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Phase 3 Study to Evaluate Efficacy of Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02970162
Recruitment Status : Completed
First Posted : November 21, 2016
Results First Posted : December 24, 2018
Last Update Posted : December 24, 2018
Sponsor:
Information provided by (Responsible Party):
Catalyst Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE November 16, 2016
First Posted Date  ICMJE November 21, 2016
Results First Submitted Date  ICMJE September 24, 2018
Results First Posted Date  ICMJE December 24, 2018
Last Update Posted Date December 24, 2018
Study Start Date  ICMJE November 2016
Actual Primary Completion Date October 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2018)
  • Quantitative Myasthenia Gravis (QMG) Score [ Time Frame: change from baseline in QMG score at end of day 4 ]
    The QMG is a physician-rated test including 13 assessments such as facial strength, swallowing, grip strength, and duration of time that limbs can be maintained in outstretched positions. Each assessment is graded as 0 (none), 1 (mild), 2 (moderate), or 3 (severe), for a total range of 0-39. A higher total score indicates a worse outcome.
  • Subject Global Impression (SGI) Score [ Time Frame: change from baseline in SGI score at end of day 4 ]
    The SGI is a 7-point scale on which the patient rates their global impression of the effects of a study treatment (1=terrible to 7=delighted). The SGI was assessed by the patient or the patient's parent/guardian/caregiver if the patient was unable to complete the SGI. The SGI has demonstrated concordance with the physician's assessment of improvement.
Original Primary Outcome Measures  ICMJE
 (submitted: November 17, 2016)
  • Quantitative Myasthenia Gravis (QMG) Score [ Time Frame: change from baseline in QMG score at end of day 4 ]
  • Subject Global Impression (SGI) Score [ Time Frame: change from baseline in SGI score at end of day 4 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2018)
Change in Clinician's Global Impression of Improvement (CGI-I) at Day 4 Compared to Baseline [ Time Frame: change from baseline in CGI-I score at end of day 4 ]
The CGI-I captures the Investigator's global impression of the patient's improvement or worsening from baseline status. The 7-point scale is scored by the Investigator based on changes in symptoms, behavior, and functional abilities. Each symptom is rated as 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), or 7 (very much worse). The total score can range from 0 to 49. A higher score indicates a worse outcome.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2016)
Clinician's Global Impression of Improvement (CGI-I) [ Time Frame: change from baseline in CGI-I score at end of day 4 ]
Current Other Pre-specified Outcome Measures
 (submitted: December 20, 2018)
Triple Timed Up and Go Walk Test (3TUG) [ Time Frame: change from baseline in 3TUG at end of day 4 ]
The 3TUG is a functional mobility test that requires a patient to stand up from a straight-backed armchair, walk 3 meters, turn around, walk back, and sit down in the chair. A modification of this is where the individual performs the test 3 times without pause, and the measurement is the average time required to complete each of the 3 repetitions. Based upon literature reports that a significant change in gait for a similar walk-test is an increase in time of more than 20%, this has been incorporated into the endpoint.
Original Other Pre-specified Outcome Measures
 (submitted: November 17, 2016)
Triple Timed Up and Go Walk Test (3TUG) [ Time Frame: change from baseline in time to complete test on day 4 ]
 
Descriptive Information
Brief Title  ICMJE Phase 3 Study to Evaluate Efficacy of Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS)
Official Title  ICMJE A Phase 3, Double-Blind, Placebo-controlled, Randomized, Parallel-Group Study to Evaluate the Efficacy and Safety of Amifampridine Phosphate in Patients With Lambert-Eaton Myasthenic Syndrome
Brief Summary This study evaluates the effect of withdrawing amifampridine phosphate treatment from patients with LEMS. One half of the patients will continue to receive amifampridine phosphate and the other half will receive placebo, during this double-blind study.
Detailed Description

This was a randomized (1:1), double-blind, placebo-controlled, parallel-group, withdrawal study designed to evaluate the efficacy and safety of amifampridine phosphate in patients diagnosed with LEMS. The study was planned to include approximately 28 male and female patients.

Prior to the study, patients were receiving unblinded treatment in the expanded access program (EAP-001). Patients had to be on a stable dose and frequency of amifampridine phosphate for at least 1 week prior to randomization into LMS-003. Screening and randomization (Day 0) may have been into a single visit.

Patients who met eligibility criteria were randomized 1:1 to amifampridine phosphate (at the patient's optimal dose) or placebo on Day 0.

Baseline assessments were obtained on Study Day 0, while the patient has been on open-label amifampridine phosphate and in relationship to the usual dosing schedule. Patients took blinded study medication on Day 1 through Day 3. On Day 4, a dose of blinded study medication was administered by the site study personnel. This was the same medication that the patient took on Day 1 through Day 3. The assessments listed below were performed following either the second, third, or fourth dose of medication taken on Day 4, and this should be the same dose after which Day 0 assessments were performed. For example, if the patient took their second dose of amifampridine in the clinic on Day 0 and had assessments started 40 minutes later, then on Day 4, that patient should be assessed after taking their second dose of investigational product (IP).

Beginning with the next dose after all Day 0 baseline assessments were completed, the patient received IP through Day 4, with a clinic visit on the last day (Day 4) for assessments.

The planned duration of participation for each patient was up to 12 days, including screening (up to 7 days), Day 0 assessments and randomization, and IP administration (Day 1 through Day 4).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Lambert-Eaton Myasthenic Syndrome
Intervention  ICMJE
  • Drug: Amifampridine Phosphate
  • Drug: Placebo Oral Tablet
Study Arms  ICMJE
  • Experimental: amifampridine phosphate
    amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days
    Intervention: Drug: Amifampridine Phosphate
  • Placebo Comparator: placebo (for amifampridine phosphate)
    placebo by mouth 3 to 4 times per day for 4 days
    Intervention: Drug: Placebo Oral Tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 23, 2017)
26
Original Estimated Enrollment  ICMJE
 (submitted: November 17, 2016)
28
Actual Study Completion Date  ICMJE October 2017
Actual Primary Completion Date October 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female ≥18 years of age and currently receiving amifampridine phosphate for LEMS.
  2. Diagnosis of LEMS by antibody testing or electromyography (EMG).
  3. Completion of anti-cancer treatment at least 3 months (90 days) prior to Screening.
  4. If receiving peripherally acting cholinesterase inhibitors (e.g. pyridostigmine), a stable dose of cholinesterase inhibitors is required for at least 7 days prior to randomization and throughout the study.
  5. If receiving permitted oral immunosuppressants (prednisone or other corticosteroid), a stable dose is required for at least 30 days prior to randomization and throughout the study.
  6. Female patients of childbearing potential must practice an effective, reliable contraceptive regimen during the study.
  7. Able to perform all study procedures and assessments.
  8. Willing and able to travel to study site and attend all clinic study visits.
  9. Willing and able to provide written informed consent.

Exclusion Criteria:

  1. Clinically significant long corrected QT (QTc) interval on ECG in previous 12 months.
  2. Seizure disorder.
  3. Active brain metastases.
  4. Unable to ambulate.
  5. Pregnant or lactating females.
  6. Any other condition which, in the opinion of the Investigator, might interfere with the patient's participation in the study or confound the assessment of the patient.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02970162
Other Study ID Numbers  ICMJE LMS-003
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Catalyst Pharmaceuticals, Inc.
Study Sponsor  ICMJE Catalyst Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Perry Shieh, MD, PhD University of California, Los Angeles
PRS Account Catalyst Pharmaceuticals, Inc.
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP