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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02055482




Registration number
NCT02055482
Ethics application status
Date submitted
4/02/2014
Date registered
5/02/2014
Date last updated
22/11/2017

Titles & IDs
Public title
Long-term Pre-dialysis Extension in Europe and Asia Pacific
Scientific title
A Controlled, Parallel Group, Open-label, Multicenter Extension Study to Investigate Efficacy and Safety of Oral BAY85-3934 and Darbepoetin Alfa Comparator in the Long Term Treatment of Anemia in Pre-dialysis Subjects With Chronic Kidney Disease in Europe and Asia Pacific
Secondary ID [1] 0 0
2013-001190-24
Secondary ID [2] 0 0
15653
Universal Trial Number (UTN)
Trial acronym
DIALOGUE 3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anemia 0 0
Renal Insufficiency, Chronic 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Blood 0 0 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Molidustat (BAY85-3934)
Other interventions - Darbepoetin

Experimental: BAY85-3934 -

Active Comparator: Darbepoetin -


Treatment: Drugs: Molidustat (BAY85-3934)
BAY85-3934 will be titrated at the scheduled dose control visits to maintain the Hb in the target range of 10.0 to 12.0 g/dL. Available doses include 15, 25, 50, 75, 100, and 150 mg/day OD. Treatment will be for minimum of 6 months to up to a maximum of 36 months.

Other interventions: Darbepoetin
Darbepoetin will be administered according to the local label and titrated at the scheduled dose by intravenous injection. Treatment will be for a minimum of 6 months to up to a maximum of 36 months.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in local laboratory hemoglobin level from baseline
Timepoint [1] 0 0
Baseline up to 36 months
Primary outcome [2] 0 0
Number of participants with serious adverse events (SAEs) and adjucated adverse events as a measure of safety and tolerability
Timepoint [2] 0 0
Up to 36 months
Primary outcome [3] 0 0
Number of participants with liver function-related AEs including abnormal liver function tests and any hospitalization
Timepoint [3] 0 0
Up to 36 months
Secondary outcome [1] 0 0
Time within hemoglobin target range (10.0 to 12.0 g/dL)
Timepoint [1] 0 0
Up to 36 months
Secondary outcome [2] 0 0
Duration of treatment exposure
Timepoint [2] 0 0
Up to 36 months
Secondary outcome [3] 0 0
Number of subjects requiring titration of dose
Timepoint [3] 0 0
Up to 36 months
Secondary outcome [4] 0 0
Change of reticulocyte count from baseline of this study
Timepoint [4] 0 0
Baseline up to 36 months
Secondary outcome [5] 0 0
Change of red blood cell count from baseline of this study
Timepoint [5] 0 0
Baseline up to 36 months
Secondary outcome [6] 0 0
Change of hematocrit from baseline of this study
Timepoint [6] 0 0
Baseline up to 36 months
Secondary outcome [7] 0 0
Change of central laboratory hemoglobin level from baseline of this study
Timepoint [7] 0 0
Baseline up to 36 months
Secondary outcome [8] 0 0
Responders in Hb levels
Timepoint [8] 0 0
Up to 36 months
Secondary outcome [9] 0 0
Number of subjects meeting specific Hb criteria
Timepoint [9] 0 0
Baseline up to 36 months
Secondary outcome [10] 0 0
Number of subjects with Hb values >13 g/dL or having excessive Hb increase
Timepoint [10] 0 0
Baseline up to 36 months
Secondary outcome [11] 0 0
Number of participants with non-serious adverse events
Timepoint [11] 0 0
Up to 36 months
Secondary outcome [12] 0 0
Change in heart rate (HR)
Timepoint [12] 0 0
Up to 36 months
Secondary outcome [13] 0 0
Change in blood pressure (BP)
Timepoint [13] 0 0
Up to 36 months
Secondary outcome [14] 0 0
Laboratory abnormalities
Timepoint [14] 0 0
Up to 36 months

Eligibility
Key inclusion criteria
- Men who agree to use adequate contraception when sexually active or women without
childbearing potential

- Not on dialysis at study entry

- Serum ferritin levels = 100 µg/L and < 1000 µg/L or transferrin saturation = 20%

- Inclusion criteria for inclusion into the Hb Stabilization (HbS) Phase: Requires Hb
stabilization (at 10.0 to 12..0g/dL for a minimum of 4 weeks) as follows: Received BAY
85-3934 and reached a stopping event in Study 15141 or received placebo and reached a
stopping event in Study 15141 or completed 16 weeks of treatment with BAY 85-3934 in
Study 15141or 15261 but had mean Hb during the evaluation period outside the target
range of 10.0 to 12.0 g/dL, or Completed 16 weeks of treatment with placebo in Study
15141 and was re-assessed at 4 weeks after end of study as eligible for Study 15653
(this study)

- Inclusion criteria for inclusion into the Main Phase: Mean Hb concentration of 10.0 to
12.0 g/dL who completed 16 weeks of treatment (BAY85-3934 arm) in Study 15141, or
completed 16 weeks of treatment (BAY-3934 or darbepoetin arm)in study 15261 without a
dose suspension lasting > 6 consecutive weeks, or mean Hb concentration of 10.0 to
12.0g/dL during the HbS phase of Study 15653 for a minimum of 4 weeks after visit 3.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- A scheduled kidney transplant or any other organ transplant within the next 6 months
(being on a waiting list does not exclude the subject)

- Red blood cell (RBC) containing transfusion within the 8 weeks before baseline

- Phosphodiesterase type 5 (PDE5) inhibitor (e.g., sildenafil, vardenafil, tadalafil) or
nitrates

- Sustained, poorly controlled arterial hypertension or hypotension at baseline, defined
as blood pressure = 180/110 mmHg or systolic blood pressure < 95 mmHg, respectively

- Severe rhythm or conduction disorders (e.g., heart rate [HR] < 50 or > 110 bpm, atrial
flutter, prolonged QT > 500 msec, second or third degree atrioventricular [AV] block),
if not reacted with a pace marker)

- New York Heart Association Class III or IV congestive heart failure

- Severe hepatic insufficiency (defined as alanine aminotransferase [ALT], aspartate
aminotransferase [AST]>3x the upper limit of normal [ULN], total bilirubin > 2 mg/dL,
or Child Pugh B or C) or active hepatitis, in the investigator's opinion

- An ongoing serious adverse event (SAE) from Study 15141 or Study 15261 that is
assessed as related to study drug

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/12/2016
Sample size
Target
Accrual to date
Final
166
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
- Gosford
Recruitment hospital [2] 0 0
- Melbourne
Recruitment hospital [3] 0 0
- Reservoir
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment postcode(s) [2] 0 0
3052 - Melbourne
Recruitment postcode(s) [3] 0 0
3073 - Reservoir
Recruitment outside Australia
Country [1] 0 0
Bulgaria
State/province [1] 0 0
Burgas
Country [2] 0 0
Bulgaria
State/province [2] 0 0
Dobrich
Country [3] 0 0
Bulgaria
State/province [3] 0 0
Gabrovo
Country [4] 0 0
Bulgaria
State/province [4] 0 0
Karlovo
Country [5] 0 0
Bulgaria
State/province [5] 0 0
Lovech
Country [6] 0 0
Bulgaria
State/province [6] 0 0
Montana
Country [7] 0 0
Bulgaria
State/province [7] 0 0
Pazardjik
Country [8] 0 0
Bulgaria
State/province [8] 0 0
Sofia
Country [9] 0 0
Bulgaria
State/province [9] 0 0
Stara Zagora
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Veliko Tarnovo
Country [11] 0 0
France
State/province [11] 0 0
Brest Cedex
Country [12] 0 0
France
State/province [12] 0 0
Grenoble Cedex 9
Country [13] 0 0
France
State/province [13] 0 0
Limoges Cedex1
Country [14] 0 0
France
State/province [14] 0 0
Pierre Benite Cedex
Country [15] 0 0
France
State/province [15] 0 0
Valenciennes
Country [16] 0 0
Germany
State/province [16] 0 0
Baden-Württemberg
Country [17] 0 0
Germany
State/province [17] 0 0
Nordrhein-Westfalen
Country [18] 0 0
Germany
State/province [18] 0 0
Sachsen-Anhalt
Country [19] 0 0
Germany
State/province [19] 0 0
Berlin
Country [20] 0 0
Germany
State/province [20] 0 0
Wuppertal
Country [21] 0 0
Hungary
State/province [21] 0 0
Baja
Country [22] 0 0
Hungary
State/province [22] 0 0
Budapest
Country [23] 0 0
Hungary
State/province [23] 0 0
Debrecen
Country [24] 0 0
Hungary
State/province [24] 0 0
Esztergom
Country [25] 0 0
Hungary
State/province [25] 0 0
Kaposvar
Country [26] 0 0
Hungary
State/province [26] 0 0
Pecs
Country [27] 0 0
Hungary
State/province [27] 0 0
Szigetvar
Country [28] 0 0
Israel
State/province [28] 0 0
Ashkelon
Country [29] 0 0
Israel
State/province [29] 0 0
Hadera
Country [30] 0 0
Israel
State/province [30] 0 0
Jerusalem
Country [31] 0 0
Israel
State/province [31] 0 0
Kfar Saba
Country [32] 0 0
Israel
State/province [32] 0 0
Nahariya
Country [33] 0 0
Italy
State/province [33] 0 0
Abruzzo
Country [34] 0 0
Italy
State/province [34] 0 0
Campania
Country [35] 0 0
Italy
State/province [35] 0 0
Emilia-Romagna
Country [36] 0 0
Italy
State/province [36] 0 0
Lombardia
Country [37] 0 0
Italy
State/province [37] 0 0
Toscana
Country [38] 0 0
Japan
State/province [38] 0 0
Fukuoka
Country [39] 0 0
Japan
State/province [39] 0 0
Hokkaido
Country [40] 0 0
Japan
State/province [40] 0 0
Ishikawa
Country [41] 0 0
Japan
State/province [41] 0 0
Iwate
Country [42] 0 0
Japan
State/province [42] 0 0
Kanagawa
Country [43] 0 0
Japan
State/province [43] 0 0
Mie
Country [44] 0 0
Japan
State/province [44] 0 0
Chiba
Country [45] 0 0
Japan
State/province [45] 0 0
Nagano
Country [46] 0 0
Japan
State/province [46] 0 0
Nara
Country [47] 0 0
Korea, Republic of
State/province [47] 0 0
Gyeonggido
Country [48] 0 0
Korea, Republic of
State/province [48] 0 0
Seoul
Country [49] 0 0
Poland
State/province [49] 0 0
Bialystok
Country [50] 0 0
Poland
State/province [50] 0 0
Poznan
Country [51] 0 0
Poland
State/province [51] 0 0
Radom
Country [52] 0 0
Poland
State/province [52] 0 0
Szczecin
Country [53] 0 0
Poland
State/province [53] 0 0
Zyrardow
Country [54] 0 0
Romania
State/province [54] 0 0
Brasov
Country [55] 0 0
Romania
State/province [55] 0 0
Bucharest
Country [56] 0 0
Romania
State/province [56] 0 0
Constanta
Country [57] 0 0
Romania
State/province [57] 0 0
Oradea
Country [58] 0 0
Romania
State/province [58] 0 0
Targu-Mures
Country [59] 0 0
Spain
State/province [59] 0 0
A Coruña
Country [60] 0 0
Spain
State/province [60] 0 0
Barcelona
Country [61] 0 0
Spain
State/province [61] 0 0
Madrid
Country [62] 0 0
Spain
State/province [62] 0 0
Alicante
Country [63] 0 0
Spain
State/province [63] 0 0
Córdoba
Country [64] 0 0
Turkey
State/province [64] 0 0
Ankara
Country [65] 0 0
Turkey
State/province [65] 0 0
Izmir
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Berkshire
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Cambridgeshire
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Dundee City
Country [69] 0 0
United Kingdom
State/province [69] 0 0
East Sussex
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Manchester
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Northumberland
Country [72] 0 0
United Kingdom
State/province [72] 0 0
South Yorkshire
Country [73] 0 0
United Kingdom
State/province [73] 0 0
West Yorkshire
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Chorley
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Glasgow
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Liverpool
Country [77] 0 0
United Kingdom
State/province [77] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Anaemia is a condition in which blood has a lower than normal number of red blood cells. It
can also occur if red blood cells do not contain enough haemoglobin, an oxygen carrying part
of blood. Anaemia is common in patients with chronic kidney disease. Healthy kidneys produce
a hormone called erythropoietin, which stimulates the bone marrow to produce the proper
number of red blood cells needed to carry oxygen to vital organs. Chronic kidney disease is a
general term that means that the kidneys are not functioning to their full potential. The
study drug, BAY85-3934, is being evaluated as a drug to increase the body's ability to
produce erythropoietin.

The purpose of this extension study is to find out if the study drug, a tablet taken orally,
is safe and effective for the treatment of anaemia associated with chronic kidney disease.

The extension study will enroll up to 240 patients at multiple locations in Europe, Asia and
Australia. Patients who participated in Studies 15141 or 15261 may be eligible to take part
in the extension study. The study consists of the Haemoglobin (Hb) Stabilisation Phase and
the Main Phase. The Hb Stabilisation Phase involves up to 10 study visits scheduled over 16
weeks. The Main Phase will last for at least 6 months and up to a maximum of 36 months, with
visits every 4 weeks. During these scheduled visits patients will undergo a number of
procedures to confirm efficacy and safety of the study drug, including measurement of heart
rate and blood pressure, physical examination, Electrocardiogram and blood/urine sample
collection for laboratory tests.

The study will be conducted at 5 hospitals in the UK. Bayer HealthCare AG is funding this
research. This study will include subjects who either completed the treatment period in their
respective Phase 2 parent study (i.e., Study 15141 or Study 15261) or experienced a stopping
event in the fixed dose parent study (Study 15141). As Study 15141 is a double-blind study,
subjects will be unblinded as per the Study 15141 protocol prior to entry into the extension
study.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02055482
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02055482