Clinical trial NCT02055482: Long-term Pre-dialysis Extension in Europe and Asia Pacific
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Renal Insufficiency, Chronic
Keywords: Anemia on CKD
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2014-02-05
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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

Primary outcomes:
measure: Change in local laboratory hemoglobin level from baseline
timeFrame: Baseline up to 36 months
measure: Number of participants with serious adverse events (SAEs) and adjucated adverse events as a measure of safety and tolerability
timeFrame: Up to 36 months
measure: Number of participants with liver function-related AEs including abnormal liver function tests and any hospitalization
timeFrame: Up to 36 months
Secondary outcomes:
measure: Time within hemoglobin target range (10.0 to 12.0 g/dL)
timeFrame: Up to 36 months
measure: Duration of treatment exposure
timeFrame: Up to 36 months
measure: Number of subjects requiring titration of dose
timeFrame: Up to 36 months
measure: Change of reticulocyte count from baseline of this study
timeFrame: Baseline up to 36 months
measure: Change of red blood cell count from baseline of this study
timeFrame: Baseline up to 36 months
measure: Change of hematocrit from baseline of this study
timeFrame: Baseline up to 36 months
measure: Change of central laboratory hemoglobin level from baseline of this study
timeFrame: Baseline up to 36 months
measure: Responders in Hb levels
timeFrame: Up to 36 months
measure: Number of subjects meeting specific Hb criteria
timeFrame: Baseline up to 36 months
measure: Number of subjects with Hb values >13 g/dL or having excessive Hb increase
timeFrame: Baseline up to 36 months
measure: Number of participants with non-serious adverse events
timeFrame: Up to 36 months
measure: Change in heart rate (HR)
timeFrame: Up to 36 months
measure: Change in blood pressure (BP)
timeFrame: Up to 36 months
measure: Laboratory abnormalities
timeFrame: Up to 36 months
Other outcomes:
measure: Change of reticulocyte count from baseline of study 15141 or 15261
timeFrame: Baseline up to 36 months
measure: Change of red blood cell count from baseline of study 15141 or 15261
timeFrame: Baseline up to 36 months
measure: Change of hematocrit from baseline of study 15141 or 15261
timeFrame: Baseline up to 36 months
measure: Change of central laboratory hemoglobin level from baseline of study 15141 or 15261
timeFrame: Baseline up to 36 months
Locations:
city: Gosford
country: Australia
state: New South Wales
city: Melbourne
country: Australia
state: Victoria
city: Reservoir
country: Australia
city: Burgas
country: Bulgaria
city: Dobrich
country: Bulgaria
city: Gabrovo
country: Bulgaria
city: Karlovo
country: Bulgaria
city: Lovech
country: Bulgaria
city: Montana
country: Bulgaria
city: Pazardjik
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Stara Zagora
country: Bulgaria
city: Veliko Tarnovo
country: Bulgaria
city: Brest Cedex
country: France
city: Grenoble Cedex 9
country: France
city: Limoges Cedex1
country: France
city: Pierre Benite Cedex
country: France
city: Valenciennes
country: France
city: Pirmasens
country: Germany
state: Baden-Württemberg
city: Villingen-Schwenningen
country: Germany
state: Baden-Württemberg
city: Bonn
country: Germany
state: Nordrhein-Westfalen
city: Düsseldorf
country: Germany
state: Nordrhein-Westfalen
city: Halle (Saale)
country: Germany
state: Sachsen-Anhalt
city: Berlin
country: Germany
city: Wuppertal
country: Germany
city: Baja
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Esztergom
country: Hungary
city: Kaposvar
country: Hungary
city: Pecs
country: Hungary
city: Szigetvar
country: Hungary
city: Ashkelon
country: Israel
city: Hadera
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Nahariya
country: Israel
city: Chieti
country: Italy
state: Abruzzo
city: Napoli
country: Italy
state: Campania
city: Modena
country: Italy
state: Emilia-Romagna
city: Brescia
country: Italy
state: Lombardia
city: Cremona
country: Italy
state: Lombardia
city: Lecco
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Pavia
country: Italy
state: Lombardia
city: Livorno
country: Italy
state: Toscana
city: Kitakyushu
country: Japan
state: Fukuoka
city: Okawa
country: Japan
state: Fukuoka
city: Muroran
country: Japan
state: Hokkaido
city: Hakusan
country: Japan
state: Ishikawa
city: Morioka
country: Japan
state: Iwate
city: Fujisawa
country: Japan
state: Kanagawa
city: Kamakura
country: Japan
state: Kanagawa
city: Kuwana
country: Japan
state: Mie
city: Chiba
country: Japan
city: Fukuoka
country: Japan
city: Nagano
country: Japan
city: Nara
country: Japan
city: Bucheon-si
country: Korea, Republic of
state: Gyeonggido
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Bialystok
country: Poland
city: Poznan
country: Poland
city: Radom
country: Poland
city: Szczecin
country: Poland
city: Zyrardow
country: Poland
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Constanta
country: Romania
city: Oradea
country: Romania
city: Targu-Mures
country: Romania
city: Santiago de Compostela
country: Spain
state: A Coruña
city: L'Hospitalet de Llobregat
country: Spain
state: Barcelona
city: San Sebastián de los Reyes
country: Spain
state: Madrid
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Córdoba
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Ankara
country: Turkey
facility: Ankara Univ. Medical Faculty
city: Ankara
country: Turkey
facility: Baskent University Medical Faculty
city: Izmir
country: Turkey
facility: Sifa University Medical Faculty
city: Reading
country: United Kingdom
state: Berkshire
city: Cambridge
country: United Kingdom
state: Cambridgeshire
city: Dundee
country: United Kingdom
state: Dundee City
city: Brighton
country: United Kingdom
state: East Sussex
city: Salford
country: United Kingdom
state: Manchester
city: Hexham
country: United Kingdom
state: Northumberland
city: Doncaster
country: United Kingdom
state: South Yorkshire
city: Leeds
country: United Kingdom
state: West Yorkshire
city: Chorley
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Liverpool
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: