Download Slides - Clinical Trial Results

Presenter Disclosure Information
John R. Teerlink, M.D., F.A.C.C., F.A.H.A., F.E.S.C., F.R.C.P.
Professor of Medicine, University of California San Francisco
Director of Heart Failure, San Francisco Veterans Affairs Medical Center
•
•
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Financial Disclosure
– This study was funded by Amgen Inc.
– J.R. Teerlink has received research grants and/or consulting fees from
Amgen, Corthera, Cytokinetics, Merck, Novartis, Sorbent, and Trevena
Unlabeled/unapproved uses disclosure
– Use of omecamtiv mecarbil in patients with heart failure is investigational.
The technical support of Karen Driver is acknowledged and was supported by Amgen Inc.
UCSF
A Phase 2 Study of
Intravenous Omecamtiv Mecarbil,
A Novel Cardiac Myosin Activator,
In Patients With Acute Heart Failure
John R. Teerlink, G. Michael Felker, John J. V. McMurray,
Piotr Ponikowski, Marco Metra, Gerasimos S. Filippatos,
Kenneth Dickstein, Justin A. Ezekowitz, John G. Cleland,
Jae B. Kim, Lei Lei, Beat Knusel, Andrew A. Wolff,
Fady I. Malik and Scott M. Wasserman
on behalf of the ATOMIC-AHF Investigators and Patients
Omecamtiv Mecarbil (OM) is a Novel
Selective Cardiac Myosin Activator
Mechanochemical Cycle of Myosin
Omecamtiv mecarbil increases the
entry rate of myosin into the
tightly-bound, force-producing
state with actin
“More hands pulling on the rope”
Increases duration of systole
Increases stroke volume
No increase in myocyte calcium
Force production
No change in dP/dtmax
No increase in MVO2
Malik FI, et al. Science 2011; 331:1439-43.
Increases in Systolic Ejection Time
Underlie Increases in Cardiac Function
Healthy Volunteers
20
15
Healthy Volunteers vs. Heart Failure Patients
SET (msec)
Change from Baseline
160
Δ Stroke Volume
(mL)
10
5
SET Healthy Volunteers
SET Heart Failure
0
120
-5
80
16
12
40
Δ Fractional Shortening
(% points)
8
0
300
600
900
1200
4
-40
0
-80
12
[Omecamtiv mecarbil] (ng/mL)
8
Δ Ejection Fraction
(% points)
4
Teerlink JR, et al. Lancet 2011; 378: 667–75.
Cleland JGF, et al. Lancet 2011; 378: 676–83.
0
-4
0
20
40
60
Δ SET (msec)
80
100
Δ = placebo corrected
change from baseline
Mean ± SEM
ATOMIC-AHF
Acute Treatment with Omecamtiv Mecarbil to
Increase Contractility in Acute Heart Failure
Objective:
• To evaluate the safety, pharmacokinetics/ pharmacodynamics,
and efficacy of IV omecamtiv mecarbil (OM) in patients with
acute heart failure (AHF)
Hypothesis:
• At least 1 dose level of IV OM will be well tolerated and will
result in improvement of dyspnoea in subjects with left
ventricular systolic dysfunction hospitalised for AHF
Study Design: Sequential Dosing Cohort
Cohort 1
Cohort 2
Cohort 3
Omecamtiv
Omecamtiv
Omecamtiv
1:1 Randomization (n≈200)
Placebo
DMC
Pharmacokinetic simulations
Cohort 1
7.5 mg/hr @ 0-4 hr
1.5 mg/hr @ 4-48 hr
Target: 115 ng/mL
Cmax: 30-250 ng/mL
SET: ~3-28 msec
1:1 randomization (n≈200)
1:1 randomization (n≈200)
Placebo
Cohort 2
15 mg/hr @ 0-4 hr
3 mg/hr @ 4-48 hr
Target: 230 ng/mL
Cmax: 75-500 ng/mL
SET: ~8-55 msec
DMC
Placebo
Cohort 3
20 mg/hr @ 0-4 hr
4 mg/hr @ 4-48 hr
Target: 310 ng/mL
Cmax: 125-700 ng/mL
SET: ~14-78 msec
Teerlink JR, et al. Lancet 2011; 378: 667–75; Cleland JGF, et al. Lancet 2011; 378: 676–83.
Randomisation*
1:1
Randomised, double-blind, placebo-controlled,
sequential cohort study
Omecamtiv mecarbil IV
Vital Status
(phone call)
Screening
Presentation for AHF
Study Design
Placebo IV
MANDATORY IN - HOSPITAL STAY
Time (hrs)
Study drug administration
0
4
Loading
Dose
6
15
24
Maintenance
Dose
48
72
96
Day 6/
DC
1⁰ EP dyspnoea response
PK sampling
all subjects
PK/PD sub-study
Cardiac troponin/CK-MB
Echo (PK/PD sub-study)
* Randomisation within 24 hours of initial IV diuretic (Amendment 2)
Day 30
EOS
Month 6
Key Inclusion and Exclusion Criteria
Key Inclusion Criteria
• Male/female ≥ 18 and ≤ 85 y
• History of HF and LVEF ≤40%
• Hospitalised for AHF requiring
IV therapy
• Dyspnoea due to HF at rest or
with minimal exertion ≥2 hours
after iv diuretic
• Screening BNP ≥ 400 pg/mL or
NT-proBNP ≥ 1600 pg/mL
(BNP ≥ 600 pg/mL or NTproBNP ≥2400 pg/mL, if the
subject has atrial fibrillation)
Key Exclusion Criteria
• Receiving IV vasopressor, inotropic
or mechanical support
• Acute coronary syndrome (ACS) on
presentation
• Recent vascular event or cardiac
procedure
• Severe obstructive valvular or
myocardial disease
• BP >160/100 or SBP <90 mmHg, or
HR >110 or <60 bpm
• eGFR (MDRD) <20 mL/min/1.73m2
Randomised within 24 hours of initial IV diuretic treatment
Efficacy Endpoints
Primary:
• Dyspnoea symptom response (7-point Likert scale) through 48 hours
Secondary:
• Death (any cause) and/or worsening heart failure within 7 days
• Dyspnoea area under the curve (AUC) (baseline to 5th day or discharge)
as measured by subject self-assessed Numerical Rating Scale (NRS)
• Dyspnoea by 7-point Likert scale at each scheduled assessment
• Patient Global Assessment response through 48 hours
• Change from baseline in NT-proBNP
• Length of initial hospital stay
• Days alive out of hospital until day 30
PK/PD (Echo) Sub-study
Baseline Characteristics (1)
Pooled
Placebo
(N = 303)
Cohort 1
OM
(N = 103)
Cohort 2
OM
(N = 99)
Cohort 3
OM
(N = 101)
66 (11)
65 (12)
67 (10)
68 (10)
Gender – male, %
76
76
82
76
Region, %
*
Characteristic
Age , mean (SD)
Eastern Europe
53
45
56
62
North America
25
37
24
18
Australia
2
0
1
0
Western Europe
21
18
19
20
62
62
59
66
Years from HF diagnosis, mean (SD)
6 (6)
6 (6)
6 (5)
6 (5)
Most recent LVEF (%), mean (SD)
26 (8)
26 (8)
25 (7)
28 (7)
Persistent Atrial Fibrillation or Flutter, %
33
29
32
36
Diabetes Mellitus, %
45
49
41
42
Hypertension, %
81
84
81
82
Ischaemic heart disease, %
*p
< 0.05 for a difference in cohorts 1-3 Placebo arms compared to each other
Baseline Characteristics (2)
Pooled
Placebo
(N = 303)
Cohort 1
OM
(N = 103)
Cohort 2
OM
(N = 99)
Cohort 3
OM
(N = 101)
119 (18)*
118 (18)
117 (17)
117 (15)
78 (13)
78 (13)
79 (13)
78 (14)
6 (2)
6 (2)
6 (2)
6 (2)
ACE inhibitors/Angiotensin Receptor Blockers, %
78
79
74
84
Beta blocker, %
86*
90
87
90
Digoxin, %
20
28
26
22
Mineralocorticoid Receptor Antagonist, %
55
54
59
58
Ivabradine, %
3
4
4
6
0.044*
0.060
0.044
0.056
9026
7674
10488
10416
eGFR (mL/min/1.73m2), mean (SD)
53 (18)*
52 (18)
53 (19)
50 (18)
Time from presentation to randomisation, mean (SD)
15 (8)*
12 (8)
16 (10)
15 (9)
Characteristic
Systolic BP (mmHg), mean (SD)
Heart rate (beats/min), mean (SD)
Dyspnoea Numerical Rating Scale (NRS), Mean (SD)
Troponin-I, median (URL 0.04 ng/mL)
NT-proBNP (pg/mL), median
*p
< 0.05 for a difference in cohorts 1-3 Placebo arms compared to each other;
URL= upper reference limit
Primary Efficacy Endpoint
Dyspnoea Response (Likert Scale)
Responder defined as:
• Minimally, moderately or markedly better at 6 hours
AND
• Moderately or markedly better at both 24 and 48 hours
WITHOUT
• Worsening heart failure or death for any cause
by 48 hours
Primary Efficacy Endpoint:
Dyspnoea Response (Likert Scale)
Dyspnoea Response Rate
(% Responders)
Pooled Placebo
Overall p-value = 0.33
55
50
45
40
35
30
25
20
15
10
5
0
51%
47%
41%
42%
Pooled
Placebo
OM
Cohort 1
OM
Cohort 2
OM
Cohort 3
1.03
1.15
1.23
(0.79, 1.35)
(0.90, 1.47)
(0.97, 1.55)
Response Rate
Ratio*
95% CI
*Ratio of response rate to Pooled Placebo
p-value of a CMH test among all 3 Placebo arms = 0.32
Supplemental Primary Analysis:
Dyspnoea Response (Likert Scale)
Dyspnoea Response Rate
(% Responders)
Paired Placebo
55
50
45
40
35
30
25
20
15
10
5
0
Response
Rate Ratio
95% CI
p = 0.03
p = NS
p = NS
41%
46%
51%
47%
42%
37%
Placebo OM
Cohort 1
Placebo OM
Cohort 2
Placebo OM
Cohort 3
1.02
1.02
1.41
(0.74, 1.42)
(0.76, 1.37)
(1.02, 1.93)
Response rate ratio: ratio of response rate to Placebo within each cohort
Exploratory Analyses: Dose and Concentration
Relationship to Dyspnoea Response
For Increases
of…
Response Rate
Ratio
Increases…
95% CI
P-value
Dose*
50 mg total OM
administered
5.5%
0.7% – 10.6%
0.025
Plasma
concentration*
4000 hr*ng/mL
AUC48h
6.4%
1.7% – 11.4%
0.007
* Adjusted for region, cohort, age, baseline NRS, presentation-randomisation duration (continuous)
Secondary Efficacy Endpoint:
Worsening Heart Failure (WHF)
Within 7 days of IP initiation
Death or WHF*
Yes - n(%)
Relative risk
(95% CI)
p-value
Pooled
Placebo
(N = 303)
Cohort 1
OM
(N = 103)
Cohort 2
OM
(N = 99)
Cohort 3
OM
(N = 101)
52 (17)
13 (13)
0.67
(0.38, 1.18)
0.151
9 (9)
0.54
(0.28, 1.04)
0.054
9 (9)
0.54
(0.27, 1.08)
0.067
WHF*
Yes - n(%)
51 (17)
13 (13)
8 (8)
9 (9)
Relative risk
0.68
0.49
0.55
(95% CI)
(0.38, 1.21)
(0.24, 0.98)
(0.28, 1.09)
p-value
0.179
0.034
0.075
*Worsening heart failure is defined as clinical evidence of persistent or deteriorating
heart failure requiring at least one of the following treatments:
• Initiation, reinstitution or intensification of IV vasodilator
• Initiation of IV positive inotropes, or IV vasopressors
• Initiation of ultrafiltration, hemofiltration, or dialysis
• Initiation of mechanical ventilatory or circulatory support
Other Secondary Efficacy Endpoints
Pooled
Placebo
(N = 303)
Cohort 1
OM
(N = 103)
Cohort 2
OM
(N = 99)
Cohort 3
OM
(N = 101)
Dyspnoea Numerical Response AUC
through Day 6, mean (95% CI)
3.5
(3.3, 3.8)
3.5
(3.1, 3.9)
3.6
(3.2, 4.0)
3.7
(3.3, 4.0)
Patient Global Assessment response,
n (%)
127
(42)
44
(43)
48
(48)
51
(50)
Length of initial hospital stay,
median days (95% CI)
9
(8, 9)
8
(7, 9)
7
(7, 8)
9
(8, 10)
22
(21, 23)
23
(21, 24)
23
(23, 24)
22
(21, 23)
Days alive out of hospital through
30 days, median (95% CI)
NT-proBNP change from BL (pg/mL)
at 48 hours, median (95% CI)
-1805
(-2271, -1370)
All comparisons to Pooled Placebo not significant (p > 0.05)
-2076
-2161
-1742
(-2746, -1292) (-4273, -1336) (-2517, -1017)
Supraventricular and Ventricular
Tachyarrhythmias
Pooled
Placebo
(N = 303)
Pooled
OM
(N = 303)
Cohort 1
OM
(N = 103)
Cohort 2
OM
(N = 99)
Cohort 3
OM
(N = 101)
34 (11.2)
26 (8.6)
13 (12.6)
5 (5.1)
8 (7.9)
Supraventricular Tachyarrhythmias
Atrial Fibrillation or Atrial Flutter
Atrial Tachycardia
Sinus Tachycardia
Supraventricular Tachycardia
20 (6.6)
15 (5.0)
10 (3.3)
6 (2.0)
6 (5.8)
3 (2.9)
0 (0.0)
0 (0.0)
4 (4.0)
3 (3.0)
3 (1.0)
1 (0.3)
2 (0.7)
1 (0.3)
0 (0.0)
4 (1.3)
1 (1.0)
0 (0.0)
3 (2.9)
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
1 (1.0)
Ventricular Tachyarrhythmias
Ventricular Arrhythmia
Ventricular Extrasystoles
Ventricular Fibrillation
Ventricular Tachyarrhythmia
Ventricular Tachycardia
Extrasystoles
18 (5.9)
4 (1.3)
1 (0.3)
2 (0.7)
0 (0.0)
11 (3.6)
0 (0.0)
17 (5.6)
0 (0.0)
2 (0.7)
1 (0.3)
1 (0.3)
13 (4.3)
1 (0.3)
8 (7.8)
0 (0.0)
1 (1.0)
0 (0.0)
1 (1.0)
7 (6.8)
0 (0.0)
5 (5.1)
0 (0.0)
1 (1.0)
1 (1.0)
0 (0.0)
3 (3.0)
0 (0.0)
4 (4.0)
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
3 (3.0)
1 (1.0)
Preferred Term
Patient Incidence, n (%)
Number of subjects reporting AEs of
Supraventricular or Ventricular
Tachyarrhythmia
Post-Randomization Adjudicated Events
Pooled
Placebo
(N = 303)
Pooled
OM
(N = 303)
Cohort 1
OM
(N = 103)
Cohort 2
OM
(N = 99)
Cohort 3
OM
(N = 101)
Death
Cardiovascular
ACS/MI (fatal)
10 (3.3)
10 (3.3)
0
8 (2.6)
8 (2.6)
1 (0.3)
1 (1.0)
1 (1.0)
0
4 (4.0)
4 (4.0)
0
3 (3.0)
3 (3.0)
1 (1.0)
All Rehospitalisations
Acute MI
Unstable angina
Heart failure
Other
37 (12.2)
1 (0.3)
0
19 (6.3)
18 (5.9)
29 (9.6)
1 (0.3)
0
22 (7.3)
7 (2.3)
11 (10.7)
1 (1.0)
0
6 (5.8)
4 (3.9)
11 (11.1)
0
0
11 (11.1)
0
7 (6.9)
0
0
5 (5.0)
3 (3.0)
All Index hospitalisation MI (non-fatal)
Investigator reported
Troponin triggered
2 (0.7)
0 (0.0)
2 (0.7)
5 (1.7)
2 (0.7)
3 (1.0)
1 (1.0)
0 (0.0)
1 (1.0)
0
0
0
4 (4.0)
2 (2.0)
2 (2.0)
Total MIs
(Fatal + Rehosp + Nonfatal Index Hosp)
3 (1.0)
7 (2.3)
2 (1.9)
0
5 (5.0)
Patient Incidence, n (%)
ACS/MI = Acute Coronary Syndrome/Myocardial Infarction. 66 patients had 73 positively adjudicated rehospitalisations.
Troponin-I Change from Baseline (ng/mL)
Compared with Pooled Placebo
Troponin Change from Baseline (ng/mL)
0.03
0.03
0.02
0.02
0.01
0.01
-1E-16
0.00
-0.01
–0.01
-0.02
–0.02
Q3
-0.03
–0.03
Median
-0.04
–0.04
-0.05
–0.05
4HR4
hours
Baseline TnI (ng/mL)
Median
(Q1, Q3)
15 hours
HR15
24 hours
HR24
Pooled
Placebo
0.044
0.023, 0.080
48 hours
HR48
Day
Day 44
Q1
Day
Day 66
Time
Cohort 1
Cohort 2
Cohort 3
0.060
0.028, 0.141
0.044
0.030, 0.084
0.056
0.026, 0.092
Omecamtiv mecarbil Cmax
100
Omecamtiv mecarbil AUC0-48
100
80
80
60
60
40
40
20
20
0
0
-20
Red lines represent
linear regression line
and its +/- SE.
Baseline troponin-I
is adjusted.
-20
-40
0
200
400
600
-40
800 1000 1200 1400
0
10000
OM Cmax (ng/mL)
Max Troponin
Change from Baseline(ng/mL)
Max Troponin
Change from Baseline(ng/mL)
Omecamtiv Mecarbil Concentrations vs.
Troponin-I Maximal Change from Baseline
30000
40000
OM AUC0-48 (ng*hr/mL)
4
4
2
2
p=0.95
0
p=0.83
0
-2
-2
-4
20000
-4
0
200
400
600
800 1000 1200 1400
OM Cmax (ng/mL)
0
10000
20000
30000
OM AUC0-48 (ng*hr/mL)
40000
Adverse Events
Adverse Events (AEs),
Patient Incidence, n (%)
Pooled
Placebo
(N = 303)
Pooled
OM
(N = 303)
Cohort 1
OM
(N = 103)
Cohort 2
OM
(N = 99)
Cohort 3
OM
(N = 101)
All AEs
187 (61.7)
175 (57.8)
73 (70.9)
49 (49.5)
53 (52.5)
Cardiac Failure*
53 (17.5)
46 (15.2)
17 (16.5)
14 (14.1)
15 (14.9)
Hypokalaemia
18 (5.9)
20 (6.6)
7 (6.8)
7 (7.1)
6 (5.9)
Hypotension
14 (4.6)
24 (7.9)
14 (13.6)
5 (5.1)
5 (5.0)
69 (22.8)
66 (21.8)
24 (23.3)
24 (24.2)
18 (17.8)
Cardiac Failure*
29 (9.6)
26 (8.6)
8 (7.8)
11 (11.1)
7 (6.9)
Renal Failure Acute
4 (1.3)
6 (2.0)
2 (1.9)
2 (2.0)
2 (2.0)
Hypotension
0 (0.0)
3 (1.0)
3 (2.9)
0 (0.0)
0 (0.0)
Deaths
11 (3.6)
9 (3.0)
2 (1.9)
4 (4.0)
3 (3.0)
AEs leading to discontinuation of IP
15 (5.0)
15 (5.0)
7 (6.8)
4 (4.0)
4 (4.0)
3 most common AEs
Serious AEs
3 most common serious AEs
N = Number of patients in the analysis set; IP = Investigational Product.
* Cardiac failure includes both “Cardiac failure” and “Cardiac Failure Congestive” Preferred Terms.
PK/PD Substudy Endpoint:
Change in Systolic Ejection Time (SET)
PK Concentration Bin Analysis
Control
OM concentration range (ng/ml)
OM
OM
OM
Concentration Concentration Concentration
Bin 1
Bin 2
Bin 3
≥88-200
>200-300
>300-787
Change in SET (msec)
N(n)
45 (88)
10 (18)
15 (23)
12 (19)
-6.7
16.6
26.9
46.4
23.4
33.6
53.2
95% CI
(7.4, 39.4)
(19.8, 47.4)
(38.0, 68.3)
p-value
0.005
<0.0001
<0.0001
LS mean
Difference from control
Linear regression slope
p < 0.0001
Baseline systolic ejection time for all patients was 258 msec. N: number of patients in the bin,
n: number of observations in the bin; Control = observations in Placebo + PK below quantification
limit; PK bin concentration analysis: repeated measures analysis of covariance; Linear regression
slope analysis: repeated measures multiple linear regression.
Change in Heart Rate and SBP
PK Concentration Bin Analysis
Control
OM concentration range (ng/ml)
Heart Rate (beats/min)
LS means
Difference from control
95% CI
p-value
Linear regression slope
-4.3
OM Conc. Bin 1 OM Conc. Bin 2 OM Conc. Bin 3
≥88-200
>200-300
>300-787
-4.4
-0.1
(-1.4, 1.1)
0.835
-6.3
-2.0
(-3.6, -0.4)
0.016
p < 0.0001
-6.5
-2.3
(-3.9, -0.6)
0.008
SBP (mmHg)
LS means
-4.6
-4.4
-4.0
-2.2
Difference from control
0.3
0.6
2.4
(0.6, 4.2)
95% CI
(-1.2, 2.4)
(-1.2, 1.7)
p-value
0.719
0.521
0.009
Linear regression slope
p = 0.0017
N: number of patients in the bin, n: number of observations in the bin. Heart rate measured by
ECG. Control = observations in Placebo + PK below quantification limit. PK bin concentration
analysis: repeated measures analysis of covariance. Linear regression slope analysis: repeated
measures multiple linear regression.
Summary
• Efficacy
– OM did not meet the 1° endpoint of dyspnoea relief
– Appeared to improve dyspnoea in Cohort 3
– Trends towards reduction of worsening HF
• Safety
– Overall SAE profile and tolerability similar to placebo
– Increase in troponin; no clear relationship to OM concentration
– Numerical imbalance in MIs in Cohort 3
– No evidence of pro-arrhythmia
• Pharmacology
– PK similar to healthy volunteers and stable HF patients
– Systolic ejection time significantly increased consistent with MOA
– Small fall in heart rate & rise in systolic BP at higher doses
Committees
• Executive Committee:
– Michael Felker
– John McMurray
– John Teerlink (Chair)
• Steering Committee:
–
–
–
–
–
–
John Cleland
Kenneth Dickstein
Justin Ezekowitz
Gerasimos Filippatos
Marco Metra
Piotr Ponikowski
• Data Monitoring Committee:
– Henry Dargie
– Barry Greenberg
– James Januzzi (Advisor)
– Julie Johnson (Advisor)
– Marv Konstam (Chair)
– Joseph Massaro
– Barry Massie
Investigators
Joanna Szachniewicz, Mikhail Kotelnikov, Zhanna Kobalava, Jindrich Spinar, Veselin Mitrovic, Janos
Tomcsanyi, Bela Merkely, Dinesh Gupta, Mason Weiss, Kalman Toth, Pranas Serpytis, Andrzej Wysokinski,
Alain Cohen Solal, Kirkwood Adams, Michel Galinier, Gintare Sakalyte, Hans Vandekerckhove, Fedya Nikolov,
Marco Metra, Steven Krueger, Boycho Boychev, Eustathios Iliodromitis, Ioannis Nanas, Jooyoung Shin, Javed
Butler, Petar Lazov, Guy Proulx, Gaetano De Ferrari, Dmitry Zateyshchikov, Ivan Gordeev,
Boris Goloshchekin, Peter MacDonald, Borislav Atzev, Assen Goudev, Jan Belohlavek, Kumudha Ramasubbu,
Nina Shehova-Iankova, Haissam Haddad, Richard Isnard, Kenneth Dickstein, Jadwiga Nessler, Svetlana
Boldueva, Glenn Hamroff, John Morrow, Lynne Wagoner, Jiri Vitovec, Jans Stevlik, Stephen Gottlieb, Frank
McGrew, Arthur Eberly, Thao Huynh, Henning Ebelt, Thomas Heitzer, Panagiotis Vardas, Dirk Lok, Sergey
Tereshenko, Nina Novikova, Marian Hranai, Debra Weinstein, Eugene Chung, David Lanfear, Denise Barnard,
Chetan Patel, Mark Dunlap, James Maher, Inder Anand, Marc Vanderheyden, Michel de Ceuninck, Ditmar
Raev, Robert Stewart, Pavel Cervinka, Angelika Costard-Jäckle, Athanasios Manolis, Jaroslaw Kasprak,
Vladimir Simanenkov, David Smull, Mitchell Saltzberg, Peter McCullough, Andrew Wilson, Filip Charlier,
Serge Lepage, Justin Ezekowitz, Gordon Moe, Manohara Senaratne, David Zemanek, Pascal De Groote, Rémi
Sabatier, Christian Hengstenberg, Tim Schäufele, Andreas Zeiher, Stephan Felix, Dimitrios Alexopoulos, Bela
Herczeg, Laszlo Zoltan, Eelko Ronner, Wlodzimierz Musial, Piotr Jankowski, Eugeny Shlyakhto, Tatyana
Novikova, Elena Vasilieva, Arsenio Rodriguez, John Teerlink, Alexander Adler, Andrew McRae, Garrie Haas,
Daniel Lenihan, Henry Krum, Carmine De Pasquale, Dariusz Korczyk, Aleksandra Bankova, Stefan Denchev,
Debra Isaac, John David Parker, Veli-Pekka Harjola, Heikki Ukkonen, François Roubille, Gérald Roul, Michael
Böhm, Ruth Strasser, Sebastian Maier, Gerhard Cieslinski, Hans-Georg Olbrich, Noemi Nyolczas, Maurizio
Porcu, Claudio Fresco, Folkert Asselbergs, Lars Gullestad, Andrzej Rynkiewicz, Grigory Aroutiounov, Daniel
Pella, Jozef Kaluzay, John Cleland, Hugh Bethell, Angus Nightingale, John McMurray, Philip Adamson, Todd
Kovach, Jalal Ghali, Andrew Keller, Adrian Van Bakel, James Mudd, Gregory Ewald, Stephanie Dunlap,
Edward McMillan, Freidoon Ghazi, Glenn Barquet, Joshua Larned, Rami Alharethi