## Protocol Section
### Identification Module
**NCT ID:** NCT03781479

**Brief Title:** Controlled Trial to Evaluate Amifampridine Phosphate in Spinal Muscular Atrophy Type 3 Patients

**Official Title:** A Randomized, Placebo-Controlled, Crossover Study to Evaluate the Safety and Efficacy of Amifampridine Phosphate in Ambulatory Patients With Spinal Muscular Atrophy (SMA) Type 3

#### Organization Study ID Info
**ID:** SMA-001
#### Organization
**Class:** INDUSTRY
**Full Name:** Catalyst Pharmaceuticals, Inc.
### Status Module
#### Completion Date
**Date:** 2020-07-23

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2021-06-01

**Type:** ACTUAL

**Last Update Submit Date:** 2021-05-28

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2020-07-23

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2021-06-01

**Type:** ACTUAL

**Results First Submit Date:** 2021-04-06

**Results First Submit QC Date:** 2021-05-28

#### Start Date
**Date:** 2019-01-21

**Type:** ACTUAL

**Status Verified Date:** 2021-05

#### Study First Post Date
**Date:** 2018-12-20
**Type:** ACTUAL
**Study First Submit Date:** 2018-12-18
**Study First Submit QC Date:** 2018-12-18
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Catalyst Pharmaceuticals, Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** A two-period, two-treatment, crossover study to evaluate the safety, tolerability and efficacy of amifampridine phosphate in ambulatory patients diagnosed with spinal muscular atrophy (SMA) Type 3.

**Detailed Description:** This randomized (1:1), double-blind, placebo-controlled, 2-period, 2-treatment, crossover, outpatient study is designed to evaluate the safety, tolerability and efficacy of amifampridine phosphate in ambulatory patients diagnosed with SMA Type 3. The study is planned to include approximately 12 male and female SMA Type 3 patients. The planned duration of participation for each patient is approximately 2 months, based upon length of dose titration and excluding the screening period, which can last up to 14 days. Patients should only be taking the assigned investigational product (amifampridine phosphate 10 mg tablets or matching placebo tablets), no new therapies are permitted during the study.

### Conditions Module

**Conditions:**

- Muscular Atrophy, Spinal

**Keywords:**

- Type 3

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 13

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Oral tablets, 30 to 80 mg per day in divided doses 3 to 4 times a day for 4 weeks

**Intervention Names:**

- Drug: Amifampridine Phosphate

- Drug: Placebo Oral Tablet

**Label:** Amifampridine Phosphate - Placebo

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Oral tablets, 30 to 80 mg per day in divided doses 3 to 4 times a day for 4 weeks

**Intervention Names:**

- Drug: Amifampridine Phosphate

- Drug: Placebo Oral Tablet

**Label:** Placebo - Amifampridine Phosphate

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Amifampridine Phosphate - Placebo

- Placebo - Amifampridine Phosphate

**Description:** Amifampridine phosphate tablets 10 mg will be provided in round, white-scored tablets, and containing amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet.

**Name:** Amifampridine Phosphate

**Other Names:**

- 3,4 diaminopyridine phosphate

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Amifampridine Phosphate - Placebo

- Placebo - Amifampridine Phosphate

**Description:** Placebo Oral Tablet

**Name:** Placebo Oral Tablet

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** Hammersmith Functional Motor Scale Expanded (HFMSE) Summary Statistics and Mixed Model Analysis

**Time Frame:** 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

### Eligibility Module

**Eligibility Criteria:** 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 between the ages of 6 and 50 years.
3. Genetically confirmed diagnosis of SMA Type 3.
4. Able to walk independently for at least 30 meters.
5. Not taking Nusinersen for the treatment of SMA (Nusinersen should be stopped at least 6 months before screening). Salbutamol is permitted only if the dose has been stable during the 6 months before screening.
6. Able to swallow oral medication.
7. Female patients of childbearing potential must have a negative pregnancy test (serum human chorionic gonadotropin \[HCG\] at Screening); and must practice an effective, reliable contraceptive regimen during the study and for up to 30 days following discontinuation of treatment.
8. Ability to participate in the study based on overall health of the patient and disease prognosis, as applicable, in the opinion of the Investigator; and able to comply with all requirements of the protocol, including completion of study questionnaires.

Exclusion Criteria:

1. Epilepsy and currently on medication for epilepsy.
2. Concomitant use of medicinal products with a known potential to cause QTc prolongation.
3. Patients with long QT syndromes.
4. An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormalities, in the opinion of the Investigator.
5. Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study.
6. Treatment with an investigational drug (other than amifampridine), device, or biological agent within 6 months prior to Screening or while participating in this study.
7. Surgery for scoliosis or joint contractures within the previous 6 months.
8. Any medical condition that, in the opinion of the Investigator, might interfere with the patient's participation in the study, poses an added risk for the patient, or confound the assessment of the patient.
9. History of drug allergy to any pyridine-containing substances or any amifampridine excipient(s).
10. Less than a 3-point improvement in HFSME from start of the Open label Run -in period to end of Run-in (Day 0).

**Maximum Age:** 50 Years

**Minimum Age:** 6 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Milano

**Country:** Italy

**Facility:** Neurological Institute Carlo Besta

**State:** Lombardy

**Zip:** 20133

#### Overall Officials

**Official 1:**

**Affiliation:** Carlo Besta Institute, Milan, Italy

**Name:** Lorenzo Maggi, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Bonanno S, Giossi R, Zanin R, Porcelli V, Iannacone C, Baranello G, Ingenito G, Iyadurai S, Stevic Z, Peric S, Maggi L. Amifampridine safety and efficacy in spinal muscular atrophy ambulatory patients: a randomized, placebo-controlled, crossover phase 2 trial. J Neurol. 2022 Nov;269(11):5858-5867. doi: 10.1007/s00415-022-11231-7. Epub 2022 Jun 28.

**PMID:** 35763114

## Document Section

### Large Document Module

#### Large Docs

- Date: 2019-09-27

- Filename: Prot_000.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: False

- Label: Study Protocol

- Size: 2833864

- Type Abbrev: Prot

- Upload Date: 2021-04-06T12:26

- Date: 2020-05-11

- Filename: SAP_001.pdf

- Has ICF: False

- Has Protocol: False

- Has SAP: True

- Label: Statistical Analysis Plan

- Size: 973511

- Type Abbrev: SAP

- Upload Date: 2021-04-06T12:27

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020763

- Term: Pathological Conditions, Anatomical

- ID: D000020879

- Term: Neuromuscular Manifestations

- ID: D000009461

- Term: Neurologic Manifestations

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000013118

- Term: Spinal Cord Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000016472

- Term: Motor Neuron Disease

- ID: D000019636

- Term: Neurodegenerative Diseases

- ID: D000009468

- Term: Neuromuscular Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M12090

- Name: Muscular Atrophy

- Relevance: HIGH

- As Found: Muscular Atrophy

- ID: M12091

- Name: Muscular Atrophy, Spinal

- Relevance: HIGH

- As Found: Muscular Atrophy, Spinal

- ID: M4589

- Name: Atrophy

- Relevance: HIGH

- As Found: Atrophy

- ID: M22519

- Name: Pathological Conditions, Anatomical

- Relevance: LOW

- As Found: Unknown

- ID: M22619

- Name: Neuromuscular Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M15915

- Name: Spinal Cord Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M18879

- Name: Motor Neuron Disease

- Relevance: LOW

- As Found: Unknown

- ID: M4024

- Name: Amyotrophic Lateral Sclerosis

- Relevance: LOW

- As Found: Unknown

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12411

- Name: Neuromuscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T5342

- Name: Spinal Muscular Atrophy

- Relevance: HIGH

- As Found: Spinal Muscular Atrophy

- ID: T5347

- Name: Spinal Muscular Atrophy Type 3

- Relevance: LOW

- As Found: Unknown

- ID: T349

- Name: Amyotrophic Lateral Sclerosis

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009133

- Term: Muscular Atrophy

- ID: D000009134

- Term: Muscular Atrophy, Spinal

- ID: D000001284

- Term: Atrophy

### Intervention Browse Module - Ancestors

- ID: D000009465

- Term: Neuromuscular Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000026902

- Term: Potassium Channel Blockers

- ID: D000049990

- Term: Membrane Transport Modulators

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: ChanBlk

- Name: Channel Blockers

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M1902

- Name: Amifampridine

- Relevance: HIGH

- As Found: Drain removal

- ID: M23171

- Name: Potassium Channel Blockers

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000077770

- Term: Amifampridine

### Misc Info Module

#### Submission Tracking

##### First MCP Info

###### Post Date

- Date: 2021-05-03

- Type: ACTUAL

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

**Description:** Serious classification based on the FDA regulatory definition of a serious AE.

#### Event Groups

**Group ID:** EG000

**Title:** Amifampridine

**Deaths Num At Risk:** 12

**Description:** Treatment administered to the patient at the time of onset of the AE.

**ID:** EG000

**Other Num Affected:** 5

**Other Num at Risk:** 12

**Serious Number At Risk:** 12

**Title:** Amifampridine

**Group ID:** EG001

**Title:** Placebo

**Deaths Num At Risk:** 12

**Description:** Treatment administered to the patient at the time of onset of the AE.

**ID:** EG001

**Other Num Affected:** 3

**Other Num at Risk:** 12

**Serious Number At Risk:** 12

**Title:** Placebo

**Frequency Threshold:** 5

#### Other Events

**Term:** Hypoaesthesia oral

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (19.0)

**Term:** Paraesthesia oral

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (19.0)

**Term:** Fatigue

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA (19.0)

**Term:** Gait disturbance

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA (19.0)

**Term:** Influenza like illness

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA (19.0)

**Term:** Influenza

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (19.0)

**Term:** Fall

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA (19.0)

**Term:** Transaminases increased

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA (19.0)

**Term:** Muscular weakness

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA (19.0)

**Term:** Headache

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA (19.0)

**Term:** Paraesthesia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA (19.0)

**Term:** Intranasal Paraesthesia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Respiratory, thoracic and mediastinal disorders

**Source Vocabulary:** MedDRA (19.0)

**Time Frame:** Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks.

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 6

**Group ID:** BG001

**Value:** 6

**Group ID:** BG002

**Value:** 1

**Group ID:** BG003

**Value:** 13

**Units:** Participants

### Group

**ID:** BG000

**Title:** Amifampridine Phosphate - Placebo

**Description:** Each patient participated in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate was achieved for 7 days. After this phase, half of the subjects were randomized to receive amifampridine in Period 1 and then crossed over to receive placebo in Period 2. Each randomized treatment period was 14 days in duration.

Dosing was up to 80 mg per day and frequency was between 3-4 times per day. Amifampridine Phosphate: Amifampridine phosphate tablets 10 mg were provided in round, white-scored tablets, and contained amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet.

Placebo: A placebo equivalent was provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate.

### Group

**ID:** BG001

**Title:** Placebo - Amifampridine Phosphate

**Description:** Each patient participated in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate was achieved for 7 days. After this phase, half of the subjects were randomized to receive placebo in Period 1 and then crossed over to receive amifampridine in Period 2. Each randomized treatment period was 14 days in duration.

Dosing was up to 80 mg per day and frequency was between 3-4 times per day. Placebo: A placebo equivalent was provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate.

Amifampridine Phosphate: Amifampridine phosphate tablets 10 mg were provided in round, white-scored tablets, and contained amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet.

### Group

**ID:** BG002

**Title:** Not Randomized

**Description:** Patients receiving amifampridine during the open-label run-in period but were not randomized to receive treatment.

### Group

**ID:** BG003

**Title:** Total

**Description:** Total of all reporting groups

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 8.5

**Value:** 37.2

#### Measurement

**Group ID:** BG001

**Spread:** 13.5

**Value:** 30.2

#### Measurement

**Group ID:** BG002

**Value:** 45.0

#### Measurement

**Group ID:** BG003

**Spread:** 11.3

**Value:** 34.5

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 4

#### Measurement

**Group ID:** BG001

**Value:** 1

#### Measurement

**Group ID:** BG002

**Value:** 0

#### Measurement

**Group ID:** BG003

**Value:** 5

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 2

#### Measurement

**Group ID:** BG001

**Value:** 5

#### Measurement

**Group ID:** BG002

**Value:** 1

#### Measurement

**Group ID:** BG003

**Value:** 8

**Category Title:** Male

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

#### Measurement

**Group ID:** BG003

**Value:** 0

**Category Title:** American Indian or Alaska Native

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 1

#### Measurement

**Group ID:** BG002

**Value:** 0

#### Measurement

**Group ID:** BG003

**Value:** 1

**Category Title:** Asian

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

#### Measurement

**Group ID:** BG003

**Value:** 0

**Category Title:** Native Hawaiian or Other Pacific Islander

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

#### Measurement

**Group ID:** BG003

**Value:** 0

**Category Title:** Black or African American

#### Measurement

**Group ID:** BG000

**Value:** 6

#### Measurement

**Group ID:** BG001

**Value:** 5

#### Measurement

**Group ID:** BG002

**Value:** 1

#### Measurement

**Group ID:** BG003

**Value:** 12

**Category Title:** White

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

#### Measurement

**Group ID:** BG003

**Value:** 0

**Category Title:** More than one race

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

#### Measurement

**Group ID:** BG003

**Value:** 0

**Category Title:** Unknown or Not Reported

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 9.3

**Value:** 64.7

#### Measurement

**Group ID:** BG001

**Spread:** 11.8

**Value:** 67.8

#### Measurement

**Group ID:** BG002

**Value:** 76.9

#### Measurement

**Group ID:** BG003

**Spread:** 10.2

**Value:** 67.0

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 9.0

**Value:** 169.3

#### Measurement

**Group ID:** BG001

**Spread:** 6.1

**Value:** 174.8

#### Measurement

**Group ID:** BG002

**Value:** 170.0

#### Measurement

**Group ID:** BG003

**Spread:** 7.6

**Value:** 171.9

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 1.4

**Value:** 22.5

#### Measurement

**Group ID:** BG001

**Spread:** 4.3

**Value:** 22.3

#### Measurement

**Group ID:** BG002

**Value:** 26.6

#### Measurement

**Group ID:** BG003

**Spread:** 3.1

**Value:** 22.7

**Class Title:** 

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Race (NIH/OMB)
**Unit of Measure:** Participants
### Measure 4
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Weight
**Unit of Measure:** kg
### Measure 5
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Height
**Unit of Measure:** cm
### Measure 6
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** BMI
**Unit of Measure:** kg/m^2
**Population Description:** The analysis of baseline characteristics included all patients in the Safety population, who are those patients who enrolled and received at least one dose of amifampridine. Patients who began the Run-in period regardless of whether they were randomized to double blind medication on Day 0 belong to the Safety population.
## Results Section - More Information Module
### Certain Agreement
### Point of Contact
**Email:** gingenito@catalystpharma.com
**Organization:** Catalyst Pharmaceuticals, Inc.
**Phone:** 3054203200
**Title:** Gary Ingenito
## Results Section - Outcome Measures Module
### Outcome Measure 1
#### Analysis
**CI Lower Limit:** 0.22
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** 1.37
**CI Upper Limit Comment:** 
**Dispersion Type:** 
**Dispersion Value:** 
**Estimate Comment:** Results show the LSMeans for the estimated difference between treatments along with a 95% confidence interval for this difference.
**Group Description:** 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.
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** OTHER
**Other Analysis Description:** 
**P-Value:** 0.0083
**P-Value Comment:** 
**Parameter Type:** Mean Difference (Net)
**Parameter Value:** 0.792
**Statistical Comment:** 
**Statistical Method:** Mixed Models Analysis
**Tested Non-Inferiority:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.326
- **Upper Limit:** 
- **Value:** 0.208
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.326
- **Upper Limit:** 
- **Value:** -0.583
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** 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.
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** The analysis of primary outcome data was based on the Full Analysis Set population, which included all randomized patients who received at least one dose of study medication (amifampridine or placebo) and had at least one post-treatment efficacy assessment. Patients are compared for efficacy according to the treatment to which they were randomized, regardless of the treatment actually received.
**Reporting Status:** POSTED
**Time Frame:** 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
**Title:** Hammersmith Functional Motor Scale Expanded (HFMSE) Summary Statistics and Mixed Model Analysis
**Type:** PRIMARY
**Unit of Measure:** Overall Score
##### Group
**Description:** 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 were randomized to receive amifampridine in Period 1 and then crossed over to receive placebo in Period 2 and the other were randomized to receive placebo in Period 1 and then crossed over to receive amifampridine in Period 2.

Each randomized treatment period is 14 days in duration.

Dosing was up to 80 mg per day and frequency was between 3-4 times per day.

Amifampridine Phosphate: Amifampridine phosphate tablets 10 mg were provided in round, white-scored tablets, and contained amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet.

Placebo: A placebo equivalent was provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate.

The Amifampridine study arm includes all patients in the FAS population who received Amifampridine during the treatment period, regardless of which Period the treatment was administered.
**ID:** OG000
**Title:** Amifampridine Phosphate
##### Group
**Description:** 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 were randomized to receive amifampridine in Period 1 and then crossed over to receive placebo in Period 2 and the other were randomized to receive placebo in Period 1 and then crossed over to receive amifampridine in Period 2.

Each randomized treatment period is 14 days in duration.

Dosing was up to 80 mg per day and frequency was between 3-4 times per day.

Amifampridine Phosphate: Amifampridine phosphate tablets 10 mg were provided in round, white-scored tablets, and contained amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet.

Placebo: A placebo equivalent was provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate.

The Placebo study arm includes all patients in the FAS population who received Placebo during the treatment period, regardless of which Period the treatment was administered.
**ID:** OG001
**Title:** Placebo
### Participant Flow Module
#### Group
**Description:** Each patient participated in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate was achieved for 7 days. After this phase, half of the subjects were randomized to receive amifampridine in Period 1 and then crossed over to receive placebo in Period 2. Each randomized treatment period was 14 days in duration.

Dosing was up to 80 mg per day and frequency was between 3-4 times per day.

Amifampridine Phosphate: Amifampridine phosphate tablets 10 mg were provided in round, white-scored tablets, and contained amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet.

Placebo: A placebo equivalent was provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate.
**ID:** FG000
**Title:** Amifampridine Phosphate - Placebo
#### Group
**Description:** Each patient participated in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate was achieved for 7 days. After this phase, half of the subjects were randomized to receive placebo in Period 1 and then crossed over to receive amifampridine in Period 2. Each randomized treatment period was 14 days in duration.

Dosing was up to 80 mg per day and frequency was between 3-4 times per day.

Placebo: A placebo equivalent was provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate.

Amifampridine Phosphate: Amifampridine phosphate tablets 10 mg were provided in round, white-scored tablets, and contained amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet.
**ID:** FG001
**Title:** Placebo - Amifampridine Phosphate
#### Group
**Description:** Patients receiving amifampridine during the open-label run-in period but were not randomized to receive treatment.
**ID:** FG002
**Title:** Not Randomized
#### Period
**Title:** Overall Study
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 6
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 6
###### Achievement
**Group ID:** FG002
**Number of Subjects:** 1
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 6
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 6
###### Achievement
**Group ID:** FG002
**Number of Subjects:** 0
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG002
**Number of Subjects:** 1
**Pre-Assignment Details:** A screening visit was conducted to ensure that each patient met inclusion/exclusion criteria for the study. Those patients successfully completing screening had procedures/assessments conducted at the start of the Run-in period (Day 1, before starting study medication) and during Run-in, until stable dose and frequency of amifampridine was established for at least 7 days, and at least a 3-point improvement in HFMSE score was achieved from start of Run-in to be eligible for randomization (Day 0).
**Recruitment Details:** The study was conducted from 14 January 2019 - 17 September 2020 at two sites in Europe.
**Has Results:** True