A Phase 3 interventional study of IncobulinumtoxinA (Xeomin), 25 Units and IncobotulinumtoxinA (Xeomin), 12.5 Units in Bilateral Blepharospasm (BEB), sponsored by Merz Pharmaceuticals GmbH. Completed at 11 sites in 3 countries. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2018-03-01.
Sponsored by Merz Pharmaceuticals GmbH (part of Merz Pharma) · Phase 3, Interventional, and Treatment
This phase 3 study will serve to collect efficacy and safety data of two different doses of NT 201 in subjects suffering from Bilateral Blepharospasm (BEB) who are BTX treatment-naïve.
In this study, BTX treatment-naïve subjects are defined as those who have not received BTX treatment within the last 12 months for the treatment of BEB. This definition aims to avoid bias by comparison of treatment effects in the subject's assessments. Furthermore, this study will substantiate the existing efficacy and safety database for the indication BEB.
Subjects to receive one injection with NT 201 or placebo at baseline of the placebo-controlled first cycle. Thereafter, all subjects entering the Open-Label Extension Period (OLEX) to receive a second injection of NT 201 (second injection cycle).
42 studies on the registry are indexed under Blepharospasm; 1 is open to participants now.
This study's enrollment of 61 is above the median of 40 across 28 interventional studies indexed under Blepharospasm.
Browse Blepharospasm studies →Merz Pharmaceuticals GmbH is the lead sponsor of 61 studies on the registry; none are open to participants now.
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Main Period: one injection session, 25 Units per eye. Open-Label Extension: one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
Drug: IncobulinumtoxinA (Xeomin), 25 Units · Drug: IncobotulinumtoxinA (Xeomin), 35 Units
Main Period: one injection session, 12.5 Units per eye. Open-Label Extension Period: one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
Drug: IncobotulinumtoxinA (Xeomin), 12.5 Units · Drug: IncobotulinumtoxinA (Xeomin), 35 Units
Main Period: Placebo to IncobotulinumtoxinA (Xeomin)(12.5 or 25U/eye), one injection session. Open-Label Extension: IncobotulinumtoxinA (Xeomin), one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
Drug: Placebo · Drug: IncobotulinumtoxinA (Xeomin), 35 Units
IncobotulinumtoxinA (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl). Main Period: 25 Units per eye.
Also known as: NT 201, Xeomin, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
IncobotulinumtoxinA (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl). Main Period: 12.5 Units per eye.
Also known as: NT 201, Xeomin, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
Main Period: Placebo to IncobotulinumtoxinA (Xeomin), powder for solution for injection, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
IncobotulinumtoxinA (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl). Open-Label Extension: up to 35 Units per eye.
Also known as: NT 201, Xeomin, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
Double-blind MP: Change From Baseline in JRS Severity Subscore at Day 43 (Visit 4)
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.
Time frame: Baseline, Day 43 (Visit 4)
Double-blind MP: Change From Baseline in Blepharospasm Disability Index (BSDI) at Day 43 (Visit 4)
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.
Time frame: Baseline, Day 43 (Visit 4)
Double-blind MP: Patient Evaluation of Global Response (PEGR) at Final Visit (Day 43-Day 141)
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.
Time frame: Baseline, Final Visit (Day 43-Day 141)
| Milestone | Double-blind MP: Placebo | Double-blind MP: IncobotulinumtoxinA 25 Units | Double-blind MP: IncobotulinumtoxinA 50 Units | OLEX: IncobotulinumtoxinA 70 Units |
|---|---|---|---|---|
| Started | 20 | 22 | 19 | 0 |
| Completed | 19 | 20 | 16 | 0 |
| Not completed | 1 | 2 | 3 | 0 |
| Withdrew: Physician decision | 0 | 0 | 1 | 0 |
| Withdrew: Withdrawal by subject | 0 | 2 | 1 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 | 1 | 0 |
| Milestone | Double-blind MP: Placebo | Double-blind MP: IncobotulinumtoxinA 25 Units | Double-blind MP: IncobotulinumtoxinA 50 Units | OLEX: IncobotulinumtoxinA 70 Units |
|---|---|---|---|---|
| Started | 0 | 0 | 0 | 39 |
| Completed | 0 | 0 | 0 | 39 |
| Not completed | 0 | 0 | 0 | 0 |
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.
| score on a scale | Double-blind MP: Placebo | Double-blind MP: IncobotulinumtoxinA 25 Units | Double-blind MP: IncobotulinumtoxinA 50 Units |
|---|---|---|---|
| Double-blind MP: Change From Baseline in JRS Severity Subscore at Day 43 (Visit 4) | -0.6 (-1.0 to -0.1) | -1.0 (-1.5 to -0.6) | -1.8 (-2.3 to -1.3) |
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.
| score on a scale | Double-blind MP: Placebo | Double-blind MP: IncobotulinumtoxinA 25 Units | Double-blind MP: IncobotulinumtoxinA 50 Units |
|---|---|---|---|
| Double-blind MP: Change From Baseline in Blepharospasm Disability Index (BSDI) at Day 43 (Visit 4) | -0.4 (-0.8 to 0.0) | -0.5 (-0.9 to -0.2) | -0.7 (-1.1 to -0.3) |
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.
| score on a scale | Double-blind MP: Placebo | Double-blind MP: IncobotulinumtoxinA 25 Units | Double-blind MP: IncobotulinumtoxinA 50 Units |
|---|---|---|---|
| Double-blind MP: Patient Evaluation of Global Response (PEGR) at Final Visit (Day 43-Day 141) | 1.3 (0.7 to 1.9) | 1.8 (1.2 to 2.4) | 2.2 (1.5 to 2.8) |
Collected over 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). Non-serious events are listed at a 4.5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Double-blind MP: Placebo | 0/20 (0%) | 0/20 (0%) | 6/20 (30%) |
| Double-blind MP: IncobotulinumtoxinA 25 Units | 0/22 (0%) | 2/22 (9.1%) | 7/22 (31.8%) |
| Double-blind MP: IncobotulinumtoxinA 50 Units | 0/19 (0%) | 1/19 (5.3%) | 7/19 (36.8%) |
| OLEX: IncobotulinumtoxinA 70 Units | 0/39 (0%) | 0/39 (0%) | 4/39 (10.3%) |
| Event | Double-blind MP: Placebo | Double-blind MP: IncobotulinumtoxinA 25 Units | Double-blind MP: IncobotulinumtoxinA 50 Units | OLEX: IncobotulinumtoxinA 70 Units |
|---|---|---|---|---|
| Atrioventricular block completeCardiac disorders | 0/20 | 0/22 | 1/19 | 0/39 |
| Acute myocardial infarctionCardiac disorders | 0/20 | 1/22 | 0/19 | 0/39 |
| GoitreEndocrine disorders | 0/20 | 1/22 | 0/19 | 0/39 |
| Event | Double-blind MP: Placebo | Double-blind MP: IncobotulinumtoxinA 25 Units | Double-blind MP: IncobotulinumtoxinA 50 Units | OLEX: IncobotulinumtoxinA 70 Units |
|---|---|---|---|---|
| Eyelid ptosisEye disorders | 0/20 | 2/22 | 3/19 | 2/39 |
| Dry eyeEye disorders | 2/20 | 0/22 | 0/19 | 2/39 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/20 | 0/22 | 1/19 | 0/39 |
| HypoaesthesiaNervous system disorders | 0/20 | 0/22 | 1/19 | 0/39 |
| Eyelid disorderEye disorders | 0/20 | 0/22 | 1/19 | 0/39 |
| Abdominal painGastrointestinal disorders | 0/20 | 0/22 | 1/19 | 0/39 |
| CholelithiasisHepatobiliary disorders | 0/20 | 0/22 | 1/19 | 0/39 |
| Hepatic steatosisHepatobiliary disorders | 0/20 | 0/22 | 1/19 | 0/39 |
| EczemaSkin and subcutaneous tissue disorders | 0/20 | 0/22 | 1/19 | 0/39 |
| Muscular weaknessMusculoskeletal and connective tissue disorders | 0/20 | 0/22 | 1/19 | 0/39 |
Full analysis set (FAS) was subset of participants in the safety evaluation set (SES) of the double-blind MP for whom at least a baseline value of the Jankovic Rating Scale (JRS) severity subscore was available.
| Age, Categorical(Participants) | Double-blind MP: Placebo | Double-blind MP: IncobotulinumtoxinA 25 Units | Double-blind MP: IncobotulinumtoxinA 50 Units | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 17 | 13 | 14 | 44 |
| >=65 years | 3 | 9 | 5 | 17 |
| Age, Continuous(years) | Double-blind MP: Placebo | Double-blind MP: IncobotulinumtoxinA 25 Units | Double-blind MP: IncobotulinumtoxinA 50 Units | Total |
|---|---|---|---|---|
| Mean | 55.4 ± 12.01 | 55.8 ± 15.70 | 53.5 ± 13.82 | 55.0 ± 13.79 |
| Sex: Female, Male(Participants) | Double-blind MP: Placebo | Double-blind MP: IncobotulinumtoxinA 25 Units | Double-blind MP: IncobotulinumtoxinA 50 Units | Total |
|---|---|---|---|---|
| Female | 12 | 11 | 13 | 36 |
| Male | 8 | 11 | 6 | 25 |
| Region of Enrollment(participants) | Double-blind MP: Placebo | Double-blind MP: IncobotulinumtoxinA 25 Units | Double-blind MP: IncobotulinumtoxinA 50 Units | Total |
|---|---|---|---|---|
| Greece | 4 | 6 | 4 | 14 |
| Sri Lanka | 10 | 10 | 10 | 30 |
| Malaysia | 6 | 6 | 5 | 17 |
The record gives a start of Nov 2013, a primary completion of Apr 2016 and a completion of Nov 2016. It does not say whether these dates are actual or estimated.
Results were first posted in Mar 2018, 1 year 11 months after primary completion. A results delay was requested in Mar 2017.
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This study is completed, as verified in Jan 2018. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Botulinum toxin type A