Clinical Trials Register

Summary
EudraCT Number:	2019-004935-22
Sponsor's Protocol Code Number:	TA-8995-303
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-07-08
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2019-004935-22

A.3

Full title of the trial

A Placebo-Controlled, Double-Blind, Randomized Phase 2 Study to Evaluate the Effect of Obicetrapib in Combination with Ezetimibe in Participants with Mild Dyslipidemia

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Study to Evaluate the Effect of Obicetrapib in Combination with Ezetimibe in Mild Dyslipidemia

A.3.2

Name or abbreviated title of the trial where available

OCEAN

A.4.1

Sponsor's protocol code number

TA-8995-303

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	NewAmsterdam Pharma BV
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	NewAmsterdam Pharma BV
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NewAmsterdam Pharma BV
B.5.2	Functional name of contact point	Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	Gooimeer 2-35
B.5.3.2	Town/ city	Naarden
B.5.3.3	Post code	1411 DC
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31352062971
B.5.5	Fax number	+31202400779
B.5.6	E-mail	marc.ditmarsch@newamsterdampharma.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	obicetrapib
D.3.2	Product code	TA-8995
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	obicetrapib
D.3.9.1	CAS number	866399-89-5
D.3.9.2	Current sponsor code	TA-8995
D.3.9.4	EV Substance Code	SUB188624
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Ezetrol
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ezetrol
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EZETIMIBE
D.3.9.1	CAS number	163222-33-1
D.3.9.2	Current sponsor code	ezetimibe
D.3.9.4	EV Substance Code	SUB16430MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

mild dyslipidemia

E.1.1.1

Medical condition in easily understood language

Treatment of high cholesterol

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10020049
E.1.2	Term	High cholesterol
E.1.2	System Organ Class	100000004848

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to evaluate the effect of obicetrapib in combination with ezetimibe compared to placebo on low-density lipoprotein cholesterol (LDL-C) at Day 85.

E.2.2

Secondary objectives of the trial

•To evaluate the effect of obicetrapib monotherapy compared to placebo on LDL-C at Day 85;
•To evaluate the effect of obicetrapib in combination with ezetimibe compared to placebo on apolipoprotein B (ApoB) at Day 85;
•To evaluate the effect of obicetrapib monotherapy compared to placebo on ApoB at Day 85;
•To evaluate the effect of ezetimibe monotherapy compared to placebo on LDL-C at Day 85;
•To evaluate the effect of ezetimibe monotherapy compared to placebo on ApoB at Day 85;
•To evaluate the effect of obicetrapib in combination with ezetimibe compared to obicetrapib monotherapy on LDL-C at Day 85; and
•To evaluate the effect of obicetrapib in combination with ezetimibe compared to obicetrapib monotherapy on ApoB at Day 85.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Understanding of the study procedures, willingness to adhere to the study schedules and diet, and agreement to participate in the study by giving written informed consent prior to Screening procedures;

2. Men or women 18 to 70 years of age, inclusive;
o Women may be enrolled if all 3 of the following criteria are met:
 -They are not pregnant;
 -They are not breastfeeding; and
 -They do not plan on becoming pregnant during the study;
o Women of childbearing potential must have a negative urine pregnancy test at the Screening Visit. Note: Women are not considered to be of childbearing potential if they meet 1 of the following criteria as documented by the Investigator:
 -They have had a hysterectomy or tubal ligation at a minimum of 1 cycle prior to signing the ICF; or
 -They are post-menopausal, defined as 1 year since their last menstrual period for women 55 years of age or 1 year since their last menstrual period and have a follicle stimulating hormone (FSH) level in the menopausal range for women <55 years of age;
o Women of childbearing potential must agree to use an effective method of avoiding pregnancy from the Screening Visit to 90 days after the last visit. Men whose partners are of childbearing potential must agree to use an effective method of avoiding pregnancy from the Screening Visit to 90 days after the last visit. Effective methods of avoiding pregnancy are contraceptive methods with a Pearl index of <1 used consistently and correctly (including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, diaphragm with spermicide, male or female condoms with spermicide, or cervical cap) or a sterile sexual partner;

3. Fasting LDL-C levels >2.5 mmol/L and <4.5 mmol/L and TG levels <4.5 mmol/L (Visit 1); and

4. Willingness to maintain a stable diet and physical activity level throughout the study.

E.4

Principal exclusion criteria

1. Body mass index 40 kg/m2;
2. Participation in another clinical study involving an investigational or marketed drug within 30 days prior to the Screening Visit;
3. Currently taking any lipid-altering therapy;
4. Any clinical manifestation of atherosclerotic CVD or any evidence of ischemic coronary disease present on the 12-lead ECG at the Screening Visit;
5. Diagnosis of type 1 or type 2 diabetes mellitus; or glycosylated hemoglobin (HbA1c) 6.5% at the Screening Visit if no prior diagnosis of diabetes mellitus;
6. Uncontrolled hypertension, ie, sitting systolic blood pressure >160 mmHg and/or sitting diastolic blood pressure >90 mmHg. One retest will be allowed, at which point if the retest result is no longer exclusionary, the participant may be randomized;
7. Active muscle disease or persistent creatine kinase concentration >3  the upper limit of normal (ULN). One retest will be allowed after 1 week to verify the result, at which point if the retest result is no longer exclusionary, the participant may be randomized;
8. History of torsades de pointes;
9. Estimated glomerular filtration rate <60 mL/min calculated using the Chronic Kidney Disease Epidemiology Collaboration equation;
10. Hepatic dysfunction as evidenced by any laboratory abnormality as follows: gamma-glutamyl transferase, alanine aminotransferase, or aspartate aminotransferase >2  ULN, or total bilirubin >1.5  ULN;
11. Anemia, defined as hemoglobin concentration <11 g/dL for males and hemoglobin concentration <9 g/dL for females;
12. History of malignancy within the past 5 years, with the exception of non-melanoma skin cancers;
13. Evidence of any other clinically significant non-cardiac disease or condition that, in the opinion of the Investigator, would preclude participation in the study; or
14. Known ezetimibe or CETP inhibitor allergy or intolerance.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is percent change from Day 1 to Day 85 in LDL-C, as measured by preparative ultracentrifugation, also referred to as beta quantification, for the combination therapy group compared to the placebo group.

E.5.1.1

Timepoint(s) of evaluation of this end point

Screening, Day 1, Day 29, day 57 and Day 85

E.5.2

Secondary end point(s)

The secondary efficacy endpoints include the following, in hierarchical order:
• Percent change from Day 1 to Day 85 in LDL-C, as measured by preparative ultracentrifugation, also referred to as beta quantification, for the obicetrapib monotherapy group compared to the placebo group;
• Percent change from Day 1 to Day 85 in ApoB for the combination therapy group compared to the placebo group;
• Percent change from Day 1 to Day 85 in ApoB for the obicetrapib monotherapy group compared to the placebo group;
• Percent change from Day 1 to Day 85 in LDL-C, as measured by preparative ultracentrifugation, also referred to as beta quantification, for the ezetimibe monotherapy group compared to the placebo group;
• Percent change from Day 1 to Day 85 in ApoB for the ezetimibe monotherapy group compared to the placebo group;
• Percent change from Day 1 to Day 85 in LDL-C, as measured by preparative ultracentrifugation, also referred to as beta quantification, for the combination therapy group compared to the obicetrapib monotherapy group; and
• Percent change from Day 1 to Day 85 in ApoB for the combination therapy group compared to the obicetrapib monotherapy group.

E.5.2.1

Timepoint(s) of evaluation of this end point

Screening, Day 1, Day 29, day 57 and Day 85

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Date of the last protocol-specified visit/assessment (including telephone contact) for the last participant in the study

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

127

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

152

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Vascular Research Network (VRN)
G.4.3.4	Network Country	Netherlands

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-07-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-10-01

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-06-30

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials