Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39233   clinical trials with a EudraCT protocol, of which   6427   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A MULTICENTER, PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, DOSE-RANGING STUDY TO EVALUATE THE EFFICACY AND SAFETY OF BIMEKIZUMAB IN ACTIVE PSORIATIC ARTHRITIS

    Summary
    EudraCT number
    2016-001103-23
    Trial protocol
    HU   CZ   DE   GB  
    Global end of trial date
    16 Jul 2018

    Results information
    Results version number
    v2(current)
    This version publication date
    13 Dec 2020
    First version publication date
    08 Sep 2019
    Other versions
    v1
    Version creation reason
    • Correction of full data set
    Alignment with final posting on ClinicalTrials.gov after NIH review.

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    PA0008
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02969525
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    UCB Biopharma SPRL
    Sponsor organisation address
    Allée de la Recherche 60, Brussels, Belgium, 1070
    Public contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
    Scientific contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Dec 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Jul 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Assess the dose-response based on the efficacy of bimekizumab.
    Protection of trial subjects
    During this study all study participants were closely monitored.
    Background therapy
    Background therapy as permitted in the protocol. No medication increases or decreases were permitted for medications taken for psoriatic arthritis (PsA) until after the Week 16 protocol assessments. However, a decrease in dosing or dosing frequency of any agent was permitted for reasons of intolerance/Adverse Events (AEs)/side effects at any time.
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    27 Oct 2016
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Efficacy, Safety
    Long term follow-up duration
    2 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Czechia: 26
    Country: Number of subjects enrolled
    Germany: 16
    Country: Number of subjects enrolled
    Hungary: 3
    Country: Number of subjects enrolled
    Poland: 108
    Country: Number of subjects enrolled
    Russian Federation: 13
    Country: Number of subjects enrolled
    United States: 40
    Worldwide total number of subjects
    206
    EEA total number of subjects
    153
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    185
    From 65 to 84 years
    21
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The study started to enroll patients in October 2016 and concluded in July 2018.

    Pre-assignment
    Screening details
    The study included a 28-Day Screening Period, followed by a Double-blind Period from Day 1 to Week 12, prior to treatment re-randomization, a Dose-blind Period, from Week 12 after the treatment re-randomization and up to Week 48 and a Safety Follow-Up (SFU) Period, post week 48. The Participant Flow refers to the Randomized Set and Dose-Blind Set.

    Period 1
    Period 1 title
    Double-Blind Period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Carer, Investigator, Assessor, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Participants received Placebo during the 12 Weeks Double-Blind Period.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    PBO
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects were administered Placebo, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

    Arm title
    BKZ 16 mg
    Arm description
    Participants received Bimekizumab (BKZ) 16 milligrams (mg) every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

    Arm title
    BKZ 160 mg
    Arm description
    Participants received Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

    Arm title
    BKZ 160 mg LD
    Arm description
    Participants received Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

    Arm title
    BKZ 320 mg
    Arm description
    Participants received Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

    Number of subjects in period 1
    Placebo BKZ 16 mg BKZ 160 mg BKZ 160 mg LD BKZ 320 mg
    Started
    42
    41
    41
    41
    41
    Completed Double-Blind Period
    42
    41
    40
    39
    41
    Completed Wk12 and started Dose-Blind
    40
    41
    40
    37
    41
    Completed
    40
    41
    40
    37
    41
    Not completed
    2
    0
    1
    4
    0
         Adverse event, non-fatal
    -
    -
    1
    1
    -
         Study medication discontinued prior Wk12
    2
    -
    -
    2
    -
         LOW EGFR
    -
    -
    -
    1
    -
    Period 2
    Period 2 title
    Dose-Blind Period
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Assessor, Carer, Investigator, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo - BKZ 160 mg
    Arm description
    After the 12 Weeks Double-Blind Period participants randomized to Placebo were re-randomized to receive Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) for 36 weeks in the Dose-Blind Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

    Arm title
    Placebo - BZK 320 mg
    Arm description
    After the 12 Weeks Double-Blind Period participants randomized to Placebo were re-randomized to receive Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) for 36 weeks in the Dose-Blind Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

    Arm title
    BKZ 16 mg - BKZ 160 mg
    Arm description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 16 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

    Arm title
    BZK 16 mg - BZK 320 mg
    Arm description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 16 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 320 mg Q4W for 36 weeks in the Dose-Blind Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

    Arm title
    BZK 160 mg LD - BZK 160 mg
    Arm description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

    Arm title
    BZK 160 mg - BKZ dose 160 mg
    Arm description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

    Arm title
    BKZ 320 mg - BKZ 320 mg
    Arm description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 320 mg Q4W for 36 weeks in the Dose-Blind Period.
    Arm type
    Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects were administered different BKZ doses, as 2 subcutaneous injections, in the lateral abdominal wall, or upper outer thigh.

    Number of subjects in period 2
    Placebo - BKZ 160 mg Placebo - BZK 320 mg BKZ 16 mg - BKZ 160 mg BZK 16 mg - BZK 320 mg BZK 160 mg LD - BZK 160 mg BZK 160 mg - BKZ dose 160 mg BKZ 320 mg - BKZ 320 mg
    Started
    20
    20
    22
    19
    37
    40
    41
    Completed
    20
    18
    22
    18
    34
    38
    39
    Not completed
    0
    2
    0
    1
    3
    2
    2
         Non-cooperating patient
    -
    -
    -
    -
    -
    -
    1
         Withdrew before Safety Follow-up visit
    -
    -
    -
    -
    -
    1
    -
         Adverse event, non-fatal
    -
    -
    -
    -
    1
    1
    1
         Consent withdrawn by subject
    -
    2
    -
    1
    2
    -
    -

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants received Placebo during the 12 Weeks Double-Blind Period.

    Reporting group title
    BKZ 16 mg
    Reporting group description
    Participants received Bimekizumab (BKZ) 16 milligrams (mg) every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period.

    Reporting group title
    BKZ 160 mg
    Reporting group description
    Participants received Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period.

    Reporting group title
    BKZ 160 mg LD
    Reporting group description
    Participants received Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period.

    Reporting group title
    BKZ 320 mg
    Reporting group description
    Participants received Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period.

    Reporting group values
    Placebo BKZ 16 mg BKZ 160 mg BKZ 160 mg LD BKZ 320 mg Total
    Number of subjects
    42 41 41 41 41 206
    Age categorical
    Units: Subjects
        <=18 years
    0 0 0 0 0 0
        Between 18 and 65 years
    38 35 40 36 36 185
        >=65 years
    4 6 1 5 5 21
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    49.02 ± 12.07 49.98 ± 13.56 48.00 ± 11.65 49.05 ± 12.99 50.39 ± 12.08 -
    Gender categorical
    Units: Subjects
        Male
    24 24 20 14 23 105
        Female
    18 17 21 27 18 101

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants received Placebo during the 12 Weeks Double-Blind Period.

    Reporting group title
    BKZ 16 mg
    Reporting group description
    Participants received Bimekizumab (BKZ) 16 milligrams (mg) every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period.

    Reporting group title
    BKZ 160 mg
    Reporting group description
    Participants received Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period.

    Reporting group title
    BKZ 160 mg LD
    Reporting group description
    Participants received Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period.

    Reporting group title
    BKZ 320 mg
    Reporting group description
    Participants received Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period.
    Reporting group title
    Placebo - BKZ 160 mg
    Reporting group description
    After the 12 Weeks Double-Blind Period participants randomized to Placebo were re-randomized to receive Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) for 36 weeks in the Dose-Blind Period.

    Reporting group title
    Placebo - BZK 320 mg
    Reporting group description
    After the 12 Weeks Double-Blind Period participants randomized to Placebo were re-randomized to receive Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) for 36 weeks in the Dose-Blind Period.

    Reporting group title
    BKZ 16 mg - BKZ 160 mg
    Reporting group description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 16 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period.

    Reporting group title
    BZK 16 mg - BZK 320 mg
    Reporting group description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 16 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 320 mg Q4W for 36 weeks in the Dose-Blind Period.

    Reporting group title
    BZK 160 mg LD - BZK 160 mg
    Reporting group description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period.

    Reporting group title
    BZK 160 mg - BKZ dose 160 mg
    Reporting group description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period.

    Reporting group title
    BKZ 320 mg - BKZ 320 mg
    Reporting group description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 320 mg Q4W for 36 weeks in the Dose-Blind Period.

    Subject analysis set title
    Placebo (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants received Placebo during the 12 Weeks Double-Blind Period, forming the Full Analysis Set (FAS).

    Subject analysis set title
    BKZ 16 mg (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants received Bimekizumab (BKZ) 16 milligrams (mg) every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period, forming the Full Analysis Set (FAS).

    Subject analysis set title
    BKZ 160 mg (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants received Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the Full Analysis Set (FAS).

    Subject analysis set title
    BKZ 160 mg LD (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants received Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period, forming the Full Analysis Set (FAS).

    Subject analysis set title
    BKZ 320 mg (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants received Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the Full Analysis Set (FAS).

    Subject analysis set title
    Placebo - BKZ 160 mg (DBS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    After the 12 Weeks Double-Blind Period participants randomized to Placebo were re-randomized to receive Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

    Subject analysis set title
    Placebo - BZK 320 mg (DBS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    After the 12 Weeks Double-Blind Period participants randomized to Placebo were re-randomized to receive Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

    Subject analysis set title
    BKZ 16 mg - BKZ 160 mg (DBS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 16 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

    Subject analysis set title
    BZK 16 mg - BZK 320 mg (DBS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 16 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 320 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

    Subject analysis set title
    BZK 160 mg LD - BZK 160 mg (DBS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

    Subject analysis set title
    BZK 160 mg - BKZ 160 mg (DBS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 160 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

    Subject analysis set title
    BKZ 320 mg - BKZ 320 mg (DBS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    After the 12 Weeks Double-Blind Period participants randomized to Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) were re-randomized to receive BKZ 320 mg Q4W for 36 weeks in the Dose-Blind Period. Participants are a subgroup from the Dose-Blind Set (DBS). The subgroup contained participants who were part of the PK-PPS and DBS.

    Subject analysis set title
    Placebo (SS)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants received Placebo during the 12 Weeks Double-Blind Period, forming the Safety Set (SS).

    Subject analysis set title
    BKZ 16 mg (SS)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants received Bimekizumab (BKZ) 16 milligrams (mg) every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period, forming the SS.

    Subject analysis set title
    BKZ 160 mg (SS)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants received Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the SS.

    Subject analysis set title
    BKZ 160 mg LD (SS)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants received Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period, forming the SS.

    Subject analysis set title
    BKZ 320 mg (SS)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants received Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) during the 12 Weeks Double-Blind Period followed by the same dose during the 36 Weeks Dose-Blind Period, forming the SS.

    Subject analysis set title
    Placebo (SS) - up to Wk 12
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    This arm consisted of all participants who received Placebo at any time in the study (up to Week 12). Participants formed the Safety Set (SS).

    Subject analysis set title
    BKZ 16 mg (SS) - up to Wk 12
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    This arm consisted of all participants who received Bimekizumab (BKZ) 16 milligrams (mg) every 4 weeks (Q4W) at any time in the study (up to Week 12). Participants formed the SS.

    Subject analysis set title
    BKZ 160 mg & 160 mg LD (SS) - up to Wk 68
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    This arm consisted of all participants who received Bimekizumab (BKZ) 320 mg at Baseline followed by 160 mg every 4 weeks (Q4W) and Bimekizumab (BKZ) 160 mg every 4 weeks (Q4W) at any time in the study (up to Week 68). Participants formed the SS.

    Subject analysis set title
    BKZ 320 mg (SS) - up to Wk 68
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    This arm consisted of all participants who received Bimekizumab (BKZ) 320 mg every 4 weeks (Q4W) at any time in the study (up to Week 68). Participants formed the SS.

    Primary: ACR50 (American College of Rheumatology 50% Improvement) Response at Week 12

    Close Top of page
    End point title
    ACR50 (American College of Rheumatology 50% Improvement) Response at Week 12
    End point description
    The ACR50 response rate was based on 50% improvement relative to Baseline in the following measures: •Tender Joint Count (TJC) based on 78 joints •Swollen Joint Count (SJC) based on 76 joints •3 of the 5 remaining core set measures: -Disease activity as assessed by Patient’s Global Assessment of Disease Activity (PGADA) -Disease activity as assessed by Physician’s Global Assessment of Disease Activity (PhGADA) -Pain as assessed by Patient’s Assessment of Arthritis Pain (PtAAP) -Physical function as assessed by Health Assessment Questionnaire – Disability Index (HAQ-DI) -Acute phase response as assessed by high sensitivity C-reactive protein (hs CRP). The Full Analysis Set (FAS) consisted of all randomized study participants who received at least 1 dose of investigational medicinal product (IMP) and had a valid measurement of the primary efficacy variable at Baseline.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    Placebo (FAS) BKZ 16 mg (FAS) BKZ 160 mg (FAS) BKZ 160 mg LD (FAS) BKZ 320 mg (FAS)
    Number of subjects analysed
    42
    41
    41
    41
    41
    Units: percentage of subjects
        number (not applicable)
    7.1
    26.8
    41.5
    46.3
    24.4
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Statistic and p-value were calculated using a Cochran-Mantel-Haenszel test (test for non-zero correlation statistic) based on modified ridit scores and including geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure as stratification factors. The 160 loading dose arm was not considered in the dose-response because this is a mixed dose and the test is examining linear dose response.
    Comparison groups
    Placebo (FAS) v BKZ 16 mg (FAS) v BKZ 160 mg (FAS) v BKZ 160 mg LD (FAS) v BKZ 320 mg (FAS)
    Number of subjects included in analysis
    206
    Analysis specification
    Pre-specified
    Analysis type
    other [1]
    P-value
    = 0.031
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Correlation statistic
    Point estimate
    999
    Confidence interval
         level
    0%
         sides
    2-sided
         lower limit
    999
         upper limit
    999
    Notes
    [1] - 999 and 0% CI are used as placeholders. Using this methodology no point estimator was calculated. The respective correlation statistic was 4.6.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    For differences in relation to placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Factor Necrosis (TNF) inhibitor exposure.
    Comparison groups
    Placebo (FAS) v BKZ 16 mg (FAS)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other [2]
    P-value
    = 0.032 [3]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    4.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.13
         upper limit
    15.23
    Notes
    [2] - The pairwise testing of each bimekizumab dose versus placebo accounted for multiplicity by using a fixed sequence testing procedure with each bimekizumab dose being tested sequentially from the highest dose to the lowest dose. If the sequential testing failed to reach significance at a significance level of alpha=0.05, then the pairwise testing continued and the comparison was seen as non-significant.
    [3] - The p-values were displayed as nominal p-values.
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    For differences in relation to placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Factor Necrosis (TNF) inhibitor exposure.
    Comparison groups
    Placebo (FAS) v BKZ 160 mg (FAS)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other [4]
    P-value
    = 0.001 [5]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    8.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.28
         upper limit
    28.74
    Notes
    [4] - The pairwise testing of each bimekizumab dose versus placebo accounted for multiplicity by using a fixed sequence testing procedure with each bimekizumab dose being tested sequentially from the highest dose to the lowest dose. If the sequential testing failed to reach significance at a significance level of alpha=0.05, then the pairwise testing continued and the comparison was seen as non-significant.
    [5] - The p-values were displayed as nominal p-values.
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    For differences in relation to placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Factor Necrosis (TNF) inhibitor exposure.
    Comparison groups
    Placebo (FAS) v BKZ 160 mg LD (FAS)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other [6]
    P-value
    < 0.001 [7]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    9.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.73
         upper limit
    34.26
    Notes
    [6] - The pairwise testing of each bimekizumab dose versus placebo accounted for multiplicity by using a fixed sequence testing procedure with each bimekizumab dose being tested sequentially from the highest dose to the lowest dose. If the sequential testing failed to reach significance at a significance level of alpha=0.05, then the pairwise testing continued and the comparison was seen as non-significant.
    [7] - The p-values were displayed as nominal p-values.
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    For differences in relation to placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Factor Necrosis (TNF) inhibitor exposure.
    Comparison groups
    Placebo (FAS) v BKZ 320 mg (FAS)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other [8]
    P-value
    = 0.051 [9]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    3.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1
         upper limit
    13.68
    Notes
    [8] - The pairwise testing of each bimekizumab dose versus placebo accounted for multiplicity by using a fixed sequence testing procedure with each bimekizumab dose being tested sequentially from the highest dose to the lowest dose. If the sequential testing failed to reach significance at a significance level of alpha=0.05, then the pairwise testing continued and the comparison was seen as non-significant.
    [9] - The p-values were displayed as nominal p-values.

    Secondary: ACR20 (American College of Rheumatology 20% Improvement) Response at Week 12

    Close Top of page
    End point title
    ACR20 (American College of Rheumatology 20% Improvement) Response at Week 12
    End point description
    The ACR20 response rate was based on 20% improvement relative to Baseline in the following measures: •TJC based on 78 joints •SJC based on 76 joints •3 of the 5 remaining core set measures: -Disease activity as assessed by PGADA -Disease activity as assessed by PhGADA -Pain as assessed by PtAAP -Physical function as assessed by HAQ-DI -Acute phase response as assessed by hs CRP Note: Nonresponder imputation was used to account for missing data in the primary analysis, the study participants with a missing ACR score at Week 12 or who discontinued IMP prior to the Week 12 Visit were considered nonresponders for the primary analysis. The FAS consisted of all randomized study participants who received at least 1 dose of IMP and had a valid measurement of the primary efficacy variable at Baseline.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Placebo (FAS) BKZ 16 mg (FAS) BKZ 160 mg (FAS) BKZ 160 mg LD (FAS) BKZ 320 mg (FAS)
    Number of subjects analysed
    42
    41
    41
    41
    41
    Units: percentage of subjects
        number (not applicable)
    19.0
    53.7
    73.2
    61.0
    51.2
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.
    Comparison groups
    Placebo (FAS) v BKZ 16 mg (FAS)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.002 [10]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    4.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.73
         upper limit
    12.39
    Notes
    [10] - No sequential testing procedure was used for the secondary efficacy variables. The p-values were displayed as nominal p-values.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.
    Comparison groups
    Placebo (FAS) v BKZ 160 mg (FAS)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001 [11]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.91
         upper limit
    30.95
    Notes
    [11] - No sequential testing procedure was used for the secondary efficacy variables. The p-values were displayed as nominal p-values.
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.
    Comparison groups
    Placebo (FAS) v BKZ 160 mg LD (FAS)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001 [12]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    6.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.31
         upper limit
    16.84
    Notes
    [12] - No sequential testing procedure was used for the secondary efficacy variables. The p-values were displayed as nominal p-values.
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.
    Comparison groups
    Placebo (FAS) v BKZ 320 mg (FAS)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.004 [13]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    4.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.59
         upper limit
    11.35
    Notes
    [13] - No sequential testing procedure was used for the secondary efficacy variables. The p-values were displayed as nominal p-values.

    Secondary: ACR70 (American College of Rheumatology 70% Improvement) Response at Week 12

    Close Top of page
    End point title
    ACR70 (American College of Rheumatology 70% Improvement) Response at Week 12
    End point description
    The ACR70 response rate was based on 70% improvement relative to Baseline in the following measures: •TJC based on 78 joints •SJC based on 76 joints •3 of the 5 remaining core set measures: -Disease activity as assessed by PGADA -Disease activity as assessed by PhGADA -Pain as assessed by PtAAP -Physical function as assessed by HAQ-DI -Acute phase response as assessed by hs CRP Note: Nonresponder imputation was used to account for missing data in the primary analysis, the study participants with a missing ACR score at Week 12 or who discontinued IMP prior to the Week 12 Visit were considered nonresponders for the primary analysis. The FAS consisted of all randomized study participants who received at least 1 dose of IMP and had a valid measurement of the primary efficacy variable at Baseline.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Placebo (FAS) BKZ 16 mg (FAS) BKZ 160 mg (FAS) BKZ 160 mg LD (FAS) BKZ 320 mg (FAS)
    Number of subjects analysed
    42
    41
    41
    41
    41
    Units: percentage of subjects
        number (not applicable)
    4.8
    12.2
    19.5
    31.7
    14.6
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.
    Comparison groups
    Placebo (FAS) v BKZ 16 mg (FAS)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.279 [14]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.5
         upper limit
    11.31
    Notes
    [14] - No sequential testing procedure was used for the secondary efficacy variables. The p-values were displayed as nominal p-values.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.
    Comparison groups
    Placebo (FAS) v BKZ 160 mg (FAS)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.065 [15]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    4.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.92
         upper limit
    17.88
    Notes
    [15] - No sequential testing procedure was used for the secondary efficacy variables. The p-values were displayed as nominal p-values.
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.
    Comparison groups
    Placebo (FAS) v BKZ 160 mg LD (FAS)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.006 [16]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    7.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.77
         upper limit
    31.28
    Notes
    [16] - No sequential testing procedure was used for the secondary efficacy variables. The p-values were displayed as nominal p-values.
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    For differences in relation to Placebo: Odds Ratio, confidence interval, and p-value were derived from a logistic regression model including fixed effects for treatment, geographic region and prior Tumor Necrosis Factor (TNF) inhibitor exposure.
    Comparison groups
    Placebo (FAS) v BKZ 320 mg (FAS)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.172 [17]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.63
         upper limit
    13.39
    Notes
    [17] - No sequential testing procedure was used for the secondary efficacy variables. The p-values were displayed as nominal p-values.

    Secondary: PASI90 (Psoriasis Area Severity Index) Response at Week 12 in the Subgroup of Subjects With Psoriasis Involving at Least 3 % Body Surface Area (BSA) at Baseline/Day 1

    Close Top of page
    End point title
    PASI90 (Psoriasis Area Severity Index) Response at Week 12 in the Subgroup of Subjects With Psoriasis Involving at Least 3 % Body Surface Area (BSA) at Baseline/Day 1
    End point description
    PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. This is a scoring system that averages the redness/thickness/scaliness of the psoriatic lesions (0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head/arms/trunk to groin/legs to top of buttocks. Assignment of an average score for the redness/thickness/scaling for each of the 4 body areas with a score of 0 (clear)-4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0-6 scale. Final PASI=average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. Minimum possible PASI score is 0=no disease, maximum score is 72=maximal disease. Subset of study participants in the FAS with ≥3% PSO BSA at Baseline (NRI).
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Placebo (FAS) BKZ 16 mg (FAS) BKZ 160 mg (FAS) BKZ 160 mg LD (FAS) BKZ 320 mg (FAS)
    Number of subjects analysed
    20
    14
    16
    17
    11
    Units: percentage of subjects
        number (not applicable)
    10.0
    35.7
    62.5
    52.9
    45.5
    No statistical analyses for this end point

    Secondary: PASI75 (Psoriasis Area Severity Index) Response at Week 12 in the Subgroup of Subjects With Psoriasis Involving at Least 3 % Body Surface Area (BSA) at Baseline/Day 1

    Close Top of page
    End point title
    PASI75 (Psoriasis Area Severity Index) Response at Week 12 in the Subgroup of Subjects With Psoriasis Involving at Least 3 % Body Surface Area (BSA) at Baseline/Day 1
    End point description
    PASI75 response assessments are based on at least 75% improvement in the PASI score from Baseline. This is a scoring system that averages the redness/thickness/scaliness of the psoriatic lesions (0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head/arms/trunk to groin/legs to top of buttocks. Assignment of an average score for the redness/thickness/scaling for each of the 4 body areas with a score of 0 (clear)-4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0-6 scale. Final PASI=average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. Minimum possible PASI score is 0=no disease, maximum score is 72=maximal disease. Subset of study participants in the FAS with ≥3% PSO BSA at Baseline (NRI).
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Placebo (FAS) BKZ 16 mg (FAS) BKZ 160 mg (FAS) BKZ 160 mg LD (FAS) BKZ 320 mg (FAS)
    Number of subjects analysed
    20
    14
    16
    17
    11
    Units: percentage of subjects
        number (not applicable)
    10.0
    57.1
    68.8
    70.6
    72.7
    No statistical analyses for this end point

    Secondary: Percentage of participants with at least one adverse event (AE) during the study

    Close Top of page
    End point title
    Percentage of participants with at least one adverse event (AE) during the study
    End point description
    An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. The Safety Set (SS) consisted of all randomized study participants who received at least 1 dose of IMP. The 160mg LD group and 160mg groups are combined into one column to see the effect of the 160mg dose overall.   
    End point type
    Secondary
    End point timeframe
    From Screening Period until the Safety Follow-Up Visit (up to Week 72)
    End point values
    Placebo (SS) - up to Wk 12 BKZ 16 mg (SS) - up to Wk 12 BKZ 160 mg & 160 mg LD (SS) - up to Wk 68 BKZ 320 mg (SS) - up to Wk 68
    Number of subjects analysed
    42
    39
    126
    80
    Units: percentage of participants
        number (not applicable)
    57.1
    33.33
    74.6
    72.5
    No statistical analyses for this end point

    Secondary: Percentage of participants with at least one serious adverse event (SAE) during the study

    Close Top of page
    End point title
    Percentage of participants with at least one serious adverse event (SAE) during the study
    End point description
    A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: • Results in death • Is life-threatening • Requires in patient hospitalization or prolongation of existing hospitalization • Is a congenital anomaly or birth defect • Is an infection that requires treatment parenteral antibiotics • Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above. The Safety Set (SS) consisted of all randomized study participants who received at least 1 dose of IMP. The 160mg LD group and 160mg groups are combined into one column to see the effect of the 160mg dose overall.   
    End point type
    Secondary
    End point timeframe
    From Screening Period until the Safety Follow-Up Visit (up to Week 72)
    End point values
    Placebo (SS) - up to Wk 12 BKZ 16 mg (SS) - up to Wk 12 BKZ 160 mg & 160 mg LD (SS) - up to Wk 68 BKZ 320 mg (SS) - up to Wk 68
    Number of subjects analysed
    42
    39
    126
    80
    Units: percentage of participants
        number (not applicable)
    2.4
    0
    6.3
    0
    No statistical analyses for this end point

    Secondary: Percentage of participants who withdrew due to an adverse event (AE) during the study

    Close Top of page
    End point title
    Percentage of participants who withdrew due to an adverse event (AE) during the study
    End point description
    An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. The Safety Set (SS) consisted of all randomized study participants who received at least 1 dose of IMP. The 160mg LD group and 160mg groups are combined into one column to see the effect of the 160mg dose overall.   
    End point type
    Secondary
    End point timeframe
    From Screening Period until the Safety Follow-Up Visit (up to Week 72)
    End point values
    Placebo (SS) - up to Wk 12 BKZ 16 mg (SS) - up to Wk 12 BKZ 160 mg & 160 mg LD (SS) - up to Wk 68 BKZ 320 mg (SS) - up to Wk 68
    Number of subjects analysed
    42
    39
    126
    80
    Units: percentage of participants
        number (not applicable)
    4.8
    0
    4.8
    2.5
    No statistical analyses for this end point

    Secondary: Changes from Baseline in vital signs during the study (diastolic blood pressure, systolic blood pressure)

    Close Top of page
    End point title
    Changes from Baseline in vital signs during the study (diastolic blood pressure, systolic blood pressure)
    End point description
    Diastolic and systolic blood pressure (BP) were measured in millimeters of mercury (mmHg). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, 30 min and 1 hour post dose, Week 1, Week 2, pre- and post dose for the following Weeks: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    42
    39
    43
    41
    41
    Units: mmHg
    arithmetic mean (standard deviation)
        Diastolic BP 30 min post dose (42, 39, 43, 41, 41)
    1.3 ± 8.9
    -1.2 ± 4.9
    -1.2 ± 5.4
    0.6 ± 6.1
    -0.6 ± 5.3
        Diastolic BP 1 h post dose (42, 39, 43, 41, 41)
    1.1 ± 8.8
    -2.0 ± 6.3
    -0.7 ± 8.1
    1.2 ± 6.7
    -1.0 ± 5.5
        Diastolic BP Wk 1 (41, 39, 43, 41, 41)
    0.1 ± 9.6
    -0.3 ± 6.5
    0.6 ± 11.4
    -0.9 ± 6.6
    -0.4 ± 6.5
        Diastolic BP Wk 2 (42, 39, 43, 41, 41)
    0.7 ± 10.4
    -0.7 ± 6.5
    -1.0 ± 8.9
    -2.7 ± 8.3
    -0.1 ± 9.0
        Diastolic BP Wk 4 pre-dose (41, 39, 42, 41, 41)
    0.0 ± 8.2
    -1.7 ± 8.4
    -1.4 ± 10.7
    -0.8 ± 7.8
    -1.3 ± 7.4
        Diastolic BP Wk 4 post dose (41, 39, 41, 40, 40)
    -2.0 ± 8.7
    -1.0 ± 7.3
    -1.2 ± 8.9
    -0.9 ± 8.3
    -1.6 ± 7.6
        Diastolic BP Wk 8 pre-dose (41, 39, 43, 39, 41)
    1.0 ± 8.2
    -1.3 ± 8.7
    0.3 ± 8.7
    -0.5 ± 7.0
    0.2 ± 6.9
        Diastolic BP Wk 8 post dose (41, 39, 42, 39, 41)
    -0.9 ± 9.1
    -1.1 ± 8.4
    0.6 ± 8.7
    -0.7 ± 7.3
    -2.2 ± 7.4
        Diastolic BP Wk 12 pre-dose (42, 39, 42, 39, 41)
    0.2 ± 9.1
    -1.1 ± 10.4
    0.2 ± 8.5
    -1.5 ± 7.9
    -0.6 ± 8.2
        Diastolic BP Wk 12 post dose (40, 39, 42, 37, 41)
    -0.3 ± 9.6
    -2.0 ± 10.0
    0.3 ± 8.3
    -1.8 ± 7.9
    -2.6 ± 8.0
        Diastolic BP Wk 16 pre-dose (42, 39, 42, 38, 41)
    -2.7 ± 9.6
    -3.5 ± 8.9
    -0.8 ± 8.6
    -1.2 ± 8.7
    -0.4 ± 7.9
        Diastolic BP Wk 16 post dose (40, 39, 39, 36, 39)
    -3.0 ± 9.1
    -1.9 ± 8.3
    -1.7 ± 9.2
    -1.1 ± 7.9
    -2.4 ± 8.7
        Diastolic BP Wk 20 pre-dose (40, 39, 42, 37, 40)
    0.5 ± 10.3
    -1.8 ± 9.0
    -0.6 ± 8.3
    -1.4 ± 8.3
    -1.8 ± 7.3
        Diastolic BP Wk 20 post dose (39, 39, 38, 36, 40)
    0.1 ± 9.5
    -3.1 ± 8.3
    -0.4 ± 9.2
    -3.0 ± 9.3
    -2.6 ± 7.1
        Diastolic BP Wk 24 pre-dose (39, 39, 41, 36, 40)
    -0.4 ± 7.6
    -1.6 ± 7.2
    -0.7 ± 9.3
    1.0 ± 6.9
    -1.0 ± 6.6
        Diastolic BP Wk 24 post dose (39, 38, 38, 35, 39)
    -0.6 ± 7.5
    -1.7 ± 7.9
    -0.3 ± 8.2
    -0.3 ± 7.6
    -1.4 ± 7.9
        Diastolic BP Wk 28 pre-dose (39, 39, 41, 35, 40)
    1.4 ± 7.9
    -0.6 ± 9.7
    0.9 ± 9.5
    -0.6 ± 6.9
    -0.5 ± 7.5
        Diastolic BP Wk 28 post dose (38, 39, 39, 34, 39)
    1.2 ± 8.7
    -2.0 ± 9.4
    1.2 ± 9.0
    -0.2 ± 7.1
    -1.8 ± 7.1
        Diastolic BP Wk 32 pre-dose (39, 39, 40, 35, 39)
    0.2 ± 8.5
    -1.7 ± 8.6
    1.6 ± 9.2
    -0.3 ± 9.3
    -1.2 ± 8.6
        Diastolic BP Wk 32 post dose (36, 39, 37, 34, 39)
    0.7 ± 10.0
    -3.0 ± 8.6
    0.1 ± 9.6
    -0.6 ± 8.5
    -2.1 ± 8.5
        Diastolic BP Wk 36 pre-dose (38, 38, 41, 34, 39)
    0.0 ± 8.6
    -0.6 ± 9.2
    1.4 ± 8.9
    -0.9 ± 7.2
    0.8 ± 7.5
        Diastolic BP Wk 36 post dose (37, 38, 38, 31, 38)
    1.6 ± 7.7
    -1.6 ± 9.2
    1.3 ± 9.3
    -1.7 ± 6.8
    -0.1 ± 7.1
        Diastolic BP Wk 40 pre-dose (37, 38, 41, 34, 40)
    0.8 ± 7.6
    -2.5 ± 9.7
    1.0 ± 9.5
    -1.0 ± 7.2
    -1.9 ± 6.8
        Diastolic BP Wk 40 post dose (37, 38, 40, 33, 37)
    0.9 ± 7.7
    -1.8 ± 9.1
    0.2 ± 8.3
    -0.8 ± 6.6
    -0.1 ± 7.3
        Diastolic BP Wk 44 pre-dose (38, 38, 41, 34, 40)
    1.4 ± 9.3
    -2.1 ± 7.7
    1.3 ± 9.2
    -0.4 ± 6.7
    -2.4 ± 10.9
        Diastolic BP Wk 44 post dose (36, 38, 40, 33, 39)
    2.3 ± 9.2
    -1.3 ± 7.6
    -0.7 ± 8.7
    -1.4 ± 8.1
    -1.5 ± 6.5
        Diastolic BP Wk 48 (38, 38, 41, 34, 40)
    1.8 ± 9.2
    0.4 ± 9.7
    1.1 ± 9.1
    0.6 ± 8.7
    -0.8 ± 6.4
        Systolic BP 30 min post dose (42, 39, 43, 41, 41)
    0.8 ± 8.1
    0.5 ± 9.7
    -0.8 ± 8.2
    1.5 ± 8.8
    -2.5 ± 9.7
        Systolic BP 1 hour post dose (42, 39, 43, 41, 41)
    -0.6 ± 9.4
    -2.0 ± 10.5
    0.2 ± 8.7
    1.0 ± 8.4
    -1.8 ± 7.1
        Systolic BP Wk 1 (41, 39, 43, 41, 41)
    -1.7 ± 10.8
    -1.3 ± 10.0
    1.7 ± 12.9
    -2.4 ± 8.3
    -1.6 ± 11.0
        Systolic BP Wk 2 (42, 39, 43, 41, 41)
    -0.7 ± 12.9
    -0.2 ± 9.8
    -0.1 ± 13.2
    -2.7 ± 8.2
    -0.4 ± 11.9
        Systolic BP Wk 4 pre-dose (41, 39, 42, 41, 41)
    -2.6 ± 11.4
    -1.5 ± 10.6
    -1.0 ± 13.0
    -2.3 ± 10.5
    -2.7 ± 11.2
        Systolic BP Wk 4 post dose (41, 39, 41, 40, 40)
    -3.5 ± 12.1
    -0.6 ± 10.4
    -2.2 ± 11.8
    -0.6 ± 9.1
    -3.7 ± 11.3
        Systolic BP Wk 8 pre-dose (41, 39, 43, 39, 41)
    -2.1 ± 13.1
    -0.8 ± 10.7
    -1.1 ± 11.3
    -3.6 ± 11.7
    -1.3 ± 10.4
        Systolic BP Wk 8 post dose (41, 39, 42, 39, 41)
    -3.2 ± 12.6
    -1.9 ± 11.6
    -0.3 ± 11.1
    -2.8 ± 10.2
    -1.9 ± 12.0
        Systolic BP Wk 12 pre-dose (42, 39, 42, 39, 41)
    -3.3 ± 12.4
    1.6 ± 13.7
    -3.1 ± 11.7
    -4.4 ± 10.8
    -2.6 ± 9.7
        Systolic BP Wk 12 post dose (40, 39, 42, 37, 41)
    -3.9 ± 14.1
    2.1 ± 11.1
    -1.9 ± 12.0
    -3.6 ± 10.1
    -2.4 ± 10.1
        Systolic BP Wk 16 pre-dose (42, 39, 42, 38, 41)
    -3.6 ± 15.1
    -2.3 ± 12.3
    -4.3 ± 11.3
    -4.3 ± 12.5
    -2.3 ± 11.4
        Systolic BP Wk 16 post dose (40, 39, 39, 36, 39)
    -3.7 ± 17.1
    -2.6 ± 11.7
    -3.4 ± 12.7
    -2.7 ± 11.0
    -5.7 ± 8.5
        Systolic BP Wk 20 pre-dose (40, 39, 42, 37, 40)
    -2.0 ± 13.1
    -3.2 ± 12.5
    -2.6 ± 11.9
    -5.4 ± 9.7
    -4.5 ± 10.5
        Systolic BP Wk 20 post dose (39, 39, 38, 36, 40)
    -1.9 ± 14.5
    -3.2 ± 13.0
    -3.7 ± 12.2
    -7.9 ± 11.9
    -4.4 ± 9.9
        Systolic BP Wk 24 pre-dose (39, 39, 41, 36, 40)
    -3.1 ± 10.5
    -1.1 ± 9.5
    -2.7 ± 12.3
    -3.6 ± 10.1
    -0.3 ± 10.5
        Systolic BP Wk 24 post dose (39, 38, 38, 35, 39)
    -2.6 ± 10.9
    -2.8 ± 10.5
    -2.2 ± 11.7
    -3.0 ± 9.7
    -1.1 ± 10.5
        Systolic BP Wk 28 pre-dose (39, 39, 41, 35, 40)
    -0.1 ± 11.4
    -2.5 ± 12.8
    -2.5 ± 13.1
    0.4 ± 11.6
    -2.9 ± 11.3
        Systolic BP Wk 28 post dose (38, 39, 39, 34, 39)
    -1.1 ± 12.1
    -2.9 ± 11.1
    -2.6 ± 12.4
    -0.7 ± 11.9
    -4.6 ± 11.2
        Systolic BP Wk 32 pre-dose (39, 39, 40, 35, 39)
    -0.9 ± 13.1
    -1.5 ± 13.3
    -0.6 ± 12.4
    0.6 ± 11.0
    -3.7 ± 12.4
        Systolic BP Wk 32 post dose (36, 39, 37, 34, 39)
    -1.7 ± 12.6
    -2.2 ± 11.6
    0.3 ± 12.5
    -0.4 ± 11.1
    -4.8 ± 10.6
        Systolic BP Wk 36 pre-dose (38, 38, 41, 34, 39)
    -3.1 ± 11.9
    1.1 ± 13.9
    -0.2 ± 13.6
    -1.8 ± 11.2
    -3.2 ± 11.1
        Systolic BP Wk 36 post dose (37, 38, 38, 31, 38)
    -0.6 ± 11.1
    1.3 ± 12.6
    -0.5 ± 12.4
    -3.8 ± 10.8
    -3.8 ± 11.4
        Systolic BP Wk 40 pre-dose (37, 38, 41, 34, 40)
    -3.3 ± 12.1
    -3.1 ± 11.4
    -1.6 ± 12.9
    -4.0 ± 9.5
    -1.2 ± 11.0
        Systolic BP Wk 40 post dose (37, 38, 40, 33, 37)
    -2.3 ± 11.7
    -0.4 ± 12.7
    -1.2 ± 13.8
    -3.2 ± 11.6
    -2.2 ± 9.6
        Systolic BP Wk 44 pre-dose (38, 38, 41, 34, 40)
    -2.8 ± 12.3
    -2.8 ± 9.9
    0.0 ± 13.1
    -5.1 ± 9.9
    -3.9 ± 10.3
        Systolic BP Wk 44 post dose (36, 38, 40, 33, 39)
    -1.8 ± 14.5
    -1.2 ± 9.5
    -0.6 ± 10.4
    -4.6 ± 10.3
    -3.8 ± 10.5
        Systolic BP Wk 48 (38, 38, 41, 34, 40)
    -1.1 ± 14.0
    -0.1 ± 12.5
    -0.1 ± 12.6
    -2.8 ± 11.5
    -5.2 ± 9.6
    No statistical analyses for this end point

    Secondary: Changes from Baseline in vital signs during the study (pulse rate)

    Close Top of page
    End point title
    Changes from Baseline in vital signs during the study (pulse rate)
    End point description
    Pulse rate was measured in beats per minute (beats/min). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, 30 min and 1 hour post dose, Week 1, Week 2, pre- and post dose for the following Weeks: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    42
    39
    43
    41
    41
    Units: beats/min
    arithmetic mean (standard deviation)
        30 min post dose (42, 39, 43, 41, 41)
    0.4 ± 5.4
    -0.8 ± 5.6
    -1.5 ± 7.2
    -2.3 ± 7.5
    -1.1 ± 7.2
        1 hour post dose (42, 39, 43, 41, 41)
    0.3 ± 6.7
    1.0 ± 11.3
    -0.8 ± 7.6
    -0.8 ± 8.1
    -0.4 ± 7.0
        Week 1 (41, 39, 43, 41, 41)
    2.9 ± 8.3
    -1.5 ± 7.5
    -0.7 ± 7.1
    0.6 ± 8.9
    -0.8 ± 9.0
        Week 2 (42, 39, 43, 41, 41)
    1.2 ± 6.4
    -1.7 ± 5.7
    -0.7 ± 7.9
    -1.0 ± 9.1
    -0.4 ± 6.9
        Week 4 pre-dose (41, 39, 42, 41, 41)
    -0.2 ± 5.3
    -2.1 ± 6.9
    -1.9 ± 8.1
    0.1 ± 9.8
    -1.0 ± 6.6
        Week 4 post dose (41, 39, 41, 40, 40)
    0.4 ± 8.6
    -2.6 ± 6.6
    -2.7 ± 9.5
    -0.5 ± 9.4
    -1.1 ± 6.2
        Week 8 pre-dose (41, 39, 43, 39, 41)
    0.9 ± 6.5
    -0.6 ± 8.0
    -1.6 ± 8.6
    0.8 ± 6.9
    -1.3 ± 8.2
        Week 8 post dose (41, 39, 42, 39, 41)
    -0.1 ± 6.9
    -1.3 ± 8.6
    -1.9 ± 8.6
    0.0 ± 8.5
    -2.3 ± 8.3
        Week 12 pre-dose (42, 39, 42, 39, 41)
    1.1 ± 10.2
    -2.2 ± 8.5
    -2.9 ± 10.5
    -1.7 ± 9.5
    -1.1 ± 8.4
        Week 12 post dose (40, 39, 42, 37, 41)
    -0.6 ± 8.8
    -3.3 ± 8.8
    -3.6 ± 9.4
    -2.1 ± 9.7
    -2.0 ± 7.8
        Week 16 pre-dose (42, 39, 42, 38, 41)
    -0.2 ± 8.5
    -2.1 ± 5.8
    -2.9 ± 8.0
    -1.9 ± 10.1
    -1.3 ± 7.2
        Week 16 post dose (40, 39, 39, 36, 39)
    -0.1 ± 9.9
    -3.5 ± 5.5
    -3.7 ± 9.7
    -2.1 ± 9.8
    -2.2 ± 7.3
        Week 20 pre-dose (40, 39, 42, 37, 40)
    -0.1 ± 10.3
    -2.4 ± 7.0
    -1.7 ± 10.3
    0.0 ± 9.0
    -1.2 ± 9.0
        Week 20 post dose (39, 39, 38, 36, 40)
    -0.7 ± 6.8
    -2.3 ± 7.8
    -2.1 ± 9.7
    -0.1 ± 8.5
    -1.3 ± 8.9
        Week 24 pre-dose (39, 39, 41, 36, 40)
    -0.5 ± 7.9
    -2.0 ± 8.1
    -2.8 ± 10.4
    -0.7 ± 7.3
    -1.2 ± 7.8
        Week 24 post dose (39, 38, 38, 35, 39)
    -0.9 ± 7.8
    -2.9 ± 8.5
    -3.0 ± 9.6
    -1.3 ± 6.9
    -2.5 ± 7.1
        Week 28 pre-dose (39, 39, 41, 35, 40)
    1.9 ± 9.7
    -2.1 ± 10.0
    0.0 ± 9.3
    -0.5 ± 11.2
    0.2 ± 8.3
        Week 28 post dose (38, 39, 39, 34, 39)
    1.8 ± 7.5
    -3.0 ± 9.4
    -0.5 ± 8.5
    -0.8 ± 10.0
    0.0 ± 7.5
        Week 32 pre-dose (39, 39, 40, 35, 39)
    3.3 ± 10.0
    -0.9 ± 7.9
    -2.0 ± 9.2
    -1.2 ± 10.6
    -0.3 ± 7.8
        Week 32 post dose (36, 39, 37, 34, 39)
    3.3 ± 8.4
    -0.8 ± 7.8
    -3.0 ± 9.5
    -1.9 ± 9.6
    -2.0 ± 8.8
        Week 36 pre-dose (38, 38, 41, 34, 39)
    0.7 ± 8.5
    0.2 ± 7.5
    -2.6 ± 8.6
    -2.6 ± 10.2
    -0.5 ± 9.7
        Week 36 post dose (37, 38, 38, 31, 38)
    1.1 ± 7.6
    -0.8 ± 8.2
    -3.0 ± 9.8
    -2.5 ± 8.2
    -1.4 ± 9.6
        Week 40 pre-dose (37, 38, 41, 34, 40)
    2.7 ± 10.3
    -0.5 ± 8.8
    1.0 ± 10.1
    -1.7 ± 7.6
    2.0 ± 9.4
        Week 40 post dose (37, 38, 40, 33, 37)
    0.9 ± 8.3
    -1.7 ± 8.3
    0.0 ± 8.9
    -2.0 ± 8.4
    0.5 ± 9.1
        Week 44 pre-dose (38, 38, 41, 34, 40)
    2.2 ± 8.9
    -1.6 ± 6.9
    -0.4 ± 10.1
    -1.4 ± 8.2
    0.7 ± 9.7
        Week 44 post dose (36, 38, 40, 33, 38)
    2.9 ± 6.9
    -1.7 ± 8.0
    -0.5 ± 11.0
    -2.8 ± 7.7
    -0.2 ± 10.3
        Week 48 (38, 38, 41, 34, 40)
    2.0 ± 8.9
    -3.7 ± 7.8
    -2.5 ± 10.4
    -4.2 ± 9.5
    -3.1 ± 9.5
    No statistical analyses for this end point

    Secondary: Changes from Baseline in body weight during the study

    Close Top of page
    End point title
    Changes from Baseline in body weight during the study
    End point description
    Body weight was measured in kilograms. The SS consisted of all randomized study participants who received at least 1 dose of IMP. Overall number of participants analyzed include only those for whom body weight was measured and analyzed during the study. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24, Week 36 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    39
    43
    38
    41
    Units: kilograms
    arithmetic mean (standard deviation)
        Week 12 (41, 39, 43, 38, 41)
    0.14 ± 3.38
    -0.87 ± 3.12
    0.21 ± 1.78
    -0.38 ± 1.80
    -0.04 ± 2.39
        Week 24 (39, 38, 41, 36, 40)
    0.33 ± 4.10
    -0.03 ± 3.48
    -0.07 ± 2.63
    -0.13 ± 2.37
    -0.39 ± 3.73
        Week 36 (38, 38, 41, 34, 39)
    0.32 ± 5.15
    -0.14 ± 2.90
    0.27 ± 3.42
    0.15 ± 2.36
    -0.04 ± 4.19
        Week 48 (38, 38, 41, 34, 40)
    0.21 ± 4.42
    0.45 ± 3.41
    0.80 ± 3.84
    -0.14 ± 3.32
    0.11 ± 4.24
    No statistical analyses for this end point

    Secondary: Changes from Baseline in electrocardiogram (ECG) intervals during the study (QTcB, QTcF, PR, QRS, QT, RR)

    Close Top of page
    End point title
    Changes from Baseline in electrocardiogram (ECG) intervals during the study (QTcB, QTcF, PR, QRS, QT, RR)
    End point description
    Electrocardiogram (ECG) intervals (QTcB= QT interval corrected for heart rate (Bazett’s formula); QTcF= QT interval corrected for heart rate (Fridericia’s formula)) were measured in milliseconds. The SS consisted of all randomized study participants who received at least 1 dose of IMP. Overall number of participants analyzed include only those for whom electrocardiogram data was measured and analyzed during the study. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    38
    36
    42
    34
    40
    Units: msec
    arithmetic mean (standard deviation)
        QTcB Week 12 (38, 36, 42, 34, 40)
    3.4 ± 32.7
    -2.8 ± 29.9
    -5.6 ± 41.8
    1.5 ± 18.2
    -1.9 ± 31.4
        QTcB Week 48 (35, 37, 40, 31, 39)
    -2.5 ± 34.8
    -5.8 ± 36.5
    -5.9 ± 22.2
    -4.7 ± 21.0
    -5.7 ± 27.7
        QTcF Week 12 (37, 32, 35, 32, 39)
    4.5 ± 27.5
    -2.5 ± 22.4
    -2.2 ± 14.2
    -0.5 ± 17.0
    -3.0 ± 18.8
        QTcF Week 48 (35, 32, 34, 29, 38)
    -0.1 ± 30.7
    -6.1 ± 31.4
    -0.2 ± 15.6
    -2.2 ± 20.0
    4.6 ± 44.6
        PR Week 12 (39, 37, 42, 36, 41)
    -1.7 ± 23.3
    -1.0 ± 23.7
    -19.6 ± 102.1
    3.2 ± 18.2
    -9.5 ± 32.3
        PR Week 48 (37, 38, 40, 33, 40)
    2.6 ± 33.7
    17.5 ± 128.8
    4.0 ± 163.0
    0.8 ± 18.9
    -2.8 ± 26.5
        QRS Week 12 (40, 38, 42, 36, 41)
    2.6 ± 22.3
    -2.9 ± 10.8
    -1.8 ± 7.6
    -0.2 ± 5.4
    6.1 ± 42.8
        QRS Week 48 (38, 38, 40, 33, 40)
    5.6 ± 21.4
    -1.5 ± 16.1
    -4.0 ± 13.0
    0.6 ± 16.2
    0.1 ± 18.7
        QT Week 12 (40, 38, 42, 36, 41)
    -2.0 ± 46.6
    1.7 ± 34.0
    9.5 ± 21.4
    3.8 ± 25.6
    11.5 ± 80.8
        QT Week 48 (38, 38, 40, 33, 40)
    -0.7 ± 33.4
    3.1 ± 29.9
    3.9 ± 22.8
    5.4 ± 26.7
    0.7 ± 31.6
        RR Week 12 (39, 36, 42, 34, 41)
    3.3 ± 99.3
    -22.5 ± 212.6
    75.8 ± 179.3
    11.0 ± 125.1
    -17.0 ± 182.1
        RR Week 48 (37, 36, 40, 31, 40)
    -0.6 ± 116.1
    11.9 ± 187.1
    65.2 ± 139.0
    44.3 ± 124.0
    25.1 ± 148.5
    No statistical analyses for this end point

    Secondary: Changes from Baseline in hematology parameters during the study (basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils)

    Close Top of page
    End point title
    Changes from Baseline in hematology parameters during the study (basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils)
    End point description
    Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils were measured in number of white blood cells per liter (10^9/L). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    38
    43
    41
    40
    Units: 10^9 white blood cells per liter
    arithmetic mean (standard deviation)
        Basophils Week 1 (41, 38, 43, 41, 40)
    0.000 ± 0.0387
    0.000 ± 0.0329
    -0.002 ± 0.0408
    0.007 ± 0.0264
    0.008 ± 0.0350
        Basophils Week 2 (42, 38, 43, 41, 41)
    0.002 ± 0.0269
    0.003 ± 0.0283
    0.000 ± 0.0488
    0.000 ± 0.0316
    0.005 ± 0.0384
        Basophils Week 4 (41, 38, 42, 41, 41)
    0.002 ± 0.0474
    0.005 ± 0.0324
    -0.007 ± 0.0463
    0.005 ± 0.0312
    0.005 ± 0.0312
        Basophils Week 8 (41, 39, 41, 38, 41)
    -0.002 ± 0.0353
    0.000 ± 0.0229
    -0.005 ± 0.0384
    0.003 ± 0.0367
    0.002 ± 0.0418
        Basophils Week 12 (41, 39, 43, 38, 41)
    0.002 ± 0.0353
    0.003 ± 0.0280
    -0.002 ± 0.0462
    0.000 ± 0.0329
    0.010 ± 0.0374
        Basophils Week 16 (42, 38, 42, 38, 40)
    0.010 ± 0.0431
    0.005 ± 0.0324
    -0.007 ± 0.0463
    0.000 ± 0.0329
    0.008 ± 0.0417
        Basophils Week 20 (39, 39, 41, 37, 39)
    -0.003 ± 0.0362
    0.003 ± 0.0362
    0.000 ± 0.0500
    0.005 ± 0.0329
    0.000 ± 0.0397
        Basophils Week 24 (39, 38, 40, 36, 40)
    0.000 ± 0.0397
    0.005 ± 0.0324
    -0.003 ± 0.0530
    0.008 ± 0.0368
    0.005 ± 0.0389
        Basophils Week 28 (39, 38, 40, 35, 40)
    0.005 ± 0.0394
    0.000 ± 0.0329
    0.008 ± 0.0526
    0.011 ± 0.0323
    0.005 ± 0.0450
        Basophils Week 32 (39, 39, 40, 34, 39)
    0.000 ± 0.0324
    0.005 ± 0.0320
    -0.010 ± 0.0441
    0.009 ± 0.0379
    0.010 ± 0.0384
        Basophils Week 36 (37, 38, 41, 33, 39)
    0.000 ± 0.0408
    0.003 ± 0.0283
    -0.002 ± 0.0474
    0.012 ± 0.0415
    0.013 ± 0.0409
        Basophils Week 40 (36, 38, 40, 34, 38)
    0.003 ± 0.0506
    0.005 ± 0.0399
    -0.010 ± 0.0379
    0.006 ± 0.0343
    0.000 ± 0.0403
        Basophils Week 44 (36, 37, 41, 34, 36)
    0.006 ± 0.0410
    0.003 ± 0.0372
    0.000 ± 0.0387
    0.006 ± 0.0422
    0.000 ± 0.0338
        Basophils Week 48 (38, 36, 40, 32, 39)
    -0.005 ± 0.0462
    0.003 ± 0.291
    -0.010 ± 0.0441
    0.006 ± 0.0354
    0.000 ± 0.0324
        Eosinophils Week 1 (41, 38, 43, 41, 40)
    0.010 ± 0.0860
    0.016 ± 0.0718
    -0.002 ± 0.0801
    -0.005 ± 0.0999
    0.017 ± 0.0636
        Eosinophils Week 2 (42, 38, 43, 41, 41)
    0.005 ± 0.0731
    0.013 ± 0.0777
    0.002 ± 0.0913
    0.002 ± 0.0880
    0.029 ± 0.0929
        Eosinophils Week 4 (41, 38, 42, 41, 41)
    0.002 ± 0.0987
    0.016 ± 0.0594
    0.002 ± 0.0780
    0.005 ± 0.0999
    0.027 ± 0.0895
        Eosinophils Week 8 (41, 39, 41, 38, 41)
    0.024 ± 0.0969
    -0.003 ± 0.0707
    0.000 ± 0.1000
    0.008 ± 0.0941
    0.005 ± 0.0669
        Eosinophils Week 12 (41, 39, 43, 38, 41)
    0.020 ± 0.0954
    0.010 ± 0.0882
    0.002 ± 0.0831
    -0.026 ± 0.1155
    0.017 ± 0.0704
        Eosinophils Week 16 (42, 38, 42, 38, 40)
    0.045 ± 0.1253
    0.021 ± 0.0935
    0.010 ± 0.0759
    -0.005 ± 0.1559
    0.033 ± 0.0829
        Eosinophils Week 20 (39, 39, 41, 37, 39)
    0.036 ± 0.1038
    0.026 ± 0.1186
    0.024 ± 0.1157
    -0.014 ± 0.1228
    0.038 ± 0.0935
        Eosinophils Week 24 (39, 38, 40, 36, 40)
    0.031 ± 0.1301
    0.013 ± 0.0844
    0.058 ± 0.2111
    -0.019 ± 0.1238
    0.037 ± 0.1192
        Eosinophils Week 28 (39, 38, 40, 35, 40)
    0.036 ± 0.0986
    0.018 ± 0.0926
    0.053 ± 0.1826
    -0.000 ± 0.1213
    0.025 ± 0.0870
        Eosinophils Week 32 (39, 39, 40, 34, 39)
    0.049 ± 0.1502
    0.033 ± 0.0838
    0.020 ± 0.1418
    0.024 ± 0.1577
    0.041 ± 0.1141
        Eosinophils Week 36 (37, 38, 41, 33, 39)
    0.054 ± 0.1726
    0.018 ± 0.0955
    0.022 ± 0.0909
    0.027 ± 0.1526
    0.015 ± 0.0961
        Eosinophils Week 40 (36, 38, 40, 34, 38)
    0.050 ± 0.1444
    0.018 ± 0.0865
    0.018 ± 0.0958
    0.015 ± 0.1971
    0.039 ± 0.1128
        Eosinophils Week 44 (36, 37, 41, 34, 36)
    0.072 ± 0.1523
    0.019 ± 0.0908
    0.024 ± 0.0994
    -0.009 ± 0.1798
    0.006 ± 0.0893
        Eosinophils Week 48 (38, 36, 40, 32, 39)
    0.045 ± 0.1811
    0.006 ± 0.0754
    0.023 ± 0.0891
    0.009 ± 0.2833
    -0.005 ± 0.0857
        Leukocytes Week 1 (41, 38, 43, 41, 40)
    -0.271 ± 1.1885
    -0.597 ± 1.1490
    -0.656 ± 1.2593
    -1.029 ± 1.6496
    -0.285 ± 1.6896
        Leukocytes Week 2 (42, 39, 43, 41, 41)
    0.157 ± 1.3195
    -0.131 ± 2.1769
    -0.309 ± 1.3735
    -0.954 ± 2.0441
    -0.322 ± 1.5501
        Leukocytes Week 4 (41, 38, 42, 41, 41)
    -0.049 ± 1.1938
    -0.411 ± 1.1988
    -0.336 ± 1.5088
    -1.017 ± 1.9397
    -0.656 ± 1.4264
        Leukocytes Week 8 (41, 39, 41, 38, 41)
    0.429 ± 1.7036
    -0.333 ± 1.4014
    -0.185 ± 1.2889
    -1.071 ± 1.9639
    -0.629 ± 1.5489
        Leukocytes Week 12 (41, 39, 43, 38, 41)
    0.190 ± 1.6223
    -0.438 ± 1.3854
    -0.495 ± 1.6904
    -0.997 ± 2.1806
    -0.634 ± 1.6084
        Leukocytes Week 16 (42, 38, 42, 38, 40)
    -0.400 ± 1.5616
    -0.839 ± 1.8179
    -0.590 ± 1.4668
    -1.318 ± 2.3324
    -0.293 ± 1.8427
        Leukocytes Week 20 (39, 39, 41, 37, 40)
    -0.936 ± 1.2756
    -1.100 ± 1.5599
    -0.432 ± 1.3032
    -0.932 ± 2.2832
    -0.455 ± 1.7116
        Leukocytes Week 24 (39, 38, 40, 36, 40)
    -1.251 ± 1.3888
    -0.884 ± 1.7768
    -0.495 ± 1.4216
    -1.119 ± 2.2807
    -0.765 ± 1.8691
        Leukocytes Week 28 (39, 38, 41, 35, 40)
    -0.700 ± 1.8180
    -0.316 ± 2.3086
    -0.100 ± 1.4942
    -0.894 ± 1.7119
    -0.342 ± 1.5683
        Leukocytes Week 32 (39, 39, 40, 34, 39)
    -0.762 ± 1.4273
    -0.862 ± 2.0091
    -0.330 ± 1.5750
    -0.918 ± 2.6184
    -0.505 ± 1.4800
        Leukocytes Week 36 (37, 38, 41, 33, 39)
    -0.541 ± 1.5971
    -0.974 ± 1.7389
    -0.366 ± 1.4549
    -1.082 ± 2.3389
    -0.126 ± 2.2565
        Leukocytes Week 40 (36, 38, 41, 34, 38)
    -0.783 ± 1.7693
    -0.826 ± 1.5942
    -0.437 ± 1.7878
    -1.226 ± 2.3856
    -0.266 ± 1.7976
        Leukocytes Week 44 (37, 37, 41, 34, 36)
    -1.065 ± 1.6070
    -0.978 ± 1.8151
    -0.537 ± 1.5641
    -1.032 ± 2.1585
    -0.825 ± 1.8917
        Leukocytes Week 48 (38, 36, 40, 32, 39)
    -0.739 ± 1.7774
    -0.869 ± 1.7109
    -0.473 ± 1.7104
    -1.225 ± 2.5952
    -0.777 ± 1.8593
        Lymphocytes Week 1 (41, 38, 43, 41, 40)
    -0.083 ± 0.5074
    -0.024 ± 0.4142
    0.044 ± 0.5039
    -0.017 ± 0.4189
    0.020 ± 0.3006
        Lymphocytes Week 2 (42, 38, 43, 41, 41)
    0.105 ± 0.3246
    0.026 ± 0.4137
    0.021 ± 0.6006
    0.007 ± 0.3643
    0.161 ± 0.4277
        Lymphocytes Week 4 (41, 38, 42, 41, 41)
    0.037 ± 0.4386
    0.024 ± 0.3259
    0.010 ± 0.6003
    -0.032 ± 0.3996
    0.095 ± 0.3263
        Lymphocytes Week 8 (41, 39, 41, 38, 41)
    0.120 ± 0.3776
    0.054 ± 0.3783
    0.063 ± 0.5928
    0.053 ± 0.4980
    0.129 ± 0.3939
        Lymphocytes Week 12 (41, 39, 43, 38, 41)
    0.041 ± 0.3647
    0.051 ± 0.4167
    0.000 ± 0.5640
    -0.047 ± 0.3703
    0.061 ± 0.3301
        Lymphocytes Week 16 (42, 38, 42, 38, 40)
    0.052 ± 0.5567
    0.071 ± 0.3571
    0.026 ± 0.5539
    -0.029 ± 0.4991
    0.135 ± 0.4197
        Lymphocytes Week 20 (39, 39, 41, 37, 39)
    0.003 ± 0.4934
    0.008 ± 0.3970
    0.149 ± 0.4675
    -0.035 ± 0.4566
    0.126 ± 0.4216
        Lymphocytes Week 24 (39, 38, 40, 36, 40)
    -0.041 ± 0.3905
    0.050 ± 0.3630
    0.048 ± 0.4455
    -0.036 ± 0.3788
    0.053 ± 0.3974
        Lymphocytes Week 28 (39, 38, 40, 35, 40)
    0.036 ± 0.5869
    0.105 ± 0.3594
    0.210 ± 0.5999
    0.103 ± 0.5544
    0.172 ± 0.3776
        Lymphocytes Week 32 (39, 39, 40, 34, 39)
    -0.000 ± 0.5109
    0.103 ± 0.4233
    0.083 ± 0.6524
    0.112 ± 0.5056
    0.146 ± 0.3966
        Lymphocytes Week 36 (37, 38, 41, 33, 39)
    0.078 ± 0.4894
    0.039 ± 0.4227
    0.134 ± 0.5673
    0.103 ± 0.5491
    0.118 ± 0.3810
        Lymphocytes Week 40 (36, 38, 40, 34, 38)
    0.139 ± 0.4871
    0.168 ± 0.4281
    0.120 ± 0.6018
    0.038 ± 0.4335
    0.176 ± 0.3709
        Lymphocytes Week 44 (36, 37, 41, 34, 36)
    -0.008 ± 0.5390
    0.105 ± 0.4136
    0.124 ± 0.5366
    0.115 ± 0.4881
    0.153 ± 0.4462
        Lymphocytes Week 48 (38, 36, 40, 32, 39)
    0.066 ± 0.5313
    0.103 ± 0.3645
    0.078 ± 0.5041
    0.019 ± 0.3763
    0.072 ± 0.3755
        Monocytes Week 1 (41, 38, 43, 41, 40)
    0.007 ± 0.2184
    -0.008 ± 0.1477
    -0.012 ± 0.1679
    -0.088 ± 0.2315
    -0.027 ± 0.1724
        Monocytes Week 2 (42, 38, 43, 41, 41)
    0.076 ± 0.1358
    -0.011 ± 0.1673
    0.014 ± 0.1897
    -0.095 ± 0.2701
    -0.010 ± 0.1882
        Monocytes Week 4 (41, 38, 42, 41, 41)
    0.032 ± 0.1588
    -0.021 ± 0.1473
    -0.040 ± 0.1862
    -0.066 ± 0.2404
    -0.085 ± 0.1459
        Monocytes Week 8 (41, 39, 41, 38, 41)
    0.059 ± 0.1910
    -0.041 ± 0.1743
    0.005 ± 0.1580
    -0.103 ± 0.2520
    -0.071 ± 0.1834
        Monocytes Week 12 (41, 39, 43, 38, 41)
    0.020 ± 0.1913
    -0.031 ± 0.1608
    -0.033 ± 0.1686
    -0.105 ± 0.2630
    -0.059 ± 0.1414
        Monocytes Week 16 (42, 38, 42, 38, 40)
    -0.007 ± 0.1629
    -0.050 ± 0.1673
    -0.024 ± 0.1265
    -0.079 ± 0.2384
    -0.043 ± 0.1752
        Monocytes Week 20 (39, 39, 41, 37, 39)
    -0.008 ± 0.1783
    -0.041 ± 0.1534
    -0.015 ± 0.1509
    -0.081 ± 0.2448
    -0.003 ± 0.1899
        Monocytes Week 24 (39, 38, 40, 36, 40)
    -0.026 ± 0.1292
    -0.034 ± 0.1361
    0.003 ± 0.1476
    -0.056 ± 0.2602
    -0.027 ± 0.1921
        Monocytes Week 28 (39, 38, 40, 35, 40)
    0.026 ± 0.2087
    0.042 ± 0.1981
    0.055 ± 0.1724
    -0.029 ± 0.2729
    -0.012 ± 0.1911
        Monocytes Week 32 (39, 39, 40, 34, 39)
    0.064 ± 0.2356
    -0.005 ± 0.1731
    -0.003 ± 0.1271
    -0.035 ± 0.2684
    0.010 ± 0.1744
        Monocytes Week 36 (37, 38, 41, 33, 39)
    0.054 ± 0.1626
    -0.024 ± 0.1792
    0.032 ± 0.1404
    -0.036 ± 0.2644
    0.049 ± 0.2327
        Monocytes Week 40 (36, 38, 40, 34, 38)
    0.053 ± 0.1647
    0.008 ± 0.1323
    0.020 ± 0.1636
    -0.059 ± 0.2830
    -0.018 ± 0.1504
        Monocytes Week 44 (36, 37, 41, 34, 36)
    0.019 ± 0.1939
    -0.008 ± 0.1588
    0.044 ± 0.1644
    -0.032 ± 0.2446
    -0.019 ± 0.2202
        Monocytes Week 48 (38, 36, 40, 32, 39)
    0.021 ± 0.2145
    0.000 ± 0.1707
    -0.013 ± 0.1399
    -0.078 ± 0.2511
    -0.077 ± 0.1709
        Neutrophils Week 1 (41, 38, 43, 41, 40)
    -0.200 ± 1.0959
    -0.558 ± 0.9627
    -0.693 ± 1.2971
    -0.934 ± 1.4768
    -0.325 ± 1.5720
        Neutrophils Week 2 (42, 38, 43, 41, 41)
    -0.026 ± 1.1945
    -0.418 ± 1.1627
    -0.337 ± 1.3109
    -0.880 ± 1.8457
    -0.537 ± 1.3989
        Neutrophils Week 4 (41, 38, 42, 41, 41)
    -0.102 ± 1.0044
    -0.405 ± 1.1246
    -0.290 ± 1.3463
    -0.924 ± 1.9975
    -0.732 ± 1.4028
        Neutrophils Week 8 (41, 39, 41, 38, 41)
    0.249 ± 1.5358
    -0.346 ± 1.2640
    -0.256 ± 1.3898
    -1.021 ± 1.7129
    -0.717 ± 1.4589
        Neutrophils Week 12 (41, 39, 43, 38, 41)
    0.117 ± 1.5103
    -0.456 ± 1.1227
    -0.458 ± 1.6879
    -0.832 ± 2.2192
    -0.673 ± 1.3887
        Neutrophils Week 16 (42, 38, 42, 38, 40)
    -0.490 ± 1.6866
    -0.879 ± 1.5752
    -0.617 ± 1.6027
    -1.203 ± 2.2840
    -0.448 ± 1.6816
        Neutrophils Week 20 (39, 39, 41, 37, 39)
    -0.972 ± 1.2085
    -1.069 ± 1.4219
    -0.595 ± 1.4319
    -0.827 ± 2.2663
    -0.618 ± 1.5716
        Neutrophils Week 24 (39, 38, 40, 36, 40)
    -1.210 ± 1.4067
    -0.895 ± 1.6288
    -0.593 ± 1.5309
    -1.011 ± 2.2968
    -0.850 ± 1.6461
        Neutrophils Week 28 (39, 38, 40, 35, 40)
    -0.774 ± 1.8189
    -0.484 ± 2.2620
    -0.555 ± 1.2608
    -0.949 ± 1.7676
    -0.568 ± 1.3889
        Neutrophils Week 32 (39, 39, 40, 34, 39)
    -0.869 ± 1.2796
    -0.969 ± 1.8241
    -0.433 ± 1.7889
    -1.038 ± 2.4800
    -0.718 ± 1.4299
        Neutrophils Week 36 (37, 38, 41, 33, 39)
    -0.722 ± 1.6422
    -0.992 ± 1.6583
    -0.541 ± 1.5519
    -1.185 ± 2.1881
    -0.354 ± 2.1441
        Neutrophils Week 40 (36, 38, 40, 34, 38)
    -1.006 ± 1.7393
    -0.992 ± 1.4740
    -0.575 ± 1.9567
    -1.229 ± 2.4065
    -0.495 ± 1.5857
        Neutrophils Week 44 (36, 37, 41, 34, 36)
    -0.978 ± 1.2444
    -1.086 ± 1.6049
    -0.717 ± 1.6966
    -1.109 ± 2.2673
    -0.983 ± 1.6556
        Neutrophils Week 48 (38, 36, 40, 32, 39)
    -0.861 ± 1.6858
    -0.939 ± 1.5670
    -0.558 ± 1.7944
    -1.178 ± 2.6503
    -0.805 ± 1.6631
    No statistical analyses for this end point

    Secondary: Changes from Baseline in hematology parameters during the study (erythrocytes mean corpuscular hemoglobin (HGB) concentration, hemoglobin)

    Close Top of page
    End point title
    Changes from Baseline in hematology parameters during the study (erythrocytes mean corpuscular hemoglobin (HGB) concentration, hemoglobin)
    End point description
    Erythrocytes mean corpuscular hemoglobin concentration (MCHC) and hemoglobin were measured in grams per liter (g/L). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    38
    43
    41
    40
    Units: g/L
    arithmetic mean (standard deviation)
        MCHC Week 1 (41, 38, 43, 41, 40)
    -2.293 ± 8.4594
    0.789 ± 8.9719
    -1.860 ± 8.0551
    0.927 ± 9.1088
    1.200 ± 12.2395
        MCHC Week 2 (42, 39, 43, 41, 41)
    -2.310 ± 7.9923
    2.564 ± 9.8216
    0.465 ± 8.4778
    0.707 ± 8.6263
    2.854 ± 10.1822
        MCHC Week 4 (41, 38, 42, 41, 41)
    -3.927 ± 10.0633
    1.474 ± 10.5849
    -2.500 ± 11.5045
    -0.878 ± 9.4026
    1.756 ± 11.8697
        MCHC Week 8 (41, 39, 41, 38, 41)
    -5.195 ± 11.7158
    -1.897 ± 11.3249
    -3.780 ± 10.7576
    -3.079 ± 10.7033
    0.610 ± 12.7493
        MCHC Week 12 (41, 39, 43, 38, 41)
    -7.927 ± 14.6704
    -3.179 ± 13.4122
    -3.907 ± 11.5404
    -2.684 ± 9.4099
    1.732 ± 13.3959
        MCHC Week 16 (42, 38, 42, 38, 40)
    -6.286 ± 12.3393
    -3.000 ± 14.5751
    -5.262 ± 12.1917
    -1.026 ± 11.6816
    -0.700 ± 16.1026
        MCHC Week 20 (40, 39, 41, 37, 40)
    -5.050 ± 12.8102
    0.923 ± 11.8108
    -1.902 ± 12.8078
    0.919 ± 8.7349
    0.200 ± 16.1725
        MCHC Week 24 (39, 38, 40, 36, 40)
    1.000 ± 10.9232
    4.132 ± 10.3849
    -0.625 ± 14.6685
    4.583 ± 11.3121
    4.250 ± 13.4064
        MCHC Week 28 (39, 38, 41, 35, 40)
    2.179 ± 10.3285
    4.658 ± 9.6906
    1.707 ± 9.9505
    4.400 ± 13.7524
    6.150 ± 12.5382
        MCHC Week 32 (39, 39, 40, 34, 39)
    6.308 ± 9.7796
    10.231 ± 9.5957
    4.850 ± 11.3692
    7.971 ± 12.3497
    10.462 ± 12.9855
        MCHC Week 36 (38, 38, 41, 33, 39)
    5.500 ± 9.7779
    10.921 ± 10.2229
    2.732 ± 12.4097
    6.788 ± 12.2034
    9.462 ± 12.7998
        MCHC Week 40 (37, 38, 41, 34, 38)
    3.108 ± 9.8736
    8.237 ± 12.0706
    4.976 ± 11.5639
    9.088 ± 11.5480
    9.079 ± 11.5393
        MCHC Week 44 (37, 38, 41, 34, 36)
    6.297 ± 10.6975
    7.289 ± 12.6254
    3.415 ± 12.6293
    6.353 ± 14.3038
    9.278 ± 12.8076
        MCHC Week 48 (38, 37, 41, 33, 40)
    5.079 ± 10.4916
    7.216 ± 9.3812
    2.122 ± 11.8769
    5.394 ± 12.9300
    8.250 ± 11.3448
        Hemoglobin Week 1 (41, 38, 43, 41, 40)
    -4.854 ± 5.6726
    0.000 ± 5.6569
    1.302 ± 5.1480
    0.512 ± 6.0462
    -0.875 ± 4.8368
        Hemoglobin Week 2 (42, 39, 43, 41, 41)
    -4.810 ± 6.5154
    -0.359 ± 5.2339
    0.070 ± 6.5915
    -1.561 ± 6.7047
    0.317 ± 5.3499
        Hemoglobin Week 4 (41, 38, 42, 41, 41)
    -4.390 ± 7.5162
    0.895 ± 7.6434
    0.881 ± 6.4551
    0.512 ± 5.7189
    1.195 ± 5.8916
        Hemoglobin Week 8 (41, 39, 41, 38, 41)
    -4.561 ± 7.0995
    0.308 ± 7.0865
    2.195 ± 7.7628
    0.553 ± 6.8010
    1.195 ± 7.4439
        Hemoglobin Week 12 (41, 39, 43, 38, 41)
    -5.220 ± 6.7879
    0.692 ± 7.7601
    2.488 ± 7.6512
    0.868 ± 7.3344
    2.488 ± 8.2344
        Hemoglobin Week 16 (42, 38, 42, 38, 40)
    -1.619 ± 6.4768
    2.579 ± 8.3880
    1.524 ± 8.7853
    1.737 ± 7.3547
    3.125 ± 7.7400
        Hemoglobin Week 20 (40, 39, 41, 37, 40)
    -0.400 ± 7.3233
    2.667 ± 8.6764
    2.268 ± 6.9822
    1.892 ± 7.6186
    2.925 ± 7.7207
        Hemoglobin Week 24 (39, 38, 40, 36, 40)
    0.564 ± 8.1879
    3.658 ± 9.0622
    4.075 ± 8.0714
    2.000 ± 6.6462
    3.425 ± 6.2834
        Hemoglobin Week 28 (39, 38, 41, 35, 40)
    -1.513 ± 8.0259
    3.342 ± 8.9511
    3.122 ± 8.6261
    0.857 ± 7.2645
    3.400 ± 8.6730
        Hemoglobin Week 32 (39, 39, 40, 34, 39)
    -0.282 ± 8.2684
    4.487 ± 8.3094
    4.300 ± 9.4032
    2.118 ± 7.4254
    5.615 ± 8.6378
        Hemoglobin Week 36 (38, 38, 41, 33, 39)
    0.947 ± 9.1738
    6.053 ± 8.1405
    4.293 ± 9.5766
    3.818 ± 7.3334
    4.949 ± 8.4851
        Hemoglobin Week 40 (37, 38, 41, 34, 38)
    1.432 ± 9.1090
    5.868 ± 8.7863
    4.317 ± 9.6552
    3.618 ± 7.8277
    4.132 ± 7.7987
        Hemoglobin Week 44 (37, 38, 41, 34, 36)
    1.486 ± 10.1040
    5.000 ± 9.2998
    3.659 ± 9.1750
    4.912 ± 8.5895
    4.722 ± 8.5511
        Hemoglobin Week 48 (38, 37, 41, 33, 40)
    2.474 ± 9.7002
    5.270 ± 9.1974
    3.780 ± 9.9210
    4.030 ± 9.2550
    4.725 ± 7.3554
    No statistical analyses for this end point

    Secondary: Changes from Baseline in hematology parameters during the study (erythrocytes mean corpuscular hemoglobin (HGB))

    Close Top of page
    End point title
    Changes from Baseline in hematology parameters during the study (erythrocytes mean corpuscular hemoglobin (HGB))
    End point description
    Erythrocytes mean corpuscular hemoglobin (HGB) was measured in picograms (pg). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    38
    43
    41
    40
    Units: picograms (pg)
    arithmetic mean (standard deviation)
        Week 1 (41, 38, 43, 41, 40)
    -0.073 ± 0.4980
    0.058 ± 0.4624
    -0.049 ± 0.4050
    0.073 ± 0.3975
    -0.055 ± 0.4455
        Week 2 (42, 39, 43, 41, 41)
    -0.050 ± 0.3890
    0.126 ± 0.5149
    0.023 ± 0.4225
    0.066 ± 0.4357
    0.085 ± 0.4287
        Week 4 (41, 38, 42, 41, 41)
    -0.112 ± 0.5501
    0.089 ± 0.5584
    0.060 ± 0.5910
    0.012 ± 0.4691
    0.066 ± 0.6085
        Week 8 (41, 39, 41, 38, 41)
    -0.110 ± 0.6778
    0.141 ± 0.6801
    0.007 ± 0.5926
    0.034 ± 0.6851
    0.095 ± 0.7994
        Week 12 (41, 39, 43, 38, 41)
    -0.285 ± 0.6770
    0.023 ± 0.7253
    0.091 ± 0.8358
    -0.132 ± 0.8335
    0.039 ± 1.0454
        Week 16 (42, 38, 42, 38, 40)
    -0.233 ± 0.7281
    0.097 ± 0.8824
    0.014 ± 0.9236
    -0.118 ± 0.8440
    -0.067 ± 1.1713
        Week 20 (40, 39, 41, 37, 40)
    -0.290 ± 0.8145
    -0.033 ± 0.9172
    0.029 ± 0.9819
    -0.035 ± 0.7013
    0.075 ± 1.0824
        Week 24 (39, 38, 40, 36, 40)
    -0.249 ± 1.0443
    0.108 ± 0.9947
    -0.057 ± 1.1804
    -0.097 ± 0.7284
    -0.007 ± 1.2338
        Week 28 (39, 38, 41, 35, 40)
    -0.103 ± 1.0101
    0.029 ± 0.7241
    -0.122 ± 1.1130
    -0.211 ± 0.8277
    0.020 ± 1.2950
        Week 32 (39, 39, 40, 34, 39)
    0.003 ± 1.2619
    0.297 ± 0.8561
    0.058 ± 1.1522
    0.026 ± 0.7684
    0.167 ± 1.2472
        Week 36 (38, 38, 41, 33, 39)
    -0.082 ± 1.3242
    0.237 ± 0.8722
    -0.093 ± 1.0792
    -0.248 ± 0.8581
    0.118 ± 1.1473
        Week 40 (37, 38, 41, 34, 38)
    -0.170 ± 1.3453
    0.134 ± 0.8960
    -0.134 ± 1.2095
    -0.147 ± 0.8645
    0.034 ± 1.0839
        Week 44 (37, 38, 41, 34, 36)
    0.097 ± 1.3103
    0.129 ± 0.8742
    -0.080 ± 1.1771
    -0.159 ± 0.7480
    0.108 ± 1.2532
        Week 48 (38, 37, 41, 33, 40)
    0.137 ± 1.4139
    0.178 ± 0.9369
    -0.120 ± 1.1279
    -0.030 ± 0.7888
    0.140 ± 1.2161
    No statistical analyses for this end point

    Secondary: Changes from Baseline in hematology parameters during the study (erythrocytes mean corpuscular volume)

    Close Top of page
    End point title
    Changes from Baseline in hematology parameters during the study (erythrocytes mean corpuscular volume)
    End point description
    Erythrocytes mean corpuscular volume was measured in femtolitres (fL). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    38
    43
    41
    40
    Units: femtolitres (fL)
    arithmetic mean (standard deviation)
        Week 1 (41, 38, 43, 41, 40)
    0.422 ± 1.8855
    -0.087 ± 1.9540
    0.386 ± 2.2542
    -0.017 ± 2.1066
    -0.510 ± 2.7686
        Week 2 (42, 39, 43, 41, 41)
    0.450 ± 1.8867
    -0.362 ± 2.1689
    -0.021 ± 1.8767
    -0.039 ± 2.3876
    -0.549 ± 2.5751
        Week 4 (41, 38, 42, 41, 41)
    0.829 ± 2.3409
    -0.163 ± 2.4631
    0.945 ± 3.2325
    0.354 ± 2.8851
    -0.259 ± 2.5328
        Week 8 (41, 39, 41, 38, 41)
    1.163 ± 3.6524
    0.938 ± 2.9445
    1.110 ± 3.0283
    0.916 ± 3.0058
    0.090 ± 3.5125
        Week 12 (41, 39, 43, 38, 41)
    1.478 ± 3.9560
    0.951 ± 3.4617
    1.367 ± 3.8471
    0.342 ± 3.1129
    -0.390 ± 3.3907
        Week 16 (42, 38, 42, 38, 40)
    1.107 ± 3.4022
    1.168 ± 3.7760
    1.571 ± 4.3326
    -0.016 ± 3.6944
    0.048 ± 4.4345
        Week 20 (40, 39, 41, 37, 40)
    0.497 ± 3.5197
    -0.349 ± 2.8975
    0.649 ± 3.7758
    -0.338 ± 2.5959
    0.202 ± 4.2993
        Week 24 (39, 38, 40, 36, 40)
    -1.033 ± 2.9007
    -0.858 ± 2.1793
    0.143 ± 4.9985
    -1.522 ± 3.1692
    -1.195 ± 3.5759
        Week 28 (39, 38, 41, 35, 40)
    -0.910 ± 2.6477
    -1.184 ± 2.3264
    -0.754 ± 3.3662
    -1.854 ± 3.6605
    -1.638 ± 3.3447
        Week 32 (39, 39, 40, 34, 39)
    -1.654 ± 2.7565
    -1.851 ± 2.4024
    -1.075 ± 3.5390
    -2.071 ± 3.7652
    -2.351 ± 3.1052
        Week 36 (38, 38, 41, 33, 39)
    -1.724 ± 3.1037
    -2.266 ± 2.3516
    -0.912 ± 3.9627
    -2.558 ± 3.8468
    -2.236 ± 3.2869
        Week 40 (37, 38, 41, 34, 38)
    -1.386 ± 2.8575
    -1.882 ± 3.1285
    -1.698 ± 3.0263
    -2.885 ± 3.1443
    -2.421 ± 2.9445
        Week 44 (37, 38, 41, 34, 36)
    -1.405 ± 3.4627
    -1.632 ± 3.4207
    -1.117 ± 3.4616
    -2.171 ± 4.4367
    -2.186 ± 3.4915
        Week 48 (38, 37, 41, 33, 40)
    -0.942 ± 3.5913
    -1.492 ± 2.5065
    -0.846 ± 3.1243
    -1.527 ± 3.6540
    -1.788 ± 3.5554
    No statistical analyses for this end point

    Secondary: Changes from Baseline in hematology parameters during the study (erythrocytes)

    Close Top of page
    End point title
    Changes from Baseline in hematology parameters during the study (erythrocytes)
    End point description
    Erythrocytes was measured in number of red blood cells per liter (10^12/L). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    38
    43
    41
    40
    Units: 10^12 red blood cells per liter
    arithmetic mean (standard deviation)
        Week 1 (41, 38, 43, 41, 40)
    -0.148 ± 0.2071
    -0.008 ± 0.1927
    0.050 ± 0.1773
    0.008 ± 0.2109
    -0.017 ± 0.1609
        Week 2 (42, 39, 43, 41, 41)
    -0.149 ± 0.2244
    -0.029 ± 0.1788
    -0.004 ± 0.2280
    -0.063 ± 0.2236
    0.000 ± 0.1809
        Week 4 (41, 38, 42, 41, 41)
    -0.132 ± 0.2780
    0.018 ± 0.2535
    0.023 ± 0.2135
    0.013 ± 0.1955
    0.031 ± 0.2065
        Week 8 (41, 39, 41, 38, 41)
    -0.135 ± 0.2546
    -0.011 ± 0.2206
    0.074 ± 0.2466
    0.014 ± 0.2190
    0.026 ± 0.2264
        Week 12 (41, 39, 43, 38, 41)
    -0.131 ± 0.2678
    0.021 ± 0.2561
    0.069 ± 0.2419
    0.051 ± 0.2243
    0.075 ± 0.2393
        Week 16 (42, 38, 42, 38, 40)
    -0.020 ± 0.2375
    0.075 ± 0.2898
    0.047 ± 0.2810
    0.074 ± 0.2255
    0.110 ± 0.2533
        Week 20 (40, 39, 41, 37, 40)
    0.036 ± 0.2618
    0.096 ± 0.2855
    0.068 ± 0.2089
    0.064 ± 0.2273
    0.081 ± 0.2191
        Week 24 (39, 38, 40, 36, 40)
    0.059 ± 0.2639
    0.110 ± 0.2974
    0.142 ± 0.2573
    0.074 ± 0.2250
    0.110 ± 0.1931
        Week 28 (39, 38, 41, 35, 40)
    -0.034 ± 0.2453
    0.108 ± 0.2681
    0.122 ± 0.2445
    0.058 ± 0.2359
    0.106 ± 0.2567
        Week 32 (39, 39, 40, 34, 39)
    -0.010 ± 0.2461
    0.104 ± 0.2660
    0.133 ± 0.2716
    0.061 ± 0.2555
    0.156 ± 0.2714
        Week 36 (38, 38, 41, 33, 39)
    0.044 ± 0.2524
    0.166 ± 0.2542
    0.156 ± 0.2849
    0.161 ± 0.2399
    0.145 ± 0.2377
        Week 40 (37, 38, 41, 34, 38)
    0.079 ± 0.2682
    0.177 ± 0.2733
    0.163 ± 0.2736
    0.141 ± 0.2535
    0.129 ± 0.2403
        Week 44 (37, 38, 41, 34, 36)
    0.035 ± 0.2645
    0.146 ± 0.2846
    0.133 ± 0.2622
    0.188 ± 0.2933
    0.135 ± 0.2128
        Week 48 (38, 37, 41, 33, 40)
    0.061 ± 0.2693
    0.146 ± 0.2994
    0.141 ± 0.2747
    0.135 ± 0.2934
    0.129 ± 0.2354
    No statistical analyses for this end point

    Secondary: Changes from Baseline in hematology parameters during the study (hematocrit)

    Close Top of page
    End point title
    Changes from Baseline in hematology parameters during the study (hematocrit)
    End point description
    Hematocrit was measured in volume percentage (%) of red blood cells in blood. The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    38
    43
    41
    40
    Units: volume % of red blood cells
    arithmetic mean (standard deviation)
        Week 1 (41, 38, 43, 41, 40)
    -0.011 ± 0.0189
    -0.001 ± 0.0211
    0.007 ± 0.0181
    0.000 ± 0.0206
    -0.004 ± 0.0206
        Week 2 (42, 39, 43, 41, 41)
    -0.011 ± 0.0230
    -0.004 ± 0.0204
    -0.000 ± 0.0205
    -0.006 ± 0.0220
    -0.003 ± 0.0174
        Week 4 (41, 38, 42, 41, 41)
    -0.008 ± 0.0254
    0.001 ± 0.0211
    0.006 ± 0.0220
    0.003 ± 0.0190
    0.001 ± 0.0209
        Week 8 (41, 39, 41, 38, 41)
    -0.007 ± 0.0239
    0.003 ± 0.0244
    0.012 ± 0.0237
    0.005 ± 0.0208
    0.003 ± 0.0232
        Week 12 (41, 39, 43, 38, 41)
    -0.005 ± 0.0287
    0.007 ± 0.0281
    0.013 ± 0.0276
    0.006 ± 0.0219
    0.005 ± 0.0231
        Week 16 (42, 38, 42, 38, 40)
    0.004 ± 0.0202
    0.012 ± 0.0259
    0.011 ± 0.0254
    0.006 ± 0.0240
    0.010 ± 0.0252
        Week 20 (40, 39, 41, 37, 40)
    0.006 ± 0.0217
    0.007 ± 0.0270
    0.010 ± 0.0211
    0.004 ± 0.0241
    0.008 ± 0.0246
        Week 24 (39, 38, 40, 36, 40)
    0.001 ± 0.0192
    0.006 ± 0.0253
    0.014 ± 0.0256
    -0.000 ± 0.0222
    0.005 ± 0.0219
        Week 28 (39, 38, 41, 35, 40)
    -0.007 ± 0.0210
    0.004 ± 0.0248
    0.008 ± 0.0241
    -0.003 ± 0.0229
    0.002 ± 0.0238
        Week 32 (39, 39, 40, 34, 39)
    -0.009 ± 0.0207
    0.000 ± 0.0249
    0.007 ± 0.0225
    -0.004 ± 0.0196
    0.003 ± 0.0248
        Week 36 (38, 38, 41, 33, 39)
    -0.004 ± 0.0222
    0.004 ± 0.0228
    0.009 ± 0.0258
    0.003 ± 0.0221
    0.003 ± 0.0234
        Week 40 (37, 38, 41, 34, 38)
    0.000 ± 0.0231
    0.007 ± 0.0278
    0.007 ± 0.0246
    -0.001 ± 0.0221
    0.000 ± 0.0206
        Week 44 (37, 38, 41, 34, 36)
    -0.003 ± 0.0272
    0.006 ± 0.0297
    0.007 ± 0.0239
    0.007 ± 0.0246
    0.002 ± 0.0194
        Week 48 (38, 37, 41, 33, 40)
    0.001 ± 0.0243
    0.007 ± 0.0257
    0.009 ± 0.0260
    0.005 ± 0.0252
    0.004 ± 0.0212
    No statistical analyses for this end point

    Secondary: Changes from Baseline in hematology parameters during the study (platelets)

    Close Top of page
    End point title
    Changes from Baseline in hematology parameters during the study (platelets)
    End point description
    Platelets was measured in number of platelets per liter (10^9/L). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    38
    43
    41
    40
    Units: 10^9 platelets per liter
    arithmetic mean (standard deviation)
        Week 1 (41, 38, 43, 41, 40)
    -5.073 ± 30.2609
    -3.368 ± 25.9515
    3.209 ± 30.5883
    -2.098 ± 24.6412
    -9.325 ± 23.4109
        Week 2 (42, 39, 42, 41, 41)
    4.000 ± 27.3112
    -5.179 ± 38.2800
    -3.810 ± 41.8250
    -15.122 ± 32.8414
    -15.415 ± 31.7025
        Week 4 (41, 38, 41, 41, 41)
    -3.927 ± 29.6643
    -6.868 ± 29.7487
    -13.878 ± 43.7568
    -19.415 ± 32.6450
    -27.073 ± 41.9299
        Week 8 (41, 39, 40, 38, 41)
    1.561 ± 29.1042
    -12.077 ± 28.9876
    -5.475 ± 44.7718
    -17.605 ± 29.8442
    -26.195 ± 44.1719
        Week 12 (41, 39, 42, 38, 41)
    -2.171 ± 32.0795
    -17.359 ± 35.4308
    -11.286 ± 40.7451
    -10.079 ± 44.8977
    -23.171 ± 47.2995
        Week 16 (42, 38, 42, 38, 40)
    -18.833 ± 50.4844
    -18.263 ± 37.3259
    -13.952 ± 50.7173
    -9.895 ± 35.3246
    -25.425 ± 37.6556
        Week 20 (40, 39, 41, 37, 40)
    -18.625 ± 50.3988
    -23.077 ± 39.6534
    -10.512 ± 48.0755
    -15.324 ± 28.8329
    -22.725 ± 42.2502
        Week 24 (39, 38, 40, 36, 40)
    -19.974 ± 49.0196
    -14.000 ± 37.7760
    -4.600 ± 49.4025
    -10.972 ± 36.8375
    -22.900 ± 47.4092
        Week 28 (39, 38, 41, 35, 40)
    -24.256 ± 51.8001
    -16.868 ± 40.6635
    -7.683 ± 47.8155
    -12.800 ± 30.7904
    -19.600 ± 42.3052
        Week 32 (39, 39, 40, 34, 39)
    -22.410 ± 51.9553
    -18.590 ± 41.7226
    -13.575 ± 51.9304
    -20.618 ± 38.8969
    -23.179 ± 42.2018
        Week 36 (38, 38, 41, 33, 39)
    -25.000 ± 52.6990
    -16.474 ± 46.8844
    -14.561 ± 50.2106
    -18.848 ± 40.0563
    -23.846 ± 45.1340
        Week 40 (37, 38, 41, 34, 38)
    -23.432 ± 53.2747
    -20.895 ± 41.4845
    -14.927 ± 51.2652
    -24.088 ± 33.4133
    -21.789 ± 46.1467
        Week 44 (37, 38, 39, 34, 36)
    -22.703 ± 57.8383
    -22.474 ± 41.0627
    -18.051 ± 49.1646
    -24.735 ± 38.4710
    -31.389 ± 48.5306
        Week 48 (38, 37, 41, 33, 39)
    -27.395 ± 56.2963
    -23.811 ± 47.1150
    -24.220 ± 46.2458
    -22.273 ± 37.4243
    -28.974 ± 42.9960
    No statistical analyses for this end point

    Secondary: Changes from Baseline in biochemistry parameters during the study (alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transferase, lactate dehydrogenase)

    Close Top of page
    End point title
    Changes from Baseline in biochemistry parameters during the study (alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transferase, lactate dehydrogenase)
    End point description
    Alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH) were measured in units per liter (U/L). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    38
    43
    41
    40
    Units: U/L
    arithmetic mean (standard deviation)
        ALT Week 1 (41, 38, 43, 41, 40)
    -1.366 ± 12.7451
    2.526 ± 15.5211
    2.628 ± 42.1234
    3.122 ± 10.2791
    0.700 ± 9.5868
        ALT Week 2 (42, 39, 43, 41, 41)
    -1.714 ± 15.4624
    2.026 ± 8.9428
    -1.047 ± 41.1223
    4.927 ± 20.9623
    1.171 ± 10.2978
        ALT Week 4 (41, 38, 42, 41, 41)
    -3.854 ± 15.1897
    1.553 ± 16.2758
    -3.952 ± 38.9546
    22.756 ± 139.8531
    -1.561 ± 10.1392
        ALT Week 8 (41, 39, 43, 39, 41)
    -4.707 ± 13.6478
    -1.385 ± 9.4580
    5.465 ± 68.0764
    0.795 ± 11.4321
    -1.659 ± 11.1009
        ALT Week 12 (41, 39, 42, 38, 41)
    -4.220 ± 15.1765
    0.359 ± 12.2356
    -4.429 ± 38.1756
    1.184 ± 13.0692
    -1.390 ± 8.1941
        ALT Week 16 (42, 38, 42, 38, 41)
    -2.048 ± 18.0026
    2.684 ± 16.3229
    -4.857 ± 38.6211
    0.579 ± 12.9273
    0.829 ± 11.5432
        ALT Week 20 (40, 39, 42, 37, 40)
    0.300 ± 39.9482
    3.821 ± 13.0139
    -4.881 ± 39.1808
    -0.838 ± 11.1118
    -1.350 ± 10.5479
        ALT Week 24 (39, 38, 41, 36, 40)
    -1.564 ± 19.4974
    2.789 ± 14.5475
    -5.659 ± 39.6652
    1.528 ± 11.0259
    -3.475 ± 8.6202
        ALT Week 28 (39, 38, 41, 35, 40)
    -3.385 ± 17.7373
    2.658 ± 12.8174
    -3.244 ± 43.4688
    -0.171 ± 8.7228
    -2.775 ± 10.4280
        ALT Week 32 (39, 39, 40, 34, 39)
    -4.487 ± 16.5400
    2.385 ± 12.8956
    -4.150 ± 44.0126
    -2.176 ± 12.7742
    -0.821 ± 11.5482
        ALT Week 36 (38, 38, 41, 34, 39)
    0.579 ± 10.5411
    0.184 ± 11.8660
    -2.976 ± 42.9275
    -0.471 ± 11.2848
    -1.103 ± 10.6296
        ALT Week 40 (37, 38, 41, 34, 38)
    -0.622 ± 10.2506
    0.816 ± 12.6680
    -2.780 ± 44.9719
    -3.853 ± 11.1059
    -1.385 ± 13.1061
        ALT Week 44 (37, 38, 41, 34, 36)
    2.649 ± 19.7993
    1.474 ± 13.1514
    -3.415 ± 43.2966
    -3.882 ± 12.8741
    -2.692 ± 10.2525
        ALT Week 48 (38, 37, 41, 34, 40)
    2.605 ± 14.0646
    2.216 ± 12.8542
    -4.561 ± 43.1926
    -3.794 ± 13.1628
    -0.575 ± 9.6181
        ALP Week 1 (41, 38, 43, 41, 40)
    -1.098 ± 6.0034
    -1.342 ± 8.0983
    -2.721 ± 7.2056
    -3.244 ± 4.9989
    -4.275 ± 7.1360
        ALP Week 2 (42, 39, 43, 41, 41)
    -1.905 ± 6.7960
    -3.282 ± 7.8370
    -4.349 ± 9.5963
    -4.805 ± 7.8237
    -3.585 ± 8.8430
        ALP Week 4 (41, 39, 42, 41, 41)
    -1.634 ± 9.0630
    -1.077 ± 10.4236
    -3.262 ± 9.9144
    -1.439 ± 18.3508
    -4.829 ± 10.9268
        ALP Week 8 (41, 39, 43, 39, 41)
    -2.220 ± 8.3711
    0.308 ± 12.6515
    1.233 ± 37.8014
    -5.026 ± 10.2019
    -3.585 ± 9.8336
        ALP Week 12 (41, 39, 42, 38, 41)
    -2.463 ± 8.8122
    -0.462 ± 12.1066
    -5.952 ± 11.0695
    -4.947 ± 12.0538
    -3.146 ± 17.2476
        ALP Week 16 (42, 38, 42, 38, 41)
    -8.357 ± 12.7276
    -0.895 ± 13.1515
    -7.238 ± 10.7722
    -4.605 ± 11.6539
    -1.512 ± 25.7722
        ALP Week 20 (40, 39, 42, 37, 40)
    -10.425 ± 14.0510
    -5.410 ± 15.1895
    -10.143 ± 13.0264
    -7.027 ± 11.8544
    -6.650 ± 14.8143
        ALP Week 24 (39, 39, 41, 36, 40)
    -12.795 ± 15.4752
    -4.769 ± 13.8097
    -9.463 ± 11.3448
    -6.361 ± 12.7843
    -7.225 ± 18.4231
        ALP Week 28 (39, 38, 41, 35, 40)
    -12.795 ± 16.9351
    -5.684 ± 15.7259
    -11.244 ± 12.6249
    -8.314 ± 10.9054
    -8.525 ± 16.8523
        ALP Week 32 (39, 39, 41, 35, 40)
    -13.667 ± 16.1870
    -4.769 ± 16.1530
    -10.900 ± 13.0026
    -9.118 ± 12.5765
    -8.385 ± 17.5988
        ALP Week 36 (38, 38, 41, 34, 39)
    -11.816 ± 19.2436
    -6.368 ± 15.4735
    -11.122 ± 12.3495
    -8.059 ± 9.5217
    -6.487 ± 19.2434
        ALP Week 40 (37, 38, 41, 34, 38)
    -11.000 ± 16.9706
    -5.658 ± 15.7485
    -11.024 ± 12.9180
    -10.559 ± 11.6987
    -8.175 ± 17.8884
        ALP Week 44 (37, 38, 41, 34, 40)
    -12.622 ± 17.6373
    -6.421 ± 14.9099
    -10.537 ± 13.5759
    -8.647 ± 10.5483
    -8.950 ± 18.3162
        ALP Week 48 (38, 38, 41, 34, 40)
    -12.211 ± 19.0379
    -6.500 ± 16.5313
    -11.049 ± 14.4827
    -7.765 ± 12.3290
    -7.875 ± 20.1370
        AST Week 1 (41, 38, 43, 41, 40)
    -2.854 ± 10.3212
    1.447 ± 6.2155
    -0.023 ± 27.5409
    2.244 ± 6.7889
    0.475 ± 5.2963
        AST Week 2 (42, 39, 43, 41, 41)
    -1.762 ± 10.5294
    0.487 ± 4.0967
    -2.233 ± 26.3266
    3.805 ± 14.7635
    0.780 ± 6.1746
        AST Week 4 (41, 38, 42, 41, 41)
    -3.976 ± 10.6642
    1.289 ± 7.5584
    -3.262 ± 25.1047
    8.927 ± 52.0660
    -1.195 ± 4.2791
        AST Week 8 (41, 39, 43, 39, 41)
    -3.537 ± 10.5477
    -0.077 ± 5.8687
    2.279 ± 34.7805
    1.410 ± 5.5900
    0.366 ± 6.1877
        AST Week 12 (41, 39, 42, 38, 41)
    -3.049 ± 12.2106
    0.436 ± 5.3054
    -2.595 ± 22.5324
    1.053 ± 6.9006
    1.122 ± 6.2897
        AST Week 16 (42, 38, 42, 38, 41)
    -1.048 ± 12.1313
    2.974 ± 8.3649
    -2.595 ± 24.3852
    1.526 ± 6.6688
    2.122 ± 6.1733
        AST Week 20 (40, 39, 42, 37, 40)
    6.375 ± 60.1309
    2.821 ± 6.6367
    -1.095 ± 25.1317
    1.324 ± 7.1065
    0.500 ± 4.8569
        AST Week 24 (39, 38, 41, 36, 40)
    1.718 ± 23.7940
    2.237 ± 6.9182
    -1.902 ± 26.1054
    2.889 ± 6.2554
    0.325 ± 4.3759
        AST Week 28 (39, 38, 41, 35, 40)
    -1.179 ± 13.4905
    2.289 ± 6.9512
    -1.805 ± 27.4583
    2.229 ± 6.3063
    0.175 ± 4.1255
        AST Week 32 (39, 39, 40, 34, 39)
    -1.385 ± 12.2895
    1.949 ± 6.2826
    -0.575 ± 28.3177
    0.324 ± 6.2654
    2.051 ± 4.9997
        AST Week 36 (38, 38, 41, 34, 39)
    0.711 ± 7.3113
    1.026 ± 5.5140
    -1.220 ± 25.5798
    1.588 ± 6.6017
    1.667 ± 6.0755
        AST Week 40 (37, 38, 41, 34, 39)
    0.946 ± 12.1494
    1.316 ± 5.5269
    0.244 ± 29.2701
    -0.647 ± 6.0597
    2.462 ± 8.4972
        AST Week 44 (37, 38, 41, 34, 39)
    2.838 ± 15.4641
    2.553 ± 7.9175
    -1.268 ± 28.4280
    -0.588 ± 7.7190
    1.590 ± 6.9347
        AST Week 48 (38, 37, 41, 34, 40)
    2.158 ± 9.7939
    3.459 ± 6.3403
    -1.927 ± 28.3182
    0.441 ± 6.6796
    2.900 ± 6.2339
        GGT Week 1 (41, 38, 43, 41, 40)
    0.171 ± 5.4447
    -2.737 ± 7.0354
    -0.535 ± 10.8745
    0.171 ± 5.0245
    -2.300 ± 6.2684
        GGT Week 2 (42, 39, 43, 41, 41)
    -0.190 ± 5.8736
    -2.026 ± 7.6828
    -4.116 ± 25.7527
    -0.341 ± 5.2517
    -1.268 ± 7.8773
        GGT Week 4 (41, 39, 42, 41, 41)
    -0.220 ± 7.2129
    -2.641 ± 9.9167
    -6.143 ± 35.5504
    1.171 ± 17.6265
    0.512 ± 16.3968
        GGT Week 8 (41, 39, 43, 39, 41)
    -1.829 ± 5.9745
    -4.410 ± 11.6319
    11.581 ± 103.8974
    -1.795 ± 5.7454
    -1.805 ± 9.0698
        GGT Week 12 (41, 39, 42, 38, 41)
    -0.585 ± 5.9033
    -2.154 ± 10.7643
    -5.762 ± 34.8767
    -0.447 ± 8.3785
    3.244 ± 21.8229
        GGT Week 16 (42, 38, 42, 38, 41)
    -0.357 ± 9.6445
    -1.842 ± 13.4476
    -4.357 ± 34.0020
    -0.947 ± 8.1868
    15.024 ± 77.1617
        GGT Week 20 (40, 39, 42, 37, 40)
    -0.750 ± 9.5051
    -2.769 ± 13.0555
    -5.452 ± 32.1970
    -1.649 ± 5.5137
    1.475 ± 22.2722
        GGT Week 24 (39, 39, 41, 36, 40)
    -0.615 ± 12.4173
    -2.769 ± 10.9339
    -4.122 ± 36.6832
    -2.639 ± 9.4360
    -2.625 ± 10.3272
        GGT Week 28 (39, 38, 41, 35, 40)
    -0.462 ± 11.5618
    -2.132 ± 11.7638
    -6.341 ± 36.7434
    -2.629 ± 7.6354
    -0.200 ± 11.5585
        GGT Week 32 (39, 39, 40, 34, 39)
    0.359 ± 15.7872
    -1.538 ± 13.2463
    -7.875 ± 36.9103
    -3.676 ± 8.6435
    2.795 ± 21.1501
        GGT Week 36 (38, 38, 41, 34, 39)
    -0.026 ± 14.7162
    -4.289 ± 11.4559
    -8.195 ± 38.6899
    -2.735 ± 7.1236
    1.410 ± 18.0200
        GGT Week 40 (37, 38, 41, 34, 40)
    -2.568 ± 9.3676
    -3.842 ± 13.9275
    -9.073 ± 40.5792
    -4.088 ± 7.5573
    0.925 ± 20.1066
        GGT Week 44 (37, 38, 41, 34, 39)
    1.081 ± 23.2108
    -1.289 ± 21.3730
    -7.488 ± 34.4145
    -3.824 ± 7.0430
    -0.949 ± 11.5643
        GGT Week 48 (38, 38, 41, 34, 40)
    1.474 ± 17.6723
    -2.184 ± 12.0850
    -7.805 ± 35.4924
    -2.941 ± 8.8247
    2.525 ± 20.6112
        LDH Week 1 (41, 38, 43, 41, 40)
    -7.000 ± 16.1509
    0.026 ± 19.6118
    -1.163 ± 33.1669
    -0.585 ± 16.6673
    -1.075 ± 18.4341
        LDH Week 2 (42, 39, 43, 41, 41)
    -5.929 ± 18.4858
    -0.410 ± 14.9045
    -5.930 ± 32.8325
    -2.439 ± 19.2146
    0.537 ± 19.7270
        LDH Week 4 (41, 39, 42, 41, 41)
    -5.634 ± 25.5693
    4.846 ± 21.4372
    -6.190 ± 29.5265
    0.854 ± 26.6238
    -4.293 ± 17.4732
        LDH Week 8 (41, 39, 43, 39, 41)
    -3.561 ± 17.3249
    0.026 ± 19.0449
    0.140 ± 38.8413
    3.513 ± 18.6503
    1.439 ± 24.0230
        LDH Week 12 (41, 39, 42, 38, 41)
    -0.927 ± 28.3058
    4.077 ± 21.0905
    2.119 ± 27.5134
    3.342 ± 17.0346
    1.049 ± 22.9303
        LDH Week 16 (42, 38, 42, 38, 41)
    0.881 ± 26.0180
    15.447 ± 62.0267
    -4.381 ± 35.9600
    0.474 ± 19.8967
    1.488 ± 21.8325
        LDH Week 20 (40, 39, 42, 37, 40)
    1.200 ± 35.1817
    2.154 ± 22.8825
    2.500 ± 31.6145
    0.676 ± 20.9206
    2.025 ± 23.0401
        LDH Week 24 (39, 39, 41, 36, 40)
    4.462 ± 31.9282
    1.333 ± 22.1862
    2.878 ± 44.9662
    1.944 ± 23.5638
    8.550 ± 25.3093
        LDH Week 28 (39, 38, 41, 35, 40)
    1.436 ± 21.1122
    -4.763 ± 21.2138
    -2.902 ± 34.3590
    8.143 ± 44.0929
    1.250 ± 22.0962
        LDH Week 32 (39, 39, 40, 34, 39)
    -6.333 ± 23.0587
    -6.410 ± 23.8324
    -4.525 ± 35.2762
    -2.971 ± 27.9171
    -1.615 ± 24.8052
        LDH Week 36 (38, 38, 41, 34, 39)
    0.553 ± 37.3889
    -4.658 ± 16.8383
    -7.585 ± 35.0442
    -6.147 ± 21.6895
    5.436 ± 30.0436
        LDH Week 40 (37, 38, 41, 34, 40)
    -0.216 ± 34.5214
    -8.289 ± 17.4896
    -6.366 ± 36.6898
    -10.618 ± 24.4293
    0.000 ± 29.3852
        LDH Week 44 (37, 38, 41, 34, 40)
    -0.757 ± 32.2847
    -5.316 ± 21.4805
    -5.000 ± 34.6259
    -5.059 ± 22.2683
    1.675 ± 24.9588
        LDH Week 48 (38, 38, 41, 34, 40)
    4.447 ± 34.3493
    -1.395 ± 23.8061
    -4.707 ± 38.6654
    -7.441 ± 23.0443
    4.500 ± 37.8120
    No statistical analyses for this end point

    Secondary: Changes from Baseline in biochemistry parameters during the study (albumin)

    Close Top of page
    End point title
    Changes from Baseline in biochemistry parameters during the study (albumin)
    End point description
    Albumin was measured in grams per liter (g/L). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    38
    43
    41
    40
    Units: g/L
    arithmetic mean (standard deviation)
        Week 1 (41, 38, 43, 41, 40)
    -1.000 ± 1.7464
    -0.079 ± 2.1357
    0.279 ± 1.8038
    -0.439 ± 1.8715
    -0.350 ± 1.6259
        Week 2 (42, 39, 43, 41, 41)
    -0.500 ± 2.0982
    0.051 ± 1.5719
    0.419 ± 1.9908
    -0.537 ± 2.0988
    -0.073 ± 1.8220
        Week 4 (41, 39, 42, 41, 41)
    -0.683 ± 2.4743
    0.538 ± 2.1007
    0.595 ± 1.9514
    -0.171 ± 1.9862
    0.220 ± 1.9687
        Week 8 (41, 39, 43, 39, 41)
    -0.634 ± 2.0094
    0.154 ± 2.1829
    0.581 ± 2.0843
    0.077 ± 2.2051
    0.195 ± 1.7638
        Week 12 (41, 39, 42, 38, 41)
    0.073 ± 2.4020
    0.538 ± 2.1986
    0.857 ± 1.8685
    0.211 ± 1.9474
    0.415 ± 2.1210
        Week 16 (42, 38, 42, 38, 41)
    0.833 ± 1.8468
    1.132 ± 2.2800
    0.881 ± 2.0025
    0.316 ± 2.0678
    0.683 ± 1.9422
        Week 20 (40, 39, 42, 37, 40)
    0.175 ± 1.9333
    0.487 ± 2.4047
    0.976 ± 1.7873
    -0.081 ± 2.1000
    0.575 ± 1.8659
        Week 24 (39, 39, 41, 36, 40)
    0.385 ± 1.7262
    0.949 ± 2.3164
    1.341 ± 1.8790
    0.722 ± 2.2502
    0.875 ± 2.3004
        Week 28 (39, 38, 41, 35, 40)
    -0.462 ± 2.0881
    0.632 ± 2.1362
    0.976 ± 1.9169
    0.114 ± 1.9819
    0.525 ± 2.0999
        Week 32 (39, 39, 40, 34, 39)
    -0.179 ± 1.7452
    0.359 ± 1.8706
    0.700 ± 1.9897
    -0.235 ± 1.6341
    0.667 ± 1.9912
        Week 36 (38, 38, 41, 34, 39)
    -0.289 ± 2.6397
    0.816 ± 1.7220
    0.659 ± 1.6064
    -0.029 ± 2.0815
    0.436 ± 1.9166
        Week 40 (37, 38, 41, 34, 40)
    -0.108 ± 2.0109
    0.763 ± 1.9650
    0.805 ± 1.8196
    0.000 ± 1.8749
    0.400 ± 1.9716
        Week 44 (37, 38, 41, 34, 40)
    -0.297 ± 2.0120
    0.132 ± 2.3269
    0.659 ± 2.2429
    -0.206 ± 1.9661
    0.175 ± 2.2858
        Week 48 (38, 38, 41, 34, 40)
    0.132 ± 2.2800
    0.632 ± 2.9903
    0.366 ± 3.1682
    0.088 ± 2.6671
    0.150 ± 2.3044
    No statistical analyses for this end point

    Secondary: Changes from Baseline in biochemistry parameters during the study (bilirubin, creatinine, urate)

    Close Top of page
    End point title
    Changes from Baseline in biochemistry parameters during the study (bilirubin, creatinine, urate)
    End point description
    Bilirubin, creatinine, urate were measured in micromols per liter (μmol/L). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    38
    43
    41
    40
    Units: μmol/L
    arithmetic mean (standard deviation)
        Bilirubin Week 1 (41, 38, 43, 41, 40)
    -0.841 ± 2.8968
    -1.195 ± 3.1083
    -0.465 ± 3.4868
    0.471 ± 3.0332
    0.385 ± 2.2726
        Bilirubin Week 2 (42, 39, 43, 41, 41)
    -0.762 ± 2.9415
    0.492 ± 3.1202
    0.516 ± 2.7030
    0.978 ± 2.9538
    1.395 ± 4.0672
        Bilirubin Week 4 (41, 38, 42, 41, 41)
    -0.290 ± 3.4900
    0.789 ± 2.8952
    -0.119 ± 3.2318
    1.066 ± 3.4454
    1.344 ± 3.7625
        Bilirubin Week 8 (41, 39, 43, 39, 41)
    -0.776 ± 3.7242
    0.541 ± 3.1822
    0.442 ± 3.8005
    0.972 ± 3.4557
    0.639 ± 2.8243
        Bilirubin Week 12 (41, 39, 42, 38, 41)
    -0.261 ± 2.6113
    0.341 ± 3.0050
    0.095 ± 2.5793
    0.629 ± 3.2367
    2.073 ± 4.0034
        Bilirubin Week 16 (42, 38, 42, 38, 41)
    0.607 ± 3.7361
    0.637 ± 3.7786
    0.740 ± 3.2505
    1.092 ± 3.7662
    2.024 ± 3.7217
        Bilirubin Week 20 (40, 39, 42, 37, 40)
    -0.007 ± 3.3543
    0.136 ± 3.4239
    1.062 ± 3.8164
    1.030 ± 3.8636
    1.225 ± 2.9632
        Bilirubin Week 24 (39, 38, 41, 36, 40)
    0.146 ± 3.2508
    0.592 ± 4.4981
    0.383 ± 3.1235
    1.081 ± 2.8708
    1.128 ± 2.8112
        Bilirubin Week 28 (39, 38, 41, 35, 40)
    -0.200 ± 3.6974
    -0.068 ± 3.8885
    0.105 ± 2.5550
    0.449 ± 3.4106
    1.595 ± 3.4093
        Bilirubin Week 32 (39, 39, 40, 34, 39)
    0.233 ± 3.2668
    0.262 ± 3.7358
    0.655 ± 3.1125
    0.994 ± 2.6879
    1.669 ± 4.0868
        Bilirubin Week 36 (38, 38, 41, 34, 39)
    0.942 ± 3.6870
    0.776 ± 4.3703
    0.078 ± 3.8443
    1.012 ± 3.5311
    1.095 ± 2.3971
        Bilirubin Week 40 (37, 38, 41, 34, 39)
    0.600 ± 3.8064
    0.679 ± 3.4707
    0.415 ± 3.3481
    1.065 ± 3.1718
    1.433 ± 3.3425
        Bilirubin Week 44 (37, 38, 41, 34, 39)
    -0.019 ± 3.6800
    -0.276 ± 3.1827
    -0.102 ± 3.1253
    0.871 ± 2.8347
    1.851 ± 3.7976
        Bilirubin Week 48 (38, 37, 41, 34, 40)
    0.716 ± 4.0370
    0.559 ± 3.2460
    0.285 ± 3.8393
    1.124 ± 3.2882
    1.160 ± 3.9493
        Creatinine Week 1 (41, 38, 43, 41, 40)
    -0.512 ± 6.6788
    0.368 ± 7.3757
    2.442 ± 7.8628
    1.366 ± 8.9044
    1.300 ± 6.7300
        Creatinine Week 2 (42, 39, 43, 41, 41)
    2.310 ± 11.1300
    0.026 ± 6.1194
    2.093 ± 8.4426
    2.537 ± 6.8304
    3.317 ± 6.7470
        Creatinine Week 4 (41, 39, 42, 41, 41)
    0.854 ± 10.2508
    1.256 ± 7.0812
    1.762 ± 8.8229
    -0.561 ± 7.3418
    2.171 ± 6.9279
        Creatinine Week 8 (41, 39, 43, 39, 41)
    1.366 ± 8.3269
    1.487 ± 8.3756
    3.674 ± 10.1997
    1.590 ± 7.9131
    3.073 ± 5.7810
        Creatinine Week 12 (41, 39, 42, 38, 41)
    1.268 ± 8.0282
    0.949 ± 8.6113
    6.214 ± 9.5062
    1.947 ± 9.1236
    2.220 ± 8.2417
        Creatinine Week 16 (42, 38, 42, 38, 41)
    1.833 ± 8.4678
    1.421 ± 10.7945
    3.738 ± 7.7964
    0.658 ± 8.7897
    3.976 ± 8.2719
        Creatinine Week 20 (40, 39, 42, 37, 40)
    3.150 ± 8.3468
    1.051 ± 7.7966
    4.976 ± 10.5818
    2.270 ± 8.5461
    4.525 ± 7.4144
        Creatinine Week 24 (39, 39, 41, 36, 40)
    1.359 ± 8.1741
    0.103 ± 6.8817
    3.829 ± 11.4256
    1.972 ± 9.3914
    4.650 ± 7.2627
        Creatinine Week 28 (38, 38, 41, 35, 40)
    2.921 ± 7.0227
    1.737 ± 7.4858
    4.634 ± 8.9576
    1.371 ± 8.3634
    4.900 ± 7.2388
        Creatinine Week 32 (39, 39, 40, 34, 39)
    1.718 ± 8.8227
    2.462 ± 9.1360
    2.500 ± 8.9299
    4.118 ± 12.0825
    4.974 ± 7.7408
        Creatinine Week 36 (38, 38, 41, 34, 39)
    0.289 ± 7.5656
    1.632 ± 7.1600
    1.024 ± 8.8218
    1.853 ± 10.8492
    3.462 ± 6.8127
        Creatinine Week 40 (37, 38, 41, 34, 40)
    3.838 ± 9.5205
    2.974 ± 7.3796
    4.122 ± 9.7575
    0.647 ± 10.7672
    3.200 ± 7.0208
        Creatinine Week 44 (35, 36, 41, 33, 40)
    4.543 ± 10.6670
    4.250 ± 8.7876
    3.659 ± 8.5311
    3.364 ± 10.6853
    3.925 ± 8.0012
        Creatinine Week 48 (35, 33, 39, 33, 39)
    3.000 ± 10.3299
    4.667 ± 8.5355
    3.923 ± 7.7371
    2.879 ± 9.8513
    3.256 ± 7.0290
        Urate Week 1 (41, 38, 43, 41, 40)
    -1.220 ± 37.4503
    -0.237 ± 43.0100
    11.953 ± 60.5652
    8.732 ± 39.4088
    11.650 ± 61.0924
        Urate Week 2 (42, 39, 43, 41, 41)
    12.405 ± 47.5795
    -2.974 ± 44.8826
    9.791 ± 61.4009
    9.073 ± 39.3430
    15.610 ± 49.0693
        Urate Week 4 (41, 39, 42, 41, 41)
    10.171 ± 41.5493
    0.308 ± 47.3193
    13.452 ± 49.1633
    5.659 ± 31.2591
    -4.293 ± 47.5753
        Urate Week 8 (41, 39, 43, 39, 41)
    5.415 ± 42.9500
    -6.231 ± 40.4198
    11.791 ± 64.9910
    3.410 ± 33.9518
    8.024 ± 44.0043
        Urate Week 12 (41, 39, 42, 38, 41)
    10.707 ± 40.2208
    6.795 ± 54.4814
    13.881 ± 55.3332
    7.553 ± 33.4904
    2.805 ± 37.6651
        Urate Week 16 (42, 38, 42, 38, 41)
    25.810 ± 44.1965
    8.079 ± 50.0062
    15.357 ± 59.0311
    14.026 ± 40.5173
    21.683 ± 41.1670
        Urate Week 20 (40, 39, 42, 37, 40)
    28.950 ± 53.8602
    4.692 ± 59.0420
    16.048 ± 63.4346
    10.622 ± 42.1567
    10.600 ± 44.3262
        Urate Week 24 (39, 39, 41, 36, 40)
    17.410 ± 45.0045
    9.923 ± 54.9648
    3.683 ± 58.6977
    6.667 ± 45.2580
    6.950 ± 45.8638
        Urate Week 28 (39, 38, 41, 35, 40)
    -0.897 ± 29.4331
    9.447 ± 59.8655
    18.976 ± 62.4894
    -6.371 ± 40.1227
    1.250 ± 45.8972
        Urate Week 32 (39, 39, 40, 34, 39)
    17.026 ± 47.8185
    2.821 ± 48.9042
    5.800 ± 56.2017
    3.971 ± 45.1103
    17.077 ± 40.3089
        Urate Week 36 (38, 38, 41, 34, 39)
    0.211 ± 37.5630
    -4.868 ± 49.1419
    -10.927 ± 59.4228
    4.735 ± 42.4309
    5.846 ± 49.4259
        Urate Week 40 (37, 38, 41, 34, 40)
    9.730 ± 43.5295
    15.605 ± 53.8931
    9.976 ± 62.8739
    -5.029 ± 41.2630
    7.255 ± 46.0833
        Urate Week 44 (37, 38, 41, 34, 40)
    20.541 ± 57.9164
    7.605 ± 64.3342
    -8.854 ± 67.3523
    1.382 ± 47.9558
    10.675 ± 50.8963
        Urate Week 48 (38, 38, 41, 34, 40)
    8.684 ± 53.6208
    3.895 ± 48.5831
    -3.220 ± 64.9282
    1.853 ± 54.8762
    8.050 ± 49.1956
    No statistical analyses for this end point

    Secondary: Changes from Baseline in biochemistry parameters during the study (calcium, chloride, cholesterol, glucose, magnesium, potassium, sodium)

    Close Top of page
    End point title
    Changes from Baseline in biochemistry parameters during the study (calcium, chloride, cholesterol, glucose, magnesium, potassium, sodium)
    End point description
    Calcium, chloride, cholesterol, glucose, magnesium, potassium, sodium were measured in millimoles per liter (mmol/L). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    38
    43
    41
    40
    Units: mmol/L
    arithmetic mean (standard deviation)
        Calcium Week 1 (41, 38, 43, 41, 40)
    -0.034 ± 0.0810
    -0.017 ± 0.0984
    -0.008 ± 0.0858
    -0.002 ± 0.0990
    -0.014 ± 0.0897
        Calcium Week 2 (42, 39, 43, 41, 41)
    -0.021 ± 0.0951
    0.002 ± 0.0973
    0.009 ± 0.1304
    -0.024 ± 0.1001
    -0.022 ± 0.0938
        Calcium Week 4 (41, 39, 42, 41, 41)
    -0.029 ± 0.1079
    -0.011 ± 0.1015
    -0.021 ± 0.0973
    -0.047 ± 0.1147
    -0.020 ± 0.0917
        Calcium Week 8 (41, 39, 43, 39, 41)
    -0.024 ± 0.0942
    -0.006 ± 0.0926
    0.008 ± 0.1260
    -0.004 ± 0.1105
    -0.022 ± 0.0975
        Calcium Week 12 (41, 39, 42, 38, 41)
    -0.021 ± 0.1009
    -0.025 ± 0.1090
    0.021 ± 0.1057
    -0.020 ± 0.1088
    -0.025 ± 0.0923
        Calcium Week 16 (42, 38, 42, 38, 41)
    0.004 ± 0.0826
    -0.006 ± 0.1079
    0.023 ± 0.1334
    -0.004 ± 0.1027
    0.005 ± 0.0888
        Calcium Week 20 (40, 39, 42, 37, 40)
    0.002 ± 0.0931
    0.000 ± 0.1013
    0.017 ± 0.0999
    -0.008 ± 0.0948
    -0.018 ± 0.0919
        Calcium Week 24 (39, 39, 41, 36, 40)
    0.011 ± 0.1019
    -0.002 ± 0.1028
    0.015 ± 0.0845
    0.004 ± 0.0896
    0.003 ± 0.0974
        Calcium Week 28 (39, 38, 41, 35, 40)
    -0.027 ± 0.1117
    0.002 ± 0.0877
    0.009 ± 0.1068
    0.008 ± 0.0909
    -0.021 ± 0.1043
        Calcium Week 32 (39, 39, 40, 34, 39)
    -0.023 ± 0.1069
    0.000 ± 0.0952
    0.001 ± 0.1074
    -0.017 ± 0.0932
    -0.008 ± 0.1024
        Calcium Week 36 (38, 38, 41, 34, 39)
    -0.013 ± 0.1172
    0.007 ± 0.0804
    -0.005 ± 0.1096
    0.001 ± 0.0972
    -0.015 ± 0.0936
        Calcium Week 40 (37, 38, 41, 34, 40)
    0.003 ± 0.0905
    0.001 ± 0.0807
    -0.007 ± 0.1084
    -0.019 ± 0.0809
    -0.025 ± 0.0947
        Calcium Week 44 (37, 38, 41, 34, 40)
    -0.027 ± 0.0920
    -0.018 ± 0.0861
    -0.008 ± 0.1023
    -0.019 ± 0.0839
    -0.042 ± 0.0972
        Calcium Week 48 (38, 38, 41, 34, 40)
    -0.010 ± 0.0881
    -0.009 ± 0.1033
    -0.014 ± 0.1126
    -0.014 ± 0.0912
    -0.034 ± 0.0861
        Chloride Week 1 (41, 38, 43, 41, 40)
    -0.195 ± 2.1121
    -0.105 ± 2.5446
    -0.674 ± 4.1388
    -0.244 ± 2.5572
    -0.125 ± 2.3986
        Chloride Week 2 (42, 39, 43, 41, 41)
    -0.214 ± 2.1131
    0.308 ± 2.6273
    0.093 ± 2.7500
    0.415 ± 2.5296
    -0.439 ± 2.4192
        Chloride Week 4 (41, 39, 42, 41, 41)
    -0.293 ± 1.9525
    -0.333 ± 2.2750
    0.000 ± 2.4792
    0.024 ± 2.6409
    0.000 ± 2.6363
        Chloride Week 8 (41, 39, 43, 39, 41)
    -0.537 ± 2.1920
    0.615 ± 2.4346
    0.047 ± 2.6988
    0.538 ± 2.3038
    0.683 ± 2.4025
        Chloride Week 12 (41, 39, 42, 38, 41)
    0.341 ± 2.2205
    -0.282 ± 2.3946
    0.548 ± 2.5681
    -0.211 ± 2.3499
    0.000 ± 2.4393
        Chloride Week 16 (42, 38, 42, 38, 41)
    -0.310 ± 1.8934
    0.026 ± 2.2837
    0.190 ± 2.0864
    -0.184 ± 2.2644
    -0.268 ± 2.1334
        Chloride Week 20 (40, 39, 42, 37, 40)
    -0.325 ± 2.4640
    -0.538 ± 2.1502
    0.262 ± 2.3484
    0.162 ± 2.6616
    0.075 ± 2.3685
        Chloride Week 24 (39, 39, 41, 36, 40)
    -0.615 ± 2.0081
    -0.128 ± 2.5462
    -0.390 ± 2.6351
    -0.306 ± 2.1885
    -0.050 ± 2.5415
        Chloride Week 28 (39, 38, 41, 35, 40)
    0.128 ± 2.3190
    0.000 ± 2.6913
    0.195 ± 2.3154
    0.086 ± 2.5365
    0.250 ± 2.5090
        Chloride Week 32 (39, 39, 40, 34, 39)
    -0.154 ± 2.2069
    0.436 ± 2.3708
    0.500 ± 2.2072
    0.794 ± 2.3196
    0.282 ± 2.0641
        Chloride Week 36 (38, 38, 41, 34, 39)
    0.237 ± 1.9923
    0.684 ± 2.4285
    0.732 ± 1.9239
    0.294 ± 2.5999
    0.205 ± 2.4299
        Chloride Week 40 (37, 38, 41, 34, 40)
    -0.054 ± 2.5380
    0.263 ± 2.6271
    0.707 ± 2.4418
    0.824 ± 2.4676
    0.500 ± 2.4495
        Chloride Week 44 (37, 38, 41, 34, 40)
    0.135 ± 1.9027
    0.579 ± 2.6977
    0.756 ± 2.1069
    0.882 ± 2.8044
    0.200 ± 2.5840
        Chloride Week 48 (38, 38, 41, 34, 40)
    0.605 ± 2.0994
    0.737 ± 2.8158
    1.024 ± 2.4545
    0.971 ± 2.5044
    0.725 ± 2.7826
        Cholesterol Week 1 (41, 38, 43, 41, 40)
    -0.254 ± 0.4371
    0.032 ± 0.4307
    0.244 ± 0.5220
    0.105 ± 0.4690
    0.102 ± 0.3965
        Cholesterol Week 2 (42, 39, 43, 41, 41)
    -0.224 ± 0.4154
    0.108 ± 0.5132
    0.295 ± 0.5178
    0.054 ± 0.5441
    0.222 ± 0.6101
        Cholesterol Week 4 (41, 39, 42, 41, 41)
    -0.198 ± 0.6334
    -0.023 ± 0.5905
    0.210 ± 0.8027
    0.093 ± 0.6525
    0.151 ± 0.4178
        Cholesterol Week 8 (41, 39, 43, 39, 41)
    -0.190 ± 0.6935
    -0.023 ± 0.5770
    0.284 ± 0.8012
    0.074 ± 0.7920
    0.061 ± 0.6268
        Cholesterol Week 12 (41, 39, 42, 38, 41)
    -0.124 ± 0.6719
    0.013 ± 0.7473
    0.117 ± 0.7616
    0.005 ± 0.6045
    0.212 ± 0.7491
        Cholesterol Week 16 (42, 38, 42, 38, 41)
    0.095 ± 0.6811
    0.184 ± 0.6378
    0.138 ± 0.6814
    0.068 ± 0.6014
    0.249 ± 0.7075
        Cholesterol Week 20 (40, 39, 42, 37, 40)
    0.053 ± 0.7609
    0.126 ± 0.6889
    0.186 ± 0.9669
    0.116 ± 0.7101
    0.115 ± 0.7718
        Cholesterol Week 24 (39, 39, 41, 36, 40)
    0.041 ± 0.8729
    0.013 ± 0.8673
    0.127 ± 1.0682
    -0.003 ± 0.6984
    0.077 ± 0.5686
        Cholesterol Week 28 (39, 38, 41, 35, 40)
    -0.044 ± 0.9797
    -0.037 ± 0.8930
    0.076 ± 1.1434
    -0.037 ± 0.5801
    0.100 ± 0.5923
        Cholesterol Week 32 (39, 39, 40, 34, 39)
    -0.085 ± 0.8540
    -0.079 ± 0.8918
    0.175 ± 1.0895
    -0.050 ± 0.5945
    0.256 ± 0.6920
        Cholesterol Week 36 (38, 38, 41, 34, 39)
    0.005 ± 0.7322
    0.024 ± 0.7951
    0.117 ± 0.8408
    -0.038 ± 0.6597
    0.144 ± 0.7950
        Cholesterol Week 40 (37, 38, 41, 34, 40)
    -0.103 ± 0.7541
    -0.118 ± 0.9109
    0.183 ± 0.8947
    -0.135 ± 0.7454
    0.110 ± 0.7824
        Cholesterol Week 44 (37, 38, 41, 34, 39)
    -0.170 ± 0.8082
    -0.176 ± 1.0874
    0.071 ± 0.9341
    -0.218 ± 0.9150
    -0.000 ± 0.8407
        Cholesterol Week 48 (38, 38, 41, 34, 40)
    -0.282 ± 0.7891
    -0.279 ± 0.8348
    0.012 ± 0.8883
    -0.253 ± 0.6653
    -0.083 ± 0.5817
        Glucose Week 1 (41, 38, 43, 41, 40)
    0.307 ± 1.3942
    0.103 ± 0.7027
    0.077 ± 1.1366
    0.173 ± 1.0232
    -0.060 ± 0.8445
        Glucose Week 2 (42, 39, 43, 41, 41)
    0.062 ± 0.6681
    0.013 ± 0.8348
    0.221 ± 0.9652
    0.129 ± 1.2364
    0.190 ± 0.8938
        Glucose Week 4 (41, 39, 42, 41, 41)
    0.298 ± 0.8575
    0.015 ± 0.6888
    0.248 ± 0.7693
    0.249 ± 1.0659
    0.134 ± 0.7428
        Glucose Week 8 (41, 39, 43, 39, 41)
    0.112 ± 0.9127
    0.308 ± 0.7696
    0.258 ± 0.9254
    0.344 ± 0.6939
    0.256 ± 0.7075
        Glucose Week 12 (41, 39, 42, 38, 41)
    0.110 ± 0.9146
    0.005 ± 0.6117
    0.188 ± 0.7533
    0.111 ± 0.6455
    -0.124 ± 0.6636
        Glucose Week 16 (42, 37, 42, 38, 41)
    0.176 ± 0.8363
    0.195 ± 0.6316
    0.424 ± 1.1521
    0.276 ± 0.8280
    0.398 ± 0.8332
        Glucose Week 20 (40, 39, 42, 37, 40)
    0.208 ± 1.0560
    0.315 ± 1.0225
    0.267 ± 1.0132
    0.632 ± 0.9741
    0.165 ± 1.0366
        Glucose Week 24 (39, 39, 40, 36, 40)
    0.018 ± 1.1856
    0.092 ± 0.7747
    0.328 ± 0.8554
    0.061 ± 1.0462
    0.037 ± 0.6295
        Glucose Week 28 (39, 38, 41, 35, 40)
    0.246 ± 1.1812
    0.263 ± 0.9371
    0.322 ± 1.1372
    0.263 ± 1.0053
    0.262 ± 0.6412
        Glucose Week 32 (39, 39, 40, 34, 39)
    0.333 ± 1.2671
    0.236 ± 0.7013
    0.570 ± 1.0301
    0.356 ± 1.1021
    0.203 ± 0.5945
        Glucose Week 36 (38, 38, 41, 34, 39)
    0.089 ± 0.9061
    0.342 ± 0.9406
    0.234 ± 1.0379
    0.174 ± 1.0175
    0.290 ± 0.7789
        Glucose Week 40 (37, 38, 41, 34, 40)
    0.143 ± 1.0885
    0.245 ± 1.1081
    0.507 ± 1.1257
    0.203 ± 0.7420
    0.125 ± 0.7016
        Glucose Week 44 (37, 38, 41, 34, 39)
    0.222 ± 1.4919
    0.200 ± 1.0950
    0.185 ± 0.8688
    0.303 ± 1.2760
    0.197 ± 0.8966
        Glucose Week 48 (38, 38, 41, 34, 40)
    -0.013 ± 1.2512
    0.045 ± 0.8472
    0.141 ± 0.9341
    0.276 ± 1.0841
    0.100 ± 0.7835
        Magnesium Week 1 (41, 38, 43, 41, 40)
    -0.010 ± 0.0672
    -0.007 ± 0.0676
    0.002 ± 0.0694
    -0.014 ± 0.0573
    -0.015 ± 0.0680
        Magnesium Week 2 (42, 39, 43, 41, 41)
    -0.004 ± 0.0795
    0.008 ± 0.0745
    -0.011 ± 0.0771
    -0.019 ± 0.0624
    -0.007 ± 0.0680
        Magnesium Week 4 (41, 39, 42, 41, 41)
    -0.022 ± 0.0606
    0.009 ± 0.0725
    -0.012 ± 0.0789
    -0.020 ± 0.0712
    -0.005 ± 0.0998
        Magnesium Week 8 (41, 39, 43, 39, 41)
    -0.016 ± 0.0706
    -0.008 ± 0.0593
    -0.013 ± 0.0819
    -0.015 ± 0.0706
    -0.006 ± 0.0624
        Magnesium Week 12 (41, 39, 42, 38, 41)
    0.010 ± 0.0797
    0.008 ± 0.0847
    -0.011 ± 0.0733
    -0.001 ± 0.0660
    0.003 ± 0.0730
        Magnesium Week 16 (42, 38, 42, 38, 41)
    -0.002 ± 0.0742
    0.003 ± 0.0823
    -0.021 ± 0.0659
    -0.009 ± 0.0629
    -0.002 ± 0.0731
        Magnesium Week 20 (40, 39, 42, 37, 40)
    -0.007 ± 0.0811
    -0.012 ± 0.0728
    -0.018 ± 0.0659
    -0.005 ± 0.0724
    -0.009 ± 0.0636
        Magnesium Week 24 (39, 39, 41, 36, 40)
    -0.005 ± 0.0757
    -0.004 ± 0.0572
    -0.014 ± 0.0732
    -0.009 ± 0.0559
    -0.016 ± 0.0664
        Magnesium Week 28 (39, 38, 41, 35, 40)
    -0.027 ± 0.0713
    -0.007 ± 0.0525
    -0.018 ± 0.0678
    -0.019 ± 0.0719
    -0.017 ± 0.0565
        Magnesium Week 32 (39, 39, 40, 34, 39)
    -0.023 ± 0.0727
    -0.016 ± 0.0641
    -0.016 ± 0.0603
    -0.012 ± 0.0670
    -0.013 ± 0.0572
        Magnesium Week 36 (38, 38, 41, 34, 39)
    -0.015 ± 0.0694
    -0.001 ± 0.0596
    -0.031 ± 0.0698
    -0.004 ± 0.0534
    -0.007 ± 0.0563
        Magnesium Week 40 (37, 38, 41, 34, 40)
    -0.032 ± 0.0681
    -0.007 ± 0.0541
    -0.014 ± 0.0754
    -0.024 ± 0.0636
    -0.009 ± 0.0684
        Magnesium Week 44 (37, 38, 41, 34, 40)
    -0.024 ± 0.0677
    -0.000 ± 0.0597
    -0.009 ± 0.0685
    -0.024 ± 0.0668
    -0.016 ± 0.0667
        Magnesium Week 48 (38, 38, 41, 34, 40)
    -0.004 ± 0.0633
    -0.004 ± 0.0546
    -0.014 ± 0.0569
    -0.006 ± 0.0616
    -0.009 ± 0.0648
        Potassium Week 1 (41, 38, 43, 41, 40)
    -0.095 ± 0.2701
    0.089 ± 0.3608
    0.081 ± 0.4289
    -0.017 ± 0.3098
    -0.062 ± 0.3216
        Potassium Week 2 (42, 39, 43, 41, 41)
    -0.098 ± 0.2975
    0.085 ± 0.4095
    0.002 ± 0.3327
    -0.005 ± 0.3521
    0.027 ± 0.3074
        Potassium Week 4 (41, 39, 42, 41, 41)
    -0.080 ± 0.2522
    0.008 ± 0.3821
    0.026 ± 0.2632
    0.024 ± 0.4030
    -0.063 ± 0.2853
        Potassium Week 8 (41, 39, 43, 39, 41)
    -0.056 ± 0.2907
    0.069 ± 0.3221
    0.014 ± 0.3306
    -0.010 ± 0.3135
    0.000 ± 0.2520
        Potassium Week 12 (41, 39, 42, 38, 41)
    -0.073 ± 0.3217
    0.033 ± 0.3398
    -0.024 ± 0.3192
    -0.082 ± 0.3074
    -0.080 ± 0.2977
        Potassium Week 16 (42, 36, 42, 38, 41)
    -0.086 ± 0.3258
    0.083 ± 0.3112
    0.012 ± 0.3651
    -0.037 ± 0.3035
    -0.020 ± 0.2713
        Potassium Week 20 (40, 39, 42, 37, 40)
    -0.092 ± 0.3846
    0.031 ± 0.3381
    0.055 ± 0.3494
    -0.019 ± 0.3627
    0.000 ± 0.2774
        Potassium Week 24 (39, 39, 40, 36, 40)
    -0.095 ± 0.3308
    -0.072 ± 0.3052
    0.030 ± 0.3844
    -0.094 ± 0.3414
    -0.062 ± 0.2967
        Potassium Week 28 (39, 38, 41, 35, 40)
    -0.077 ± 0.3141
    0.105 ± 0.3616
    0.063 ± 0.4265
    -0.003 ± 0.3312
    -0.030 ± 0.3480
        Potassium Week 32 (39, 39, 40, 34, 39)
    -0.062 ± 0.3306
    0.069 ± 0.3621
    0.023 ± 0.4154
    0.056 ± 0.2688
    0.046 ± 0.3094
        Potassium Week 36 (38, 38, 41, 34, 39)
    -0.092 ± 0.3388
    0.045 ± 0.3689
    0.066 ± 0.4316
    0.003 ± 0.3205
    0.033 ± 0.3359
        Potassium Week 40 (37, 38, 41, 34, 40)
    -0.092 ± 0.3616
    0.089 ± 0.3826
    0.024 ± 0.3484
    -0.003 ± 0.3407
    -0.017 ± 0.3456
        Potassium Week 44 (37, 38, 41, 34, 40)
    -0.119 ± 0.2933
    0.029 ± 0.3571
    0.068 ± 0.4344
    0.094 ± 0.3084
    -0.035 ± 0.3009
        Potassium Week 48 (38, 38, 41, 34, 40)
    -0.137 ± 0.3627
    -0.053 ± 0.3244
    -0.032 ± 0.3274
    0.003 ± 0.4123
    -0.027 ± 0.3250
        Sodium Week 1 (41, 38, 43, 41, 40)
    -0.146 ± 1.5582
    -0.184 ± 1.7531
    0.000 ± 2.0471
    -0.610 ± 2.0722
    -0.375 ± 2.1326
        Sodium Week 2 (42, 39, 43, 41, 41)
    -0.500 ± 1.6417
    -0.513 ± 1.8191
    -0.209 ± 1.9341
    -0.244 ± 2.0221
    -0.341 ± 2.1167
        Sodium Week 4 (41, 39, 42, 41, 41)
    -0.732 ± 1.8442
    -0.385 ± 1.6482
    -0.214 ± 2.3430
    -0.707 ± 2.0155
    -0.805 ± 1.8196
        Sodium Week 8 (41, 39, 43, 39, 41)
    -0.854 ± 2.0070
    -0.410 ± 1.3711
    -0.860 ± 2.2316
    -0.359 ± 1.7394
    -0.463 ± 2.2924
        Sodium Week 12 (41, 39, 42, 38, 41)
    -0.512 ± 1.8858
    -0.513 ± 1.4845
    -0.619 ± 2.0357
    -0.632 ± 2.1738
    -0.854 ± 2.3512
        Sodium Week 16 (42, 38, 42, 38, 41)
    -0.738 ± 1.8086
    -0.211 ± 1.7423
    -0.714 ± 1.7708
    -0.842 ± 2.3656
    -0.780 ± 1.7250
        Sodium Week 20 (40, 39, 42, 37, 40)
    -0.675 ± 1.7155
    -0.538 ± 1.4482
    -0.857 ± 2.1928
    -0.595 ± 2.1661
    -0.775 ± 1.9147
        Sodium Week 24 (39, 39, 41, 36, 40)
    -0.821 ± 1.7751
    -0.487 ± 1.5196
    -0.463 ± 2.0137
    -0.472 ± 1.8124
    -0.725 ± 1.7393
        Sodium Week 28 (39, 38, 41, 35, 40)
    -0.462 ± 2.2924
    -0.658 ± 1.8494
    -0.683 ± 1.8767
    -0.457 ± 2.3307
    -0.575 ± 2.5609
        Sodium Week 32 (39, 39, 40, 34, 39)
    -1.077 ± 1.8692
    -0.128 ± 1.9219
    -0.525 ± 1.8809
    -0.441 ± 1.6732
    -0.667 ± 1.8257
        Sodium Week 36 (38, 38, 41, 34, 39)
    -0.711 ± 2.0122
    -0.263 ± 1.8986
    -0.512 ± 1.8725
    -0.618 ± 1.9850
    -0.436 ± 2.2337
        Sodium Week 40 (37, 38, 41, 34, 40)
    -0.432 ± 2.1153
    -0.474 ± 1.6397
    -0.512 ± 2.1578
    -0.882 ± 1.9812
    -0.950 ± 2.0248
        Sodium Week 44 (37, 38, 41, 34, 40)
    -0.486 ± 1.8352
    -0.737 ± 2.0492
    -0.878 ± 1.9390
    -0.647 ± 1.8238
    -1.000 ± 2.4179
        Sodium Week 48 (38, 38, 41, 34, 40)
    -0.237 ± 1.7772
    -0.763 ± 1.8074
    -0.732 ± 1.8845
    -0.706 ± 1.5281
    -0.750 ± 2.1334
    No statistical analyses for this end point

    Secondary: Changes from Baseline in biochemistry parameters during the study (urea nitrogen)

    Close Top of page
    End point title
    Changes from Baseline in biochemistry parameters during the study (urea nitrogen)
    End point description
    Urea nitrogen was measured in millimoles per liter (mmol/L). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    41
    38
    43
    41
    40
    Units: mmol/L
    arithmetic mean (standard deviation)
        Week 1 (41, 38, 43, 41, 40)
    -0.093 ± 1.0815
    0.126 ± 1.2116
    -0.123 ± 1.0989
    -0.012 ± 1.0900
    0.173 ± 1.5513
        Week 2 (42, 39, 43, 41, 41)
    0.386 ± 1.8183
    -0.208 ± 1.1329
    -0.047 ± 1.0359
    0.024 ± 1.1762
    0.212 ± 1.3064
        Week 4 (41, 39, 42, 41, 41)
    0.027 ± 1.3217
    0.013 ± 1.1307
    0.083 ± 1.1244
    -0.224 ± 1.1449
    0.007 ± 1.2384
        Week 8 (41, 39, 43, 39, 41)
    0.007 ± 0.9936
    0.023 ± 1.1685
    -0.070 ± 1.1143
    -0.379 ± 1.2316
    0.080 ± 1.1265
        Week 12 (41, 39, 42, 38, 41)
    -0.166 ± 1.2654
    -0.244 ± 1.1740
    -0.231 ± 1.3357
    -0.429 ± 1.1733
    -0.151 ± 1.2426
        Week 16 (42, 38, 42, 38, 41)
    -0.133 ± 1.0656
    -0.087 ± 0.9793
    -0.200 ± 1.3083
    -0.218 ± 1.0747
    0.012 ± 1.1996
        Week 20 (40, 39, 42, 37, 40)
    -0.207 ± 1.2670
    -0.490 ± 1.0901
    -0.064 ± 1.2916
    -0.357 ± 1.1572
    -0.035 ± 1.3202
        Week 24 (39, 39, 41, 36, 40)
    -0.256 ± 1.1378
    -0.523 ± 1.1235
    -0.232 ± 1.4951
    -0.289 ± 1.1369
    -0.138 ± 1.2245
        Week 28 (39, 38, 41, 35, 40)
    -0.267 ± 1.3487
    -0.287 ± 1.0992
    0.012 ± 1.3020
    -0.263 ± 1.1835
    -0.082 ± 1.3239
        Week 32 (39, 39, 40, 34, 39)
    -0.097 ± 1.0396
    -0.141 ± 1.3098
    -0.200 ± 1.1266
    -0.326 ± 1.1199
    0.082 ± 1.1841
        Week 36 (38, 38, 41, 34, 39)
    -0.203 ± 1.0579
    -0.308 ± 1.1757
    0.015 ± 1.1094
    -0.247 ± 1.1683
    -0.018 ± 1.1014
        Week 40 (37, 38, 41, 34, 40)
    -0.214 ± 1.2537
    0.192 ± 1.3690
    0.068 ± 1.1230
    -0.132 ± 1.1834
    0.283 ± 1.3435
        Week 44 (37, 38, 41, 34, 39)
    -0.105 ± 1.3389
    -0.047 ± 1.3456
    -0.054 ± 1.1276
    -0.229 ± 1.1979
    0.210 ± 1.2264
        Week 48 (38, 38, 41, 34, 40)
    -0.111 ± 1.4431
    -0.113 ± 1.1796
    -0.222 ± 1.4085
    -0.285 ± 1.2611
    0.088 ± 1.4580
    No statistical analyses for this end point

    Secondary: Changes from Baseline in urinalysis parameters during the study (erythrocytes, leukocytes, renal epithelial casts, squamous epithelial cells, transitional epithelial cells)

    Close Top of page
    End point title
    Changes from Baseline in urinalysis parameters during the study (erythrocytes, leukocytes, renal epithelial casts, squamous epithelial cells, transitional epithelial cells)
    End point description
    Erythrocytes, leukocytes, renal epithelial casts, squamous epithelial cells, transitional epithelial cells were measured in cells per high power field (cells/HPF). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Number of participants reflect those with non-missing urinalysis results during the study. Note 1: 999 is used as a placeholder for values not evaluable because only one participant was analyzed and for groups that had 0 participants analyzed. Note 2: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    1
    4
    3
    5
    3
    Units: cells/HPF
    arithmetic mean (standard deviation)
        Erythrocytes Week 1 (1, 4, 3, 5, 3)
    -55.000 ± 999
    0.750 ± 0.9574
    0.333 ± 0.5774
    0.000 ± 0.0000
    0.333 ± 0.5774
        Erythrocytes Week 2 (1, 4, 4, 4, 3)
    -54.000 ± 999
    -0.500 ± 0.5774
    0.250 ± 0.5000
    0.000 ± 0.0000
    1.333 ± 2.5166
        Erythrocytes Week 4 (1, 3, 5, 4, 2)
    0.000 ± 999
    3.333 ± 5.7735
    0.000 ± 0.7071
    0.250 ± 0.5000
    -0.500 ± 0.7071
        Erythrocytes Week 8 (0, 3, 4, 2, 3)
    999 ± 999
    0.000 ± 0.0000
    0.000 ± 0.8165
    0.000 ± 0.0000
    0.000 ± 1.0000
        Erythrocytes Week 12 (1, 3, 5, 2, 3)
    -23.000 ± 999
    0.000 ± 0.0000
    0.800 ± 1.3038
    0.000 ± 0.0000
    -0.333 ± 0.5774
        Erythrocytes Week 16 (1, 5, 4, 5, 2)
    -55.000 ± 999
    0.800 ± 1.7889
    0.500 ± 1.7321
    0.000 ± 0.0000
    2.500 ± 3.5355
        Erythrocytes Week 20 (2, 4, 5, 6, 4)
    -30.000 ± 35.3553
    0.000 ± 0.0000
    0.400 ± 1.1402
    0.000 ± 0.0000
    0.250 ± 0.5000
        Erythrocytes Week 24 (0, 4, 4, 7, 3)
    999 ± 999
    -0.250 ± 0.5000
    0.250 ± 0.5000
    -0.143 ± 0.8997
    1.000 ± 2.6458
        Erythrocytes Week 28 (1, 4, 5, 4, 3)
    -5.000 ± 999
    0.000 ± 0.8165
    0.400 ± 1.5166
    0.000 ± 0.0000
    2.333 ± 5.7735
        Erythrocytes Week 32 (2, 3, 4, 6, 3)
    -27.500 ± 38.8909
    0.000 ± 0.0000
    0.250 ± 0.5000
    0.000 ± 0.0000
    2.000 ± 3.4641
        Erythrocytes Week 36 (1, 6, 4, 1, 1)
    -55.000 ± 999
    0.000 ± 0.0000
    0.250 ± 0.5000
    0.000 ± 999
    -1.000 ± 999
        Erythrocytes Week 40 (0, 4, 4, 4, 2)
    999 ± 999
    -0.250 ± 0.5000
    0.750 ± 1.5000
    -0.250 ± 0.5000
    0.000 ± 0.0000
        Erythrocytes Week 44 (1, 5, 5, 4, 2)
    -55.000 ± 999
    0.000 ± 0.0000
    0.400 ± 0.8944
    -0.250 ± 1.2583
    0.000 ± 0.0000
        Erythrocytes Week 48 (2, 6, 4, 3, 4)
    -27.500 ± 38.8909
    0.167 ± 0.4082
    1.750 ± 3.5000
    0.000 ± 0.0000
    0.000 ± 0.8165
        Leukocytes Week 1 (1, 4, 3, 5, 3)
    0.000 ± 999
    2.750 ± 6.1847
    -7.667 ± 13.2791
    -0.200 ± 1.0954
    0.667 ± 1.1547
        Leukocytes Week 2 (1, 4, 4, 4, 3)
    2.000 ± 999
    -2.500 ± 2.0817
    -3.000 ± 6.6833
    -0.250 ± 0.5000
    0.000 ± 0.0000
        Leukocytes Week 4 (1, 3, 5, 4, 2)
    0.000 ± 999
    0.000 ± 0.0000
    -4.600 ± 10.2372
    0.250 ± 0.5000
    2.000 ± 2.8284
        Leukocytes Week 8 (0, 2, 4, 2, 3))
    999 ± 999
    0.000 ± 0.0000
    -1.500 ± 3.6968
    0.000 ± 0.0000
    4.000 ± 6.9282
        Leukocytes Week 12 (1, 3, 4, 2, 3)
    0.000 ± 999
    1.667 ± 4.7258
    13.500 ± 26.3376
    0.000 ± 0.0000
    0.000 ± 0.0000
        Leukocytes Week 16 (1, 5, 4, 5, 2)
    0.000 ± 999
    -0.200 ± 1.7889
    33.750 ± 67.5000
    -0.400 ± 0.8944
    0.500 ± 0.7071
        Leukocytes Week 20 (2, 4, 5, 6, 4)
    0.000 ± 2.8284
    3.000 ± 6.0000
    57.800 ± 145.4036
    0.667 ± 1.5055
    -6.750 ± 14.8633
        Leukocytes Week 24 (0, 4, 4, 7, 3)
    999 ± 999
    2.750 ± 4.8563
    -6.500 ± 13.0000
    2.286 ± 4.8206
    0.333 ± 0.5774
        Leukocytes Week 28 (1, 4, 5, 4, 3)
    -2.000 ± 999
    -0.750 ± 0.9574
    -5.400 ± 12.0748
    0.000 ± 0.0000
    2.333 ± 4.0415
        Leukocytes Week 32 (2, 3, 4, 6, 3)
    0.000 ± 0.0000
    3.333 ± 5.7735
    -6.500 ± 13.0000
    -1.333 ± 1.6330
    1.333 ± 2.3094
        Leukocytes Week 36 (1, 6, 4, 1, 1)
    0.000 ± 999
    0.667 ± 2.7325
    0.000 ± 0.0000
    24.000 ± 999
    0.000 ± 999
        Leukocytes Week 40 (0, 4, 4, 4, 2)
    999 ± 999
    -0.500 ± 2.5166
    -7.500 ± 15.0000
    1.500 ± 3.0000
    0.000 ± 0.0000
        Leukocytes Week 44 (1, 5, 5, 4, 2)
    0.000 ± 999
    0.400 ± 0.8944
    -1.400 ± 3.1305
    -0.500 ± 1.0000
    0.000 ± 0.0000
        Leukocytes Week 48 (2, 6, 4, 3, 4)
    0.000 ± 0.0000
    8.000 ± 21.6148
    69.500 ± 139.0000
    -1.000 ± 1.7321
    0.250 ± 0.5000
        Renal Casts Week 1 (1, 4, 3, 5, 3)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Renal Casts Week 2 (1, 4, 4, 4, 3)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Renal Casts Week 4 (1, 3, 5, 4, 2)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Renal Casts Week 8 (0, 3, 4, 2, 3)
    999 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Renal Casts Week 12 (1, 3, 5, 2, 3)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Renal Casts Week 16 (1, 5, 4, 5, 2)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Renal Casts Week 20 (2, 4, 5, 6, 4)
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Renal Casts Week 24 (0, 4, 4, 7, 3)
    999 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Renal Casts Week 28 (1, 4, 5, 4, 3)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Renal Casts Week 32 (2, 3, 4, 6, 3)
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Renal Casts Week 36 (1, 6, 4, 1, 1)
    0.000 ± 999
    0.167 ± 0.4082
    0.000 ± 0.0000
    0.000 ± 999
    0.000 ± 999
        Renal Casts Week 40 (0, 4, 4, 4, 2)
    999 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Renal Casts Week 44 (1, 5, 5, 4, 2)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Renal Casts Week 48 (2, 6, 4, 3, 4)
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Squamous Cells Week 1 (1, 4, 3, 5, 3)
    0.000 ± 999
    0.250 ± 1.2583
    3.000 ± 5.1962
    -0.200 ± 0.4472
    -0.333 ± 0.5774
        Squamous Cells Week 2 (1, 4, 4, 4, 3)
    1.000 ± 999
    -8.000 ± 14.6969
    -0.250 ± 3.6856
    0.000 ± 0.0000
    -1.667 ± 1.5275
        Squamous Cells Week 4 (1, 3, 5, 4, 2)
    0.000 ± 999
    0.000 ± 0.0000
    -1.800 ± 7.1554
    0.000 ± 0.0000
    1.000 ± 1.4142
        Squamous Cells Week 8 (0, 2, 4, 2, 3)
    999 ± 999
    0.000 ± 0.0000
    0.500 ± 1.0000
    0.000 ± 0.0000
    0.333 ± 0.5774
        Squamous Cells Week 12 (1, 3, 5, 2, 3)
    0.000 ± 999
    -4.333 ± 7.5056
    -2.200 ± 5.4955
    0.000 ± 0.0000
    0.333 ± 0.5774
        Squamous Cells Week 16 (1, 5, 4, 5, 2)
    0.000 ± 999
    0.000 ± 0.0000
    -2.750 ± 5.5000
    -0.200 ± 0.4472
    0.000 ± 0.0000
        Squamous Cells Week 20 (2, 4, 5, 6, 4)
    1.000 ± 1.4142
    -2.750 ± 5.5000
    -1.400 ± 5.6391
    -0.167 ± 0.9832
    -0.750 ± 0.9574
        Squamous Cells Week 24 (0, 4, 4, 7, 3)
    999 ± 999
    1.000 ± 1.4142
    1.000 ± 2.0000
    -0.286 ± 0.4880
    1.333 ± 4.1633
        Squamous Cells Week 28 (1, 4, 5, 4, 3)
    0.000 ± 999
    -3.000 ± 6.0000
    0.600 ± 1.3416
    -0.250 ± 0.5000
    -1.667 ± 1.5275
        Squamous Cells Week 32 (2, 2, 4, 6, 2)
    0.500 ± 0.7071
    0.000 ± 0.0000
    0.500 ± 1.0000
    -0.667 ± 0.8165
    -0.500 ± 0.7071
        Squamous Cells Week 36 (1, 5, 4, 1, 1)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 999
    0.000 ± 999
        Squamous Cells Week 40 (0, 4, 4, 4, 2)
    999 ± 999
    -2.750 ± 5.5000
    0.750 ± 1.5000
    0.000 ± 0.0000
    -0.500 ± 0.7071
        Squamous Cells Week 44 (1, 5, 5, 4, 2)
    0.000 ± 999
    -1.000 ± 2.2361
    0.600 ± 1.3416
    -0.250 ± 0.5000
    -0.500 ± 0.7071
        Squamous Cells Week 48 (2, 6, 4, 3, 3)
    0.000 ± 0.0000
    0.667 ± 1.6330
    1.250 ± 1.8930
    0.333 ± 0.5774
    -1.000 ± 1.0000
        Transitional Cells Week 1 (1, 4, 3, 5, 3)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Transitional Cells Week 2 (1, 4, 4, 4, 3)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Transitional Cells Week 4 (1, 3, 5, 4, 2)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Transitional Cells Week 8 (0, 3, 4, 2, 3)
    999 ± 999
    1.000 ± 1.7321
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Transitional Cells Week 12 (1, 3, 5, 2, 3)
    0.000 ± 999
    0.000 ± 0.0000
    0.200 ± 0.4472
    0.000 ± 0.0000
    0.000 ± 0.0000
        Transitional Cells Week 16 (1, 5, 4, 5, 2)
    0.000 ± 999
    0.400 ± 0.8944
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Transitional Cells Week 20 (2, 4, 5, 6, 4)
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Transitional Cells Week 24 (0, 4, 4, 7, 3)
    999 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Transitional Cells Week 28 (1, 4, 5, 4, 3)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Transitional Cells Week 32 (2, 3, 4, 6, 3)
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Transitional Cells Week 36 (1, 6, 4, 1, 1)
    0.000 ± 999
    0.167 ± 0.4082
    0.000 ± 0.0000
    0.000 ± 999
    0.000 ± 999
        Transitional Cells Week 40 (0, 4, 4, 4, 2)
    999 ± 999
    0.250 ± 0.5000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Transitional Cells Week 44 (1, 5, 5, 4, 2)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Transitional Cells Week 48 (2, 6, 4, 3, 4)
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
    No statistical analyses for this end point

    Secondary: Changes from Baseline in urinalysis parameters during the study (hyaline casts)

    Close Top of page
    End point title
    Changes from Baseline in urinalysis parameters during the study (hyaline casts)
    End point description
    Hyaline casts was measured in cells per low power field (cells/LPF). The SS consisted of all randomized study participants who received at least 1 dose of IMP. Number of participants reflect those with non-missing urinalysis results during the study. Note 1: 999 is used as a placeholder for values not evaluable because only one participant was analyzed and for groups that had 0 participants analyzed. Note 2: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    1
    4
    3
    5
    3
    Units: cells/LPF
    arithmetic mean (standard deviation)
        Week 1 (1, 4, 3, 5, 3)
    0.000 ± 999
    0.000 ± 0.0000
    1.000 ± 1.7321
    -0.200 ± 0.4472
    0.000 ± 0.0000
        Week 2 (1, 4, 4, 4, 3)
    0.000 ± 999
    0.250 ± 0.5000
    1.000 ± 1.1547
    -0.250 ± 0.5000
    0.333 ± 0.5774
        Week 4 (1, 3, 5, 4, 2)
    0.000 ± 999
    0.000 ± 0.0000
    -0.800 ± 1.0954
    -0.250 ± 0.5000
    0.000 ± 0.0000
        Week 8 (0, 3, 4, 2, 3)
    999 ± 999
    0.333 ± 0.5774
    0.250 ± 0.5000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Week 12 (1, 3, 5, 2, 3)
    0.000 ± 999
    0.000 ± 0.0000
    5.000 ± 11.1803
    0.000 ± 0.0000
    0.000 ± 0.0000
        Week 16 (1, 5, 4, 5, 2)
    0.000 ± 999
    0.000 ± 0.0000
    0.500 ± 1.0000
    0.000 ± 0.0000
    0.500 ± 0.7071
        Week 20 (2, 4, 5, 6, 4)
    0.000 ± 0.0000
    0.000 ± 0.0000
    -0.600 ± 0.8944
    1.500 ± 3.6742
    -0.750 ± 1.5000
        Week 24 (0, 4, 4, 7, 3)
    999 ± 999
    0.000 ± 0.0000
    -0.250 ± 0.5000
    0.857 ± 2.2678
    0.333 ± 0.5774
        Week 28 (1, 4, 5, 4, 3)
    0.000 ± 999
    0.000 ± 0.0000
    -0.400 ± 0.8944
    0.000 ± 0.0000
    0.000 ± 0.0000
        Week 32 (2, 3, 4, 6, 3)
    0.000 ± 0.0000
    0.000 ± 0.0000
    1.250 ± 2.5000
    0.000 ± 0.0000
    13.333 ± 23.0940
        Week 36 (1, 6, 4, 1, 1)
    0.000 ± 999
    0.000 ± 0.0000
    0.000 ± 0.0000
    0.000 ± 999
    0.000 ± 999
        Week 40 (0, 4, 4, 4, 2)
    999 ± 999
    0.000 ± 0.0000
    -0.500 ± 1.0000
    0.000 ± 0.0000
    0.000 ± 0.0000
        Week 44 (1, 5, 5, 4, 2)
    0.000 ± 999
    0.400 ± 0.8944
    -0.400 ± 0.8944
    0.000 ± 0.0000
    0.000 ± 0.0000
        Week 48 (2, 6, 4, 3, 4)
    0.000 ± 0.0000
    1.167 ± 2.8577
    0.000 ± 0.0000
    0.000 ± 0.0000
    -0.250 ± 0.5000
    No statistical analyses for this end point

    Secondary: Changes from Baseline in urinalysis parameters during the study (pH)

    Close Top of page
    End point title
    Changes from Baseline in urinalysis parameters during the study (pH)
    End point description
    Urine pH was measured on a pH scale. The SS consisted of all randomized study participants who received at least 1 dose of IMP. Note: The number of participants analyzed for each timepoint is presented in parentheses following this model (PBO, BKZ 16 mg, BKZ 160 mg, BKZ 160 mg LD, BKZ 320 mg)
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
    End point values
    Placebo (SS) BKZ 16 mg (SS) BKZ 160 mg (SS) BKZ 160 mg LD (SS) BKZ 320 mg (SS)
    Number of subjects analysed
    40
    38
    43
    41
    40
    Units: pH
    arithmetic mean (standard deviation)
        Week 1 (40, 38, 43, 41, 40)
    -0.138 ± 0.9198
    0.197 ± 0.5875
    0.023 ± 0.8014
    0.085 ± 0.6011
    0.000 ± 0.8321
        Week 2 (42, 39, 43, 41, 41)
    -0.155 ± 0.9072
    0.154 ± 0.7708
    -0.081 ± 0.7149
    0.134 ± 0.8293
    -0.012 ± 0.7541
        Week 4 (41, 38, 41, 40, 41)
    -0.195 ± 0.9211
    0.026 ± 0.6571
    -0.134 ± 0.8368
    0.063 ± 0.6620
    -0.098 ± 0.6729
        Week 8 (41, 39, 42, 38, 41)
    0.000 ± 0.7826
    0.077 ± 0.7393
    -0.024 ± 0.8762
    0.263 ± 0.7235
    0.024 ± 0.7579
        Week 12 (40, 38, 43, 38, 41)
    -0.100 ± 1.0203
    0.237 ± 0.7600
    -0.047 ± 0.6971
    0.211 ± 0.6641
    0.073 ± 0.8843
        Week 16 (42, 38, 41, 38, 40)
    -0.107 ± 0.8449
    0.092 ± 0.7957
    -0.122 ± 0.8199
    0.118 ± 0.7207
    0.088 ± 0.7240
        Week 20 (40, 39, 42, 37, 40)
    -0.113 ± 0.7884
    0.269 ± 0.8649
    -0.012 ± 0.8300
    -0.054 ± 0.6539
    0.063 ± 0.8929
        Week 24 (39, 38, 41, 35, 39)
    -0.154 ± 0.9400
    -0.013 ± 0.8011
    -0.085 ± 0.6605
    0.100 ± 0.4820
    -0.026 ± 0.6973
        Week 28 (39, 38, 41, 35, 40)
    -0.090 ± 0.8419
    -0.053 ± 0.6657
    -0.122 ± 0.7313
    0.086 ± 0.6122
    -0.088 ± 0.6783
        Week 32 (39, 38, 40, 34, 39)
    -0.218 ± 0.8335
    -0.079 ± 0.7491
    0.063 ± 0.8784
    -0.103 ± 0.6717
    -0.269 ± 0.5718
        Week 36 (38, 38, 41, 34, 39)
    -0.211 ± 0.8353
    0.118 ± 0.7300
    -0.195 ± 0.8506
    -0.118 ± 0.6038
    -0.077 ± 0.7569
        Week 40 (37, 37, 40, 34, 39)
    -0.216 ± 0.9394
    -0.041 ± 0.6388
    -0.188 ± 0.8525
    -0.191 ± 0.5643
    -0.154 ± 0.7448
        Week 44 (36, 38, 41, 33, 38)
    -0.458 ± 0.7780
    -0.171 ± 0.7002
    -0.159 ± 0.9044
    -0.167 ± 0.6693
    -0.171 ± 0.7285
        Week 48 (38, 36, 40, 33, 40)
    -0.092 ± 1.0771
    -0.014 ± 0.7318
    -0.200 ± 0.8533
    -0.015 ± 0.7855
    -0.100 ± 0.7528
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AEs) were collected from Baseline until the Safety Follow-Up Visit (up to Week 68)
    Adverse event reporting additional description
    At Week 12, Placebo and BKZ 16 mg subjects were re-randomized to either BKZ 160 mg or BKZ 320 mg. Subjects randomized to BKZ 160 mg or BKZ 320 mg at Baseline were not re-randomized at Week 12 and remained on their treatment. The Safety Set is based on actual treatment, other populations are based on planned treatment. 160mg LD is considered 160mg.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Placebo (SS) - up to Wk 12
    Reporting group description
    This arm consisted of all participants who received Placebo at any time in the study (up to Week 12). Participants formed the Safety Set (SS).