Clinical trial NCT01377922: A Phase 3 Study of Amifampridine Phosphate in Patients With Lambert Eaton Myasthenic Syndrome (LEMS)
Official title: A Phase 3, Double-blind, Placebo-controlled, Randomized Discontinuation Study Followed by Open-label Extension Evaluating Efficacy and Safety of Amifampridine Phosphate in Patients With Lambert-Eaton Myasthenic Syndrome (LEMS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lambert Eaton Myasthenic Syndrome
Lead sponsor: Catalyst Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2011-06-22
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase 3 study to evaluate the efficacy and safety of Amifampridine Phosphate in patients with Lambert-Eaton Myasthenic Syndrome (LEMS).

Detailed description: This multicenter, double-blind, placebo-controlled, randomized (1:1) discontinuation study is a 4-part study designed to evaluate the efficacy and safety of multiple dose administration of amifampridine phosphate in patients with LEMS. Data from parts 2 and 3 (the double-blind parts of the study) are presented in this record.

Eligibility criteria: Inclusion Criteria: Individuals eligible to participate in this study must meet all of the following inclusion criteria:

* ≥18 years of age
* Confirmed diagnosis of LEMS
* Normal respiratory function
* Normal swallowing function
* If receiving peripherally acting cholinesterase inhibitors a stable dose is required for at least 7 days prior to Screening.
* If receiving oral immunosuppressants a stable dose is required for at least 90 days prior to Screening.
* Negative pregnancy test for females of childbearing potential
* If sexually active, willing to use 2 acceptable methods of contraception
* Willing to perform all study procedures as physically possible.
* Willing and able to provide written informed consent after the nature of the study has been explained and prior to the start of any research-related procedures.

Exclusion Criteria: Individuals who meet any of the following exclusion criteria are not eligible to participate in the study:

* History of epilepsy or seizure.
* Known active brain metastasis.
* Use of Fampridine (4-aminopyridine), and any form of 3,4-diaminopyridine other than the IP provided, such as amifampridine base or Firdapse, during the study.
* Use of medications known to lower the epileptic threshold within 7 days or 5 half-lives.
* Use of medications which inhibit neuromuscular junction function within 7 days or 5 half-lives.
* Use of IVIG, plasmapheresis (plasma exchange), or immunoadsorption within 90 days
* Use of guanidine hydrochloride within 7 days
* Use of rituximab within 12 months
* History of drug allergy to any pyridine-containing substances or any amifampridine phosphate excipient(s).
* Use of any other investigational productwithin 30 days
* Treatment with a concomitant medication that prolongs the QT/QTc interval within 7 days or 5 half-lives.
* Treatment with sultopride (4-amino-N-\[(1-ethylpyrrolidin-2-yl)methyl\]-5-ethylsulfonyl-2-methoxybenzamide) within 7 days.
* An abnormal electrocardiogram (ECG).
* Documented history of arrhythmias.
* History of additional risk factors for torsade de pointes.
* Breastfeeding or pregnant or planning to become pregnant (self or partner) at any time during the study.
* Likely or expected to require treatment for cancer within 3 months (90 days) after entering.
* History of severe renal impairment or evidence of severe renal impairment
* Any condition that places the patient at high risk of poor treatment compliance or of not completing the study.
* History of uncontrolled asthma.

Primary outcomes:
measure: Change From Baseline Quantitative Myasthenia Gravis (QMG) at 14 Days
timeFrame: Assessment at Baseline and Day 14
measure: Change in SGI Score
timeFrame: Assessment at Baseline and Day 14
Secondary outcomes:
measure: Change From Baseline Timed 25 Foot Walking Test (T25FW) at 14 Days
timeFrame: Assessment at Baseline and Day 14
measure: Change in CGI-I Score
timeFrame: Baseline and Day 14
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Scottsdale
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Kansas City
country: United States
state: Kansas
city: New York
country: United States
state: New York
city: Lyon
country: France
city: Munich
country: Germany
state: Bavaria
city: Berlin
country: Germany
city: Pecs
country: Hungary
city: Warsaw
country: Poland
city: Moscow
country: Russian Federation
city: Belgrade
country: Serbia
city: Madrid
country: Spain
Study officials:
affiliation: Chief Medical Officer
name: Charles W Gorodetzky, MD, PhD
role: STUDY_DIRECTOR
References: