Comparison of Korean Botulinum Toxin Type A Versus Botox in the Treatment of Essential Blepharospasm - Full Text View

Sponsored by:	Pacific Pharmaceuticals
Information provided by:	Pacific Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00682760

Purpose

To compare the efficacy and safety of Korean botulinum toxin A (KbtxA, Pacific Pharmaceuticals, Korea) against Botox in the treatment of essential blepharospasm, we performed a double-blinded, randomized, comparative trial comparing KbtxA and Botox for treatment of blepharospasm in 60 patients of the intention to treat population and 52 patients (26 patients from each group) of the per protocol population. The improvement of severity of spasm (SS) at 4 weeks post-injection as a primary efficacy outcome, qualifying non inferiority to the control group, Changes in eyelid closure force (CF) and functional visual status (FVS) after injection for secondary efficacy outcomes, and adverse effects for safety evaluation. Improvement of SS was noted in 90.3% of the KbtxA group and 86.2% of the Botox group. There were no significant differences between treatment groups in the changes of CF and FVS after injection (p>0.05). Adverse effects developed in 16.1% of the KbtxA group and 27.6% of the Botox group, but no serious adverse events were found in either group. KbtxA was not inferior to Botox in treatment efficacy and was clinically safe with no serious adverse effects when used to treat essential blepharospasm.

Condition	Intervention	Phase
Blepharospasm	Drug: Korean Botulinum toxin type A (KbtxA) and Botox injection	Phase III

MedlinePlus related topics: Botox

Drug Information available for: Clostridium botulinum toxin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Double-Blind, Randomized, Phase 3, Comparative Study of a New Botulinum Toxin Type A Versus Botox in the Treatment of Essential Blepharospasm

Further study details as provided by Pacific Pharmaceuticals:

Primary Outcome Measures:

The improvement of severity of spasm at 4 weeks post-injection as a primary efficacy outcome, qualifying non inferiority to the control group [ Time Frame: at 4 weeks post-injection ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Changes in eyelid closure force and functional visual status after injection for secondary efficacy outcomes [ Time Frame: at 4 weeks post-injection ] [ Designated as safety issue: Yes ]

Enrollment:	60
Study Start Date:	October 2005
Study Completion Date:	August 2006
Primary Completion Date:	February 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Korean botulinum toxin A treatment	Drug: Korean Botulinum toxin type A (KbtxA) and Botox injection Each vial of Botox and KbtxA contained 100 U of BTX-A in a sterile vacuum-derived form without preservatives. Each vial of KbtxA was identical to the placebo (Botox) vial, and all vials were reconstituted with 2.0 mL of 0.9% sterile nonpreserved saline solution to a final dilution of 5 U /0.1 mL. The dose of BTX-A per injection site was 2.5 U to 5 U, and the location, number of injection sites. Using a 30-gauge needle, injections were angled away from the center of lid to reduce the risk of spread into the levator muscle. Injection sites include the upper medial and lateral eyelid margins, lower lateral lid margins, and above the eyebrow.
2: Placebo Comparator Botox treatment	Drug: Korean Botulinum toxin type A (KbtxA) and Botox injection Each vial of Botox and KbtxA contained 100 U of BTX-A in a sterile vacuum-derived form without preservatives. Each vial of KbtxA was identical to the placebo (Botox) vial, and all vials were reconstituted with 2.0 mL of 0.9% sterile nonpreserved saline solution to a final dilution of 5 U /0.1 mL. The dose of BTX-A per injection site was 2.5 U to 5 U, and the location, number of injection sites. Using a 30-gauge needle, injections were angled away from the center of lid to reduce the risk of spread into the levator muscle. Injection sites include the upper medial and lateral eyelid margins, lower lateral lid margins, and above the eyebrow.

Arms

Assigned Interventions

1: Active Comparator

Korean botulinum toxin A treatment

Drug: Korean Botulinum toxin type A (KbtxA) and Botox injection

Each vial of Botox and KbtxA contained 100 U of BTX-A in a sterile vacuum-derived form without preservatives. Each vial of KbtxA was identical to the placebo (Botox) vial, and all vials were reconstituted with 2.0 mL of 0.9% sterile nonpreserved saline solution to a final dilution of 5 U /0.1 mL.

The dose of BTX-A per injection site was 2.5 U to 5 U, and the location, number of injection sites. Using a 30-gauge needle, injections were angled away from the center of lid to reduce the risk of spread into the levator muscle. Injection sites include the upper medial and lateral eyelid margins, lower lateral lid margins, and above the eyebrow.

2: Placebo Comparator

Botox treatment

Drug: Korean Botulinum toxin type A (KbtxA) and Botox injection

Each vial of Botox and KbtxA contained 100 U of BTX-A in a sterile vacuum-derived form without preservatives. Each vial of KbtxA was identical to the placebo (Botox) vial, and all vials were reconstituted with 2.0 mL of 0.9% sterile nonpreserved saline solution to a final dilution of 5 U /0.1 mL.

The dose of BTX-A per injection site was 2.5 U to 5 U, and the location, number of injection sites. Using a 30-gauge needle, injections were angled away from the center of lid to reduce the risk of spread into the levator muscle. Injection sites include the upper medial and lateral eyelid margins, lower lateral lid margins, and above the eyebrow.

Detailed Description:

Severity of spasm was graded clinically from grade 0 to 4. Primary efficacy outcome was assessed as the number (%) of patients with improved SS of more than 1 score at 4 weeks post-injection. Secondary efficacy outcome measures included the change in scores from baseline on the SS, closing force of eyelids, and functional visual status at 4 weeks post-injection. The duration of action (days), the time interval between injection and the moment that the patient felt the need for retreatment were also assessed as secondary efficacy outcomes.

The number (%) of patients with improvement of SS (primary efficacy outcome) and the change in scores from baseline at 4 weeks post-injection on the severity of spasm, closing force of eyelids, and functional visual status scores were not different between the KbtxA and Botox groups in the analysis of both the ITT and PP populations. Also, the duration of action was similar following KbtxA and Botox injections (two sample t-test, p=0.835). For the non-inferiority trial on primary efficacy outcome, KbtxA was not inferior to Botox in either the ITT or PP populations, as the lower limit of the 95% confidence interval (-1.76% for ITT, -1.64% for PP) was over the -15% threshold.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

All patients, aged between 18 and 75 years old, had confirmed diagnoses of bilateral essential blepharospasm.
The patients were recruited from two botulinum toxin clinics (Yonsei University and Chung-Ang University, Seoul, Korea) from October 18, 2005 until February 21, 2006.

Exclusion Criteria:

Patients were not eligible for inclusion in the study if they
- had undergone either myectomy or neurectomy
- had received anti-spastic, muscle relaxant medication within 1 month of study entry
- had been injected previously with BTX-A within 3 months of study entry
- had any muscle disorder
Women with positive urine pregnancy test, or who were pregnant or lactating were also excluded from the study.
In addition, patients who had shown hypersensitivity to BTX-A previously were not eligible for inclusion in the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00682760

Locations

Korea, Republic of
Sang Yeul Lee
Seoul, Korea, Republic of, 120-752

Sponsors and Collaborators

Pacific Pharmaceuticals

Investigators

Principal Investigator:

Sang Y Lee, MD, phD

Yonsei University College of Medicine

More Information

Publications:

Stone AV, Ma J, Whitlock PW, Koman LA, Smith TL, Smith BP, Callahan MF. Effects of Botox and Neuronox on muscle force generation in mice. J Orthop Res. 2007 Dec;25(12):1658-64.

Responsible Party:	Department of ophthalmology, Yonsei university College of Medicine ( KI-YOON, KIM/ CRA of Pacific Pharm )
Study ID Numbers:	Meditoxin_Botox, Meditoxin-05-01
Study First Received:	May 20, 2008
Last Updated:	May 21, 2008
ClinicalTrials.gov Identifier:	NCT00682760 History of Changes
Health Authority:	South Korea: Institutional Review Board; South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Pacific Pharmaceuticals:

Botulinum Toxin Type A
Blepharospasm

Study placed in the following topic categories:

Botulinum Toxins
Eye Diseases
Peripheral Nervous System Agents

Botulinum Toxin Type A
Blepharospasm
Benign Essential Blepharospasm

Additional relevant MeSH terms:

Botulinum Toxins
Anti-Dyskinesia Agents
Therapeutic Uses
Eye Diseases
Physiological Effects of Drugs
Eyelid Diseases

Neuromuscular Agents
Peripheral Nervous System Agents
Botulinum Toxin Type A
Central Nervous System Agents
Blepharospasm
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 07, 2009