebo (NNC0385-0434 15 mg)

Oral NNC0385-0434 40 mg OD

Oral placebo (NNC0385-0434 40 mg)

Oral NNC0385-0434 100 mg

Oral placebo (NNC0385-0434 100 mg)

Subcutaneous evolocumab 140 mg Q2W

Arm Description

15 mg NNC0385-0434 co-formulated with 500 mg Salcaprozate sodium (SNAC) tablet once daily

15 MG placebo administered as tablets (without SNAC) once daily

40 mg study drug co-formulated with 500 mg SNAC tablet once daily

placebo administered as tablets (without SNAC) once daily

100 mg NNC0385-0434 co-formulated with 500 mg SNAC tablet once daily (51 participants)

placebo administered as tablets (without SNAC) once daily

140 mg evolocumab Subcutaneous (s.c.) injections every 2 weeks (51 participants). The s.c. evolocumab arm is open-label to limit unnecessary injections

Outcomes

Primary Outcome Measures

Change in low-density lipoprotein (LDL)-cholesterol
percent

Secondary Outcome Measures

Change in total cholesterol
Percent
Change in high density lipoprotein (HDL)-cholesterol
percent
Change in very low density lipoprotein (VLDL)-cholesterol
Percent
Change in triglycerides
percent
Change in total Apo B
percent
Change in total Apo CIII
precent
Change in total Lipoprotein(a) ( Lp(a))
Ratio
Treatment-emergent adverse events
Number of events

Full Information

First Posted
July 28, 2021
Last Updated
July 1, 2023
Sponsor
Novo Nordisk A/S
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1. Study Identification

Unique Protocol Identification Number
NCT04992065
Brief Title
A Research Study Looking at How NNC0385-0434 Tablets Work to Lower Blood Cholesterol in People With Heart Disease or a High Risk of Heart Disease
Official Title
Dose Response and Safety of an Oral PCSK9i, NNC0385-0434, in Patients With Established Atherosclerotic Cardiovascular Disease (ASCVD) or ASCVD Risk on Maximally Tolerated Statin Dose and Other Lipid-lowering Therapy Requiring Further LDL-C Reduction
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
August 3, 2021 (Actual)
Primary Completion Date
April 26, 2022 (Actual)
Study Completion Date
June 20, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study looks at how well a new medicine, NNC0385-0434, works to lower blood cholesterol levels. Participants will either get NNC0385-0434 as a tablet (a potential new medicine), or placebo as a tablet (a dummy medicine that looks like NNC0385-0434 but has no effect on the body), or evolocumab as an injection (a medicine that doctors can already prescribe). Which treatment participants get is decided by chance. If participants get NNC0385-0434 or placebo participants will need to take 1 tablet every morning. If participants get evolocumab participants will need to take 1 injection every 2 weeks. The study will last for about 22 weeks. About 255 people will participate in the study. Participants will have 9 visits to the clinic and 2 phone calls with the study doctor. Some people will be invited to participate in a sub-study and will have 4 extra visits (13 visits in total). Participants will have blood samples taken at all visits to the clinic (except visit 0). At 4 clinic visits, participants will have an electrocardiogram (ECG). This is a test to check your heart. Women can only take part in the study if they are not able to become pregnant.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atherosclerotic Cardiovascular Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Masking Description
The trial will be double-blinded within dose level of oral NNC0385-0434 and size-matched placebo arm. The subcutaneous (s.c.) evolocumab arm will be open label.
Allocation
Randomized
Enrollment
255 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Oral NNC0385-0434 15 mg once-daily (OD)
Arm Type
Experimental
Arm Description
15 mg NNC0385-0434 co-formulated with 500 mg Salcaprozate sodium (SNAC) tablet once daily
Arm Title
Oral placebo (NNC0385-0434 15 mg)
Arm Type
Placebo Comparator
Arm Description
15 MG placebo administered as tablets (without SNAC) once daily
Arm Title
Oral NNC0385-0434 40 mg OD
Arm Type
Experimental
Arm Description
40 mg study drug co-formulated with 500 mg SNAC tablet once daily
Arm Title
Oral placebo (NNC0385-0434 40 mg)
Arm Type
Placebo Comparator
Arm Description
placebo administered as tablets (without SNAC) once daily
Arm Title
Oral NNC0385-0434 100 mg
Arm Type
Experimental
Arm Description
100 mg NNC0385-0434 co-formulated with 500 mg SNAC tablet once daily (51 participants)
Arm Title
Oral placebo (NNC0385-0434 100 mg)
Arm Type
Placebo Comparator
Arm Description
placebo administered as tablets (without SNAC) once daily
Arm Title
Subcutaneous evolocumab 140 mg Q2W
Arm Type
Active Comparator
Arm Description
140 mg evolocumab Subcutaneous (s.c.) injections every 2 weeks (51 participants). The s.c. evolocumab arm is open-label to limit unnecessary injections
Intervention Type
Drug
Intervention Name(s)
NNC0385-0434 A 15 mg
Intervention Description
15 mg administered as one oral tablet once daily in the morning in a fasting state. The tablet should be taken at least 30 min before the first food, beverage or other oral medications of the day. The tablet can be taken with up to half a glass of water (approximately 120 mL/ 4 fluid ounces).
Intervention Type
Drug
Intervention Name(s)
NNC0385-0434 A 40 mg
Intervention Description
40 mg administered as one oral tablet once daily in the morning in a fasting state. The tablet should be taken at least 30 min before the first food, beverage or other oral medications of the day. The tablet can be taken with up to half a glass of water (approximately 120 mL/ 4 fluid ounces).
Intervention Type
Other
Intervention Name(s)
Placebo I A (for NNC0385-0434 A 15 mg)
Intervention Description
Placebo administered as 1 tablet once daily in the morning in a fasting state. The tablet should be taken at least 30 min before the first food, beverage or other oral medications of the day. The tablet can be taken with up to half a glass of water (approximately 120 mL/ 4 fluid ounces). placebo tablets are sized match to the active arm within dose level
Intervention Type
Drug
Intervention Name(s)
NNC0385-0434 A 100 mg
Intervention Description
100 mg administered as one oral tablet once daily in the morning in a fasting state. The tablet should be taken at least 30 min before the first food, beverage or other oral medications of the day. The tablet can be taken with up to half a glass of water (approximately 120 mL/ 4 fluid ounces).
Intervention Type
Other
Intervention Name(s)
Placebo I A (for NNC0385-0434 A 40 mg)
Intervention Description
Placebo administered as one tablet once daily in the morning in a fasting state. The tablet should be taken at least 30 min before the first food, beverage or other oral medications of the day. The tablet can be taken with up to half a glass of water (approximately 120 mL/ 4 fluid ounces). placebo tablets are sized match to the active arm within dose level
Intervention Type
Other
Intervention Name(s)
Placebo II A (for NNC0385-0434 A 100 mg)
Intervention Description
Placebo administered as one tablet once daily in the morning in a fasting state. The tablet should be taken at least 30 min before the first food, beverage or other oral medications of the day. The tablet can be taken with up to half a glass of water (approximately 120 mL/ 4 fluid ounces). placebo tablets are sized match to the active arm within dose level
Intervention Type
Drug
Intervention Name(s)
Evolocumab 140 mg/mL, Repatha®
Intervention Description
Every 2 weeks subcutaneous (s.c.) injection of 140 mg into areas of the abdomen, thigh, or upper arm that are not tender, bruised, red, or indurated. Administered using a pre-filled SureClick® autoinjector (single-use). Dose volume: 1 mL
Primary Outcome Measure Information:
Title
Change in low-density lipoprotein (LDL)-cholesterol
Description
percent
Time Frame
From baseline (week 0) to visit 9 (week 12)
Secondary Outcome Measure Information:
Title
Change in total cholesterol
Description
Percent
Time Frame
From baseline (week 0) to visit 9 (week 12)
Title
Change in high density lipoprotein (HDL)-cholesterol
Description
percent
Time Frame
From baseline (week 0) to visit 9 (week 12)
Title
Change in very low density lipoprotein (VLDL)-cholesterol
Description
Percent
Time Frame
From baseline (week 0) to visit 9 (week 12)
Title
Change in triglycerides
Description
percent
Time Frame
From baseline (week 0) to visit 9 (week 12)
Title
Change in total Apo B
Description
percent
Time Frame
From baseline (week 0) to visit 9 (week 12)
Title
Change in total Apo CIII
Description
precent
Time Frame
From baseline (week 0) to visit 9 (week 12)
Title
Change in total Lipoprotein(a) ( Lp(a))
Description
Ratio
Time Frame
From baseline (week 0) to visit 9 (week 12)
Title
Treatment-emergent adverse events
Description
Number of events
Time Frame
From baseline (week 0) to visit 10 (19 weeks + 4 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males or females of non-childbearing potential. Established atherosclerotic cardiovascular disease (ASCVD) (criteria a) or ASCVD risk (criteria b): Age 40 years or older at the time of signing informed consent and history of ASCVD Age above 50 years at the time of signing informed consent and with ASCVD risk Serum LDL-C above or equal to 1.8 mmol/L (above or equal to 70 mg/dL) as measured by the central laboratory at screening. Japanese participants: Serum LDL-C above or equal to 2.6 mmol/L (above or equal to 100 mg/dL) for participants of 40 years of age or older and with a history of coronary heart disease, and serum LDL-C above or equal to 3.1 mmol/L (above or equal to 120 mg/dL) for all other Japanese participants Participants must be on maximally tolerated dose of statins. Participants not receiving statin must have documented evidence of intolerance to all doses of at least two different statins. Exclusion Criteria: Treatment with PCSK9i therapy (alirocumab or evolocumab within 90 days prior to screening) or PCSK9 siRNA therapy (inclisiran within 12 months prior to screening). Fasting triglyceride above 4.52 mmol/L (above 400 mg/dL) as measured by the central laboratory at screening. Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening. Renal impairment with eGFR less than 30 ml/min/1.73 m2 as measured by the central laboratory at screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Transparency (dept. 1452)
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
Facility Information:
Facility Name
Novo Nordisk Investigational Site
City
Palm Springs
State/Province
California
ZIP/Postal Code
92262
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33434
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33312
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Arlington Heights
State/Province
Illinois
ZIP/Postal Code
60005
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Hammond
State/Province
Louisiana
ZIP/Postal Code
70403
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Slidell
State/Province
Louisiana
ZIP/Postal Code
70458
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68105
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Albany
State/Province
New York
ZIP/Postal Code
12203
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
West Seneca
State/Province
New York
ZIP/Postal Code
14224
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75208
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77079
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Aalst
ZIP/Postal Code
9300
Country
Belgium
Facility Name
Novo Nordisk Investigational Site
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
Facility Name
Novo Nordisk Investigational Site
City
Genk
ZIP/Postal Code
3600
Country
Belgium
Facility Name
Novo Nordisk Investigational Site
City
Haine-Saint-Paul
ZIP/Postal Code
7100
Country
Belgium
Facility Name
Novo Nordisk Investigational Site
City
Hasselt
ZIP/Postal Code
3500
Country
Belgium
Facility Name
Novo Nordisk Investigational Site
City
Frankfurt
ZIP/Postal Code
60389
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
München
ZIP/Postal Code
80636
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Villingen-Schwenningen
ZIP/Postal Code
78048
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
Novo Nordisk Investigational Site
City
Athens
ZIP/Postal Code
GR-11528
Country
Greece
Facility Name
Novo Nordisk Investigational Site
City
Athens
ZIP/Postal Code
GR-14233
Country
Greece
Facility Name
Novo Nordisk Investigational Site
City
Athens
ZIP/Postal Code
GR-15123
Country
Greece
Facility Name
Novo Nordisk Investigational Site
City
Chaidari, Athens
ZIP/Postal Code
GR-12462
Country
Greece
Facility Name
Novo Nordisk Investigational Site
City
Chios
ZIP/Postal Code
GR82100
Country
Greece
Facility Name
Novo Nordisk Investigational Site
City
Saitama-shi, Saitama
ZIP/Postal Code
338-0837
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Sendai-shi, Miyagi
ZIP/Postal Code
983-0039
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Soka-shi, Saitama
ZIP/Postal Code
340-0034
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Tokyo
ZIP/Postal Code
192-0918
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Den Bosch
ZIP/Postal Code
5223GZ
Country
Netherlands
Facility Name
Novo Nordisk Investigational Site
City
Deventer
ZIP/Postal Code
7416 SE
Country
Netherlands
Facility Name
Novo Nordisk Investigational Site
City
Groningen
ZIP/Postal Code
9728 NT
Country
Netherlands
Facility Name
Novo Nordisk Investigational Site
City
Haarlem
ZIP/Postal Code
2035 RC
Country
Netherlands
Facility Name
Novo Nordisk Investigational Site
City
Nijmegen
ZIP/Postal Code
6532 SZ
Country
Netherlands
Facility Name
Novo Nordisk Investigational Site
City
Sneek
ZIP/Postal Code
8601 ZR
Country
Netherlands
Facility Name
Novo Nordisk Investigational Site
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Novo Nordisk Investigational Site
City
Lubin
ZIP/Postal Code
59-301
Country
Poland
Facility Name
Novo Nordisk Investigational Site
City
Swidnik
ZIP/Postal Code
21-040
Country
Poland
Facility Name
Novo Nordisk Investigational Site
City
Warszawa
ZIP/Postal Code
02-097
Country
Poland
Facility Name
Novo Nordisk Investigational Site
City
Warszawa
ZIP/Postal Code
04-073
Country
Poland
Facility Name
Novo Nordisk Investigational Site
City
Warszawa
ZIP/Postal Code
04-628
Country
Poland

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
IPD Sharing URL
http://novonordisk-trials.com

Learn more about this trial

A Research Study Looking at How NNC0385-0434 Tablets Work to Lower Blood Cholesterol in People With Heart Disease or a High Risk of Heart Disease

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