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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
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

PA0008

ISRCTN number

US NCT number

NCT02969525

WHO universal trial number (UTN)

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

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

06 Dec 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

16 Jul 2018

Was the trial ended prematurely?

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

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

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

185

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

The study started to enroll patients in October 2016 and concluded in July 2018.

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 title

Double-Blind Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Carer, Investigator, Assessor, Subject

Are arms mutually exclusive

Yes

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.

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.

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.

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.

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
Study medication discontinued prior Wk12	2	-	-	2	-
Adverse event, non-fatal	-	-	1	1	-
LOW EGFR	-	-	-	1	-

Period 2 title

Dose-Blind Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Assessor, Carer, Investigator, Subject

Are arms mutually exclusive

Yes

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.

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.

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.

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.

BZK 160 mg LD - BZK 160 mg

Arm description

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.

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.

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
Consent withdrawn by subject	-	2	-	1	2	-	-
Non-cooperating patient	-	-	-	-	-	-	1
Adverse event, non-fatal	-	-	-	-	1	1	1
Withdrew before Safety Follow-up visit	-	-	-	-	-	1	-

Baseline characteristics

Top of page

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

Top of page

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

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

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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 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

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 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

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 3

Statistical analysis description

Comparison groups

Placebo (FAS) v BKZ 160 mg (FAS)

Number of subjects included in analysis

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 4

Statistical analysis description

Comparison groups

Placebo (FAS) v BKZ 160 mg LD (FAS)

Number of subjects included in analysis

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 5

Statistical analysis description

Comparison groups

Placebo (FAS) v BKZ 320 mg (FAS)

Number of subjects included in analysis

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

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

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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 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

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 2

Statistical analysis description

Comparison groups

Placebo (FAS) v BKZ 160 mg (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[11]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

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 3

Statistical analysis description

Comparison groups

Placebo (FAS) v BKZ 160 mg LD (FAS)

Number of subjects included in analysis

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 4

Statistical analysis description

Comparison groups

Placebo (FAS) v BKZ 320 mg (FAS)

Number of subjects included in analysis

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

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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 1

Statistical analysis description

Comparison groups

Placebo (FAS) v BKZ 16 mg (FAS)

Number of subjects included in analysis

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 2

Statistical analysis description

Comparison groups

Placebo (FAS) v BKZ 160 mg (FAS)

Number of subjects included in analysis

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 3

Statistical analysis description

Comparison groups

Placebo (FAS) v BKZ 160 mg LD (FAS)

Number of subjects included in analysis

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 4

Statistical analysis description

Comparison groups

Placebo (FAS) v BKZ 320 mg (FAS)

Number of subjects included in analysis

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

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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

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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

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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

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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

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End point title

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

End point description

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)

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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)

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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

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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)

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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)

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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)

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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))

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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)

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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)

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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)

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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)

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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)

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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)

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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)

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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)

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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)

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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)

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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)

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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)

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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

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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 name

MedDRA

Dictionary version

19.0

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).

Reporting group title

BKZ 320 mg (SS) - up to Wk 68

Reporting group 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.

Reporting group title

BKZ 160 mg & 160 mg LD (SS) - up to Wk 68

Reporting group description

Reporting group title

BKZ 16 mg (SS) - up to Wk 12

Reporting group 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.

Serious adverse events	Placebo (SS) - up to Wk 12	BKZ 320 mg (SS) - up to Wk 68	BKZ 160 mg & 160 mg LD (SS) - up to Wk 68	BKZ 16 mg (SS) - up to Wk 12
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 42 (2.38%)	0 / 80 (0.00%)	8 / 126 (6.35%)	0 / 39 (0.00%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma in situ
subjects affected / exposed	0 / 42 (0.00%)	0 / 80 (0.00%)	1 / 126 (0.79%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	1 / 42 (2.38%)	0 / 80 (0.00%)	0 / 126 (0.00%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Carpal tunnel syndrome
subjects affected / exposed	0 / 42 (0.00%)	0 / 80 (0.00%)	1 / 126 (0.79%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Drug-induced liver injury
subjects affected / exposed	0 / 42 (0.00%)	0 / 80 (0.00%)	1 / 126 (0.79%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Goitre
subjects affected / exposed	0 / 42 (0.00%)	0 / 80 (0.00%)	1 / 126 (0.79%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Osteoarthritis
subjects affected / exposed	0 / 42 (0.00%)	0 / 80 (0.00%)	1 / 126 (0.79%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Cellulitis
subjects affected / exposed	0 / 42 (0.00%)	0 / 80 (0.00%)	1 / 126 (0.79%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media chronic
subjects affected / exposed	0 / 42 (0.00%)	0 / 80 (0.00%)	1 / 126 (0.79%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis E
subjects affected / exposed	0 / 42 (0.00%)	0 / 80 (0.00%)	1 / 126 (0.79%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo (SS) - up to Wk 12	BKZ 320 mg (SS) - up to Wk 68	BKZ 160 mg & 160 mg LD (SS) - up to Wk 68	BKZ 16 mg (SS) - up to Wk 12
Total subjects affected by non serious adverse events
subjects affected / exposed	8 / 42 (19.05%)	29 / 80 (36.25%)	40 / 126 (31.75%)	9 / 39 (23.08%)
Vascular disorders
Hypertension
subjects affected / exposed	4 / 42 (9.52%)	2 / 80 (2.50%)	0 / 126 (0.00%)	0 / 39 (0.00%)
occurrences all number	4	2	0	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	0 / 42 (0.00%)	1 / 80 (1.25%)	0 / 126 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	1	0	2
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 42 (0.00%)	3 / 80 (3.75%)	0 / 126 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	4	0	2
Musculoskeletal and connective tissue disorders
Psoriatic arthropathy
subjects affected / exposed	3 / 42 (7.14%)	1 / 80 (1.25%)	2 / 126 (1.59%)	2 / 39 (5.13%)
occurrences all number	4	1	2	2
Infections and infestations
Ear infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 80 (0.00%)	1 / 126 (0.79%)	2 / 39 (5.13%)
occurrences all number	0	0	1	2
Respiratory tract infection
subjects affected / exposed	0 / 42 (0.00%)	2 / 80 (2.50%)	8 / 126 (6.35%)	2 / 39 (5.13%)
occurrences all number	0	3	8	2
Bronchitis
subjects affected / exposed	1 / 42 (2.38%)	3 / 80 (3.75%)	7 / 126 (5.56%)	0 / 39 (0.00%)
occurrences all number	1	3	8	0
Nasopharyngitis
subjects affected / exposed	0 / 42 (0.00%)	11 / 80 (13.75%)	12 / 126 (9.52%)	3 / 39 (7.69%)
occurrences all number	0	11	15	3
Pharyngitis
subjects affected / exposed	0 / 42 (0.00%)	7 / 80 (8.75%)	4 / 126 (3.17%)	0 / 39 (0.00%)
occurrences all number	0	7	4	0
Upper respiratory tract infection
subjects affected / exposed	0 / 42 (0.00%)	8 / 80 (10.00%)	12 / 126 (9.52%)	1 / 39 (2.56%)
occurrences all number	0	10	12	1

More information

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Were there any global substantial amendments to the protocol? Yes

09 Mar 2018

Protocol Amendment 2 was a substantial amendment dated 09 Mar 2018. The purpose of this protocol amendment was the following: •To update the study contact details for the sponsor study physician and clinical trial biostatistician. •To revise the withdrawal criteria Section to provide instructions for the management of study participants with newly diagnosed inflammatory bowel disease (IBD) or with IBD flares during the study. •To amend the time window between doses during the Double-blind Period of the study. •To add new details for the IMP packaging. •To revise and clarify the SAE criteria for pregnancy for consistency. •To amend the table for identification/exclusion of alternative etiology to include aspartate aminotransferase (AST) and alanine aminotransferase (ALT). A total of 308 study participants were screened and 206 study participants were randomized at the time of this amendment.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Biomarker assays were not rigorously validated, thus it was not possible to use results for PD as a secondary objective. The results were interpreted with caution for exploratory purpose, and thus are not shared in this report.

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Clinical trials

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Changes from Baseline in body weight during the study

Secondary: Changes from Baseline in body weight during the study

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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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