search
Back to results

Botulism Antitoxin Effects on Paralysis Induced by Botulinum Neurotoxins in the EDB Muscle

Primary Purpose

Healthy Volunteers

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Botulism Antitoxin Bivalent (Equine) Types A and B
Botulism Antitoxin Heptavalent (Equine) Types A-G
Sponsored by
Cangene Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Healthy Volunteers focused on measuring Botulism Antitoxin,Heptavalent,Bivalent,EDB Muscle,Paralysis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Male or female
  • Age 18 - 55 years
  • Body-mass index 19-30
  • Normal and healthy as determined by medical history, physical examination, ECG, NCS, vital signs and tests of liver, kidney and hematological functions

  • Adequate form of contraception for female subjects

    • For women with child-bearing potential-using hormonal contraception (oral, injectable or implant) continuously for 3 months prior to the start of the study and willing to continue to use hormonal contraception throughout the entire study. IUD inserted or use of condoms for at least 2 months prior to dosing
    • Other forms of contraception may be considered as adequate at physician's discretion
    • Surgically-sterilized female subjects
    • For female subjects who are postmenopausal, an FSH ≥ than 40 mIU/mL must be obtained. If the FSH is < 40 mIU/mL the subject must agree to use an acceptable form of contraception (see above for acceptable forms of contraception)
  • Signed written Informed Consent

Exclusion Criteria:

  • Previously injected with BOTOX®, BOTOX® COSMETIC or MYOBLOC®
  • Any known or documented Botulinum infection/intoxication
  • Any known or documented allergies to horses (e.g. rash, wheezing, rhinitis etc. after exposure to horses)
  • Any known or documented allergies to horse serum (observation of adverse events after treatment with any kind of product containing horse serum)
  • Any moderate or severe food allergies, seasonal allergies or hay fever requiring treatment with peroral or parenteral immunosuppressive drug
  • Any known or documented hypersensitivity to blood products derived from a human or equine source
  • Any known or documented hypersensitivity to albumin
  • Positive result for Botulism Antitoxin skin sensitivity testing
  • Any known or documented allergy to rubber, latex or plastic
  • Known acute or chronic moderate or severe asthma requiring treatment with peroral and / or parenteral immunosuppressive drugs
  • Previously diagnosed or currently suspected Multiple Sclerosis or other neuromuscular degenerative disorder
  • Previously diagnosed or currently suspected motor neuron disease
  • Previously or currently diagnosed peripheral neuropathy of lower extremities' nerves
  • Current infection of the skin / skin problems at the injection site (foot)
  • Scar tissue or tattoo of the skin over the extensor digitorum brevis muscles.
  • Previously diagnosed or currently suspected diabetes
  • Previously diagnosed or currently suspected coagulopathies
  • Previously diagnosed or currently suspected vasculitis
  • Current treatment or treatment in the past 7 days with aminoglycosides, clindamycin, quinolines or aminopyridine
  • Heavy smokers (>10 cigarettes/day)
  • History of, or suspected substance abuse (including alcohol) or failure of drug screen at screening or at baseline
  • Use of any investigational product within the past 30 days (prior to screening)
  • Pregnancy or lactation
  • Positive serological test for diagnosis of HIV infection, HBV hepatitis, or HCV hepatitis
  • Abnormal (based on principle investigator assessment) nerve conduction study (NCS) results

Sites / Locations

  • Dr. Gordon Peterson
  • R. Richard Sloop, M. D.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Stage A

Stage B

Arm Description

Botulism Antitoxin Bivalent (Equine) Types A and B Vs. Placebo

Botulism Antitoxin Heptavalent (Equine) Types A-G Vs. Placebo

Outcomes

Primary Outcome Measures

Nerve Conduction Study

Secondary Outcome Measures

Hematology
Blood Chemistry
Urinalysis
Serum anti-Botulism Antitoxin Reactivity
Adverse Events
Vital Signs
Physical Examination
12-lead ECG

Full Information

First Posted
March 11, 2008
Last Updated
February 22, 2011
Sponsor
Cangene Corporation
Collaborators
Department of Health and Human Services
search

1. Study Identification

Unique Protocol Identification Number
NCT00636519
Brief Title
Botulism Antitoxin Effects on Paralysis Induced by Botulinum Neurotoxins in the EDB Muscle
Official Title
Botulism Antitoxin Effects on Paralysis Induced by Type A and Type B Botulinum Neurotoxins in the Extensor Digitorum Brevis Muscle
Study Type
Interventional

2. Study Status

Record Verification Date
February 2011
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Cangene Corporation
Collaborators
Department of Health and Human Services

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary purpose of this study is: To evaluate the model determined by the ability of botulism antitoxin (bivalent, Aventis) to neutralize Botulinum toxin in the Extensor Digitorum Brevis model of muscle paralysis in Stage A. To assess the ability of botulism antitoxin (heptavalent, Cangene) to neutralize Botulinum toxin in the Extensor Digitorum Brevis model of muscle paralysis in Stage B.
Detailed Description
Botulism is a rare disease; however Botulinum toxins (neurotoxins) may be used as biological weapon especially in the form of aerosol. Botulism is caused by neurotoxins that are produced by the obligate anaerobic, gram-positive, spore-forming bacterium Clostridium botulinum (1). C. botulinum produces 8 serologically distinct neurotoxins identified as serotypes A, B, C1, C2, D, E, F, and G (2). Therapy for botulism includes supportive care and passive immunization with antitoxin. Antitoxin should be administered to patients with neurologic signs of botulism as soon as possible after clinical diagnosis (3). Botulism antitoxin is prepared from plasma obtained from horses that have been immunized with a specific subtype of botulism toxoid and toxin. The BT-002 is an exploratory pharmacodynamic study that is being performed to evaluate the effect of Botulism Antitoxins in preventing paralysis of extensor digitorum brevis muscle following BOTOX®/ MYOBLOC® administration. This study will compare bivalent and heptavalent products to a placebo. Safety data will be collected. NP-018 (heptavalent equine-derived botulinum antitoxin) is prepared from plasma obtained from horses that have been immunized with a specific subtype of botulinum toxoid and toxin. Each individual horse is immunized against a single botulinum toxin subtype. Plasma is pooled from horses that have been immunized with the same botulinum toxin subtype. For each antitoxin serotype (A-G), a despeciated product will be produced by pepsin digestion of the IgG monomer in the equine plasma, yielding predominantly F(ab')2 fragment. Following the formulation, the seven antitoxin serotypes will be blended into a heptavalent product and filled into single-use vials. ' This research study will be conducted in two stages - Stage A and Stage B. If enrolled in the Stage A of the study, the subject will have an equal chance of getting either bivalent botulism antitoxin or placebo. If enrolled in Stage B of the study, the subject will have an equal chance of getting heptavalent botulism antitoxin (NP-018) or placebo. The subject will be receiving injections of Botox and Myobloc on the next day after the antitoxin administration in the left and right foot respectively. The subject's participation in this study will be for maximum of 57 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Volunteers
Keywords
Botulism Antitoxin,Heptavalent,Bivalent,EDB Muscle,Paralysis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stage A
Arm Type
Experimental
Arm Description
Botulism Antitoxin Bivalent (Equine) Types A and B Vs. Placebo
Arm Title
Stage B
Arm Type
Experimental
Arm Description
Botulism Antitoxin Heptavalent (Equine) Types A-G Vs. Placebo
Intervention Type
Biological
Intervention Name(s)
Botulism Antitoxin Bivalent (Equine) Types A and B
Intervention Description
One vial of Botulism Antitoxin Bivalent(Equine) Types A and B (1:10 in saline) or an Equivalent Volume of Placebo on Day 0 in Stage A
Intervention Type
Biological
Intervention Name(s)
Botulism Antitoxin Heptavalent (Equine) Types A-G
Intervention Description
One vial of Heptavalent Botulism Antitoxin (1:10 in saline) or an Equivalent Volume of Placebo on Day 0 in Stage B
Primary Outcome Measure Information:
Title
Nerve Conduction Study
Time Frame
Screening, Baseline (Day 0, -3 hrs), Day 1 (-1 hr), Day 3, Day 4, Day 7, Day 14, Day 21, Day 28 or Early Withdrawal
Secondary Outcome Measure Information:
Title
Hematology
Time Frame
Screening, Baseline (Day 0, -3 hr), Day 7, Day 14, Day 21, Day 28 or Early Withdrawal
Title
Blood Chemistry
Time Frame
Screening, Baseline (Day 0, -3 hr), Day 7, Day 14, Day 21, Day 28 or Early Withdrawal
Title
Urinalysis
Time Frame
Screening, Baseline (Day 0, -3 hr), Day 7, Day 14, Day 21, Day 28 or Early Withdrawal
Title
Serum anti-Botulism Antitoxin Reactivity
Time Frame
Baseline, Day 28 or Early Withdrawal
Title
Adverse Events
Time Frame
Day 0, Day 1( -1 hr), Day 1, Day 3, Day 4, Day 7, Day 14, Day 21, and Day 28 or Early Withdrawal
Title
Vital Signs
Time Frame
Screening, Day 0 (-3 hrs), Day 0, Day 1 (-1 hr), Day 1, Day 3, Day 4, Day 7, Day 14, Day 21, and Day 28 or Early Withdrawal
Title
Physical Examination
Time Frame
Screening, Baseline (Day 0, -3 hrs), Day 1 (-1 hr), Day 3, Day 4, Day 7, Day 21 and Day 28 or Early Withdrawal
Title
12-lead ECG
Time Frame
Screening/ Day 28 or Early Withdrawal

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or female Age 18 - 55 years Body-mass index 19-30 Normal and healthy as determined by medical history, physical examination, ECG, NCS, vital signs and tests of liver, kidney and hematological functions Adequate form of contraception for female subjects For women with child-bearing potential-using hormonal contraception (oral, injectable or implant) continuously for 3 months prior to the start of the study and willing to continue to use hormonal contraception throughout the entire study. IUD inserted or use of condoms for at least 2 months prior to dosing Other forms of contraception may be considered as adequate at physician's discretion Surgically-sterilized female subjects For female subjects who are postmenopausal, an FSH ≥ than 40 mIU/mL must be obtained. If the FSH is < 40 mIU/mL the subject must agree to use an acceptable form of contraception (see above for acceptable forms of contraception) Signed written Informed Consent Exclusion Criteria: Previously injected with BOTOX®, BOTOX® COSMETIC or MYOBLOC® Any known or documented Botulinum infection/intoxication Any known or documented allergies to horses (e.g. rash, wheezing, rhinitis etc. after exposure to horses) Any known or documented allergies to horse serum (observation of adverse events after treatment with any kind of product containing horse serum) Any moderate or severe food allergies, seasonal allergies or hay fever requiring treatment with peroral or parenteral immunosuppressive drug Any known or documented hypersensitivity to blood products derived from a human or equine source Any known or documented hypersensitivity to albumin Positive result for Botulism Antitoxin skin sensitivity testing Any known or documented allergy to rubber, latex or plastic Known acute or chronic moderate or severe asthma requiring treatment with peroral and / or parenteral immunosuppressive drugs Previously diagnosed or currently suspected Multiple Sclerosis or other neuromuscular degenerative disorder Previously diagnosed or currently suspected motor neuron disease Previously or currently diagnosed peripheral neuropathy of lower extremities' nerves Current infection of the skin / skin problems at the injection site (foot) Scar tissue or tattoo of the skin over the extensor digitorum brevis muscles. Previously diagnosed or currently suspected diabetes Previously diagnosed or currently suspected coagulopathies Previously diagnosed or currently suspected vasculitis Current treatment or treatment in the past 7 days with aminoglycosides, clindamycin, quinolines or aminopyridine Heavy smokers (>10 cigarettes/day) History of, or suspected substance abuse (including alcohol) or failure of drug screen at screening or at baseline Use of any investigational product within the past 30 days (prior to screening) Pregnancy or lactation Positive serological test for diagnosis of HIV infection, HBV hepatitis, or HCV hepatitis Abnormal (based on principle investigator assessment) nerve conduction study (NCS) results
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Sloop, M. D.
Organizational Affiliation
R. Richard Sloop, M. D.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gordon Peterson, Dr.
Organizational Affiliation
Faculty Physicains & Surgeons of Loma Linda University School of Medicine, Department of Neurology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dr. Gordon Peterson
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
R. Richard Sloop, M. D.
City
Yakima
State/Province
Washington
ZIP/Postal Code
98902
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
10517680
Citation
Benedetto AV. The cosmetic uses of Botulinum toxin type A. Int J Dermatol. 1999 Sep;38(9):641-55. doi: 10.1046/j.1365-4362.1999.00722.x. No abstract available.
Results Reference
background
PubMed Identifier
8973746
Citation
Carruthers A, Carruthers J. Cosmetic uses of botulinum A exotoxin. Adv Dermatol. 1997;12:325-47; discussion 348. No abstract available.
Results Reference
background
PubMed Identifier
6720725
Citation
Tacket CO, Shandera WX, Mann JM, Hargrett NT, Blake PA. Equine antitoxin use and other factors that predict outcome in type A foodborne botulism. Am J Med. 1984 May;76(5):794-8. doi: 10.1016/0002-9343(84)90988-4.
Results Reference
background

Learn more about this trial

Botulism Antitoxin Effects on Paralysis Induced by Botulinum Neurotoxins in the EDB Muscle

We'll reach out to this number within 24 hrs