Amyloidosis, Familial Amyloid Polyneuropathy, FAP, Transthyretin, TTR
Conditions
Keywords
FAP, Familial Amyloid Polyneuropathy, TTR, Transthyretin, Amyloidosis
Brief summary
The purpose of this study is to evaluate the efficacy and safety of inotersen given for 65 weeks in participants with Familial Amyloid Polyneuropathy (FAP).
Detailed description
FAP is a rare, hereditary disease caused by mutations in the transthyretin (TTR) protein. TTR is made by the liver and secreted into the blood. TTR mutations cause it to misfold and deposit in multiple organs causing FAP. Inotersen (also known as ISIS 420915) is an antisense drug that was designed to decrease the amount of mutant and normal TTR made by the liver. It is predicted that decreasing the amount of TTR protein would result in a decrease in the formation of TTR deposits, and thus slow or stop disease progression. The purpose of this study is to determine if inotersen can slow or stop the nerve damage caused by TTR deposits. This study will enroll late Stage 1 and early Stage 2 FAP participants. Participants will receive either inotersen or placebo for 65 weeks.
Interventions
DRUGInotersen
DRUGPlacebo
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 82 Years
Healthy volunteers
No
Inclusion criteria
* Stage 1 and Stage 2 FAP participants with the following: 1. NIS score within protocol criteria 2. Documented transthyretin variant by genotyping 3. Documented amyloid deposit by biopsy * Females of child-bearing potential must use appropriate contraception and be non-pregnant and non-lactating. Males engaging in relations of child-bearing potential are to use appropriate contraception
Exclusion criteria
* Low Retinol level at screen * Karnofsky performance status ≤50 * Poor Renal function * Known type 1 or type 2 diabetes mellitus * Other causes of sensorimotor or autonomic neuropathy (for example, autoimmune disease) * If previously treated with Vyndaqel®, will need to have discontinued treatment for 2 weeks prior to Study Day 1. If previously treated with Diflunisal, will need to have discontinued treatment for 3 days prior to Study Day 1 * Previous treatment with any oligonucleotide or siRNA within 12 months of screening * Prior liver transplant or anticipated liver transplant within 1 year of screening * New York Heart Association (NYHA) functional classification of ≥3 * Acute Coronary Syndrome or major surgery within 3 months of screening * Known Primary or Leptomeningeal Amyloidosis * Anticipated survival less than 2 years * Any other conditions in the opinion of the investigator which interfere with the participant participating in or completing the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66 | Baseline and Week 66 | The mNIS+7 composite score is a measure of neurologic impairment that evaluates muscle weakness, sensation, reflexes, nerve conduction, and autonomic function. The mNIS+7 Composite Score has a range of -22.32 to 346.32 and a higher mNIS+7 composite score indicates lower function. |
| Change From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66 | Baseline and Week 66 | The Norfolk QoL-DN score is a measure of physical function/large fiber neuropathy, symptoms, activities of daily living, small fiber neuropathy, and autonomic neuropathy. The Norfolk QoL-DN total score has a range of -4 to 136, and a higher Norfolk QoL-DN score indicates poorer QoL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65 | Week 65 | — |
| Inotersen Plasma Clearance At Steady State (CLss/F) At Week 65 | Week 65 | — |
| Maximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65 | Week 65 | — |
| Time To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65 | Week 65 | — |
| Change From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66 | Baseline and Week 66 | The Norfolk QoL-DN symptoms score is a sub-score of the total Norfolk QoL-DN Questionnaire. The Norfolk QoL-DN symptoms domain score has a range of 0-32, and a higher Norfolk QoL-DN score indicates poorer QoL. |
| Change From Baseline In The Norfolk QoL-DN Questionnaire Physical Functioning/Large Fiber Neuropathy Domain Score at Week 66 | Baseline and Week 66 | The Norfolk QoL-DN physical functioning/large fiber neuropathy domain score is a sub-score of the total Norfolk QoL-DN Questionnaire. The Norfolk QoL-DN physical function/large fiber neuropathy domain score has a range of -4 to 56, and a higher Norfolk QoL-DN domain score indicates poorer QoL. |
| Change From Baseline In Modified Body Mass Index (mBMI) at Week 65 | Baseline and Week 65 | The mBMI is the BMI multiplied by the serum albumin g/L |
| Area Under The Plasma Concentration-time Curve From 0 To 24 Hours (AUC[0-24hr]) Of Inotersen At Week 65 | Week 65 | — |
| Change From Baseline in Neuropathy Impairment Score (NIS) at Week 66 | Baseline and Week 66 | The NIS score is a measure of neurologic impairment. The NIS Score has a range of 0 to 244 and a higher NIS score indicates lower function. |
| Change From Baseline in Modified +7 at Week 66 | Baseline and Week 66 | The Modified +7 score is a version of the NIS score that is a measure of neurologic impairment. The Modified +7 Score has a range of -22.32 to 102.32 and a higher NIS score indicates lower function. |
| Change From Baseline in NIS+7 at Week 66 | Baseline and Week 66 | The NIS+7 score is a version of the NIS score that is a measure of neurologic impairment. The NIS+7 Score has a range of -26.04 to 270.04 and a higher NIS score indicates lower function. |
| Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) at Week 65 in the CM-ECHO Set | Baseline and Week 65 | GLS by ECHO is a measure of cardiac systolic function |
| Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup | Baseline and Week 65 | GLS by ECHO is a measure of cardiac systolic function |
| Change From Baseline in Transthyretin (TTR) Level at Week 65 | Baseline and Week 65 | — |
| Change From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65 | Baseline and Week 65 | — |
| Change From Baseline In Body Mass Index (BMI) at Week 65 | Baseline and Week 65 | — |
| Area Under The Plasma Concentration-time Curve From 0 To 168 Hours (AUC[0-168hr]) Of Inotersen At Week 65 | Week 65 | — |
Countries
Argentina, Brazil, France, Germany, Italy, New Zealand, Portugal, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
Participants randomized: 113 inotersen and 60 placebo; received study treatment: 112 inotersen and 60 placebo. This study consisted of a 65-week Treatment Period, 1-week End of Treatment (EOT) Period, and a 6-month Post-treatment Evaluation Period.
Participants by arm
| Arm | Count |
|---|---|
| Inotersen Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks. | 112 |
| Placebo Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks. | 60 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse event or SAE | 16 | 1 |
| Overall Study | Disease progression | 2 | 3 |
| Overall Study | Ineligibility | 1 | 0 |
| Overall Study | Liver transplant | 1 | 0 |
| Overall Study | Sponsor's decision | 2 | 0 |
| Overall Study | Stopping rule met | 2 | 1 |
| Overall Study | Voluntary withdrawal | 2 | 3 |
Baseline characteristics
| Characteristic | Placebo | Total | Inotersen |
|---|---|---|---|
| Age, Continuous | 59.5 years STANDARD_DEVIATION 14.05 | 59.2 years STANDARD_DEVIATION 13.04 | 59.0 years STANDARD_DEVIATION 12.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 24 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 148 Participants | 95 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Participants diagnosed with hATTR-CM No | 38 Participants | 105 Participants | 67 Participants |
| Participants diagnosed with hATTR-CM Yes | 22 Participants | 67 Participants | 45 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 53 Participants | 158 Participants | 105 Participants |
| Race/Ethnicity, Customized White & Grayish-Brown | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Female | 19 Participants | 54 Participants | 35 Participants |
| Sex: Female, Male Male | 41 Participants | 118 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 112 | 0 / 60 |
| other Total, other adverse events | 110 / 112 | 60 / 60 |
| serious Total, serious adverse events | 36 / 112 | 13 / 60 |
Outcome results
Primary
Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66
The mNIS+7 composite score is a measure of neurologic impairment that evaluates muscle weakness, sensation, reflexes, nerve conduction, and autonomic function. The mNIS+7 Composite Score has a range of -22.32 to 346.32 and a higher mNIS+7 composite score indicates lower function.
Time frame: Baseline and Week 66
Population: The full analysis set included all randomized participants who received at least 1 injection of study drug (inotersen or placebo) and who had a Baseline and at least 1 post-Baseline efficacy assessment for the mNIS+7 score or Norfolk QoL-DN questionnaire total score. Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66 | 4.16 Scores on a Scale | Standard Deviation 15.672 |
| Placebo | Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66 | 23.89 Scores on a Scale | Standard Deviation 24.19 |
p-value: 4e-895% CI: [-26.43, -13.03]MMRM
Primary
Change From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66
The Norfolk QoL-DN score is a measure of physical function/large fiber neuropathy, symptoms, activities of daily living, small fiber neuropathy, and autonomic neuropathy. The Norfolk QoL-DN total score has a range of -4 to 136, and a higher Norfolk QoL-DN score indicates poorer QoL.
Time frame: Baseline and Week 66
Population: The full analysis set included all randomized participants who received at least 1 injection of study drug (inotersen or placebo) and who had a Baseline and at least 1 post-Baseline efficacy assessment for the mNIS+7 score or Norfolk QoL-DN questionnaire total score. Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66 | -0.08 Scores on a Scale | Standard Deviation 18.967 |
| Placebo | Change From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66 | 10.77 Scores on a Scale | Standard Deviation 21.134 |
p-value: 0.000695% CI: [-18.29, -5.06]MMRM
Secondary
Area Under The Plasma Concentration-time Curve From 0 To 168 Hours (AUC[0-168hr]) Of Inotersen At Week 65
Time frame: Week 65
Population: The PK Set was defined as all randomized participants who received at least 1 dose of active study drug (inotersen) and had at least 1 evaluable PK sample collected and analyzed with a reportable result.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Area Under The Plasma Concentration-time Curve From 0 To 168 Hours (AUC[0-168hr]) Of Inotersen At Week 65 | 98.9 ug*hr/mL | Standard Deviation 33.5 |
| Placebo | Area Under The Plasma Concentration-time Curve From 0 To 168 Hours (AUC[0-168hr]) Of Inotersen At Week 65 | 103.0 ug*hr/mL | Standard Deviation 88.2 |
Secondary
Area Under The Plasma Concentration-time Curve From 0 To 24 Hours (AUC[0-24hr]) Of Inotersen At Week 65
Time frame: Week 65
Population: The PK Set was defined as all randomized participants who received at least 1 dose of active study drug (inotersen) and had at least 1 evaluable PK sample collected and analyzed with a reportable result.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Area Under The Plasma Concentration-time Curve From 0 To 24 Hours (AUC[0-24hr]) Of Inotersen At Week 65 | 93.1 ug*hr/mL | Standard Deviation 30.7 |
| Placebo | Area Under The Plasma Concentration-time Curve From 0 To 24 Hours (AUC[0-24hr]) Of Inotersen At Week 65 | 92.4 ug*hr/mL | Standard Deviation 77.3 |
Secondary
Change From Baseline In Body Mass Index (BMI) at Week 65
Time frame: Baseline and Week 65
Population: The full analysis set included all randomized participants who received at least 1 injection of study drug (inotersen or placebo) and who had a Baseline and at least 1 post-Baseline efficacy assessment for the mNIS+7 score or Norfolk QoL-DN questionnaire total score. Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline In Body Mass Index (BMI) at Week 65 | -0.24 kg/m^2 | Standard Deviation 1.521 |
| Placebo | Change From Baseline In Body Mass Index (BMI) at Week 65 | -0.87 kg/m^2 | Standard Deviation 1.202 |
Secondary
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) at Week 65 in the CM-ECHO Set
GLS by ECHO is a measure of cardiac systolic function
Time frame: Baseline and Week 65
Population: The CM-ECHO Set includes the subset of the Randomized Set who had a diagnosis of TTR cardiomyopathy at study entry but are not in the ECHO subgroup, plus participants who qualified to participate in the ECHO subgroup (whether consented or not). Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) at Week 65 in the CM-ECHO Set | 0.69 Percent Change | Standard Deviation 3.134 |
| Placebo | Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) at Week 65 in the CM-ECHO Set | 0.46 Percent Change | Standard Deviation 2.702 |
Secondary
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup
GLS by ECHO is a measure of cardiac systolic function
Time frame: Baseline and Week 65
Population: The full analysis set included all randomized participants who received at least 1 injection of study drug (inotersen or placebo) and who had a Baseline and at least 1 post-Baseline efficacy assessment for the mNIS+7 score or Norfolk QoL-DN questionnaire total score. Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup | 0.25 Percent Change | Standard Deviation 3.163 |
| Placebo | Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup | 1.05 Percent Change | Standard Deviation 2.745 |
Secondary
Change From Baseline in Modified +7 at Week 66
The Modified +7 score is a version of the NIS score that is a measure of neurologic impairment. The Modified +7 Score has a range of -22.32 to 102.32 and a higher NIS score indicates lower function.
Time frame: Baseline and Week 66
Population: The full analysis set included all randomized participants who received at least 1 injection of study drug (inotersen or placebo) and who had a Baseline and at least 1 post-Baseline efficacy assessment for the mNIS+7 score or Norfolk QoL-DN questionnaire total score. Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline in Modified +7 at Week 66 | -0.31 Scores on a Scale | Standard Deviation 11.134 |
| Placebo | Change From Baseline in Modified +7 at Week 66 | 6.60 Scores on a Scale | Standard Deviation 12.77 |
Secondary
Change From Baseline In Modified Body Mass Index (mBMI) at Week 65
The mBMI is the BMI multiplied by the serum albumin g/L
Time frame: Baseline and Week 65
Population: The full analysis set included all randomized participants who received at least 1 injection of study drug (inotersen or placebo) and who had a Baseline and at least 1 post-Baseline efficacy assessment for the mNIS+7 score or Norfolk QoL-DN questionnaire total score. Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline In Modified Body Mass Index (mBMI) at Week 65 | -73.32 kg/m^2*g/L | Standard Deviation 96.311 |
| Placebo | Change From Baseline In Modified Body Mass Index (mBMI) at Week 65 | -85.21 kg/m^2*g/L | Standard Deviation 91.259 |
Secondary
Change From Baseline in Neuropathy Impairment Score (NIS) at Week 66
The NIS score is a measure of neurologic impairment. The NIS Score has a range of 0 to 244 and a higher NIS score indicates lower function.
Time frame: Baseline and Week 66
Population: The full analysis set included all randomized participants who received at least 1 injection of study drug (inotersen or placebo) and who had a Baseline and at least 1 post-Baseline efficacy assessment for the mNIS+7 score or Norfolk QoL-DN questionnaire total score. Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline in Neuropathy Impairment Score (NIS) at Week 66 | 4.47 Scores on a Scale | Standard Deviation 10.329 |
| Placebo | Change From Baseline in Neuropathy Impairment Score (NIS) at Week 66 | 17.29 Scores on a Scale | Standard Deviation 16.986 |
Secondary
Change From Baseline in NIS+7 at Week 66
The NIS+7 score is a version of the NIS score that is a measure of neurologic impairment. The NIS+7 Score has a range of -26.04 to 270.04 and a higher NIS score indicates lower function.
Time frame: Baseline and Week 66
Population: The full analysis set included all randomized participants who received at least 1 injection of study drug (inotersen or placebo) and who had a Baseline and at least 1 post-Baseline efficacy assessment for the mNIS+7 score or Norfolk QoL-DN questionnaire total score. Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline in NIS+7 at Week 66 | 5.10 Scores on a Scale | Standard Deviation 10.709 |
| Placebo | Change From Baseline in NIS+7 at Week 66 | 19.00 Scores on a Scale | Standard Deviation 16.824 |
Secondary
Change From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65
Time frame: Baseline and Week 65
Population: The full analysis set included all randomized participants who received at least 1 injection of study drug (inotersen or placebo) and who had a Baseline and at least 1 post-Baseline efficacy assessment for the mNIS+7 score or Norfolk QoL-DN questionnaire total score. Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65 | -21725.9 ug/L | Standard Deviation 9884.04 |
| Placebo | Change From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65 | -1768.7 ug/L | Standard Deviation 8027.78 |
Secondary
Change From Baseline In The Norfolk QoL-DN Questionnaire Physical Functioning/Large Fiber Neuropathy Domain Score at Week 66
The Norfolk QoL-DN physical functioning/large fiber neuropathy domain score is a sub-score of the total Norfolk QoL-DN Questionnaire. The Norfolk QoL-DN physical function/large fiber neuropathy domain score has a range of -4 to 56, and a higher Norfolk QoL-DN domain score indicates poorer QoL.
Time frame: Baseline and Week 66
Population: This endpoints only measured participants who had Stage 2 hATTR-PN in Full Analysis Set. Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline In The Norfolk QoL-DN Questionnaire Physical Functioning/Large Fiber Neuropathy Domain Score at Week 66 | 1.05 Scores on a Scale | Standard Deviation 11.924 |
| Placebo | Change From Baseline In The Norfolk QoL-DN Questionnaire Physical Functioning/Large Fiber Neuropathy Domain Score at Week 66 | 8.74 Scores on a Scale | Standard Deviation 9.689 |
Secondary
Change From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66
The Norfolk QoL-DN symptoms score is a sub-score of the total Norfolk QoL-DN Questionnaire. The Norfolk QoL-DN symptoms domain score has a range of 0-32, and a higher Norfolk QoL-DN score indicates poorer QoL.
Time frame: Baseline and Week 66
Population: This endpoint only measured participants with Stage 1 hATTR-PN in Full Analysis Set. Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66 | -1.40 Scores on a Scale | Standard Deviation 4.763 |
| Placebo | Change From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66 | 1.18 Scores on a Scale | Standard Deviation 5.27 |
Secondary
Change From Baseline in Transthyretin (TTR) Level at Week 65
Time frame: Baseline and Week 65
Population: The full analysis set included all randomized participants who received at least 1 injection of study drug (inotersen or placebo) and who had a Baseline and at least 1 post-Baseline efficacy assessment for the mNIS+7 score or Norfolk QoL-DN questionnaire total score. Participants analyzed = participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Change From Baseline in Transthyretin (TTR) Level at Week 65 | -0.1570 g/L | Standard Deviation 0.0619 |
| Placebo | Change From Baseline in Transthyretin (TTR) Level at Week 65 | -0.0146 g/L | Standard Deviation 0.0402 |
Secondary
Inotersen Plasma Clearance At Steady State (CLss/F) At Week 65
Time frame: Week 65
Population: The PK Set was defined as all randomized participants who received at least 1 dose of active study drug (inotersen) and had at least 1 evaluable PK sample collected and analyzed with a reportable result.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Inotersen Plasma Clearance At Steady State (CLss/F) At Week 65 | 3.33 L/hr | Standard Deviation 1.21 |
| Placebo | Inotersen Plasma Clearance At Steady State (CLss/F) At Week 65 | 5.46 L/hr | Standard Deviation 5.13 |
Secondary
Maximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65
Time frame: Week 65
Population: The PK Set was defined as all randomized participants who received at least 1 dose of active study drug (inotersen) and had at least 1 evaluable PK sample collected and analyzed with a reportable result.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Maximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65 | 6.76 ug/mL | Standard Deviation 1.88 |
| Placebo | Maximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65 | 11.1 ug/mL | Standard Deviation 4.8 |
Secondary
Plasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65
Time frame: Week 65
Population: The PK Set was defined as all randomized participants who received at least 1 dose of active study drug (inotersen) and had at least 1 evaluable PK sample collected and analyzed with a reportable result.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Plasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65 | 3.57 L/hr | Standard Deviation 1.32 |
| Placebo | Plasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65 | 6.14 L/hr | Standard Deviation 5.92 |
Secondary
Time To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65
Time frame: Week 65
Population: The PK Set was defined as all randomized participants who received at least 1 dose of active study drug (inotersen) and had at least 1 evaluable PK sample collected and analyzed with a reportable result.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotersen | Time To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65 | 4.14 hours | Standard Deviation 1.88 |
| Placebo | Time To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65 | 3.48 hours | Standard Deviation 0.68 |