Trial Outcomes & Findings for Efficacy and Safety Study of Botulinum Toxin Type A Against Placebo to Treat Abnormal Contraction or Twitch of the Eyelid (NCT NCT01896895)

Last Updated: 2018-03-01

Results Overview

JRS severity subscore was used to classify individual symptoms of blepharospasm and to determine therapeutic efficacy. JRS severity subscore ranges from 0 to 4, where 0: None; 1: increased blinking present with external stimuli; 2: Mild but spontaneous eyelid fluttering, definitely noticeable, possibly embarrassing, but not functionally disabling, 3: Moderate, very noticeable spasm of eyelids only, mildly incapacitating, 4: Severe, incapacitating spasm of eyelids and possibly other facial muscles. Values represent least square (LS) mean differences between baseline and visit 4 resulting from analysis of covariance (ANCOVA) with treatment group, pooled site, and gender as fixed factors and baseline JRS severity subscore and age as covariates and missings replaced using the last observation carried forward (LOCF) method. Negative values denote improvement, while positive values denote deterioration vs. baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

61 participants

Primary outcome timeframe

Baseline, Day 43 (Visit 4)

Results posted on

2018-03-01

Participant Flow

A total of 68 participants were screened, 61 were enrolled and treated of which 55 completed the double-blind main period (MP). 39 participants from the double-blind MP entered the Open label Extension (OLEX) period and completed the study.

Participant milestones

Participant milestones
Measure	Double-blind MP: Placebo Participants received 1.0 milliliter (mL) placebo matched to the volume of incobotulinumtoxinA doses per injection session via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 25 Units Participants received 1.0 mL of incobotulinumtoxinA containing 25 units per injection session (12.5 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 50 Units Participants received 1.0 mL of incobotulinumtoxinA containing 50 units per injection session (25 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	OLEX: IncobotulinumtoxinA 70 Units Participants received up to 1.4 mL of incobotulinumtoxinA containing up to 70 units per injection session (35 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the OLEX Period.
Double-blind MP STARTED	20	22	19	0
Double-blind MP COMPLETED	19	20	16	0
Double-blind MP NOT COMPLETED	1	2	3	0
OLEX Period STARTED	0	0	0	39
OLEX Period COMPLETED	0	0	0	39
OLEX Period NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Double-blind MP: Placebo Participants received 1.0 milliliter (mL) placebo matched to the volume of incobotulinumtoxinA doses per injection session via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 25 Units Participants received 1.0 mL of incobotulinumtoxinA containing 25 units per injection session (12.5 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 50 Units Participants received 1.0 mL of incobotulinumtoxinA containing 50 units per injection session (25 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.
Double-blind MP Physician Decision	0	0	1
Double-blind MP Withdrawal by Subject	0	2	1
Double-blind MP Lost to Follow-up	1	0	1

Baseline Characteristics

Efficacy and Safety Study of Botulinum Toxin Type A Against Placebo to Treat Abnormal Contraction or Twitch of the Eyelid

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-blind MP: Placebo n=20 Participants Participants received 1.0 mL placebo matched to the volume of incobotulinumtoxinA doses per injection session via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 25 Units n=22 Participants Participants received 1.0 mL of incobotulinumtoxinA containing 25 units per injection session (12.5 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 50 Units n=19 Participants Participants received 1.0 mL of incobotulinumtoxinA containing 50 units per injection session (25 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Total n=61 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants	13 Participants n=7 Participants	14 Participants n=5 Participants	44 Participants n=4 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	9 Participants n=7 Participants	5 Participants n=5 Participants	17 Participants n=4 Participants
Age, Continuous	55.4 years STANDARD_DEVIATION 12.01 • n=5 Participants	55.8 years STANDARD_DEVIATION 15.70 • n=7 Participants	53.5 years STANDARD_DEVIATION 13.82 • n=5 Participants	55.0 years STANDARD_DEVIATION 13.79 • n=4 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants	36 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	11 Participants n=7 Participants	6 Participants n=5 Participants	25 Participants n=4 Participants
Region of Enrollment Greece	4 participants n=5 Participants	6 participants n=7 Participants	4 participants n=5 Participants	14 participants n=4 Participants
Region of Enrollment Sri Lanka	10 participants n=5 Participants	10 participants n=7 Participants	10 participants n=5 Participants	30 participants n=4 Participants
Region of Enrollment Malaysia	6 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	17 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Day 43 (Visit 4)

Population: FAS was subset of participants in the SES of the double-blind MP for whom at least a baseline value of the JRS severity subscore was available.

Outcome measures

Outcome measures
Measure	Double-blind MP: Placebo n=20 Participants Participants received 1.0 mL placebo matched to the volume of incobotulinumtoxinA doses per injection session via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 25 Units n=22 Participants Participants received 1.0 mL of incobotulinumtoxinA containing 25 units per injection session (12.5 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 50 Units n=19 Participants Participants received 1.0 mL of incobotulinumtoxinA containing 50 units per injection session (25 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.
Double-blind MP: Change From Baseline in JRS Severity Subscore at Day 43 (Visit 4)	-0.6 score on a scale Interval -1.0 to -0.1	-1.0 score on a scale Interval -1.5 to -0.6	-1.8 score on a scale Interval -2.3 to -1.3

SECONDARY outcome

Timeframe: Baseline, Day 43 (Visit 4)

Population: FAS was subset of participants in the SES of the double-blind MP for whom at least a baseline value of the JRS severity subscore was available.

BSDI is a scale for assessment of impairment of specific activities of daily living caused by blepharospasm. BSDI consists of six items (driving a vehicle; reading; watching TV; shopping; getting about on foot (walking); doing everyday activities), each ranging from 0 (=no impairment) to 4 (=no longer possible due to illness). The BSDI total score is a mean score for non-missing items ranging from 0 to 4. It is calculated by adding scores of all applicable and answered items, and dividing the resulting sum by the number of items answered. Outcome values represent LS mean differences between baseline and visit 4 (visit 4 value minus baseline value) resulting from ANCOVA with treatment group, pooled site, gender as fixed factors and baseline BSDI total score, age as covariates. Missings were replaced by the LOCF method. Negative values denote an improvement, while positive values denote deterioration vs. baseline.

Outcome measures

Outcome measures
Measure	Double-blind MP: Placebo n=20 Participants Participants received 1.0 mL placebo matched to the volume of incobotulinumtoxinA doses per injection session via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 25 Units n=22 Participants Participants received 1.0 mL of incobotulinumtoxinA containing 25 units per injection session (12.5 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 50 Units n=19 Participants Participants received 1.0 mL of incobotulinumtoxinA containing 50 units per injection session (25 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.
Double-blind MP: Change From Baseline in Blepharospasm Disability Index (BSDI) at Day 43 (Visit 4)	-0.4 score on a scale Interval -0.8 to 0.0	-0.5 score on a scale Interval -0.9 to -0.2	-0.7 score on a scale Interval -1.1 to -0.3

SECONDARY outcome

Timeframe: Baseline, Final Visit (Day 43-Day 141)

Population: FAS was subset of participants in the SES of the double-blind MP for whom at least a baseline value of the JRS severity subscore was available.

PEGR scale is a descriptive subjective 9-point response self-rating scale ranging from "complete abolishment of signs and symptoms" (value=+4) down to "very marked worsening" (value=-4). Outcome values represent least square means at visit 4 resulting from an ANCOVA with treatment group, pooled site, gender as fixed factors and age as covariates. Missing were set to a zero effect (value=0). Positive values denote an improvement, while negative values denote deterioration.

Outcome measures

Outcome measures
Measure	Double-blind MP: Placebo n=20 Participants Participants received 1.0 mL placebo matched to the volume of incobotulinumtoxinA doses per injection session via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 25 Units n=22 Participants Participants received 1.0 mL of incobotulinumtoxinA containing 25 units per injection session (12.5 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 50 Units n=19 Participants Participants received 1.0 mL of incobotulinumtoxinA containing 50 units per injection session (25 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.
Double-blind MP: Patient Evaluation of Global Response (PEGR) at Final Visit (Day 43-Day 141)	1.3 score on a scale Interval 0.7 to 1.9	1.8 score on a scale Interval 1.2 to 2.4	2.2 score on a scale Interval 1.5 to 2.8

Adverse Events

Double-blind MP: Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Double-blind MP: IncobotulinumtoxinA 25 Units

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Double-blind MP: IncobotulinumtoxinA 50 Units

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

OLEX: IncobotulinumtoxinA 70 Units

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Double-blind MP: Placebo n=20 participants at risk Participants received 1.0 mL placebo matched to the volume of incobotulinumtoxinA doses per injection session via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 25 Units n=22 participants at risk Participants received 1.0 mL of incobotulinumtoxinA containing 25 units per injection session (12.5 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	Double-blind MP: IncobotulinumtoxinA 50 Units n=19 participants at risk Participants received 1.0 mL of incobotulinumtoxinA containing 50 units per injection session (25 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the double-blind MP.	OLEX: IncobotulinumtoxinA 70 Units n=39 participants at risk Participants received up to 1.4 mL of incobotulinumtoxinA containing up to 70 units per injection session (35 units per eye) via intramuscular injections into orbicular oculi muscles on Day 1 in the OLEX Period.
Cardiac disorders Acute myocardial infarction	0.00% 0/20 • Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141) Adverse events were collected systematically at each visit by the investigator.	4.5% 1/22 • Number of events 1 • Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141) Adverse events were collected systematically at each visit by the investigator.	0.00% 0/19 • Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141) Adverse events were collected systematically at each visit by the investigator.	0.00% 0/39 • Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141) Adverse events were collected systematically at each visit by the investigator.
Cardiac disorders Atrioventricular block complete	0.00% 0/20 • Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141) Adverse events were collected systematically at each visit by the investigator.	0.00% 0/22 • Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141) Adverse events were collected systematically at each visit by the investigator.	5.3% 1/19 • Number of events 1 • Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141) Adverse events were collected systematically at each visit by the investigator.	0.00% 0/39 • Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141) Adverse events were collected systematically at each visit by the investigator.
Endocrine disorders Goitre	0.00% 0/20 • Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141) Adverse events were collected systematically at each visit by the investigator.	4.5% 1/22 • Number of events 1 • Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141) Adverse events were collected systematically at each visit by the investigator.	0.00% 0/19 • Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141) Adverse events were collected systematically at each visit by the investigator.	0.00% 0/39 • Double-blind MP: From the time point of first injection up to final visit (Day 43 to 141); OLEX Period: From the time point of first injection up to end of study visit (Day 43 to 141) Adverse events were collected systematically at each visit by the investigator.

Other adverse events

Additional Information

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