Trial Outcomes & Findings for IncobotulinumtoxinA (Xeomin) Versus Placebo in the Treatment of Blepharospasm (NCT NCT00406367)

Last Updated: 2013-03-15

Results Overview

The Jankovic Rating Scale (JRS) is used for classification of the patient's individual symptoms of blepharospasm and for determination of the therapeutic efficacy of study medication. The JRS sumscore is the sum of the two components of the scale: * JRS-Severity score which ranges from 0 (=absence of severity) to 4 (=maximum severity) * JRS-Frequency score which ranges from 0 (=no frequency) to 4 (=maximum frequency) The change from baseline was calculated as the score at the corresponding visit minus the baseline score.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

109 participants

Primary outcome timeframe

Baseline, week 6

Results posted on

2013-03-15

Participant Flow

Participant milestones

Participant milestones
Measure	incobotulinumtoxinA (Xeomin) incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection	Placebo Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Main Period - 6 to 20 Weeks STARTED	75	34
Main Period - 6 to 20 Weeks COMPLETED	70	32
Main Period - 6 to 20 Weeks NOT COMPLETED	5	2
Open-Label Ext. Period - up to 68 Weeks STARTED	102	0
Open-Label Ext. Period - up to 68 Weeks COMPLETED	82	0
Open-Label Ext. Period - up to 68 Weeks NOT COMPLETED	20	0

Reasons for withdrawal

Reasons for withdrawal
Measure	incobotulinumtoxinA (Xeomin) incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection	Placebo Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Main Period - 6 to 20 Weeks Withdrawal Criteria Occurred	4	0
Main Period - 6 to 20 Weeks Consent Withdrawn	1	0
Main Period - 6 to 20 Weeks Lost to Follow-up	0	1
Main Period - 6 to 20 Weeks Dosing Error At Visit 2 (Baseline)	0	1
Open-Label Ext. Period - up to 68 Weeks Lost to Follow-up	2	0
Open-Label Ext. Period - up to 68 Weeks Consent Withdrawn	6	0
Open-Label Ext. Period - up to 68 Weeks Withdrawal Criteria Occurred	4	0
Open-Label Ext. Period - up to 68 Weeks Lack of Efficacy	4	0
Open-Label Ext. Period - up to 68 Weeks Subjects Needed Further Injection	1	0
Open-Label Ext. Period - up to 68 Weeks Subject Received Botox Injection	1	0
Open-Label Ext. Period - up to 68 Weeks Injection in Wrong Muscle	1	0
Open-Label Ext. Period - up to 68 Weeks OLEX Drug Given at Baseline	1	0

Baseline Characteristics

IncobotulinumtoxinA (Xeomin) Versus Placebo in the Treatment of Blepharospasm

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	incobotulinumtoxinA (Xeomin) n=75 Participants incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection	Placebo n=34 Participants Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection	Total n=109 Participants Total of all reporting groups
Age Continuous	61.5 years STANDARD_DEVIATION 11.0 • n=5 Participants	62.6 years STANDARD_DEVIATION 8.7 • n=7 Participants	61.9 years STANDARD_DEVIATION 10.3 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	22 Participants n=7 Participants	71 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	12 Participants n=7 Participants	38 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, week 6

Population: Intention to treat population: all participants randomized were included in the primary efficacy analysis; Last Observation Carried Forward (LOCF) imputation technique used for missing values

Outcome measures

Outcome measures
Measure	incobotulinumtoxinA (Xeomin) n=75 Participants incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection	Placebo n=34 Participants Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Jankovic Rating Scale (JRS) Change From Baseline in the JRS Severity Subscore at Week 6 After Injection (Assessed by a Blinded Independent Rater)	-0.8 Points on a scale Standard Error 0.13	0.2 Points on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline, week 6

Population: Intention to treat population by using the Last Observation Carried Forward (LOCF) imputation technique for missing values

Outcome measures

Outcome measures
Measure	incobotulinumtoxinA (Xeomin) n=67 Participants incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection	Placebo n=32 Participants Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Jankovic Rating Scale (JRS) Change From Baseline in the JRS Severity Subscore at Week 6 After Injection (Assessed by Subject Diary)	-0.75 Points on a scale Standard Deviation 1.24	0.16 Points on a scale Standard Deviation 1.07

SECONDARY outcome

Timeframe: Baseline, week 6

Population: Intention to treat population by using the Last Observation Carried Forward (LOCF) imputation technique for missing values

The Blepharospasm Disability Index is a scale for the assessment of impairment of specific activities of daily living caused by blepharospasm. The BSDI consists of six items (driving a vehicle; reading; watching TV; shopping; getting about on foot (walking); doing everyday activities), each ranges from 0 (=no impairment) to 4 (=no longer possible due to illness). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.

Outcome measures

Outcome measures
Measure	incobotulinumtoxinA (Xeomin) n=75 Participants incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection	Placebo n=34 Participants Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Blepharospasm Disability Index (BSDI) Change From Baseline in the BSDI at Week 6 After Injection	-0.4 Points on a scale Standard Deviation 0.69	0.11 Points on a scale Standard Deviation 0.67

SECONDARY outcome

Timeframe: Final visit (up to week 20 after injection of the Main Period)

Population: Intention to treat population with missing values imputed by "no effect".

The PEGR is a descriptive subjective 9-point response scale ranging from "complete abolishment of signs and symptoms" (value=+4) down to "very marked worsening" (value=-4).

Outcome measures

Outcome measures
Measure	incobotulinumtoxinA (Xeomin) n=75 Participants incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection	Placebo n=34 Participants Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Patient Evaluation of Global Response (PEGR) at Final Visit	1.3 Points on a scale Standard Deviation 2.09	-0.6 Points on a scale Standard Deviation 2.16

Adverse Events

incobotulinumtoxinA (Xeomin)

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	incobotulinumtoxinA (Xeomin) n=74 participants at risk incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection	Placebo n=34 participants at risk Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/74 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	2.9% 1/34 • Number of events 1 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.

Other adverse events

Other adverse events
Measure	incobotulinumtoxinA (Xeomin) n=74 participants at risk incobotulinumtoxinA (Xeomin) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection	Placebo n=34 participants at risk Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection Dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl;Mode of administration: intramuscular injection
Gastrointestinal disorders Diarrhoea	8.1% 6/74 • Number of events 6 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	0.00% 0/34 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.
Eye disorders Dry eye	18.9% 14/74 • Number of events 16 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	11.8% 4/34 • Number of events 4 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.
Gastrointestinal disorders Dry mouth	14.9% 11/74 • Number of events 11 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	2.9% 1/34 • Number of events 1 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.
Gastrointestinal disorders Dysphagia	4.1% 3/74 • Number of events 3 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	5.9% 2/34 • Number of events 2 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.4% 4/74 • Number of events 4 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	0.00% 0/34 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.
Eye disorders Eyelid ptosis	18.9% 14/74 • Number of events 14 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	5.9% 2/34 • Number of events 2 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.
Nervous system disorders Headache	9.5% 7/74 • Number of events 7 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	2.9% 1/34 • Number of events 1 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.
Infections and infestations Nasopharyngitis	5.4% 4/74 • Number of events 4 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	5.9% 2/34 • Number of events 2 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.
Infections and infestations Respiratory tract infection	6.8% 5/74 • Number of events 5 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	2.9% 1/34 • Number of events 1 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.
Infections and infestations Upper respiratory tract infection	1.4% 1/74 • Number of events 1 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	8.8% 3/34 • Number of events 3 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.
Eye disorders Vision blurred	5.4% 4/74 • Number of events 4 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	5.9% 2/34 • Number of events 2 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.
Eye disorders Visual disturbance	8.1% 6/74 • Number of events 6 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.	0.00% 0/34 • All SAEs/AEs during Double-Blind Period After Injection, i.e. up to 6-20 weeks after Main Period injection. The table of "Other Adverse Events" includes all non-serious AEs. Only results and AEs of the Double-Blind Period are given as the Open-Label Extension Period was a non-controlled study. The investigator asked the patient for AEs systematically at each visit.

Additional Information

Angelika Hanschmann

Merz Pharmaceuticals GmbH

Phone: ++49-69-1503

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No results to be published without written agreement by sponsor; manuscripts to be sent to sponsor at least 6 weeks before submission. Sponsor to give written opinion within 30 days. Sponsor is entitled to exert influence on the contents of publications, to postpone publications up to 36 months after end of the study, and to name co-authors. In case of justified doubts of sponsor, the INVESTIGATOR will consider these doubts in the publication as long as the scientific neutrality is not affected.
Publication restrictions are in place

Restriction type: OTHER