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Clinical Trial Results Synopsis

20-NOV-2017 Study no. 15653 Page: 1 of 13

Date of study report: 19 JUL 2017

Study title: A controlled, parallel group, open-label, multicenter extension study to

investigate efficacy and safety of oral BAY 85-3934 and darbepoetin alfa

comparator in the long-term treatment of anemia in pre-dialysis subjects

with chronic kidney disease in Europe and Asia Pacific

Sponsor’s study number:

15653

NCT number: NCT02055482

EudraCT number: 2013-001190-24

Sponsor: Bayer

Clinical phase: II

Study objectives: Study objectives were assessed in pre-dialysis subjects with anemia of

chronic kidney disease (CKD) for a period of up to 36 months in the Main

Phase of this study.

Primary objectives

The primary objectives of this study were the following:

To evaluate efficacy of treatment with BAY85-3934 compared

with darbepoetin as measured by the change from baseline to post-

baseline time points in hemoglobin (Hb) levels

To evaluate safety and tolerability of treatment with BAY85-3934

compared with darbepoetin by events of special interest,

adjudicated serious adverse events (SAEs), and SAEs.

Secondary objectives

The secondary objectives of this study were the following:

To evaluate other efficacy variables of treatment with BAY85-

3934 compared with darbepoetin

To evaluate other safety variables of treatment with BAY85-3934

compared with darbepoetin.



Test drug: Molidustat (BAY85-3934)

Name of active ingredient(s):

BAY85-3934

Dose: Dose during Hb Stabilization (HbS) Phase

Fixed initial doses of BAY85-3934 (OD dose) were administered and then

titrated at each scheduled visit to maintain Hb in the target range of 10.0

to 12.0 g/dL.

Dose during Main Phase

Based on the subject’s Hb response and tolerability of previous dose,

IXRS assigned the adapted dose for each subject for BAY85-3934.

Available dose regimens included 0, 15, 25, 50, 75, 100, and 150 mg.

Route of administration:

Oral

Duration of treatment: Up to a maximum of 36 months

Reference drug: Darbepoetin alfa (hereafter called darbepoetin)

Dose: Darbepoetin was administered according to the local label and titrated at

the scheduled DC visits.

Route of administration:

Intravenous (IV) or subcutaneous (SC)

Duration of treatment: Up to a maximum of 36 months

Indication: Anemia of CKD or renal anemia



Diagnosis and main criteria for inclusion:

Subjects eligible for inclusion into the study had to meet all of the

following inclusion criteria listed below:

Men; women without childbearing potential, defines as (a)

postmenopausal women (women with 12 months of spontaneous

amenorrhea or with 6 months of spontaneous amenorrhea and

serum follicle stimulating hormone concentration > 30 millimeters

international unit / milliliter [mIU/mL]) (b) women with bilateral

tubal ligation, (c) women with bilateral ovarectomy, or (d) women

with hysterectomy

Not on dialysis at study entry

Ability to understand and follow study-related instructions as a

documented decision of the investigator.

Inclusion criteria for inclusion into the HbS Phase

Subjects who:

Received BAY85-3934 or placebo in Study 15141 and reached a

stopping event, or

Completed 16 weeks of treatment with BAY85-3934 in Study

15141 or 15261 but had a mean Hb from 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 were re-assessed within 4 weeks after end of treatment (EoT)

visit as eligible for the HbS Phase of Study 15653 (this extension

study).

Inclusion criteria for inclusion into the Main Phase

Mean Hb concentration at 10.0 to 12.0 g/dL during the evaluation

period of parent study for subjects who:

o Completed 16 weeks of treatment (BAY85-3934 arm) in

Study 15141, or

o Completed 16 weeks of treatment (BAY85-3934 or

darbepoetin arm) in Study 15261 without dose suspension

lasting > 6 consecutive weeks, or

HbS Phase subject (BAY85-3934 or darbepoetin arm) in Study

15653 (this extension study):

o Had mean Hb concentration of 10.0 to 12.0 g/dL for at least 2

consecutive visits after HbS Phase Visit 2, and

o Did not have a dose suspension lasting > 6 consecutive weeks

in the HbS Phase.



Study design: This is a controlled, parallel group, open-label, multicenter study

Methodology: Two concurrent phases were included for this study: HbS Phase (up to 16

weeks) and Main Phase (up to 36 months).

Subjects treated with placebo in Study 15141 received darbepoetin in this

study.

Hb Stabilization Phase overview

The initial study drug dose in the HbS Phase was based on the Hb level at

the time of the subject’s stopping event or the average Hb levels during

the last 4-week evaluation period if mean Hb was not within 10.0 to 12.0

g/dL, as well as the total daily dose level in Study 15141 or Study 15261.

After the first dose control (DC) visit in this extension study, Hb was

checked every 2 weeks in the HbS Phase.

Main Phase overview

Dose assessments were made every 4 (± 1) weeks. At the scheduled visits,

interactive voice / web response system (IXRS) assigned an adapted dose

regimen for BAY 85-3934 and darbepoetin [according to the local label]

for the subject to take for the next 4 weeks of treatment to achieve and

maintain Hb levels at 10.0 to 12.0 g/dL. In exceptional cases, the

investigator could intervene in the dose decision based on his / her clinical

judgment.

Measurements from portable Hb devices were prohibited in the study.

Safety laboratory parameters, heart rate (HR), blood pressure (BP),

adverse events (AEs), and concomitant medications were monitored

regularly throughout the study.

Subjects who required administration of rescue treatment (e.g., red blood

cell [RBC] containing transfusion, phlebotomy, or administration of a

marked erythropoiesis-stimulating agent [ESA] treatment) were

permanently discontinued from the study drug. Subjects who required

hemodialysis during the study were not excluded.

Three oversight committees were employed for this study, a steering

committee, a data monitoring committee (DMC), and a central

adjudication committee (CAC).

Study center(s): 50 active centers overall that enrolled subjects in 12 countries. The

participating countries were (number of centers in brackets): Bulgaria (6),

France (3), Germany (2), Hungary (5), Israel (2), Italy (6), Japan (10),

Poland (3), Republic of Korea (4), Romania (4), Spain (3), and United

Kingdom (2).



Publication(s) based on the study (references):

None at the time of report creation

Study period: Study Start Date: 24 JUN 2014

Study Completion Date: 12 DEC 2016

Early termination: Yes. The study was terminated early as the study size did not meet the

Regulatory Agency requirements to assess long-term treatment (safety) in

this product class.

Number of subjects: Planned: 190 subjects in BAY85-3934 group

50 subjects in darbepoetin group

Analyzed: 164 subjects

Criteria of evaluation:

Efficacy: Primary efficacy variable

Change in local laboratory Hb level from baseline of the Main Phase to

each post-baseline visit.

Secondary efficacy variables

Responders in Hb levels: The response defined as meeting all 3 of

the following criteria (Hb levels from local laboratory):

o Mean of Hb levels in the target range of 10.0 to 12.0 g/dL

inclusive during the Main Phase

o ≥ 50% of the Hb levels in the target range of 10.0 to 12.0 g/dL

inclusive during the Main Phase

o No RBC-containing transfusion during the active treatment.

Time within Hb target range (10.0 to 12.0 g/dL inclusive) during

study treatment measured as number of days and percentage of

time in range (defined as number of days in target range / number

of days on treatment)

Number of subjects meeting specific Hb criteria

Subjects with Hb values >13 g/dL or having excessive Hb increase

Duration of exposure, defined as duration in days between first

dose date and last dose date

Number and percentage of subjects requiring down-titration



Number and percentage of subjects requiring up-titration

Change from baseline in

o Reticulocyte counts

o Red blood cell (RBC) count and hematocrit (HcT)

o Central laboratory Hb

Safety: The following primary safety variables were evaluated:

o Adjudicated serious adverse events (SAEs): death and SAEs of the

following events: severe arrhythmias, thromboembolic events

(excluding hemodialysis vascular access events: arteriovenous

shunt / fistula and arteriovenous graft events), syncope,

symptomatic hypotension, and heart failure

o Events of special interest: liver function-related AEs, including

abnormal liver function tests and any hospitalization

o SAEs.

The following secondary safety variables were evaluated:

o Non-serious adverse events (AEs)

o HR and BP (at all time points and as change from baseline in this

study)

o Laboratory examinations: hematology, international normalized

ratio, Quick / prothrombin time (PT), partial thromboplastin time

(PTT), C-reactive protein (CRP), and chemistry, especially alanine

aminotransferase (ALT), aspartate aminotransferase (AST),

bilirubin, electrolytes, amylase, and lipase.

Statistical methods: Tables displayed the results for each treatment group, as well as overall

for the specified analysis population. As a general concept, data were

displayed as measured at each scheduled visit and the individual changes

as compared to baseline. A change was always calculated as post-baseline

value minus baseline value.

Population characteristics were summarized for modified intent-to-treat

(mITT) and safety (SAF) datasets for the Main Phase of the study and the

HbS safety set (HbSS) for the Hb Stabilization Phase.

As this is an extension study, both efficacy and safety analyses were based

on actual treatment received (BAY 85-3934 or darbepoetin). Additionally,

data from all BAY 85-3934 treatment groups were pooled for analysis of

efficacy and safety.



Efficacy:

The primary efficacy variable was the change in local laboratory Hb level

from baseline in the Main Phase to each post-baseline visit in the Main

Phase.

The primary efficacy endpoint was descriptively summarized by treatment

at each post baseline visit, along with 95% confidence intervals (CIs) for

mean and percent changes. In addition, mean difference (95% CI)

between BAY 85-3934 combined dose group and comparator group was

presented. Absolute Hb values at each visit including baseline visit was

also descriptively summarized.

Mean (with variation indicator) plots summarizing change from baseline

over time was provided.

In support of the above descriptive summaries, inferential analyses such

as constrained longitudinal data analysis (cLDA) were conducted.

Secondary efficacy analyses were descriptively summarized and defined

in the statistical analysis plan (SAP).

Analyses on changes of the following measures from baseline in parent

study were not performed in this report: Reticulocyte count, RBC count

and Hct, central laboratory Hb, HR, BP and 12-lead ECG data.

Safety:

Analyses on primary safety and tolerability were performed on the safety

analysis set defined as All subjects who received at least 1 dose of study

medication during the Main Phase. Descriptive summaries were provided

by treatment. Adverse events were coded using the Medical Dictionary for

Regulatory Activities version 19.1

Substantial protocol changes:

Global Amendment 1, dated 30 OCT 2014

To improve study feasibility and safety monitoring, Day 8HbS

visit was removed and the subjects from Study 15141 who had an

Hb stopping event after Day 15 in that study were added to the

safety monitoring at Day 15HbS visit

Heart failure was added to the list of adjudicated AEs , ECG

assessments were reduced from triplicate to single measurements

Statement of prescribed continuous dosing of acetaminophen /

paracetamol is not allowed was included in the protocol

Atrial fibrillation as an exclusion criterion was removed

Clarification on time separation of intake of BAY 85-3934 and

breast cancer resistant protein substrates.



Local Amendment 2, dated 19 NOV 2014

Protocol Amendment 2 which was a local amendment for UK and South

Korea only was dated on 19 NOV 2014 (version 2.0). The purpose of this

amendment was revised upon the request of regulatory authorities.

As the results of Segment I toxicological studies on male fertility have

become available, the male contraceptive requirements were removed as

per the integrated global protocol Amendment 1. Per local request from

competent authorities, the male contraceptive requirements were re-

instated.

Global Amendment 3, dated 24 NOV 2015

A discrepancy was identified between the BAY 85-3934 dose titrations

(dose increase, dose decrease, and dose suspension) described in the

protocol and those utilized in the IXRS system. The IXRS system has

been programmed to allow dose suspension in case of high Hb (Hb > 11.7

g/dL), which was not consistently applied everywhere in the protocol text.

For some sections, language was added to the protocol to add clarity to

dose suspension recommended by IXRS.

Subject disposition and baseline

A total of 166 subjects who were previously screened and signed informed consent in the parent

studies (15141 and 15261) were included in this extension trial. However, the data of 2 subjects who

were randomized were excluded from all analyses as a result of an audit in Poland concluding a

serious breach of compliancy issues. Thus, 164 subjects were analyzed in 15653.

Of the 164 subjects, 67 (40.9%) subjects entered the HbS Phase, 97 (59.1%) subjects were included

directly in the Main Phase, and 47 of 67 subjects (70.1%) rolled over from HbS Phase to Main

Phase.

HbS Phase

Sixty-seven subjects entered the HbS Phase, 4 (6.0%) did not receive any treatment, while 63

(94.0%) subjects were treated; 46 assigned to BAY85-3934 and 17 assigned to darbepoetin (these

previous placebo subjects were treated with ESA for the first time). Four non-treated subjects

discontinued the HbS Phase due to protocol driven decision point and a protocol violation. There

was an imbalance of discontinuations between groups; 18 (36.7%) subjects on BAY 85-3934 and 2

(11.1%) subjects on darbepoetin. Primary reasons for discontinuation were AE (6 subjects, 30.0%)

and protocol driven decision point (5 subjects, 25.0%). Two subjects withdrew treatment due to a

lack of efficacy.

Main Phase

A total of 144 subjects were treated; 103 assigned to BAY85-3934 and 41 assigned to darbepoetin.

All subjects discontinued treatment, primary reason being termination of the study per sponsor’s



decision (87 subjects, 60.4%). Other main reasons included AE (21 subjects, 14.6%) and protocol

driven decision point (19 subjects, 13.2%).

Follow-up

The proportion of subjects completing follow-up was similar between BAY85-3934 (82.2%) and

darbepoetin (73.8%) treatment groups.

Analysis sets

There were 3 datasets used in this study.

mITT: All subjects who received at least 1 dose of study medication during the Main Phase and had

at least 1 post-baseline Hb value in the Main Phase (n=144). This population was the primary dataset

for efficacy evaluation of subjects in the Main Phase.

SAF: All subjects who received at least 1 dose of study medication during the Main Phase (n=144).

This population was the primary dataset for safety evaluation of subjects in the Main Phase.

HbSS: All subjects who received at least 1 dose of study medication during HbS Phase (n=63). This

population was used to analyze and describe the effect observed in the stabilization phase only.

Subjects who entered the Main Phase directly were excluded from this population.

When analyzing data for the overall period, the mITT and HbSS combined population was used

(n=160). The HbSS and SAF combined population was used for analyzing safety data for the overall

period (n=160).

Demographics

Overall, the treatment groups were well-balanced with respect to demographics presented. The mean

age was similar with BAY 85-3934 and darbepoetin (69.6 years and 68.5 years, respectively), as was

the gender with male (48.3% and 52.4% respectively) and female participants (51.7% and 47.6%

respectively). More than half of subjects in each treatment arm were White while a single subject in

the darbepoetin group was Black. Under the BAY 85-3934 arm, the proportion of subjects who were

Asian and Japanese (38.1% and 27.1% respectively) was higher compared to subjects in the

darbepoetin group (21.4% and 11.9% respectively). Of the 160 subjects, only 4 were Hispanic or

Latino and the ethnicity for 3 subjects was unknown. Diabetes mellitus (59 subjects, 36.9%) and

hypertension (63 subjects, 39.4%) were the most frequently reported CKD etiology, which was also

highlighted for each parent study. Other CKD etiologies were reported for < 10% of total subjects.

Both groups were comparable in their mean eGFR values; BAY 85-3934: 23.41 mL/min/1.73m2 and

darbepoetin: 22.04 mL/min/1.73m2.

Efficacy evaluation

Change in local laboratory Hb level from baseline of the Main Phase to each post-baseline visit

in the Main Phase

In this open-label extension study where subjects were randomized in the parent trials 15141 and

15261, results of the primary efficacy variable of change in local laboratory Hb level from baseline

defined as:



i) as the average of scheduled Hb values from parent study visit 9-12 (evaluation period) for

subjects entering the Main Phase directly

ii) or defined as the average of values in HbS Phase used for inclusion into Main Phase (i.e.,

the last 2 clinical visits reported in the IXRS system) for subjects entering Main Phase

from HbS Phase

to each post-baseline visit using the mITT population demonstrated that BAY 85-3934 maintained

Hb levels in pre-dialysis subjects who had renal anemia due to CKD. The effect of BAY85-3934 on

the maintenance of Hb levels in CKD subjects was similar to that of darbepoetin. The mean change

from baseline at most visits was < 0.5 g/dL in both treatment groups. Mean local Hb levels were

maintained within the target range of 10.0 to 12.0 g/dL during the treatment period at all visits

except Week 108 for both BAY 85-3934 and darbepoetin groups due to study termination by the

sponsor. At Week 108, only 3 subjects in total were evaluable for local Hb assessment and therefore

the maintenance of Hb beyond 1 year could not be assessed. Mean (SD) local Hb values during

treatment were 11.10 (0.508) g/dL in the BAY 85-3934 group and 10.98 (0.571) g/dL in the

darbepoetin group.

Consistent results for the change in Hb levels from baseline were observed in the observed case and

last observation carried forward analyses. Furthermore, the sensitivity analysis conducted using

central Hb levels confirmed the results with local Hb levels demonstrating high correlation.

Responders in Hb levels

For the secondary variables, responder rate defined by 3 criteria was higher in the BAY85-3934

group than in the darbepoetin group; 95.1% versus 87.8% of subjects respectively had mean Hb

levels within target range of 10.0 to 12.0 g/dL, 92.2% and 87.8% of subjects respectively had ≥ 50%

of mean Hb within the target range, and 93.2% and 87.8% of subjects respectively had no RBC-

containing transfusion during treatment.

Time within Hb target range

The mean length of time spent within the Hb target range was similar between BAY 85-3934 and

darbepoetin (325.18 days versus 331.74 days respectively). The percentage of time spent in the

target range was also similar between the groups (80.68% versus 78.11% respectively).

At EoT, less than 22% of total subjects in each treatment group were either below or above target

range. The proportion of subjects meeting any of the 4 out of range specific local Hb criteria (i.e.

>50% of Hb levels < 10.0 g/dL, or > 12.0 g/dL, or mean Hb levels < 10.0 g/dL, or > 12.0 g/dL) was

lower in the BAY 85-3934 group compared to the darbepoetin group. The percentage of subjects

with Hb > 13.0 g/dL at any time was numerically higher for darbepoetin subjects compared to BAY

85-3934 subjects (12.2% versus 9.7% respectively). On the contrary, those subjects that had an

excessive increase > 2 g/dL over 4-week period all occurred in the BAY 85-3934 arm only (5 [4.9%]

subjects versus none).



Number of subjects meeting specific Hb criteria

Four criteria were defined for this endpoint (all occurring during the Main phase):

1. >50% of Hb levels below the lower limit

of 10.0 g/dL

3. >50% of Hb levels above the upper limit of

12.0 g/dL

2. Mean of Hb levels below the lower limit of

10 g/dL

4. Mean of Hb levels above the upper limit of

12.0 g/dL

The proportion of subjects meeting any of the critical or failing criteria was lower in the

BAY85-3934 group compared to the darbepoetin group. The number of subjects meeting each

criterion was generally low for either group, i.e. 6 subjects or less. The biggest difference between

the two groups was noted for criterion #2 (mean of Hb levels below the lower limit of 10.9 g/dL);

2.9% with BAY85-3934 and 7.3% with darbepoetin.

Subjects with Hb values >13 g/dL or having excessive Hb increase

Excessive Hb increased was defined as an increase of >2.0 g/dL over a 4-week period at any time

during the treatment period or a rise of >1.0 g/dL in 2 weeks. The rate of overshoot was comparable

between the two treatment groups, with 12.6% of subjects in BAY85-3934 group and 12.2% of

subjects in the darbepoetin group meeting any of the 2 criteria (Hb > 13 g/dL and Hb increased > 2

g/dL in 4-week period). Hb >13 g/dL was experienced by 9.7% of subjects in BAY85-3934 group

and 12.2% of subjects in the darbepoetin group. Excessive increase with >2 g/dL over 4 weeks

occurred only in the BAY85-3934 group (4.9% of subjects).

Duration of exposure

Treatment duration for the Main Phase was defined as date of last study drug (EoT date) - date of

first study drug + 1. If 0 mg occurred during the treatment period, but not as the last dose, then the

suspension period was included.

Mean treatment duration was similar for BAY85-3934 and darbepoetin groups (399.8 ± 185.92 and

414.6 ± 205.63 days, respectively).The minimum duration of exposure to BAY85-3934 was 26

days and maximum was 760 days.

Number and percentage of subjects requiring dose titration

The proportion of subjects requiring up or down-titrations during the Main phase was also similar

between the groups. Up-titrations were reported for 61.2% and 58.5% of subjects in the BAY85-

3934 and darbepoetin groups, respectively, and down-titrations were reported for 59.2% and 48.8%

of subjects in the BAY85-3934 and darbepoetin groups, respectively. On the other hand, a larger

proportion of subjects in BAY85-3934 group had dose suspensions compared to subjects in the

darbepoetin group (37.9% vs. 7.3%, respectively).

Change from baseline in reticulocyte, Hct and RBC counts and central Hb

Consistent with the maintenance of Hb during the study, reticulocyte count, RBC count and Hct

values showed little change over the study in either treatment group.



None of the pre-defined subgroups in each treatment arm were found to have a clinically significant

worsening of Hb at EoT.

Safety evaluation

The majority of subjects (n=137, 85.6%) reported at least 1 TEAE for the overall period, the

proportion of subjects was comparable between treatments (BAY85-3934: 85.6%, darbepoetin:

85.7%). The system organ classes (SOCs) investigations and vascular disorders presented the largest

percent difference between the 2 groups with 12.7% and 11.7% respectively compared to other

SOCs which were similar between BAY85-3934 and darbepoetin. The percentage of subjects

reporting the preferred term hypertension was higher in the darbepoetin group than in the BAY85-

3934 group (33.3% versus 20.3% respectively). Worsening of CKD reported as a TEAE was similar

between the treatment groups (BAY85-3934: 17.8%, darbepoetin: 19.0%). Most other preferred

terms were noted in < 10% of total subjects. Incidences of study drug-related TEAEs was low in the

study (6.3% overall) reported for 8 (6.8%) subjects in the BAY85-3934 group and 2 (4.8%) subjects

in the darbepoetin group. Incidences of study procedure-related TEAEs was also low occurring for

3 subjects in total; 2 subjects with BAY85-3934 and 1 subject with darbepoetin.

Five subjects in the BAY85-3934 group and 1 subject in the darbepoetin group died on study.

Causes of death for BAY85-3934 subjects were heart failure (2 cases, 1 case being worsening of

heart failure), acute respiratory failure, pneumonia, and gangrene. Metastatic gastric cancer was the

cause of death for the darbepoetin subject. No death was judged by the investigator as study drug-

related.

Similar rates of serious TEAEs were reported for BAY85-3934 and darbepoetin treatments (47.5%

versus 52.4% respectively). In this population, worsening of CKD, pneumonia, and ESRD were the

most commonly preferred terms in > 5 total subjects. Three subjects reported serious treatment-

related events which included hypertension reported in the darbepoetin group and melena and

intestinal adenocarcinoma reported in the BAY 85-3934 group.

The CAC adjudicated all deaths, major adverse cardiovascular event (MACE), and serious TEAEs

of severe arrhythmias, thromboembolic events (excluding hemodialysis vascular access events:

arteriovenous shunt / fistula and arteriovenous graft events), syncope or symptomatic hypotension,

and heart failure. The proportion of subjects with MACE were numerically higher in in the

BAY85-3934 group (6.8%) versus darbepoetin group (4.8%). The proportion of subjects reporting

positively adjudicated serious TEAEs was the same in each treatment group (11.9% in each group).

In addition to MACE, heart failure (total 4.4%), and death and thromboembolic events (total 3.8%

each) were the most frequently reported adjudicated TEAEs across the 2 groups.

For the Main Phase, treatment withdrawals / discontinuations due to TEAEs were reported in 17.5%

of subjects in the BAY85-3934 group and 7.3% of subjects in the darbepoetin group. This imbalance

was also observed for the overall period; 21.2% of subjects in the BAY85-3934 group and 9.5% of

subjects in the darbepoetin group. Among all reported SOCs in the Main Phase, renal and urinary

disorders were the most commonly reported SOC for treatment discontinuation across the treatment

groups (BAY85-3934: 7.8% versus darbepoetin: 4.9%). Other SOCs reported occurred for < 3% of

subjects in any arm. It should be noted that investigators may have chosen to discontinue subjects

from oral BAY85-3934, as this was an open-label study and BAY85-3934 subjects could switch to



standard of care parenteral darbepoetin once every 2 weeks (fallback option), while subjects on

darbepoetin were already receiving standard of care. This reason may have contributed to the

imbalance in discontinuations.

Dose interruptions due to TEAEs were reported by < 10% of Main Phase subjects, driven by the

SOC cardiac disorders reported for 4 out of 10 subjects. All dose interruptions were observed in the

BAY85-3934 group only. Other SOCs leading to dose interruption were reported in a total of 2

subjects or less. No TEAE leading to dose interruption was considered treatment-related by the

investigator. The preferred terms myocardial infarction, pneumonia, traumatic subdural hemorrhage,

and cardiac failure chronic were assessed as serious TEAEs that led to dose interruption.

Overall, there were no clinically meaningful changes from baseline laboratory parameters or vital

signs in either treatment group.

The overall rate of TEAEs, SAEs, and non-fatal MACE were similar between the two treatment

groups and no other safety issue was identified with BAY85-3934. The incidence of deaths under

BAY85-3934 was 4.2% relative to 2.4% under darbepoetin. The overall results of this study show a

comparable safety profile of BAY85-3934 relative to darbepoetin which is standard of care.

However, the number of subjects included in this study was too low (n=118) to draw meaningful

conclusions on the long-term safety of BAY85-3934.

Overall conclusions

In this open-label extension study, BAY85-3934 maintained mean local Hb in the target range of

10.0 –12.0 g/dL throughout the study. Hemoglobin measurements performed by the central

laboratory had results similar to local laboratory results. The magnitude of the effect of

BAY85-3934 on mean Hb levels was similar to that of darbepoetin. The results of this study show a

comparable safety profile of BAY85-3934 in comparison to darbepoetin which is standard of care.

However, the number of subjects included in this study was too low (n=118) to draw meaningful

conclusions on the long-term safety of BAY85-3934.

Documents

Clinical Study Synopsis - Bayertrialfinder.pharma.bayer.com/omr/online/15653_Study-Synopsis_CTP.… · Clinical Trial Results Synopsis 20-NOV-2017 Study no. 15653 Page: 4 of 13 Study