Clinical Trials Register

Summary
EudraCT Number:	2012-005643-24
Sponsor's Protocol Code Number:	TA-8995-03
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-08-01
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

Denmark - DHMA

A.2

EudraCT number

2012-005643-24

A.3

Full title of the trial

A Multi-Centre, Randomised, Double Blind, Placebo Controlled, Parallel Group Study of TA 8995 in Patients with Mild Dyslipidaemia, Alone and In Combination with Statin Therapy

A.3.1

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

Effects of TA 8995 given orally in patients with mild dyslipidaemia alone or in combination with atorvastatin and rostuvastatin

A.3.2

Name or abbreviated title of the trial where available

TA-8995: its use in patients with mild dyslipidaemia (TULIP)

A.4.1

Sponsor's protocol code number

TA-8995-03

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	Xention Limited
B.1.3.4	Country	United Kingdom
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	Xention Limited
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Dezima 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	Medpace UK
B.5.2	Functional name of contact point	Regulatory Submissions
B.5.3	Address:
B.5.3.1	Street Address	Kingfisher House, Elmfield Road
B.5.3.2	Town/ city	Bromley
B.5.3.3	Post code	BR1 1LT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+442083156786
B.5.5	Fax number	+442083156793
B.5.6	E-mail	b.mcdougall@medpace.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.3.2	Product code	TA-8995
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	TA-8995
D.3.9.3	Other descriptive name	TA-8995
D.3.9.4	EV Substance Code	SUB120190
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	1
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	Comparator
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	Atorvastatin
D.2.1.1.2	Name of the Marketing Authorisation holder	Sandoz Limited
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	Atorvaststin
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	Atorvastatin
D.3.9.1	CAS number	134523-03-8
D.3.9.3	Other descriptive name	ATORVASTATIN CALCIUM
D.3.9.4	EV Substance Code	SUB12958MIG
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	1
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: 3
D.1.2 and D.1.3	IMP Role	Comparator
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	Crestor
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca UK Limited
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	Crestor
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	Crestor
D.3.9.3	Other descriptive name	ROSUVASTATIN CALCIUM
D.3.9.4	EV Substance Code	SUB20721
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	1
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	Capsule
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 dyslipidaemia

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	14.1
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 trial is to evaluate the efficacy of TA 8995, alone and in combination with statin therapy, on the elevation of HDL C and reduction of LDL C following 12 weeks of treatment.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are the following:
1. To evaluate the efficacy of TA 8995 alone and in combination with statins on HDL-C and LDL-C following 12 weeks of treatment.
2. To evaluate the safety and tolerability of TA 8995 in patients with mild dyslipidaemia as assessed by adverse events and changes from baseline in ECG, laboratory values (haematology, clinical chemistry parameters, and urinalysis), vital signs (blood pressure, pulse rate, and body temperature), and salivary cortisol, plasma aldosterone, high sensitivity C reactive protein (hsCRP) and endothelin 1 levels.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients meeting the following criteria will be eligible to participate in the study:
1. Understanding of the study procedures, willing to adhere to the study schedules and diet, and agreement to participate in the study by giving written informed consent prior to screening (Visit 1);
2. Men or women 18 to 75 years of age, inclusive;
• 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;
• Women of childbearing potential must have a negative urine pregnancy test at screening (Visit 1). 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 minimum 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 an FSH level in menopausal range for women <55 years of age;
• Women of childbearing potential must agree to use an effective method of avoiding pregnancy from screening 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 screening to 90 days after the last visit. Effective methods of avoiding pregnancy are contraceptive methods with a Pearl index of less than 1 used consistently and correctly (including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices,
3. Not on lipid altering therapy at screening or on lipid altering treatment regimens at screening; patients currently taking lipid altering medications must be able to safely discontinue all lipid altering therapy during the run in/washout period;
4. Fasting LDL C levels >2.5 mmol/L and <4.5 mmol/L, HDL C levels <1.8 mmol/L and >0.8 mmol/L, and TG levels <4.5 mmol/L after run in or washout of existing therapies.; and
5. Willingness to maintain stable diet and physical activity level throughout the study.

E.4

Principal exclusion criteria

1. Body mass index >32 kg/m2;
2. Participation in another clinical study involving an investigational or marketed drug within 30 days prior to enrolment (Visit 2);
3. Any clinical manifestation of atherosclerotic vascular disease;
4. Diagnosis of type 1 diabetes;
5. Uncontrolled type 2 diabetes: haemoglobin A1c ≥ 8%;
6. Uncontrolled hypertension: sitting systolic blood pressure >160 mmHg and/or sitting diastolic blood pressure >90 mmHg;
7. History of hyperaldosteronism;
8. 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;
9. Corrected QT interval >450 ms;
10. History of Torsades de Pointes or other clinically significant arrhythmia;
11. Clinically significant renal dysfunction: serum creatinine >1.5 X ULN;
12. Clinically significant hepatic dysfunction: gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST) >2 X ULN, or bilirubin >1.5 X ULN;
13. Anaemia, defined as haemoglobin concentration <11 g/dL for males and haemoglobin concentration <9 g/dL for females;
14. History of malignancy within the past 5 years, unless non invasive and in remission (disease free for >5 years) and written approval has been obtained from Sponsor, with the exception of skin cancers not including malignant melanoma;
15. Evidence of any other clinically significant non cardiac disease or condition that, in the opinion of the Investigator, would preclude the patient’s participation in the study;
16. History (within previous 1 year of consent) of alcohol or substance dependence or abuse (except nicotine dependence) according to Diagnostic and Statistical Manual of Mental Disorders (DSM IV TR) criteria (see Appendix B);
17. Heavy smoking (>20 cigarettes/day);
18. Known statin or CETP inhibitor intolerance;
19. Known allergy to any of the drugs administered in the study; or
20. Unable or unwilling to cooperate with study procedures or TLC diet.

E.5 End points

E.5.1

Primary end point(s)

The co-primary efficacy endpoints are the percentage changes in both HDL C and LDL C levels

E.5.1.1

Timepoint(s) of evaluation of this end point

At Week 12 compared to baseline.

E.5.2

Secondary end point(s)

• Percent change in triglyceride (TG);
• Percent change in total cholesterol (TC);
• Percent change in apolipoprotein AI (ApoA1), apolipoprotein B (ApoB), apolipoprotein E (ApoE) and
• Percent change in lipoprotein(a) (Lp[a])

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 12 compared to baseline

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

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

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

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

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:

865

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

130

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

400

F.4.2

For a multinational trial

F.4.2.1

In the EEA

995

F.4.2.2

In the whole clinical trial

995

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

2013-08-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-07-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-08-14

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