Comparison of Korean Botulinum Toxin Type A Versus Botox in the Treatment of Essential Blepharospasm

NCT ID: NCT00682760

Last Updated: 2008-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2006-08-31

Brief Summary

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.

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.

Conditions

Blepharospasm

Keywords

Botulinum Toxin Type A; Blepharospasm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1

Korean botulinum toxin A treatment

Group Type: ACTIVE_COMPARATOR

Korean Botulinum toxin type A (KbtxA) and Botox injection

Intervention Type: DRUG

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

Botox treatment

Group Type: PLACEBO_COMPARATOR

Korean Botulinum toxin type A (KbtxA) and Botox injection

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

arm1 ; Meditoxin or Neuronox

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pacific Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Department of ophthalmology, Yonsei university College of Medicine

Principal Investigators

Sang Y Lee, MD, phD

Role: PRINCIPAL_INVESTIGATOR

Yonsei University

Locations

Sang Yeul Lee

Seoul, , South Korea

Countries

South Korea

References

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. doi: 10.1002/jor.20450.

Reference Type: BACKGROUND

PMID: 17600825 (View on PubMed)

Yoon JS, Kim JC, Lee SY. Double-blind, randomized, comparative study of Meditoxin versus Botox in the treatment of essential blepharospasm. Korean J Ophthalmol. 2009 Sep;23(3):137-41. doi: 10.3341/kjo.2009.23.3.137. Epub 2009 Sep 8.

Reference Type: DERIVED

PMID: 19794937 (View on PubMed)

Other Identifiers

Meditoxin-05-01

Identifier Type: -

Identifier Source: secondary_id

Meditoxin_Botox

Identifier Type: -

Identifier Source: org_study_id