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Label indication FIRDAPSE ® is indicated for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults and pediatric patients 6 years of age and older. FIRDAPSE is a potassium channel blocker indicated for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults and pediatric patients 6 years of age and older. ( 1 ) FDA label
Also known as Amifampridine Phosphate
Amifampridine · 5 trials · 5 indications
Myasthenia Gravis-Activities of Daily Living (MG-ADL) is a self-report scale to assess the patient's MG symptoms and functional performance of activities of daily living. The eight items are scored on a scale of 0-3 with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. Each item was assessed by the patient at the last day (Day 0) of the Run-in period and at the post-treatment visit. The post-treatment result will be the result obtained on Day 10. If the patient discontinued treatment early, the post-treatment result may be obtained at an earlier time point. The total MG-ADL score was calculated as the sum of each item score, with a maximum score of 24 (most severe symptoms/impairment) and minimum score of 0 (least severe symptoms/impairment). The change from baseline (CFB) at Day 10 was assessed. A Wilcoxon-Mann-Whitney Rank Sum Test of equality of change from baseline distributions between subjects diagnos
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.
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.
Subject Global Impression (SGI) rates the subject's impression of the effects of the study medication during the preceding week with max score =7 (most satisfied) and min score =1 (least satisfied). It will be completed at D0 (baseline for Study Period 1), D8, D21 (baseline for Study Period 2), and D29. Change from baseline (CFB) will be assessed for Study Period 1 (difference in SGI score from D0 to D8), Study Period 2 (difference in SGI score from D21 to D29) and the change in CFB from Study Period 1 to Study Period 2 (difference between CFB during Study Period 1 and CFB during Study Period 2). A Mann-Whitney-Wilcoxon test for equality of the CFB results in the two treatments in Period 1 and for the equality of the CFB results in the two treatment sequences will be conducted. A mixed effects liner model will be fit with the SGI raw scores as a response and study arm, treatment, period, age group and mutation type as fixed effect terms and patient as a random effect.
The QMG is a physician-rated test including 13 assessments, including facial strength, swallowing, grip strength, and duration of time that limbs can be maintained in outstretched positions. Each of the 13 items is scored from 0 (none) to 3 (severe). The total score can range from 0 to 39. Increased QMG total score correlates to worsening symptoms of LEMS.
Subject Global Impression (SGI) is a measure of changes in subject's perception of change in overall wellbeing. The patient is asked to use the 7-point scale below to rate their impression of the effects of the study medication during the preceding 3 days on their physical well being. 1. Terrible 2. Mostly dissatisfied 3. Mixed 4. Partially satisfied 5. Mostly satisfied 6. Pleased 7. Delighted
Hammersmith Functional Motor Scale Expanded (HFMSE) assesses motor function by functional item in order of progressive difficulty, with higher values showing higher function abilities. Each item is scored on a scale of 0-2 with 2 representing item achieved unaided and 0 representing inability to achieve item. Each item was assessed by the patient at Screening, the first (Day 1) and last day (Day 0) of the Run-in period, during Period 1 at Day 7 and Day 14, and during Period 2 at Day 21 and Day 28. The total HFMSE score was calculated as the sum of each item score, with a maximum score of 66 (all items achieved unaided) and minimum score of 0 (all items failed). Change from baseline (CFB) will be assessed from Day 0 to Day 28. A mixed effects liner model was fit with the HFMSE change from baseline (CFB) scores at Day 28 as a response and treatment, sequence, and treatment by sequence as fixed effect terms and patient as a random effect.
| Arm | Type | Description |
|---|---|---|
| amifamapridine phosphate tablets | EXPERIMENTAL | - |
| placebo tablets | PLACEBO_COMPARATOR | - |
| amifampridine phosphate | EXPERIMENTAL | amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days |
| placebo (for amifampridine phosphate) | PLACEBO_COMPARATOR | placebo by mouth 3 to 4 times per day for 4 days |
| amifampridine phosphate -placebo | EXPERIMENTAL | Each patient will participate in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate is achieved for 7 days. After this phase, half of the subjects will be randomized to receive amifampridine in Period I and then crossed over to receive placebo in Period II. Each randomized treatment period is 7 days in duration and is separated by a re-stabilization period of approximately two weeks where the subject will be returned to the stable dose administered at the end of the open-label run-in period. Dosing will be between 20 - 80 mg per day and frequency will be between 2-4 times per day. |
| placebo - amifampridine phosphate | EXPERIMENTAL | Each patient will participate in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate is achieved for 7 days. After this phase, half of the subjects will be randomized to receive placebo in Period I and then crossed over to receive amifampridine in Period II. Each randomized treatment period is 7 days in duration and separated by a re-stabilization period of approximately two weeks where the subject will be returned to the stable dose administered at the end of the open-label run-in period. Dosing will be between 20 - 80 mg per day and frequency will be between 2-4 times per day. |
| Placebo | PLACEBO_COMPARATOR | Matching placebo tablets administered 3-4 times a day (to the individual patient's tablet count of active at baseline) over 2 weeks. |
| Amifampridine Phosphate - Placebo | EXPERIMENTAL | Oral tablets, 30 to 80 mg per day in divided doses 3 to 4 times a day for 4 weeks |
| Name | Type | Description |
|---|---|---|
| Amifampridine Phosphate | DRUG | tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day |
| Placebo Oral Tablet | DRUG | tablets matching amifampridine phosphate, 3 to 4 times a day |
| Placebo | DRUG | A placebo equivalent will be provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo will be administered consistent with the dose regimen of amifampridine phosphate. |
Inclusion Criteria: 1. Willing and able to provide written informed consent after the nature of the study has been explained and before the start of any research-related procedures. 2. Male or female ≥18 years of age. 3. Positive serologic test for anti-MuSK antibodies or anti-AChR antibodies as co...
Amifampridine is a small molecule being developed for neurologic conditions including Lambert-Eaton Myasthenic Syndrome, spinal muscular atrophy, generalized myasthenia gravis, and congenital myasthenic syndromes. It is studied in both adult and pediatric patients, with trial eligibility starting as young as 2 years of age for congenital myasthenic syndromes.
Amifampridine is a blocker of potassium channels, specifically KCNQ1, KCND3, KCNH2, KCNA2, KCNA1, and KCNQ2. By blocking these channels, it is designed to prolong nerve terminal depolarization and enhance neurotransmitter release at the neuromuscular junction, which is the rationale for its study in myasthenic disorders.
Amifampridine is being developed by Catalyst Pharmaceuticals, Inc., which trades under the ticker CPRX. The company is the sponsor behind the clinical program evaluating amifampridine phosphate across several neuromuscular indications, including Lambert-Eaton Myasthenic Syndrome and generalized myasthenia gravis.
Amifampridine is in Phase 3 clinical development. Its program includes completed Phase 3 trials in Lambert-Eaton Myasthenic Syndrome, generalized myasthenia gravis, and congenital myasthenic syndromes, along with a completed Phase 2 trial in spinal muscular atrophy type 3. It remains an investigational therapy rather than an approved product.
Amifampridine has been studied in completed trials including NCT02970162 in Lambert-Eaton Myasthenic Syndrome, NCT03304054 in MuSK-associated generalized myasthenia gravis, NCT02562066 in congenital myasthenic syndromes, and NCT03781479 in spinal muscular atrophy type 3. These trials were randomized, double-blind, and placebo-controlled, with total enrollment across the program of 93 patients.
Yes, amifampridine phosphate is the phosphate salt form of amifampridine and is the name used in its clinical trial titles. Searches for either name refer to the same small molecule candidate developed by Catalyst Pharmaceuticals for neuromuscular junction disorders.