Clinical Trials Register

Summary
EudraCT Number:	2007-000425-22
Sponsor's Protocol Code Number:	68-4986/12484
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-04-16
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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2007-000425-22

A.3

Full title of the trial

Phase IIa Efficacy and Safety Trial of capadenoson in Patients with Chronic Stable Angina

A.4.1

Sponsor's protocol code number

68-4986/12484

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Bayer Healthcare AG
B.1.3.4	Country	Germany
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Bay 68-4986
D.3.2	Product code	Bay 68-4986
D.3.4	Pharmaceutical form	Granules for oral suspension
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Capadenoson
D.3.9.1	CAS number	544417-40-5
D.3.9.2	Current sponsor code	Bay 68-4986
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	4
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	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	Bay 68-4986
D.3.2	Product code	Bay 68-4986
D.3.4	Pharmaceutical form	Granules for oral suspension
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Capadenoson
D.3.9.1	CAS number	544417-40-5
D.3.9.2	Current sponsor code	Bay 68-4986
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	2
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	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	Bay 68-4986
D.3.2	Product code	Bay 68-4986
D.3.4	Pharmaceutical form	Granules for oral suspension
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Capadenoson
D.3.9.1	CAS number	544417-40-5
D.3.9.2	Current sponsor code	Bay 68-4986
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Granules for oral suspension
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

Patients with Chronic Stable Angina

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10049194
E.1.2	Term	Stable angina pectoris

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 main objective of this study is to demonstrate that chronic administration of BAY 68-4986 for 28 days at doses of 1 mg, 2 mg and 4 mg, is efficacious in a patient population with chronic stable angina and documented coronary heart disease. The primary efficacy parameter will be the total exercise time.

E.2.2

Secondary objectives of the trial

The following secondary efficacy variables will be analysed descriptively by dose group for difference from baseline (ETT 2): total exercise time on Day 14 (ETT3), heart rate at rest, heart rate at trough drug concentration at comparable workload levels, heart rate during exercise at 1 mm ST-segment depression, time to 1 mm ST-segment depression, time to angina onset.
The number of angina attacks and short acting nitrates usage characteristics (based on diary data) will also be analysed descriptively.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female subjects aged 35 to 75 years (if female, only if postmenopausal or permanently sterilized)
2. Stable angina of mild-moderate intensity (Canadian class II-III) with anti-anginal medication not changed for the last 5 weeks
3. ETT positive, within the previous 6 months, for myocardial ischemia (horizontal or downsloping ST segment depression of at least 1mm with respect to the isoelectric line, 80 msec after the J-point, occurring after at least 3 minutes of exercise on treadmill (according to the modified Bruce protocol) with stable ischemia threshold.
4. CAD documented by at least one of the following:
• more than 70% diameter stenosis in at least one of the epicardial coronary arteries on coronary angiography
• previous PTCA/CABG (> 6 months)
• previous MI (> 6 months)
• typical angina in male subjects aged > 55 years, who have a positive stress test result (both by the ECG and clinical criteria)
5. Subject´s written informed consent obtained at screening visit before any study-related procedures and before wash-out of pre-existing anti-anginal medication.

E.4

Principal exclusion criteria

1. Inability to withdraw current anti-anginal therapy
2. Inability to withdraw any concomitant therapy that would interfere with interpretation of study results
3. More than 3 episodes of chest pain per day that require short-acting nitrates
4. Vasospastic (Prinzmetal) angina
5. Inability to perform an exercise on treadmill for least three minutes
6. Myocardial infarction or unstable angina within the last 6 months
7. PTCA or CABG performed within the last 6 months
8. Known unprotected left main coronary artery disease
9. Resting 12-lead ECG ST-segment depression greater than 0.5 mm or any other ECG findings that may interfere with interpretation of the ECG during ETT
10. Significant ST-segment elevation at rest or during ETT in non-Q-wave leads
11. Significant rhythm or conduction disorder:
 bradycardia on physical examination at rest (HR < 50/min)
 tachycardia on physical examination at rest (HR > 100/min)
 important or complex ventricular arrythmias (on investigators discretion)
 atrial fibrillation
 intraventricular conduction disorders
 sino-atrial, second degree or third degree A-V block
 baseline QTc > 450 msec
12. Treatment with anti-arrythmic drugs
13. Hypertension with systolic blood pressure > 180 mmHg or diastolic blood pressure > 105 mmHg
14. Postural hypotension
15. Heart failure, NYHA Class II – IV (appendix 10.3)
16. Severe cardiac valvular disease
17. Significant pulmonary disease
18. Significant peripheral vascular disease, e.g., Raynaud’s syndrome or intermittent claudication
19. Stroke or TIA in the last 6 months
20. Gross obesity (BMI > 35)
21. Failure of a major organ system or a medical disorder that would impair the subject’s ability to complete this study (in the opinion of the investigator)
22. Malignancy or disease known to markedly reduce the subjects life expectancy
23. Significant mental illness
24. History of epilepsy or other seizure disorders
25. Known hypersensitivity to BAY 68-4986
26. Concurrent use of CYP 2C9 substrates such as fluvastatin, warfarin, diclofenac, losartan, rosiglitazone, glibenclamide/glyburide, tolbutamide
27. Liver function tests (AST, ALT, LDH) >2 times the upper limit of normal at screening (see also section 4.6.4)
28. Creatine kinase (CK) levels > 3 times the upper limit of normal at screening (see section 4.6.4)
29. Hematocrit value <32% at screening
30. Blood donation within 30 days
31. Serum creatinine >2.0 mg/dl or >177 micromol/L at screening (see section 4.6.4)
32. Other abnormal laboratory parameters considered clinically significant (in the opinion of the investigator)
33. Participation in an investigational drug study during which active medication was given within the last 30 days

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variable is the absolute difference in total exercise time between ETT2 (baseline) and ETT4 (day 28). ETT will be performed at trough 24 hours post-dose.
Secondary efficacy objectives will be the evaluation of the effect of BAY 68-4986 on the variables listed below, with absolute differences from baseline (ETT 2) being investigated:
- total exercise time on Day 14 (ETT3)
- time to 1 mm ST-segment depression
- heart rate at rest
- heart rates at trough drug concentration at comparable workload levels
- heart rate during exercise at 1 mm ST-segment depression
- time to angina onset
The number of angina attacks and short-acting nitrates usage characteristics (based on diary data) will also be described.
In addition, BAY 68-4986 exposure in all subjects will be assessed via sparse sampling and population pharmacokinetic approaches.

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

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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

Yes

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)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

different dosage of the same drug

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

Information not present in EudraCT

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

E.8.7

Trial has a data monitoring committee

Yes

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

Last visit of last patient undergoing trial

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 months

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	40
F.4.2	For a multinational trial
F.4.2.1	In the EEA	276
F.4.2.2	In the whole clinical trial	300

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2007-12-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-12-05

P. End of Trial
P.	End of Trial Status	Completed

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