Clinical Trials Register

Summary
EudraCT Number:	2012-002434-37
Sponsor's Protocol Code Number:	MK-0859-042
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-12-28
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

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2012-002434-37

A.3

Full title of the trial

A Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled, 12-Week
Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing
Lipid-Lowering Therapy in Adult Patients with Homozygous Familial
Hypercholesterolemia (HoFH) with a 52-Week Open-Label Extension

Celosvětové, multicentrické, dvojitě zaslepené, randomizované, placebem kontrolované 12týdenní klinické hodnocení ke zhodnocení účinnosti a snášenlivosti anacetrapidu přidaného k již zavedené lipidy-snižující léčbě u dospělých s homozygotní familiární hypercholesterolemií (HoFH) s 52týdenním nezaslepeným rozšířením

A.3.1

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

n/a

A.4.1

Sponsor's protocol code number

MK-0859-042

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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
B.1.3.4	Country	United States
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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.5.2	Functional name of contact point	Global Clinical Trials Operations (
B.5.3	Address:
B.5.3.1	Street Address	One Merck Drive
B.5.3.2	Town/ city	Whitehouse Station, NJ,
B.5.3.3	Post code	08889-0100
B.5.3.4	Country	United States
B.5.6	E-mail	christophe_dedepre@merck.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.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	MK-0859
D.3.2	Product code	(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4’-
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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	Tablet
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

Homozygous Familial Hypercholesterolemia (HoFH)

E.1.1.1

Medical condition in easily understood language

patients with extremely high LDL-C levels due to genetic mutations affecting ability to remove cholesterol from their blood

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

In adults with HoFH on a stable dose regimen of statin ± other lipid-lowering
medications, evaluate the effects of adding anacetrapib 100 mg for 12 weeks relative to placebo on
plasma concentrations of LDL-C and summarize the safety and tolerability of 12 weeks of treatment

E.2.2

Secondary objectives of the trial

In adults with HoFH on a stable dose regimen of statin ± other lipid-lowering
medications, evaluate the effects of anacetrapib 100 mg on HDL-C and ApoA-1 relative to placebo after 12 weeks of treatment and summarize the safety and tolerability of up to 64 weeks of treatment with anacetrapib100 mg.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Patient is male or female and 18 years of age on day of signing informed consent.
-Patient is diagnosed with HoFH by genotyping as defined by documented mutations causing familial hypercholesterolemia in both alleles of LDLR including, but not limited to a LDLR null mutation.
-A patient who is of reproductive potential agrees to remain abstinent* or use (or have their partner use) 2 acceptable methods of birth control for the duration of the study.
-Patients have been stabilized on statin monotherapy or statin therapy coadministered with other lipid medications for at least 6 weeks prior to randomization along with adequate stabilization of LDL apheresis regimen. A new lipid-modifying therapy or apheresis regimen should not be initiated during the first 12 weeks after randomization, but can be initiated at any time during the open-label extension.
-Patient provides written informed consent/assent for the trial.

E.4

Principal exclusion criteria

Patient has a triglyceride value >400 mg/dL (6.78 mmol/L), creatine kinase (CK) >2x upper limit of normal (ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2x upper limit of normal (ULN) [per central laboratory reference ranges].
-Patient has severe chronic heart failure defined by New York Heart Association (NYHA) Classes III or IV or uncontrolled cardiac arrhythmias, MI, PCI, CABG, unstable angina or stroke within 3 months prior to Visit 1 or has planned procedures scheduled within the first 12-weeks of the study.
-Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins, thyroid stimulating hormone (TSH) values outside the central laboratory normal ranges or chronic hepatobiliary or gall bladder disease.
-Patient has eGFR <30 mL/min/1.73m2 based on 4-variable MDRD equation, nephrotic syndrome or other clinically significant renal disease.
-Patient is pregnant or breast-feeding or plans to become pregnant during the study or
within 2 years of stopping study medication.
-Patient has history of ileal bypass, gastric bypass, or other significant condition associated with malabsorption.
-Patient is human immunodeficiency virus (HIV) positive.
- Patient has donated blood products or has had phlebotomy of >300 mL within 8 weeks of signing informed consent (excluding apheresis), or intends to donate 250 mL of blood products or receive blood products within the projected duration of the study.
- Patient has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the patient’s participation for the full duration of the study, such that it is not in the best interest of the patient to participate.
-Patient is currently taking medications that are potent inhibitors or inducers of CYP3A4 or has discontinued treatment <3 weeks prior to Visit 1. Consumption of >1 liter of grapefruit juice per day is also prohibited.
-Patient is currently participating or has participated in a study with an investigational compound or device within 3 months of signing informed consent.
-Patient consumes more than 2 alcoholic drinks per day.
- Patient is receiving treatment with systemic corticosteroids or systemic anabolic agents.

E.5 End points

E.5.1

Primary end point(s)

Effects of adding anacetrapib 100 mg to ongoing lipid therapy relative to placebo on plasma concentrations of LDL-C
Summary of safety and tolerability

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks

E.5.2

Secondary end point(s)

Effects of adding anacetrapib 100 mg to ongoing lipid therapy relative to placebo on plasma concentrations of HDL-C and apoA-1

E.5.2.1

Timepoint(s) of evaluation of this end point

12 (HDL-C and apoA-1) & 64 (safety)weeks

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

Israel

Malaysia

South Africa

United States

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

LVLS

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

F.1.3

Elderly (>=65 years)

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

continue standard of care lipid lowering therapies

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
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

2013-05-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-13

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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