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

Blepharospasm Clinical Trial

Official title:

Double-Blind, Randomized, Phase 3, Comparative Study of a New Botulinum Toxin Type A Versus Botox in the Treatment of Essential Blepharospasm

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00682760
• Other study ID #: Meditoxin_Botox
• Secondary ID: Meditoxin-05-01
• Status: Completed
• Phase: Phase 3
• First received: May 20, 2008
• Last updated: May 21, 2008
• Start date: October 2005
• Est. completion date: August 2006

Study information

• Verified date: May 2008
• Source: Pacific Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Institutional Review BoardSouth Korea: Korea Food and Drug Administration (KFDA)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: August 2006
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blepharospasm

Intervention

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.

Locations

Country	Name	City	State
Korea, Republic of	Sang Yeul Lee	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Pacific Pharmaceuticals

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The improvement of severity of spasm at 4 weeks post-injection as a primary efficacy outcome, qualifying non inferiority to the control group		at 4 weeks post-injection	Yes
Secondary	Changes in eyelid closure force and functional visual status after injection for secondary efficacy outcomes		at 4 weeks post-injection	Yes