Metachromatic Leukodystrophy (MLD)
Conditions
Keywords
Intrathecal Drug Delivery Device (IDDD), Recombinant human arylsulfatase A (rhASA), Metachromatic Leukodystrophy (MLD)
Brief summary
The purpose of this study is to determine the safety of ascending doses of HGT-1110 administered by intrathecal (IT) injection for 38 weeks (20 injections) in children with metachromatic leukodystrophy (MLD).
Detailed description
Metachromatic leukodystrophy (MLD) is an inherited, autosomal recessive disorder of lipid metabolism characterized by deficient activity of the lysosomal enzyme, arylsulfatase A (ASA). MLD is a rare disease that occurs in most parts of the world. The estimated overall incidence of the disease in the western world is approximately 1 in 100,000 live births that varies by geographic location. There are no approved therapies for MLD. This is a multicenter, open-label, dose-escalation study designed to evaluate the safety of up to 3 dose levels (10, 30, or 100 mg) of HGT-1110 administered via an intrathecal drug delivery device (IDDD) every other week (EOW) for a total of 38 weeks (20 injections, Weeks 0 to 38) to children with MLD. The study also includes the assessment of HGT-1110 drug product produced with a revised drug substance manufacturing process (referred to as Process B) in a fourth cohort (Cohort 4). Approximately 24 patients will be enrolled and will receive treatment of HGT-1110. Patients will be sequentially enrolled into 4 dose cohorts, approximately 6 patients each. Patient enrollment will be staggered in this study to facilitate adequate safety monitoring per dose cohort.
Interventions
BIOLOGICALRecombinant human arylsulfatase A
6 patients treated with HGT-1110 EOW by IT injection
Sponsors
Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Years
Healthy volunteers
No
Inclusion criteria
Inclusion For Cohorts 1-4: 1. Confirmed diagnosis of metachromatic leukodystrophy by both: * Arylsulfatase A (ASA) deficiency by assay in leukocytes AND * Elevated sulfatide in urine 2. Appearance of the first symptoms of disease at or before 30 months of age. For Cohorts 1-3 only: 3. Ambulatory at the time of screening. The minimum level of function required to meet this criterion is defined as the ability to walk forward 10 steps with one hand held. 4. The patient is less than 12 years of age at the time of screening. For Cohort 4 only: 3.1 Minimum motor function requirements: 1. A total GMFM-88 (percent) score ≥40 at the screening examination and a total GMFM-88 (percent) score ≥35 at the baseline examination, AND 2. GMFM-88 Dimension E: Walking, Running & Jumping, item 68 (walk forward 10 steps with one hand held) score of at least 1 initiates at the screening and baseline examinations (if applicable). 4.1 The patient is less than 8 years of age at the time of screening. For Cohorts 1-4: 5. Neurological signs of MLD must be present at the screening examination. 6. The patient and his/her parent/representative(s) must have the ability to comply with the clinical protocol. 7. Patient's parent(s) or legally authorized representative(s) must provide written informed consent prior to performing any study-related activities. Study-related activities are any procedures that would not have been performed during normal management of the patient.
Exclusion criteria
Patients will be excluded from the study if there is evidence or history of any of the following criteria at screening: For Cohorts 1-4: 1. History of hematopoietic stem cell transplantation (HSCT). 2. The patient has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to airway compromise or other conditions. 3. Any other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial. 4. The patient is enrolled in another clinical study that involves the use of any investigational product (drug or device) other than HGT-1110 or the IDDD used in this study within 30 days prior to study enrollment or at any time during the study. 5. The patient is pregnant or breastfeeding. 6. The patient has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use (IFU), including: 1. The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device. 2. The patient's body size is too small to support the size of the SOPH-A-PORT Mini S Access Port, as judged by the Investigator. 3. The patient has a known or suspected local or general infection. 4. The patient is at risk of abnormal bleeding due to a medical condition or therapy. 5. The patient has one or more spinal abnormalities that could complicate safe implantation or fixation. 6. The patient has a functioning CSF shunt device. 7. The patient has shown an intolerance to an implanted device.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | From start of study treatment up to Week 42 | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date. Drug-related and device-related types of TEAEs were analyzed and reported. The severity of AEs was assessed by the investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 grading scale. Severity of all AEs or SAEs was recorded as grade 1, 2, 3, 4, or 5 corresponding, respectively, to a severity of mild, moderate, severe, life-threatening, or fatal. Here SDI refers to surgical device implantation. |
| Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | From start of study treatment up to Week 40 | Clinical laboratory test included serum chemistry, hematology and urinalysis. Clinical laboratory abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date. |
| Number of Participants With Vital Sign Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | From start of study treatment up to Week 40 | Vital sign assessments included blood pressure, heart rate, respiratory rate and body temperature. Vital sign abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date. Vital sign abnormalities included pyrexia which was considered as TEAE and was reported. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | From start of study treatment up to Week 40 | 12-lead ECG was recorded and measured with the participant in rested supine position for at least 10 minutes. ECG abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date. |
| Number of Participants With Clinically Significant Abnormalities in Physical Examination Reported as Treatment Emergent Adverse Events (TEAE) | From start of study treatment up to Week 40 | Complete physical examination included evaluation of the port and catheter track. Height or length and weight were recorded and used to calculate growth. Body weight and height measurements were used to calculate the body mass index (BMI). Head circumference was measured in uniform manner for all participants. Clinical significance was defined as any variation in physical findings that had medical relevance resulting in an alteration in medical care. Clinically significant abnormalities related to physical examination were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date. |
| Number of Participants With Cerebrospinal Fluid (CSF) Chemistry Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | From start of study treatment up to Week 40 | CSF chemistry assessments (including cell counts, glucose and protein) was measured. CSF chemistry abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date. |
| Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Baseline up to Week 40 | Number of participants with positive anti-SHP611 antibody results in serum and in CSF were reported. A participant was considered positive if they had at least 1 positive result during the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | Baseline, Week 40 | Evaluation of peripheral nerve function by ENG studies was performed to measure nerve conduction velocity (NCV), amplitude (AMP),distal latency (DL), and F-wave latency. Categorized nerve conduction velocity values were assessed. Data was presented only for number of participants who reported change in nerve conduction velocity \> 0. Here MME refers to median motor elbow, WCV for wrist conduction velocity, PMA for peroneal motor ankle, FHCV to fibular head conduction velocity, TMA for tibial motor ankle, KCV for knee conduction velocity and UME for ulnar motor elbow, |
| Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | Baseline, Week 40 | Evaluation of peripheral nerve function by ENG studies was performed to measure nerve conduction velocity (NCV), amplitude (AMP),distal latency (DL), and F-wave latency. Categorized amplitude values were assessed. Data was presented only for number of participants who reported change in distal latency \> 0. Here MMW refers to median motor wrist, APB for abductor pollicis brevis, MSW for median sensory wrist, DDL for digit distal latency, PMA for peroneal motor ankle, EDB for extensor digitorum brevis, SSB-point DL for sural sensory B-point distal latency, TMA for tibial motor ankle, abductor hallucis for AH distal latency and, UMW for ulnar motor wrist. |
| Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Baseline, Week 40 | The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 4 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (ABC) (a composite of the other 4 domain). Items in each domain are rated as either 0 (does not), 1(sometimes) or 2(independently) performs a given behavior or skill. The 4 domain standard scores range from 20-160 and higher scores indicate a higher level of functioning. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160) and higher scores indicate a higher level of functioning. A positive change value indicates improvement in adaptive functioning. |
| Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Baseline, Week 40 | COMFORT questionnaire was used to assess health status and the impact of disease on the ability of participants with MLD to carry out activities of daily life. The questionnaire was organized by 8 domains (ie, personal care; positioning, transfer, or mobility; eating; pain and discomfort during the day; sleep; emotions; communication; and play and leisure activities). The COMFORT scores range from 0 to 100, with higher scores indicating a decline in the functioning. |
| Maximum Observed Serum Concentration (Cmax) of SHP611 | Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose | Cmax is the maximum observed serum concentration of SHP611. |
| Time to Reach Maximum Observed Drug Concentration (Tmax) of SHP611 in Plasma | Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose | Tmax is the time to reach maximum observed drug concentration of SHP611 during a dosing interval. |
| Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of SHP611 | Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose | The AUC0-inf is the area under the concentration-time curve from time zero to infinity of SHP611. |
| Change From Baseline in Motor Function Using Gross Motor Function Measure 88 (GMFM-88) Total Score at Week 40 | Baseline, Week 40 | The GMFM-88 was used to measure motor function. The GMFM-88 item scores were used to calculate domain-specific percent score for each of the 5 GMFM-88 dimensions (lying and rolling; sitting; crawling and kneeling; standing; walking, running, and jumping), and a total GMFM-88 (percent) score was calculated based on each dimension score. Each of the 88 items was rated on a 4-point scale: 0=does not initiate; 1=initiates; 2=partially completes; and 3=completes. The GMFM-88 total scores ranged from 0% (no mobility) to a score of 100%, that is (i.e,) the score that can be obtained by an average 5-year-old or older child with normal motor abilities. |
| Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of SHP611 | Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose | Area under the concentration-time curve over the interval from 0 to 24 hours after dosing of SHP611. |
| First Order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve for SHP611 | Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose | Lambda z is first order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve. |
| Terminal Elimination Half Life (t1/2) of SHP611 | Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose | The t1/2 is the time in hours required for the concentration of the drug to reach half of its original value. |
| Total Body Clearance (CL/F) After Intrathecal Administration of SHP611 | Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose | CL/F was defined as the total body clearance of the drug for extravascular administration divided by the fraction of dose absorbed. |
| Volume of Distribution (Vz/F) After Intrathecal Administration of SHP611 | Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose | Volume of distribution was associated with the terminal slope following extravascular administration of SHP611 divided by the fraction of dose absorbed. |
| Concentration of SHP611 in Cerebrospinal Fluid | Baseline, 4, 8, 12, 16, 20, 24, 28, 32, 36, and 40 weeks | Concentration of SHP611 in CSF was determined using validated enzyme-linked immunosorbent assay (ELISA) method. |
| Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of SHP611 | Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose | AUC0-last is the area under the concentration-time curve from the time of dosing to the last measurable concentration of SHP611. |
| Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Week 40 | The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. FEES for texture utilized was evaluated. Data was presented only for the shifts observed. |
| Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Week 40 | The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. Feeding assessment for laryngeal penetration was assessed. Data was presented only for the shifts observed. Here TL refers to thin liquids, THL refers to thickened liquids, PT refers to puree texture, WCC refers to with cough and clearance and WCNC refers to with cough and no clearance. |
| Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Week 40 | The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. Feeding assessment for aspiration through vocal cords were assessed. Data was presented only for the shifts observed. Here TL refers to thin liquids, THL refers to thickened liquids, PT refers to puree texture, WCC refers to with cough and clearance and WCNC refers to with cough and no clearance. |
| Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Week 40 | The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. FEES for dose residue clear after subsequent swallowing was assessed. Data was presented only for the shifts observed. Here TL refers to thin liquids, THL refers to thickened liquids, PT refers to puree texture. |
| Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Week 40 | The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. FEES for aspiration risk was assessed. Data was presented only for the shifts observed. Here TL refers to thin liquids, THL refers to thickened liquids, PT refers to puree texture, WCC refers to with cough and clearance and WCNC refers to with cough and no clearance. |
| Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Baseline, Week 40 | Evaluation of peripheral nerve function by ENG studies was performed to measure nerve conduction velocity (NCV), amplitude (AMP),distal latency (DL), and F-wave latency. Categorized amplitude values were assessed. Data was presented only for number of participants who reported change in amplitude greater than (\>) 0. |
Countries
Australia, Denmark, France, Germany, Japan
Participant flow
Recruitment details
The study was conducted at 5 main sites for cohorts 1 to 3 in Brazil, Denmark, Germany, France, and Australia and 3 main sites for cohort 4 in Denmark, France, and Germany between 02 February 2012 (first participant first visit) and 20 January 2017 (last participant last visit).
Pre-assignment details
A total of 34 participants were screened and 24 participants were enrolled in the study. Out of which 23 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| SHP611 10 mg (Process A) Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A. | 6 |
| SHP611 30 mg (Process A) Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A. | 6 |
| SHP611 100 mg (Process A) Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A. | 6 |
| SHP611 100 mg (Process B) Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B. | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | SHP611 100 mg (Process B) | SHP611 100 mg (Process A) | SHP611 30 mg (Process A) | SHP611 10 mg (Process A) |
|---|---|---|---|---|---|
| Age, Continuous | 44.9 Months STANDARD_DEVIATION 22.85 | 48.5 Months STANDARD_DEVIATION 24.22 | 52.2 Months STANDARD_DEVIATION 31.17 | 47.3 Months STANDARD_DEVIATION 20.23 | 31.5 Months STANDARD_DEVIATION 11.5 |
| Race/Ethnicity, Customized Ethnicity: Not Hispanic or Latino | 24 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Race/Ethnicity, Customized Race: Asian | 4 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race: Other | 5 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race: White | 15 Participants | 4 Participants | 2 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Female | 9 Participants | 2 Participants | 1 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 15 Participants | 4 Participants | 5 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 5 / 6 | 4 / 6 | 3 / 6 | 2 / 6 |
Outcome results
Primary
Number of Participants With Cerebrospinal Fluid (CSF) Chemistry Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
CSF chemistry assessments (including cell counts, glucose and protein) was measured. CSF chemistry abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date.
Time frame: From start of study treatment up to Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Cerebrospinal Fluid (CSF) Chemistry Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | CSF Protein Increased | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Cerebrospinal Fluid (CSF) Chemistry Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | CSF Albumin Increased | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Cerebrospinal Fluid (CSF) Chemistry Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | CSF Albumin Increased | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Cerebrospinal Fluid (CSF) Chemistry Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | CSF Protein Increased | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Cerebrospinal Fluid (CSF) Chemistry Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | CSF Protein Increased | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Cerebrospinal Fluid (CSF) Chemistry Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | CSF Albumin Increased | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Cerebrospinal Fluid (CSF) Chemistry Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | CSF Protein Increased | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Cerebrospinal Fluid (CSF) Chemistry Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | CSF Albumin Increased | 0 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Clinical laboratory test included serum chemistry, hematology and urinalysis. Clinical laboratory abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date.
Time frame: From start of study treatment up to Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Amylase increased | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Gamma-glutamyltransferase (GGT) increased | 2 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Aspartate aminotransferase (AST) increased | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Blood iron decreased | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Alanine aminotransferase (ALT) increased | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Blood creatine phosphokinase increased | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Hepatic enzymes increased | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Eosinophil count increased | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Eosinophilia | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Mean cell volume decreased | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Neutrophil count increased | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | White blood cell count increased | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Lymphopenia | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Leukocytosis | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Proteinuria | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Amylase increased | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Eosinophil count increased | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Aspartate aminotransferase (AST) increased | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | White blood cell count increased | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Leukocytosis | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Eosinophilia | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Blood iron decreased | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Neutrophil count increased | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Blood creatine phosphokinase increased | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Mean cell volume decreased | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Lymphopenia | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Alanine aminotransferase (ALT) increased | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Proteinuria | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Hepatic enzymes increased | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Gamma-glutamyltransferase (GGT) increased | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Gamma-glutamyltransferase (GGT) increased | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Amylase increased | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Lymphopenia | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Blood creatine phosphokinase increased | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Hepatic enzymes increased | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Proteinuria | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Eosinophil count increased | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Eosinophilia | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Leukocytosis | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Mean cell volume decreased | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Neutrophil count increased | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Alanine aminotransferase (ALT) increased | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | White blood cell count increased | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Aspartate aminotransferase (AST) increased | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Blood iron decreased | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Proteinuria | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Eosinophil count increased | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Hepatic enzymes increased | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Lymphopenia | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Gamma-glutamyltransferase (GGT) increased | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Blood creatine phosphokinase increased | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | White blood cell count increased | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Alanine aminotransferase (ALT) increased | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Amylase increased | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Blood iron decreased | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Mean cell volume decreased | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Leukocytosis | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Eosinophilia | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Aspartate aminotransferase (AST) increased | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Neutrophil count increased | 0 Participants |
Primary
Number of Participants With Clinically Significant Abnormalities in Physical Examination Reported as Treatment Emergent Adverse Events (TEAE)
Complete physical examination included evaluation of the port and catheter track. Height or length and weight were recorded and used to calculate growth. Body weight and height measurements were used to calculate the body mass index (BMI). Head circumference was measured in uniform manner for all participants. Clinical significance was defined as any variation in physical findings that had medical relevance resulting in an alteration in medical care. Clinically significant abnormalities related to physical examination were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date.
Time frame: From start of study treatment up to Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Reported as Treatment Emergent Adverse Events (TEAE) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Reported as Treatment Emergent Adverse Events (TEAE) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Reported as Treatment Emergent Adverse Events (TEAE) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Reported as Treatment Emergent Adverse Events (TEAE) | 0 Participants |
Primary
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
12-lead ECG was recorded and measured with the participant in rested supine position for at least 10 minutes. ECG abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date.
Time frame: From start of study treatment up to Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
Primary
Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum
Number of participants with positive anti-SHP611 antibody results in serum and in CSF were reported. A participant was considered positive if they had at least 1 positive result during the study.
Time frame: Baseline up to Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | CSF neutralizing anti-SHP611 antibody positive | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum anti-SHP611 antibody (Ab) positive | 4 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum neutralizing anti-SHP611 antibody positive | 3 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | CSF anti-SHP611 antibody positive | 3 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum or CSF anti-SHP611 antibody positive | 4 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum and CSF anti-SHP611 antibody positive | 3 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum or CSF neutralizing anti-SHP611 Ab positive | 3 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum and CSF neutralizing anti-SHP611 Ab positive | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum and CSF anti-SHP611 antibody positive | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum or CSF anti-SHP611 antibody positive | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum neutralizing anti-SHP611 antibody positive | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum and CSF neutralizing anti-SHP611 Ab positive | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum anti-SHP611 antibody (Ab) positive | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | CSF neutralizing anti-SHP611 antibody positive | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | CSF anti-SHP611 antibody positive | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum or CSF neutralizing anti-SHP611 Ab positive | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum neutralizing anti-SHP611 antibody positive | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | CSF anti-SHP611 antibody positive | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | CSF neutralizing anti-SHP611 antibody positive | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum or CSF anti-SHP611 antibody positive | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum and CSF anti-SHP611 antibody positive | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum and CSF neutralizing anti-SHP611 Ab positive | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum anti-SHP611 antibody (Ab) positive | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum or CSF neutralizing anti-SHP611 Ab positive | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum neutralizing anti-SHP611 antibody positive | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | CSF neutralizing anti-SHP611 antibody positive | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | CSF anti-SHP611 antibody positive | 2 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum or CSF neutralizing anti-SHP611 Ab positive | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum or CSF anti-SHP611 antibody positive | 2 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum and CSF neutralizing anti-SHP611 Ab positive | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum anti-SHP611 antibody (Ab) positive | 2 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum | Serum and CSF anti-SHP611 antibody positive | 2 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date. Drug-related and device-related types of TEAEs were analyzed and reported. The severity of AEs was assessed by the investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 grading scale. Severity of all AEs or SAEs was recorded as grade 1, 2, 3, 4, or 5 corresponding, respectively, to a severity of mild, moderate, severe, life-threatening, or fatal. Here SDI refers to surgical device implantation.
Time frame: From start of study treatment up to Week 42
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | TEAE | 6 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | SHP611-related TEAE | 3 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | SDI-related TEAE | 5 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | IDDD-related TEAE | 3 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | SOPH-A-PORT IDDD-related TEAE | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | IT administration process related TEAE | 4 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | Severe TEAE | 2 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | Serious TEAE | 5 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | IT administration process related TEAE | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | SOPH-A-PORT IDDD-related TEAE | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | SHP611-related TEAE | 4 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | Serious TEAE | 4 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | Severe TEAE | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | IDDD-related TEAE | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | SDI-related TEAE | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | TEAE | 6 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | Severe TEAE | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | SDI-related TEAE | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | IDDD-related TEAE | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | SOPH-A-PORT IDDD-related TEAE | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | IT administration process related TEAE | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | Serious TEAE | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | TEAE | 6 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | SHP611-related TEAE | 4 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | SDI-related TEAE | 4 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | IDDD-related TEAE | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | SHP611-related TEAE | 2 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | TEAE | 6 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | SOPH-A-PORT IDDD-related TEAE | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | Serious TEAE | 2 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | Severe TEAE | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity | IT administration process related TEAE | 1 Participants |
Primary
Number of Participants With Vital Sign Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Vital sign assessments included blood pressure, heart rate, respiratory rate and body temperature. Vital sign abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date. Vital sign abnormalities included pyrexia which was considered as TEAE and was reported.
Time frame: From start of study treatment up to Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Vital Sign Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | 5 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Vital Sign Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Vital Sign Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | 5 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Vital Sign Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | 5 Participants |
Secondary
Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of SHP611
Area under the concentration-time curve over the interval from 0 to 24 hours after dosing of SHP611.
Time frame: Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Population: PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP611 10 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of SHP611 | Week 38 | 1960 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 224 |
| SHP611 10 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of SHP611 | Baseline | 2530 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 1178 |
| SHP611 30 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of SHP611 | Baseline | 6258 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 2995.3 |
| SHP611 30 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of SHP611 | Week 38 | 4596 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 2316.1 |
| SHP611 100 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of SHP611 | Baseline | 11918 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 6376.1 |
| SHP611 100 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of SHP611 | Week 38 | 18264 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 2162.7 |
| SHP611 100 mg (Process B) | Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of SHP611 | Week 38 | 31115 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 15805.6 |
| SHP611 100 mg (Process B) | Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of SHP611 | Baseline | 13114 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 8012 |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of SHP611
The AUC0-inf is the area under the concentration-time curve from time zero to infinity of SHP611.
Time frame: Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Population: PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP611 10 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of SHP611 | Baseline | 4355 Hour * nanogram/milliliter (h*ng/mL) | — |
| SHP611 10 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of SHP611 | Week 38 | 2767 Hour * nanogram/milliliter (h*ng/mL) | — |
| SHP611 30 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of SHP611 | Week 38 | 9589 Hour * nanogram/milliliter (h*ng/mL) | — |
| SHP611 30 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of SHP611 | Baseline | 10105 Hour * nanogram/milliliter (h*ng/mL) | Standard Deviation 3307.4 |
| SHP611 100 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of SHP611 | Baseline | 22123 Hour * nanogram/milliliter (h*ng/mL) | Standard Deviation 4217.4 |
| SHP611 100 mg (Process B) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of SHP611 | Baseline | 23117 Hour * nanogram/milliliter (h*ng/mL) | Standard Deviation 10380.1 |
| SHP611 100 mg (Process B) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of SHP611 | Week 38 | 48648 Hour * nanogram/milliliter (h*ng/mL) | Standard Deviation 6906.8 |
Secondary
Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of SHP611
AUC0-last is the area under the concentration-time curve from the time of dosing to the last measurable concentration of SHP611.
Time frame: Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Population: PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP611 10 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of SHP611 | Baseline | 2532 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 1178.4 |
| SHP611 10 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of SHP611 | Week 38 | 1972 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 211.5 |
| SHP611 30 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of SHP611 | Week 38 | 6156 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 3904.5 |
| SHP611 30 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of SHP611 | Baseline | 8738 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 3106.4 |
| SHP611 100 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of SHP611 | Baseline | 15022 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 10755.2 |
| SHP611 100 mg (Process A) | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of SHP611 | Week 38 | 24820 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 16954.3 |
| SHP611 100 mg (Process B) | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of SHP611 | Baseline | 16288 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 10691.4 |
| SHP611 100 mg (Process B) | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of SHP611 | Week 38 | 29219 hour * nanogram per milliliter (h*ng/mL) | Standard Deviation 21261.5 |
Secondary
Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40
The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 4 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (ABC) (a composite of the other 4 domain). Items in each domain are rated as either 0 (does not), 1(sometimes) or 2(independently) performs a given behavior or skill. The 4 domain standard scores range from 20-160 and higher scores indicate a higher level of functioning. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160) and higher scores indicate a higher level of functioning. A positive change value indicates improvement in adaptive functioning.
Time frame: Baseline, Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery. Participants from SHP611 10 mg and SHP611 30 mg were excluded from the analysis. Since, analysis was planned for participants received SHP611 100 mg with different manufacturing processes (Process A and B).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP611 10 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Adaptive Behavior CSS(Baseline) | 43.0 Score on a scale | — |
| SHP611 10 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Communication(Week 40) | -10.0 Score on a scale | — |
| SHP611 10 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Daily Living Skills(Baseline) | 49.0 Score on a scale | Standard Deviation 1.41 |
| SHP611 10 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Daily Living Skills(Week 40) | -4.0 Score on a scale | Standard Deviation 5.66 |
| SHP611 10 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Socialization(Baseline) | 50.0 Score on a scale | Standard Deviation 1.41 |
| SHP611 10 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Motor Skills(Baseline) | 31.0 Score on a scale | Standard Deviation 0 |
| SHP611 10 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Motor Skills(Week 40) | 6.0 Score on a scale | Standard Deviation 16.97 |
| SHP611 10 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Adaptive Behavior CSS(Week 40) | -5.0 Score on a scale | — |
| SHP611 10 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Communication(Baseline) | 52.0 Score on a scale | — |
| SHP611 10 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Socialization(Week 40) | -0.5 Score on a scale | Standard Deviation 0.71 |
| SHP611 30 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Socialization(Baseline) | 86.0 Score on a scale | Standard Deviation 3.61 |
| SHP611 30 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Motor Skills(Week 40) | -43.3 Score on a scale | Standard Deviation 23.18 |
| SHP611 30 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Communication(Week 40) | -25.0 Score on a scale | Standard Deviation 18.19 |
| SHP611 30 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Adaptive Behavior CSS(Baseline) | 84.0 Score on a scale | Standard Deviation 10.54 |
| SHP611 30 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Daily Living Skills(Baseline) | 80.3 Score on a scale | Standard Deviation 9.02 |
| SHP611 30 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Communication(Baseline) | 97.3 Score on a scale | Standard Deviation 2.52 |
| SHP611 30 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Daily Living Skills(Week 40) | -27.0 Score on a scale | Standard Deviation 19.47 |
| SHP611 30 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Adaptive Behavior CSS(Week 40) | -25.3 Score on a scale | Standard Deviation 16.44 |
| SHP611 30 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Socialization(Week 40) | -18.0 Score on a scale | Standard Deviation 17.09 |
| SHP611 30 mg (Process A) | Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40 | Motor Skills(Baseline) | 83.7 Score on a scale | Standard Deviation 24.83 |
Secondary
Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40
COMFORT questionnaire was used to assess health status and the impact of disease on the ability of participants with MLD to carry out activities of daily life. The questionnaire was organized by 8 domains (ie, personal care; positioning, transfer, or mobility; eating; pain and discomfort during the day; sleep; emotions; communication; and play and leisure activities). The COMFORT scores range from 0 to 100, with higher scores indicating a decline in the functioning.
Time frame: Baseline, Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery. Participants from SHP611 10 mg and SHP611 30 mg were excluded from the analysis. Since, analysis was planned for participants received SHP611 100 mg with different manufacturing processes (Process A and B).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Pain and discomfort during the day (Week 40) | 13.5 Score on a scale | Standard Deviation 15.23 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Communication (Week 40) | 24.7 Score on a scale | Standard Deviation 26.81 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Eating difficulty (Week 40) | 25.1 Score on a scale | Standard Deviation 22.44 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Personal care (Baseline) | 48.0 Score on a scale | Standard Deviation 21.26 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Emotions (Baseline) | 60.0 Score on a scale | Standard Deviation 9.13 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Personal care (Week 40) | 18.1 Score on a scale | Standard Deviation 37.94 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Emotions (Week 40) | -15.0 Score on a scale | Standard Deviation 21.57 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Pain and discomfort during the day (Baseline) | 16.6 Score on a scale | Standard Deviation 10.16 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Positioning, transfer or mobility (Baseline) | 42.2 Score on a scale | Standard Deviation 19.44 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Play and leisure activities (Baseline) | 46.0 Score on a scale | Standard Deviation 19.81 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Positioning, transfer or mobility (Week 40) | 6.7 Score on a scale | Standard Deviation 21.82 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Eating difficulty (Baseline) | 21.1 Score on a scale | Standard Deviation 22.94 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Sleep (Baseline) | 11.9 Score on a scale | Standard Deviation 5.52 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Play and leisure activities (Week 40) | 1.0 Score on a scale | Standard Deviation 28.15 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Sleep (Week 40) | 6.8 Score on a scale | Standard Deviation 17.08 |
| SHP611 10 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Communication (Baseline) | 27.3 Score on a scale | Standard Deviation 13.27 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Sleep (Week 40) | 4.5 Score on a scale | Standard Deviation 15.6 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Communication (Baseline) | 16.9 Score on a scale | Standard Deviation 8.65 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Communication (Week 40) | 21.4 Score on a scale | Standard Deviation 20.92 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Emotions (Week 40) | -1.4 Score on a scale | Standard Deviation 6.27 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Pain and discomfort during the day (Baseline) | 6.9 Score on a scale | Standard Deviation 11.05 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Pain and discomfort during the day (Week 40) | 0.0 Score on a scale | Standard Deviation 11.74 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Personal care (Week 40) | 7.3 Score on a scale | Standard Deviation 18.95 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Play and leisure activities (Baseline) | 16.7 Score on a scale | Standard Deviation 16.33 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Play and leisure activities (Week 40) | 30.0 Score on a scale | Standard Deviation 25.88 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Eating difficulty (Baseline) | 2.4 Score on a scale | Standard Deviation 5.77 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Eating difficulty (Week 40) | 11.8 Score on a scale | Standard Deviation 10.29 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Emotions (Baseline) | 55.6 Score on a scale | Standard Deviation 12.55 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Personal care (Baseline) | 36.0 Score on a scale | Standard Deviation 17.99 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Positioning, transfer or mobility (Baseline) | 18.0 Score on a scale | Standard Deviation 18.8 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Positioning, transfer or mobility (Week 40) | 8.8 Score on a scale | Standard Deviation 13.14 |
| SHP611 30 mg (Process A) | Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40 | Sleep (Baseline) | 18.9 Score on a scale | Standard Deviation 6.52 |
Secondary
Change From Baseline in Motor Function Using Gross Motor Function Measure 88 (GMFM-88) Total Score at Week 40
The GMFM-88 was used to measure motor function. The GMFM-88 item scores were used to calculate domain-specific percent score for each of the 5 GMFM-88 dimensions (lying and rolling; sitting; crawling and kneeling; standing; walking, running, and jumping), and a total GMFM-88 (percent) score was calculated based on each dimension score. Each of the 88 items was rated on a 4-point scale: 0=does not initiate; 1=initiates; 2=partially completes; and 3=completes. The GMFM-88 total scores ranged from 0% (no mobility) to a score of 100%, that is (i.e,) the score that can be obtained by an average 5-year-old or older child with normal motor abilities.
Time frame: Baseline, Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SHP611 10 mg (Process A) | Change From Baseline in Motor Function Using Gross Motor Function Measure 88 (GMFM-88) Total Score at Week 40 | -31.9 Score on a Scale | Standard Error 8.76 |
| SHP611 30 mg (Process A) | Change From Baseline in Motor Function Using Gross Motor Function Measure 88 (GMFM-88) Total Score at Week 40 | -29.0 Score on a Scale | Standard Error 8.58 |
| SHP611 100 mg (Process A) | Change From Baseline in Motor Function Using Gross Motor Function Measure 88 (GMFM-88) Total Score at Week 40 | -19.5 Score on a Scale | Standard Error 8.54 |
| SHP611 100 mg (Process B) | Change From Baseline in Motor Function Using Gross Motor Function Measure 88 (GMFM-88) Total Score at Week 40 | -18.1 Score on a Scale | Standard Error 9.14 |
Secondary
Concentration of SHP611 in Cerebrospinal Fluid
Concentration of SHP611 in CSF was determined using validated enzyme-linked immunosorbent assay (ELISA) method.
Time frame: Baseline, 4, 8, 12, 16, 20, 24, 28, 32, 36, and 40 weeks
Population: PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP611 10 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Baseline | 280.00 Nanogram per milliliter (ng/mL) | Standard Deviation 685.857 |
| SHP611 10 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 12 | 57.50 Nanogram per milliliter (ng/mL) | Standard Deviation 57.365 |
| SHP611 10 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 28 | 525.06 Nanogram per milliliter (ng/mL) | Standard Deviation 874.71 |
| SHP611 10 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 4 | 182.93 Nanogram per milliliter (ng/mL) | Standard Deviation 165.913 |
| SHP611 10 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 24 | 132.57 Nanogram per milliliter (ng/mL) | Standard Deviation 235.783 |
| SHP611 10 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 16 | 93.83 Nanogram per milliliter (ng/mL) | Standard Deviation 147.188 |
| SHP611 10 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 8 | 85.47 Nanogram per milliliter (ng/mL) | Standard Deviation 79.316 |
| SHP611 10 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 40 | 659.15 Nanogram per milliliter (ng/mL) | Standard Deviation 1602.414 |
| SHP611 10 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 36 | 72.40 Nanogram per milliliter (ng/mL) | Standard Deviation 125.574 |
| SHP611 10 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 20 | 112.78 Nanogram per milliliter (ng/mL) | Standard Deviation 143.216 |
| SHP611 10 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 32 | 70.12 Nanogram per milliliter (ng/mL) | Standard Deviation 126.513 |
| SHP611 30 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 20 | 1364.65 Nanogram per milliliter (ng/mL) | Standard Deviation 2784.474 |
| SHP611 30 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 32 | 573.62 Nanogram per milliliter (ng/mL) | Standard Deviation 376.224 |
| SHP611 30 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 24 | 802.67 Nanogram per milliliter (ng/mL) | Standard Deviation 903.025 |
| SHP611 30 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 28 | 3274.62 Nanogram per milliliter (ng/mL) | Standard Deviation 4493.212 |
| SHP611 30 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 8 | 1854.07 Nanogram per milliliter (ng/mL) | Standard Deviation 2633.858 |
| SHP611 30 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 40 | 243.60 Nanogram per milliliter (ng/mL) | Standard Deviation 313.107 |
| SHP611 30 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 12 | 1556.17 Nanogram per milliliter (ng/mL) | Standard Deviation 1557.666 |
| SHP611 30 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 36 | 1046.05 Nanogram per milliliter (ng/mL) | Standard Deviation 1087.321 |
| SHP611 30 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 16 | 2805.68 Nanogram per milliliter (ng/mL) | Standard Deviation 3499.878 |
| SHP611 30 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 4 | 78.00 Nanogram per milliliter (ng/mL) | Standard Deviation 102.516 |
| SHP611 30 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Baseline | 0 Nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| SHP611 100 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 36 | 3917.50 Nanogram per milliliter (ng/mL) | Standard Deviation 4650.791 |
| SHP611 100 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Baseline | 0 Nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| SHP611 100 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 4 | 2935.17 Nanogram per milliliter (ng/mL) | Standard Deviation 2632.398 |
| SHP611 100 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 8 | 4171.20 Nanogram per milliliter (ng/mL) | Standard Deviation 4874.122 |
| SHP611 100 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 12 | 2310.00 Nanogram per milliliter (ng/mL) | Standard Deviation 2544.814 |
| SHP611 100 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 16 | 2395.00 Nanogram per milliliter (ng/mL) | Standard Deviation 1550.648 |
| SHP611 100 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 20 | 5182.50 Nanogram per milliliter (ng/mL) | Standard Deviation 5081.08 |
| SHP611 100 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 24 | 5402.50 Nanogram per milliliter (ng/mL) | Standard Deviation 7352.246 |
| SHP611 100 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 28 | 6273.83 Nanogram per milliliter (ng/mL) | Standard Deviation 6839.101 |
| SHP611 100 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 32 | 1831.40 Nanogram per milliliter (ng/mL) | Standard Deviation 988.294 |
| SHP611 100 mg (Process A) | Concentration of SHP611 in Cerebrospinal Fluid | Week 40 | 2931.83 Nanogram per milliliter (ng/mL) | Standard Deviation 4098.389 |
| SHP611 100 mg (Process B) | Concentration of SHP611 in Cerebrospinal Fluid | Week 20 | 4423.33 Nanogram per milliliter (ng/mL) | Standard Deviation 4195.406 |
| SHP611 100 mg (Process B) | Concentration of SHP611 in Cerebrospinal Fluid | Week 40 | 6663.75 Nanogram per milliliter (ng/mL) | Standard Deviation 7947.148 |
| SHP611 100 mg (Process B) | Concentration of SHP611 in Cerebrospinal Fluid | Week 32 | 6110.00 Nanogram per milliliter (ng/mL) | Standard Deviation 4099.5 |
| SHP611 100 mg (Process B) | Concentration of SHP611 in Cerebrospinal Fluid | Week 16 | 2606.20 Nanogram per milliliter (ng/mL) | Standard Deviation 1212.857 |
| SHP611 100 mg (Process B) | Concentration of SHP611 in Cerebrospinal Fluid | Week 12 | 2304.00 Nanogram per milliliter (ng/mL) | Standard Deviation 2155.558 |
| SHP611 100 mg (Process B) | Concentration of SHP611 in Cerebrospinal Fluid | Week 8 | 3825.00 Nanogram per milliliter (ng/mL) | Standard Deviation 2182.056 |
| SHP611 100 mg (Process B) | Concentration of SHP611 in Cerebrospinal Fluid | Week 36 | 3116.67 Nanogram per milliliter (ng/mL) | Standard Deviation 336.502 |
| SHP611 100 mg (Process B) | Concentration of SHP611 in Cerebrospinal Fluid | Week 4 | 6152.50 Nanogram per milliliter (ng/mL) | Standard Deviation 6546.986 |
| SHP611 100 mg (Process B) | Concentration of SHP611 in Cerebrospinal Fluid | Baseline | 0 Nanogram per milliliter (ng/mL) | Standard Deviation 0 |
| SHP611 100 mg (Process B) | Concentration of SHP611 in Cerebrospinal Fluid | Week 28 | 3682.58 Nanogram per milliliter (ng/mL) | Standard Deviation 4331.13 |
| SHP611 100 mg (Process B) | Concentration of SHP611 in Cerebrospinal Fluid | Week 24 | 7914.60 Nanogram per milliliter (ng/mL) | Standard Deviation 8243.114 |
Secondary
First Order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve for SHP611
Lambda z is first order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
Time frame: Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Population: PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP611 10 mg (Process A) | First Order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve for SHP611 | Week 38 | 0.0506 Per hour (/h) | — |
| SHP611 10 mg (Process A) | First Order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve for SHP611 | Baseline | 0.0934 Per hour (/h) | — |
| SHP611 30 mg (Process A) | First Order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve for SHP611 | Baseline | 0.0561 Per hour (/h) | Standard Deviation 0.019 |
| SHP611 30 mg (Process A) | First Order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve for SHP611 | Week 38 | 0.0640 Per hour (/h) | — |
| SHP611 100 mg (Process A) | First Order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve for SHP611 | Baseline | 0.0461 Per hour (/h) | Standard Deviation 0.02439 |
| SHP611 100 mg (Process B) | First Order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve for SHP611 | Week 38 | 0.0857 Per hour (/h) | Standard Deviation 0.04415 |
| SHP611 100 mg (Process B) | First Order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve for SHP611 | Baseline | 0.0607 Per hour (/h) | Standard Deviation 0.01949 |
Secondary
Maximum Observed Serum Concentration (Cmax) of SHP611
Cmax is the maximum observed serum concentration of SHP611.
Time frame: Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Population: Pharmacokinetic (PK) set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP611 10 mg (Process A) | Maximum Observed Serum Concentration (Cmax) of SHP611 | Week 38 | 157.50 Nanogram per milliliter (ng/mL) | Standard Deviation 36.062 |
| SHP611 10 mg (Process A) | Maximum Observed Serum Concentration (Cmax) of SHP611 | Baseline | 214.53 Nanogram per milliliter (ng/mL) | Standard Deviation 162.104 |
| SHP611 30 mg (Process A) | Maximum Observed Serum Concentration (Cmax) of SHP611 | Baseline | 500.83 Nanogram per milliliter (ng/mL) | Standard Deviation 260.978 |
| SHP611 30 mg (Process A) | Maximum Observed Serum Concentration (Cmax) of SHP611 | Week 38 | 275.40 Nanogram per milliliter (ng/mL) | Standard Deviation 156.329 |
| SHP611 100 mg (Process A) | Maximum Observed Serum Concentration (Cmax) of SHP611 | Week 38 | 888.75 Nanogram per milliliter (ng/mL) | Standard Deviation 225.457 |
| SHP611 100 mg (Process A) | Maximum Observed Serum Concentration (Cmax) of SHP611 | Baseline | 715.17 Nanogram per milliliter (ng/mL) | Standard Deviation 339.856 |
| SHP611 100 mg (Process B) | Maximum Observed Serum Concentration (Cmax) of SHP611 | Week 38 | 1494.83 Nanogram per milliliter (ng/mL) | Standard Deviation 1297.295 |
| SHP611 100 mg (Process B) | Maximum Observed Serum Concentration (Cmax) of SHP611 | Baseline | 799.60 Nanogram per milliliter (ng/mL) | Standard Deviation 494.452 |
Secondary
Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40
Evaluation of peripheral nerve function by ENG studies was performed to measure nerve conduction velocity (NCV), amplitude (AMP),distal latency (DL), and F-wave latency. Categorized amplitude values were assessed. Data was presented only for number of participants who reported change in amplitude greater than (\>) 0.
Time frame: Baseline, Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Knee Amplitude (Baseline) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Elbow Amplitude (Baseline) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Wrist Amplitude (Week 40) | 3 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Knee Amplitude (Week 40) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Wrist Amplitude (Baseline) | 4 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Sensory Wrist Amplitude (Week 40) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Wrist Amplitude (Baseline) | 6 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Wrist Amplitude (Week 40) | 2 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Elbow Amplitude (Baseline) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Fibular Head Amplitude (Baseline) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Elbow Amplitude (Week 40) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Fibular Head Amplitude (Week 40) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Ankle Amplitude (Baseline) | 6 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Sural Sensory B-point (Baseline) | 2 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Sural Sensory B-point (Week 40) | 2 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Ankle Amplitude (Week 40) | 4 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Ankle Amplitude (Baseline) | 4 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Elbow Amplitude (Week 40) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Ankle Amplitude (Week 40) | 2 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Sensory Wrist Amplitude (Baseline) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Fibular Head Amplitude (Week 40) | 4 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Knee Amplitude (Baseline) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Elbow Amplitude (Week 40) | 4 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Sural Sensory B-point (Baseline) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Sensory Wrist Amplitude (Baseline) | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Elbow Amplitude (Baseline) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Wrist Amplitude (Baseline) | 5 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Ankle Amplitude (Baseline) | 5 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Wrist Amplitude (Baseline) | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Elbow Amplitude (Week 40) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Ankle Amplitude (Week 40) | 5 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Ankle Amplitude (Baseline) | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Wrist Amplitude (Week 40) | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Elbow Amplitude (Baseline) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Ankle Amplitude (Week 40) | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Sural Sensory B-point (Week 40) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Fibular Head Amplitude (Baseline) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Wrist Amplitude (Week 40) | 5 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Knee Amplitude (Week 40) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Sensory Wrist Amplitude (Week 40) | 5 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Sural Sensory B-point (Week 40) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Wrist Amplitude (Week 40) | 6 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Elbow Amplitude (Week 40) | 6 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Sensory Wrist Amplitude (Baseline) | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Sensory Wrist Amplitude (Week 40) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Fibular Head Amplitude (Baseline) | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Fibular Head Amplitude (Week 40) | 5 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Ankle Amplitude (Baseline) | 5 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Ankle Amplitude (Baseline) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Ankle Amplitude (Week 40) | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Knee Amplitude (Baseline) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Knee Amplitude (Week 40) | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Wrist Amplitude (Baseline) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Wrist Amplitude (Baseline) | 5 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Elbow Amplitude (Baseline) | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Ankle Amplitude (Week 40) | 5 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Sural Sensory B-point (Baseline) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Wrist Amplitude (Week 40) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Elbow Amplitude (Baseline) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Elbow Amplitude (Week 40) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Ankle Amplitude (Week 40) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Ankle Amplitude (Baseline) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Sural Sensory B-point (Week 40) | 4 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Ankle Amplitude (Baseline) | 6 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Elbow Amplitude (Baseline) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Ankle Amplitude (Week 40) | 4 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Fibular Head Amplitude (Week 40) | 4 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Elbow Amplitude (Week 40) | 4 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Sural Sensory B-point (Baseline) | 4 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Peroneal Motor Fibular Head Amplitude (Baseline) | 6 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Wrist Amplitude (Week 40) | 5 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Wrist Amplitude (Week 40) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Sensory Wrist Amplitude (Week 40) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Wrist Amplitude (Baseline) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Knee Amplitude (Week 40) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Sensory Wrist Amplitude (Baseline) | 4 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Wrist Amplitude (Baseline) | 6 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Tibial Motor Knee Amplitude (Baseline) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Ulnar Motor Elbow Amplitude (Week 40) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40 | Median Motor Elbow Amplitude (Baseline) | 6 Participants |
Secondary
Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40
Evaluation of peripheral nerve function by ENG studies was performed to measure nerve conduction velocity (NCV), amplitude (AMP),distal latency (DL), and F-wave latency. Categorized amplitude values were assessed. Data was presented only for number of participants who reported change in distal latency \> 0. Here MMW refers to median motor wrist, APB for abductor pollicis brevis, MSW for median sensory wrist, DDL for digit distal latency, PMA for peroneal motor ankle, EDB for extensor digitorum brevis, SSB-point DL for sural sensory B-point distal latency, TMA for tibial motor ankle, abductor hallucis for AH distal latency and, UMW for ulnar motor wrist.
Time frame: Baseline, Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MMW to APB distal latency (Baseline) | 6 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | TMA to AH Distal Latency (Baseline) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | PMA to EDB Distal Latency (Baseline) | 6 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | UMW to ADM Distal Latency (Week 40) | 2 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | UMW to ADM Distal Latency (Baseline) | 4 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | PMA to EDB Distal Latency (Week 40) | 4 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MSW to DDL (Baseline) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | SS B-Point Distal Latency (Baseline) | 2 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | SS B-Point Distal Latency (Week 40) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MSW to DDL (Week 40) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MMW to APB distal latency (Week 40) | 3 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | TMA to AH Distal Latency (Week 40) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | TMA to AH Distal Latency (Baseline) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | UMW to ADM Distal Latency (Week 40) | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MMW to APB distal latency (Baseline) | 5 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MSW to DDL (Baseline) | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | TMA to AH Distal Latency (Week 40) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MSW to DDL (Week 40) | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | PMA to EDB Distal Latency (Baseline) | 5 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | SS B-Point Distal Latency (Week 40) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | PMA to EDB Distal Latency (Week 40) | 5 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | UMW to ADM Distal Latency (Baseline) | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | SS B-Point Distal Latency (Baseline) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MMW to APB distal latency (Week 40) | 5 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MSW to DDL (Week 40) | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MMW to APB distal latency (Baseline) | 5 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MMW to APB distal latency (Week 40) | 6 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | PMA to EDB Distal Latency (Week 40) | 5 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | SS B-Point Distal Latency (Baseline) | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | TMA to AH Distal Latency (Baseline) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | UMW to ADM Distal Latency (Week 40) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MSW to DDL (Baseline) | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | PMA to EDB Distal Latency (Baseline) | 5 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | SS B-Point Distal Latency (Week 40) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | TMA to AH Distal Latency (Week 40) | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | UMW to ADM Distal Latency (Baseline) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | PMA to EDB Distal Latency (Week 40) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | PMA to EDB Distal Latency (Baseline) | 6 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MMW to APB distal latency (Baseline) | 6 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | SS B-Point Distal Latency (Week 40) | 4 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MSW to DDL (Week 40) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MSW to DDL (Baseline) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | UMW to ADM Distal Latency (Baseline) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | UMW to ADM Distal Latency (Week 40) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | TMA to AH Distal Latency (Week 40) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | MMW to APB distal latency (Week 40) | 5 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | TMA to AH Distal Latency (Baseline) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40 | SS B-Point Distal Latency (Baseline) | 3 Participants |
Secondary
Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40
Evaluation of peripheral nerve function by ENG studies was performed to measure nerve conduction velocity (NCV), amplitude (AMP),distal latency (DL), and F-wave latency. Categorized nerve conduction velocity values were assessed. Data was presented only for number of participants who reported change in nerve conduction velocity \> 0. Here MME refers to median motor elbow, WCV for wrist conduction velocity, PMA for peroneal motor ankle, FHCV to fibular head conduction velocity, TMA for tibial motor ankle, KCV for knee conduction velocity and UME for ulnar motor elbow,
Time frame: Baseline, Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | MME to WCV (Baseline) | 6 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | PMA to FHCV (Baseline) | 6 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | PMA to FHCV (Week 40) | 4 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | TMA to KCV (Week 40) | 2 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | UME to WCV (Baseline) | 4 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | UME to WCV (Week 40) | 2 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | MME to WCV (Week 40) | 3 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | TMA to KCV (Baseline) | 4 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | PMA to FHCV (Baseline) | 6 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | MME to WCV (Week 40) | 5 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | UME to WCV (Baseline) | 4 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | TMA to KCV (Week 40) | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | MME to WCV (Baseline) | 6 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | PMA to FHCV (Week 40) | 5 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | UME to WCV (Week 40) | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | TMA to KCV (Baseline) | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | UME to WCV (Week 40) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | MME to WCV (Baseline) | 6 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | PMA to FHCV (Baseline) | 6 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | TMA to KCV (Week 40) | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | TMA to KCV (Baseline) | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | UME to WCV (Baseline) | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | PMA to FHCV (Week 40) | 5 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | MME to WCV (Week 40) | 6 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | MME to WCV (Baseline) | 6 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | TMA to KCV (Baseline) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | PMA to FHCV (Week 40) | 4 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | TMA to KCV (Week 40) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | UME to WCV (Baseline) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | UME to WCV (Week 40) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | MME to WCV (Week 40) | 5 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40 | PMA to FHCV (Baseline) | 6 Participants |
Secondary
Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40
The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. FEES for texture utilized was evaluated. Data was presented only for the shifts observed.
Time frame: Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Solids | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Puree Texture | 3 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Thin Liquids | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Thickened Liquids | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Solids | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Thin Liquids | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Thickened Liquids | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Puree Texture | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Thickened Liquids | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Thickened Liquids | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Puree Texture | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Solids | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Puree Texture | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Thin Liquids | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Solids | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Thin Liquids | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Solids | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Solids | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Thin Liquids | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Puree Texture | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Thickened Liquids | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Puree Texture | 4 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Puree Texture | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Thin Liquids | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Solids | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Solids | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Thin Liquids | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Thin Liquids | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Thickened Liquids | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Thickened Liquids | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Puree Texture | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Thickened Liquids | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Thickened Liquids | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Thin Liquids | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Thickened Liquids | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Puree Texture | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Solids | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Thin Liquids | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Thickened Liquids | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Puree Texture | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Solids | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Thin Liquids | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Thickened Liquids | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Puree Texture | 4 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Solids | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Thin Liquids | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Puree Texture | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Solids | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Puree Texture | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Solids | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Puree Texture | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Thin Liquids | 4 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Thin Liquids | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Thickened Liquids | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Thin Liquids | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Solids | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Thickened Liquids | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Puree Texture | 4 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thin Liquids to Thickened Liquids | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Thickened Liquids | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Solids to Solids | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Puree Texture | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Puree Texture to Thin Liquids | 2 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40 | Thickened Liquids to Solids | 0 Participants |
Secondary
Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40
The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. FEES for aspiration risk was assessed. Data was presented only for the shifts observed. Here TL refers to thin liquids, THL refers to thickened liquids, PT refers to puree texture, WCC refers to with cough and clearance and WCNC refers to with cough and no clearance.
Time frame: Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (TL) | 2 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (THL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Moderate to Moderate (PT) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to High (PT) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (Solids) | NA Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (PT) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to High (TL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Moderate to Low (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Moderate to Low (PT) | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (PT) | 3 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to High (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (THL) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to High (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Moderate to Moderate (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (Solids) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (TL) | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to High (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Moderate to Low (PT) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (Solids) | NA Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (TL) | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Moderate to Moderate (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to High (TL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (THL) | 3 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (PT) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (Solids) | NA Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to High (TL) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to High (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Moderate to Low (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (TL) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (THL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Low to Low (PT) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40 | Moderate to Moderate (PT) | 0 Participants |
Secondary
Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40
The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. FEES for dose residue clear after subsequent swallowing was assessed. Data was presented only for the shifts observed. Here TL refers to thin liquids, THL refers to thickened liquids, PT refers to puree texture.
Time frame: Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (Solids) | NA Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Yes (TL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to No (PT) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Normal (THL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Normal (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (TL) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (PT) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to No (PT) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Normal (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to No (TL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Yes (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | No to Yes (TL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (THL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | No to Normal (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Normal (TL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | No to No (TL) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Yes (THL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | No to No (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Yes (THL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (THL) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Normal (PT) | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to No (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (Solids) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (PT) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Normal (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Yes (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Normal (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (TL) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Normal (THL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to No (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | No to Yes (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | No to Normal (PT) | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to No (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Yes (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (THL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to No (TL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Yes (THL) | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to No (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Normal (TL) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Yes (TL) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (TL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | No to Yes (TL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | No to No (TL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Normal (THL) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Normal (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Yes (PT) | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to No (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Normal (PT) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | No to Normal (PT) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (Solids) | NA Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | No to Normal (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to No (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (TL) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Yes (TL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Yes (THL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Normal (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to No (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to No (TL) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (PT) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Yes (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Normal (TL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (THL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Normal to Normal (PT) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Normal (THL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | Yes to Yes (Solids) | NA Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | No to No (TL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40 | No to Yes (TL) | 1 Participants |
Secondary
Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40
The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. Feeding assessment for aspiration through vocal cords were assessed. Data was presented only for the shifts observed. Here TL refers to thin liquids, THL refers to thickened liquids, PT refers to puree texture, WCC refers to with cough and clearance and WCNC refers to with cough and no clearance.
Time frame: Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Normal to Normal (THL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (Solids) | NA Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Normal to Normal (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Without Cough to Normal (THL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (THL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to Normal (THL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCNC to Normal (PT) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Normal to Normal (TL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Without Cough to Normal (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Without Cough to Without Cough (TL) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Normal to Normal (PT) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Normal to Normal (THL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCNC to Normal (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to Normal (THL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Without Cough to Without Cough (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Without Cough to Normal (THL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Normal to Normal (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (THL) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (Solids) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (PT) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (TL) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Without Cough to Normal (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (THL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to Normal (THL) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Without Cough to Normal (PT) | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCNC to Normal (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Normal to Normal (TL) | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (TL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Normal to Normal (THL) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Without Cough to Normal (THL) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Without Cough to Without Cough (TL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Normal to Normal (PT) | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (Solids) | NA Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (THL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Normal to Normal (THL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (TL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (Solids) | NA Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Normal to Normal (PT) | 2 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Normal to Normal (TL) | 3 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to WCC (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCNC to Normal (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Without Cough to Normal (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | WCC to Normal (THL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Without Cough to Normal (THL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40 | Without Cough to Without Cough (TL) | 0 Participants |
Secondary
Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40
The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. Feeding assessment for laryngeal penetration was assessed. Data was presented only for the shifts observed. Here TL refers to thin liquids, THL refers to thickened liquids, PT refers to puree texture, WCC refers to with cough and clearance and WCNC refers to with cough and no clearance.
Time frame: Week 40
Population: Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to WCC (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to Normal (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to Normal (THL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCNC to Without Cough (PT) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (THL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to Normal (THL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to Without Cough (TL) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to Without Cough (TL) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (TL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCNC to Normal (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to Without Cough (TL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to Normal (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to WCC (PT) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (Solids) | NA Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to Normal (PT) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to WCNC (PT) | 1 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to WCC (THL) | 0 Participants |
| SHP611 10 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to Normal (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to WCC (THL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to Normal (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to Without Cough (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to Without Cough (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (TL) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to Normal (THL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to Normal (THL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (THL) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to Normal (PT) | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to WCC (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to WCNC (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to WCC (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to Normal (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (PT) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCNC to Normal (PT) | 1 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCNC to Without Cough (PT) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (Solids) | 2 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to Normal (TL) | 0 Participants |
| SHP611 30 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to Without Cough (TL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to WCC (THL) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to WCC (PT) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to WCNC (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (TL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to Normal (PT) | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to WCC (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to Without Cough (TL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (Solids) | NA Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to Normal (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to Without Cough (TL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to Without Cough (TL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to Normal (TL) | 2 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCNC to Normal (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to Normal (THL) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to Normal (THL) | 1 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (THL) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCNC to Without Cough (PT) | 0 Participants |
| SHP611 100 mg (Process A) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to Normal (PT) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to Normal (THL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to Normal (PT) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to WCC (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (TL) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to Normal (TL) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to WCNC (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCNC to Without Cough (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (THL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to Normal (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to Without Cough (TL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to Without Cough (TL) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCNC to Normal (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to WCC (PT) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to Normal (THL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to WCC (Solids) | NA Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Normal to WCC (THL) | 0 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | WCC to Normal (PT) | 1 Participants |
| SHP611 100 mg (Process B) | Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40 | Without Cough to Without Cough (TL) | 0 Participants |
Secondary
Terminal Elimination Half Life (t1/2) of SHP611
The t1/2 is the time in hours required for the concentration of the drug to reach half of its original value.
Time frame: Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Population: PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP611 10 mg (Process A) | Terminal Elimination Half Life (t1/2) of SHP611 | Baseline | 7.42 Hour (h) | — |
| SHP611 10 mg (Process A) | Terminal Elimination Half Life (t1/2) of SHP611 | Week 38 | 13.70 Hour (h) | — |
| SHP611 30 mg (Process A) | Terminal Elimination Half Life (t1/2) of SHP611 | Week 38 | 10.83 Hour (h) | — |
| SHP611 30 mg (Process A) | Terminal Elimination Half Life (t1/2) of SHP611 | Baseline | 13.60 Hour (h) | Standard Deviation 4.932 |
| SHP611 100 mg (Process A) | Terminal Elimination Half Life (t1/2) of SHP611 | Baseline | 17.47 Hour (h) | Standard Deviation 9.238 |
| SHP611 100 mg (Process B) | Terminal Elimination Half Life (t1/2) of SHP611 | Baseline | 12.34 Hour (h) | Standard Deviation 4.373 |
| SHP611 100 mg (Process B) | Terminal Elimination Half Life (t1/2) of SHP611 | Week 38 | 9.32 Hour (h) | Standard Deviation 4.8 |
Secondary
Time to Reach Maximum Observed Drug Concentration (Tmax) of SHP611 in Plasma
Tmax is the time to reach maximum observed drug concentration of SHP611 during a dosing interval.
Time frame: Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Population: PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP611 10 mg (Process A) | Time to Reach Maximum Observed Drug Concentration (Tmax) of SHP611 in Plasma | Baseline | 7.06 Hour (h) | Standard Deviation 1.086 |
| SHP611 10 mg (Process A) | Time to Reach Maximum Observed Drug Concentration (Tmax) of SHP611 in Plasma | Week 38 | 5.08 Hour (h) | Standard Deviation 1.45 |
| SHP611 30 mg (Process A) | Time to Reach Maximum Observed Drug Concentration (Tmax) of SHP611 in Plasma | Week 38 | 11.22 Hour (h) | Standard Deviation 1.78 |
| SHP611 30 mg (Process A) | Time to Reach Maximum Observed Drug Concentration (Tmax) of SHP611 in Plasma | Baseline | 6.81 Hour (h) | Standard Deviation 3.462 |
| SHP611 100 mg (Process A) | Time to Reach Maximum Observed Drug Concentration (Tmax) of SHP611 in Plasma | Week 38 | 18.16 Hour (h) | Standard Deviation 11.661 |
| SHP611 100 mg (Process A) | Time to Reach Maximum Observed Drug Concentration (Tmax) of SHP611 in Plasma | Baseline | 5.97 Hour (h) | Standard Deviation 4.802 |
| SHP611 100 mg (Process B) | Time to Reach Maximum Observed Drug Concentration (Tmax) of SHP611 in Plasma | Week 38 | 7.02 Hour (h) | Standard Deviation 3.824 |
| SHP611 100 mg (Process B) | Time to Reach Maximum Observed Drug Concentration (Tmax) of SHP611 in Plasma | Baseline | 9.61 Hour (h) | Standard Deviation 8.344 |
Secondary
Total Body Clearance (CL/F) After Intrathecal Administration of SHP611
CL/F was defined as the total body clearance of the drug for extravascular administration divided by the fraction of dose absorbed.
Time frame: Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Population: PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP611 10 mg (Process A) | Total Body Clearance (CL/F) After Intrathecal Administration of SHP611 | Baseline | 2.30 Liter per hour (L/h) | — |
| SHP611 10 mg (Process A) | Total Body Clearance (CL/F) After Intrathecal Administration of SHP611 | Week 38 | 3.61 Liter per hour (L/h) | — |
| SHP611 30 mg (Process A) | Total Body Clearance (CL/F) After Intrathecal Administration of SHP611 | Week 38 | 3.13 Liter per hour (L/h) | — |
| SHP611 30 mg (Process A) | Total Body Clearance (CL/F) After Intrathecal Administration of SHP611 | Baseline | 3.25 Liter per hour (L/h) | Standard Deviation 1.185 |
| SHP611 100 mg (Process A) | Total Body Clearance (CL/F) After Intrathecal Administration of SHP611 | Baseline | 4.60 Liter per hour (L/h) | Standard Deviation 0.878 |
| SHP611 100 mg (Process B) | Total Body Clearance (CL/F) After Intrathecal Administration of SHP611 | Baseline | 5.28 Liter per hour (L/h) | Standard Deviation 3.179 |
| SHP611 100 mg (Process B) | Total Body Clearance (CL/F) After Intrathecal Administration of SHP611 | Week 38 | 2.08 Liter per hour (L/h) | Standard Deviation 0.295 |
Secondary
Volume of Distribution (Vz/F) After Intrathecal Administration of SHP611
Volume of distribution was associated with the terminal slope following extravascular administration of SHP611 divided by the fraction of dose absorbed.
Time frame: Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Population: PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP611 10 mg (Process A) | Volume of Distribution (Vz/F) After Intrathecal Administration of SHP611 | Week 38 | 71.41 Liter (L) | — |
| SHP611 10 mg (Process A) | Volume of Distribution (Vz/F) After Intrathecal Administration of SHP611 | Baseline | 24.58 Liter (L) | — |
| SHP611 30 mg (Process A) | Volume of Distribution (Vz/F) After Intrathecal Administration of SHP611 | Week 38 | 48.88 Liter (L) | — |
| SHP611 30 mg (Process A) | Volume of Distribution (Vz/F) After Intrathecal Administration of SHP611 | Baseline | 69.97 Liter (L) | Standard Deviation 49.912 |
| SHP611 100 mg (Process A) | Volume of Distribution (Vz/F) After Intrathecal Administration of SHP611 | Baseline | 121.88 Liter (L) | Standard Deviation 83.481 |
| SHP611 100 mg (Process B) | Volume of Distribution (Vz/F) After Intrathecal Administration of SHP611 | Week 38 | 28.95 Liter (L) | Standard Deviation 18.345 |
| SHP611 100 mg (Process B) | Volume of Distribution (Vz/F) After Intrathecal Administration of SHP611 | Baseline | 106.95 Liter (L) | Standard Deviation 100.026 |