Painful Diabetic Neuropathy
Conditions
Brief summary
This is a study investigating the effect of MEDI7352 on chronic pain in participants with painful diabetic neuropathy. The study incudes a screening period of up to 45 days and a 12-week treatment period during which MEDI7352 or placebo will be administered intravenously (IV) on 6 occasions, with each dose separated by 14 days. There will be a 6-week follow-up period. Participants will randomly be assigned to double-blind treatment with one of 4 dose levels of MEDI7352 or placebo.
Interventions
DRUGMEDI7352
Participants will receive IV infusion of MEDI7352 as stated in arm description.
OTHERPlacebo
Participants will receive IV infusion of placebo as stated in arm description.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion criteria: * Male, or postmenopausal or surgically sterile female, 18 to 80 years of age * Body mass index of ≤ 42 kg/m\^2. * Chronic painful diabetic neuropathy (PDN) persistent for 6 months or longer, not adequately controlled by standard of care treatments. * Mean pain intensity score of ≥ 4, as measured on an 11-point (0-10) numerical rating scale (NRS). * Willing and able to discontinue all non-steroidal anti-inflammatory drug (NSAID) or cyclooxygenase-2 (COX-2) analgesic therapy. * Currently be taking medication for the treatment of PDN. Participants should be taking at least one of the first-line medications (consistent with regional or local standard of care guidelines for PDN). Key
Exclusion criteria
* Presence of other clinically significant neuropathy (eg, hereditary neuropathy, inflammatory neuropathy) or other clinically significant disorder (eg, nerve compression injury) involving abnormal peripheral sensation, with an aetiology that is considered to be distinct from that of PDN, and that is likely to interfere with assessment of peripheral nerve function, as judged by the investigator. * History of osteonecrosis, rapidly progressing osteoarthritis (OA), subchondral insufficiency fractures, neurogenic arthropathy, or analgesia-induced arthropathy. * Diagnosis of clinically significant OA currently affecting a major joint in the upper extremity (shoulder, elbow, or wrist) or lower extremity (hip, knee, or ankle) or axial spine; or other degenerative disease affecting any joint in participants for whom, in the opinion of the investigator, there is an identified risk of osteonecrosis, rapidly progressing OA, subchondral insufficiency fractures, neurogenic arthropathy, or analgesia-induced arthropathy. * Chronic pain condition, other than PDN, that is likely to interfere with the evaluation of the participant's PDN pain, as judged by the investigator. * Haemoglobin A1C greater than 10.0% (\> 10.0%).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Average of Average Daily Pain Score to Week 12 | Baseline (Day -7 to Day -1, inclusive) through Week 12 | Change from baseline to Week 12 in weekly average of average daily pain score is reported. Participants assessed their perceived daily average neuropathic pain over the previous 24 hours using an 11-point numerical rating scale (NRS), with 0 representing no pain and 10 representing the worst pain imaginable. Participants were instructed to assess their average daily pain at approximately the same time every morning, and to record the response in a subject diary (electronic patient-reported outcome \[ePRO\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up) | Percentage of participants with \>= 30% and \>= 50% decrease in weekly average of average daily pain score from baseline is reported. Participants assessed their perceived daily average neuropathic pain over the previous 24 hours using an 11-point NRS, with 0 representing no pain and 10 representing the worst pain imaginable. Participants were instructed to assess their average daily pain at approximately the same time every morning, and to record the response in a subject diary (ePRO). |
| Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up) | Participants were assessed for their neuropathic pain using the Galer NPS, which included 2 descriptors of pain, including intensity and unpleasantness, and 8 descriptors that assessed specific qualities of neuropathic pain: sharp, hot, dull, cold, sensitive, itchy, deep, and surface pain. Each of these 10 dimensions had a 0 to 10 NRS in which 0 is equal to no pain and 10 equals most intense pain. Galer NPS total score (ranges from 0 to 100; with 0 and 100 representing the no and highest degree of neuropathic-like symptoms, respectively) is sum of pain intensity, pain unpleasantness, pain sharpness, pain hotness, pain dullness, pain coldness, pain sensitivity, pain itching, deep pain intensity, and surface pain intensity (all in an 11-point NRS). Change from baseline to Weeks 4, 8, 12, and 18 (follow-up) in Galer NPS total score is reported. |
| Change From Baseline in Daily Sleep Interference Scale (DSIS) | Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up) | Participants were assessed for how their neuropathic pain interferes with their sleep using the DSIS. It has an 11 point Likert response scale (0-10) that asked participants to select the number that best describes how much your pain has interfered with your sleep during the past 24 hours. Responses vary from 0 (did not interfere with sleep) to 10 (completely interfered with sleep-unable to sleep due to pain). The DSIS was completed by participants once a day (upon awakening) to accurately capture variability in sleep interference due to pain on a daily basis, thus minimizing recall bias. Change from baseline to Weeks 4, 8, 12, and 18 (follow-up) in DSIS is reported. |
| Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up) | Participants rated their overall improvement in health status using the PGIC. The PGIC consisted of a 7-point scale where 1 = very much improved and 7 = very much worse. The participants were asked the following question: How would you rate your overall improvement with treatment during the clinical study?, where the response options included the following: Very Much Improved, Much Improved, Minimally Improved, No Change, Minimally Worse, Much Worse, and Very Much Worse. |
| Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Baseline (Day -7 to Day -1, inclusive) and Week 12 | Change from baseline to Week 12 in SF-36 is reported. The SF-36 assesses 8 health concepts: 1) limitations in physical activities because of health problems (physical functioning); 2) limitations in social activities because of physical or emotional problems (social functioning); 3) limitations in usual role activities because of physical health problems (role physical); 4) bodily pain; 5) general mental health; 6) limitations in usual role activities because of emotional problems (role emotional); 7) vitality; and 8) general health perceptions. The items use Likert-type scales with either 5 or 6 points, or 2 or 3 points. Higher SF-36 scores indicate a better state of health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). |
| Percentage of Participants Taking Any Rescue Medication | Baseline (Day -7 to Day -1, inclusive) through Week 12 | Percentage of participants taking any rescue medication are reported. Participants were asked to record all rescue medications they take for neuropathic pain in a paper diary. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Day 1 through 20.42 weeks (maximum observed duration) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. |
| Number of Participants With Abnormal Vital Signs Reported as TEAEs | Day 1 through 20.42 weeks (maximum observed duration) | Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, diastolic blood pressure, systolic blood pressure, heart \[pulse\] rate, and respiratory rate). |
| Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Day 1 through 20.42 weeks (maximum observed duration) | Number of participants with clinically significant abnormal ECGs are reported. |
| Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Day 1 through 20.42 weeks (maximum observed duration) | Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of hematology, clinical chemistry, coagulation, and urinalysis. |
| Change From Baseline in Weekly Average of Average Daily Pain Score | Baseline (Day -7 to Day -1, inclusive), Weeks 2, 4, 6, 8, 10, and 18 | Change from baseline to Weeks 2, 4, 6, 8, 10, and 18 in weekly average of average daily pain score is reported. Participants assessed their perceived daily average neuropathic pain over the previous 24 hours using an 11-point NRS, with 0 representing no pain and 10 representing the worst pain imaginable. Participants were instructed to assess their average daily pain at approximately the same time every morning, and to record the response in a subject diary (ePRO). |
| Number of Participants With Clinically Significant Findings in Neurological Examination | Day 1 through 20.42 weeks (maximum observed duration) | Number of participants with clinically significant findings in neurological examination is reported. |
| Number of Participants With Abnormal Dorsiflexion Strength | Day 1 through 20.42 weeks (maximum observed duration) | Number of participants with abnormal dorsiflexion strength is reported. Dorsiflexion strength is scored on 0-4 scale. The scale indicated 0 = normal power, 1 = mild weakness, 2 = moderate weakness, 3 = severe weakness, and 4 = paralysis. |
| Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Day 1 through 20.42 weeks (maximum observed duration) | Number of participants with abnormal deep tendon reflex are reported. Deep tendon reflex (knee and ankle) strength is scored on 0-4 scale. The scale indicated 0 = normal, 1 = ankle reflex reduced, 2 = ankle reflex absent, 3 = ankle reflex absent and knee reflex reduced, and 4 = all reflexes (both ankle and knee) absent. Participants within a specific row are not included in any other row in the data table below. |
| Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Baseline (Day -45 to -1), pre-dose on Day 1, Weeks 2, 4, 6, 8, 10, 12, and 18/early termination | The TNSn, a semi-quantitative clinical assessment of peripheral nervous system function, was administered at baseline (Screening), Day 1, Weeks 2, 4, 6, 8, 10, 12 and Week 18/early termination. The TNSn provides for an assessment of motor symptom score, autonomic symptom score, pin sensibility score, and vibration sensibility score. Each neuropathy item is scored on a 0-4 scale. The scores are summed to obtain a total score ranging from 0 to 20. Higher total scores correlate with more severe neuropathy. Not all of the early terminated participants completed the 18 week assessment. Only 3 early terminated participants contributed data at the Week 18 assessment. |
| Number of Participants With Investigator Reported Significant Changes From Baseline in Motor and Sensory Nerve Conduction | Day 1 through 20.42 weeks (maximum observed duration) | Motor and sensory nerve conduction studies were performed in relevant lower and upper limb nerves (sural, peroneal, median/ulnar, fibular, and tibial nerves) wherein amplitude, peak latency, conduction velocity, and duration of nerve action potentials were recorded. |
| Number of Participants With at Least One Concomitant Medication | Day 1 through 20.42 weeks (maximum observed duration) | Number of participants with at least one concomitant medication is reported. A concomitant medication is defined as any medication continuing or starting after first dose of study medication. |
| Number of Participants With Injection Site Reaction | Day 1 through 20.42 weeks (maximum observed duration) | Number of participants with injection site reaction is reported. |
| Number of Participants With Infusion Reaction | Day 1 through 20.42 weeks (maximum observed duration) | Number of participants with infusion reaction is reported. |
| Serum Total Nerve Growth Factor (NGF) Concentrations | Day 1 (pre-dose; baseline), Weeks 2, 4, 6, 8, 10 (Day 70; pre-dose, immediately before end of infusion, 8 hours and 24 hours post Day 70 infusion [Day 71]), 11, and 12 (approximately same time of day as Week 10 infusion) | Serum concentrations of total NGF in ADA positive or negative participants are reported. |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Pre-dose at baseline (Day -45 to -1) and Study Weeks 2, 4, 8, 10, 12, and 18 (follow-up) | Number of participants with positive ADA to MEDI7352 are reported. Treatment-induced ADA positive is defined as ADA negative at baseline and positive at least 1 post-baseline assessment. Treatment-boosted ADA positive is defined as ADA positive at baseline with pre-existing titre boosted by 4-fold or greater during the study period. Persistent positive is defined as ADA negative at baseline and positive at least 2 post-baseline assessments (with \>= 16 weeks between first and last positive) or ADA positive at last post-baseline assessment. Transiently positive is defined as ADA negative at baseline and at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. |
| Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs | Day 1 through 20.42 weeks (maximum observed duration) | Number of participants with clinically significant findings in physical examination reported as TEAE are reported. A complete physical examination (excluding the genitourinary examination, unless warranted) was performed. |
Countries
Denmark, Hungary, Poland, Romania, United Kingdom
Participant flow
Recruitment details
The study was conducted at 45 sites in 4 countries (the United Kingdom, Hungary, Poland, and Romania).
Pre-assignment details
A total of 112 participants were randomized, of which 107 participants received at least one dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period. | 54 |
| MEDl7352 Low Dose Participants received 6 doses of IV MEDl7352 during 12-week treatment period. | 6 |
| MEDl7352 Meduim Dose Participants received 6 doses of IV MEDl7352 during 12-week treatment period. | 16 |
| MEDI7352 High Dose Participants received 6 doses of IV MEDl7352 during 12-week treatment period. | 36 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 | 1 | 3 |
| Overall Study | Other | 3 | 1 | 3 | 1 |
| Overall Study | Physician Decision | 2 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | MEDl7352 Low Dose | MEDl7352 Meduim Dose | MEDI7352 High Dose |
|---|---|---|---|---|---|
| Age, Continuous | 60.4 Years STANDARD_DEVIATION 9.73 | 60.7 Years STANDARD_DEVIATION 8.02 | 60.7 Years STANDARD_DEVIATION 17.14 | 60.1 Years STANDARD_DEVIATION 11.49 | 60.1 Years STANDARD_DEVIATION 10.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 112 Participants | 54 Participants | 6 Participants | 16 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 109 Participants | 53 Participants | 6 Participants | 14 Participants | 36 Participants |
| Sex: Female, Male Female | 40 Participants | 20 Participants | 0 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 72 Participants | 34 Participants | 6 Participants | 11 Participants | 21 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 / 54 | 0 / 4 | 0 / 14 | 0 / 35 |
| other Total, other adverse events | 30 / 54 | 4 / 4 | 10 / 14 | 23 / 35 |
| serious Total, serious adverse events | 1 / 54 | 0 / 4 | 0 / 14 | 0 / 35 |
Outcome results
Primary
Change From Baseline in Weekly Average of Average Daily Pain Score to Week 12
Change from baseline to Week 12 in weekly average of average daily pain score is reported. Participants assessed their perceived daily average neuropathic pain over the previous 24 hours using an 11-point numerical rating scale (NRS), with 0 representing no pain and 10 representing the worst pain imaginable. Participants were instructed to assess their average daily pain at approximately the same time every morning, and to record the response in a subject diary (electronic patient-reported outcome \[ePRO\]).
Time frame: Baseline (Day -7 to Day -1, inclusive) through Week 12
Population: Modified intent-to-treat (mITT) population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Weekly Average of Average Daily Pain Score to Week 12 | -1.244 Units on a scale | Standard Deviation 1.7327 |
| MEDl7352 Low Dose | Change From Baseline in Weekly Average of Average Daily Pain Score to Week 12 | -3.387 Units on a scale | Standard Deviation 1.9605 |
| MEDl7352 Meduim Dose | Change From Baseline in Weekly Average of Average Daily Pain Score to Week 12 | -0.615 Units on a scale | Standard Deviation 1.0431 |
| MEDI7352 High Dose | Change From Baseline in Weekly Average of Average Daily Pain Score to Week 12 | -2.699 Units on a scale | Standard Deviation 2.0819 |
p-value: 0.043795% CI: [-3.87, -0.06]ANCOVA
p-value: 0.187895% CI: [-0.36, 1.79]ANCOVA
p-value: 0.000995% CI: [-2.19, -0.58]ANCOVA
Secondary
Change From Baseline in 36-item Short-Form Health Survey (SF-36)
Change from baseline to Week 12 in SF-36 is reported. The SF-36 assesses 8 health concepts: 1) limitations in physical activities because of health problems (physical functioning); 2) limitations in social activities because of physical or emotional problems (social functioning); 3) limitations in usual role activities because of physical health problems (role physical); 4) bodily pain; 5) general mental health; 6) limitations in usual role activities because of emotional problems (role emotional); 7) vitality; and 8) general health perceptions. The items use Likert-type scales with either 5 or 6 points, or 2 or 3 points. Higher SF-36 scores indicate a better state of health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Time frame: Baseline (Day -7 to Day -1, inclusive) and Week 12
Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Physical Functioning | 11.282 Units on a scale | Standard Deviation 17.0412 |
| Placebo | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Role Physical | 7.372 Units on a scale | Standard Deviation 18.0159 |
| Placebo | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Bodily Pain | 8.3 Units on a scale | Standard Deviation 20.51 |
| Placebo | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | General Health | -2.6 Units on a scale | Standard Deviation 17.7 |
| Placebo | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Vitality | -0.160 Units on a scale | Standard Deviation 20.6039 |
| Placebo | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Social Functioning | 1.92 Units on a scale | Standard Deviation 19.772 |
| Placebo | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Role Emotional | -1.923 Units on a scale | Standard Deviation 25.3248 |
| Placebo | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Mental Health | -5.9 Units on a scale | Standard Deviation 21.82 |
| MEDl7352 Low Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Social Functioning | 31.25 Units on a scale | Standard Deviation 23.936 |
| MEDl7352 Low Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Vitality | 3.125 Units on a scale | Standard Deviation 16.5359 |
| MEDl7352 Low Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Role Physical | 28.125 Units on a scale | Standard Deviation 27.7169 |
| MEDl7352 Low Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Mental Health | 10.0 Units on a scale | Standard Deviation 20.41 |
| MEDl7352 Low Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Role Emotional | 8.333 Units on a scale | Standard Deviation 31.911 |
| MEDl7352 Low Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | General Health | -2.5 Units on a scale | Standard Deviation 5 |
| MEDl7352 Low Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Bodily Pain | 9.8 Units on a scale | Standard Deviation 22.75 |
| MEDl7352 Low Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Physical Functioning | 21.248 Units on a scale | Standard Deviation 13.1526 |
| MEDl7352 Meduim Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Role Emotional | -5.556 Units on a scale | Standard Deviation 34.8748 |
| MEDl7352 Meduim Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Bodily Pain | 12.1 Units on a scale | Standard Deviation 23.11 |
| MEDl7352 Meduim Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | General Health | -5.3 Units on a scale | Standard Deviation 17.72 |
| MEDl7352 Meduim Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Vitality | -0.521 Units on a scale | Standard Deviation 17.7695 |
| MEDl7352 Meduim Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Social Functioning | -1.04 Units on a scale | Standard Deviation 24.108 |
| MEDl7352 Meduim Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Mental Health | -1.3 Units on a scale | Standard Deviation 14.48 |
| MEDl7352 Meduim Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Physical Functioning | 0.417 Units on a scale | Standard Deviation 19.7084 |
| MEDl7352 Meduim Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Role Physical | 0.000 Units on a scale | Standard Deviation 37.3101 |
| MEDI7352 High Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Bodily Pain | 14.9 Units on a scale | Standard Deviation 17.3 |
| MEDI7352 High Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | General Health | 0.0 Units on a scale | Standard Deviation 19.98 |
| MEDI7352 High Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Role Physical | 6.681 Units on a scale | Standard Deviation 17.4338 |
| MEDI7352 High Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Physical Functioning | 12.759 Units on a scale | Standard Deviation 16.6141 |
| MEDI7352 High Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Vitality | -4.095 Units on a scale | Standard Deviation 24.0486 |
| MEDI7352 High Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Mental Health | -0.7 Units on a scale | Standard Deviation 18.41 |
| MEDI7352 High Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Role Emotional | -1.724 Units on a scale | Standard Deviation 19.9681 |
| MEDI7352 High Dose | Change From Baseline in 36-item Short-Form Health Survey (SF-36) | Social Functioning | 9.05 Units on a scale | Standard Deviation 23.121 |
Secondary
Change From Baseline in Daily Sleep Interference Scale (DSIS)
Participants were assessed for how their neuropathic pain interferes with their sleep using the DSIS. It has an 11 point Likert response scale (0-10) that asked participants to select the number that best describes how much your pain has interfered with your sleep during the past 24 hours. Responses vary from 0 (did not interfere with sleep) to 10 (completely interfered with sleep-unable to sleep due to pain). The DSIS was completed by participants once a day (upon awakening) to accurately capture variability in sleep interference due to pain on a daily basis, thus minimizing recall bias. Change from baseline to Weeks 4, 8, 12, and 18 (follow-up) in DSIS is reported.
Time frame: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)
Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Here, number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 4 | -0.760 Units on a scale | Standard Deviation 1.1212 |
| Placebo | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 8 | -1.417 Units on a scale | Standard Deviation 1.7654 |
| Placebo | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 12 | -1.668 Units on a scale | Standard Deviation 2.1928 |
| Placebo | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 18 (follow-up) | -1.824 Units on a scale | Standard Deviation 2.2582 |
| MEDl7352 Low Dose | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 8 | -3.143 Units on a scale | Standard Deviation 2.743 |
| MEDl7352 Low Dose | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 12 | -3.735 Units on a scale | Standard Deviation 2.7598 |
| MEDl7352 Low Dose | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 18 (follow-up) | -3.036 Units on a scale | Standard Deviation 2.6557 |
| MEDl7352 Low Dose | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 4 | -2.810 Units on a scale | Standard Deviation 2.6979 |
| MEDl7352 Meduim Dose | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 12 | -1.077 Units on a scale | Standard Deviation 1.4769 |
| MEDl7352 Meduim Dose | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 8 | -1.127 Units on a scale | Standard Deviation 1.4907 |
| MEDl7352 Meduim Dose | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 18 (follow-up) | -0.865 Units on a scale | Standard Deviation 1.2795 |
| MEDl7352 Meduim Dose | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 4 | -0.979 Units on a scale | Standard Deviation 1.793 |
| MEDI7352 High Dose | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 18 (follow-up) | -2.602 Units on a scale | Standard Deviation 2.4427 |
| MEDI7352 High Dose | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 8 | -2.373 Units on a scale | Standard Deviation 2.1368 |
| MEDI7352 High Dose | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 4 | -1.790 Units on a scale | Standard Deviation 1.5688 |
| MEDI7352 High Dose | Change From Baseline in Daily Sleep Interference Scale (DSIS) | Week 12 | -2.725 Units on a scale | Standard Deviation 2.2484 |
Secondary
Change From Baseline in Galer Neuropathic Pain Scale (NPS)
Participants were assessed for their neuropathic pain using the Galer NPS, which included 2 descriptors of pain, including intensity and unpleasantness, and 8 descriptors that assessed specific qualities of neuropathic pain: sharp, hot, dull, cold, sensitive, itchy, deep, and surface pain. Each of these 10 dimensions had a 0 to 10 NRS in which 0 is equal to no pain and 10 equals most intense pain. Galer NPS total score (ranges from 0 to 100; with 0 and 100 representing the no and highest degree of neuropathic-like symptoms, respectively) is sum of pain intensity, pain unpleasantness, pain sharpness, pain hotness, pain dullness, pain coldness, pain sensitivity, pain itching, deep pain intensity, and surface pain intensity (all in an 11-point NRS). Change from baseline to Weeks 4, 8, 12, and 18 (follow-up) in Galer NPS total score is reported.
Time frame: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)
Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Here, number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 4 | -13.333 Units on a scale | Standard Deviation 29.0461 |
| Placebo | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 8 | -19.136 Units on a scale | Standard Deviation 31.5577 |
| Placebo | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 12 | -24.385 Units on a scale | Standard Deviation 31.1081 |
| Placebo | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 18 (follow-up) | -25.722 Units on a scale | Standard Deviation 33.6151 |
| MEDl7352 Low Dose | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 8 | -8.750 Units on a scale | Standard Deviation 18.2094 |
| MEDl7352 Low Dose | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 12 | -28.750 Units on a scale | Standard Deviation 16.6808 |
| MEDl7352 Low Dose | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 18 (follow-up) | -23.000 Units on a scale | Standard Deviation 23.3095 |
| MEDl7352 Low Dose | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 4 | -5.750 Units on a scale | Standard Deviation 10.5317 |
| MEDl7352 Meduim Dose | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 12 | -22.000 Units on a scale | Standard Deviation 28.9379 |
| MEDl7352 Meduim Dose | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 8 | -19.333 Units on a scale | Standard Deviation 23.7538 |
| MEDl7352 Meduim Dose | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 18 (follow-up) | -27.909 Units on a scale | Standard Deviation 30.3725 |
| MEDl7352 Meduim Dose | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 4 | -10.727 Units on a scale | Standard Deviation 21.3967 |
| MEDI7352 High Dose | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 18 (follow-up) | -25.414 Units on a scale | Standard Deviation 25.8947 |
| MEDI7352 High Dose | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 8 | -29.516 Units on a scale | Standard Deviation 32.314 |
| MEDI7352 High Dose | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 4 | -26.387 Units on a scale | Standard Deviation 26.9922 |
| MEDI7352 High Dose | Change From Baseline in Galer Neuropathic Pain Scale (NPS) | Week 12 | -34.586 Units on a scale | Standard Deviation 31.2622 |
Secondary
Change From Baseline in Total Neuropathy Score-Nurse (TNSn)
The TNSn, a semi-quantitative clinical assessment of peripheral nervous system function, was administered at baseline (Screening), Day 1, Weeks 2, 4, 6, 8, 10, 12 and Week 18/early termination. The TNSn provides for an assessment of motor symptom score, autonomic symptom score, pin sensibility score, and vibration sensibility score. Each neuropathy item is scored on a 0-4 scale. The scores are summed to obtain a total score ranging from 0 to 20. Higher total scores correlate with more severe neuropathy. Not all of the early terminated participants completed the 18 week assessment. Only 3 early terminated participants contributed data at the Week 18 assessment.
Time frame: Baseline (Day -45 to -1), pre-dose on Day 1, Weeks 2, 4, 6, 8, 10, 12, and 18/early termination
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Here, number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Day 1 | -0.25 Units on a scale | Standard Deviation 0.957 |
| Placebo | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 8 | -1.40 Units on a scale | Standard Deviation 2.082 |
| Placebo | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 6 | -1.40 Units on a scale | Standard Deviation 2.071 |
| Placebo | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 18 | -2.00 Units on a scale | Standard Deviation 2.631 |
| Placebo | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 12 | -1.73 Units on a scale | Standard Deviation 2.562 |
| Placebo | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 10 | -1.90 Units on a scale | Standard Deviation 2.458 |
| Placebo | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 4 | -0.90 Units on a scale | Standard Deviation 1.982 |
| Placebo | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 2 | -0.54 Units on a scale | Standard Deviation 1.304 |
| MEDl7352 Low Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 8 | -2.50 Units on a scale | Standard Deviation 3 |
| MEDl7352 Low Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 2 | -1.25 Units on a scale | Standard Deviation 1.258 |
| MEDl7352 Low Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 4 | -2.50 Units on a scale | Standard Deviation 3.786 |
| MEDl7352 Low Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 6 | -0.75 Units on a scale | Standard Deviation 2.872 |
| MEDl7352 Low Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 10 | -2.00 Units on a scale | Standard Deviation 3.916 |
| MEDl7352 Low Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 12 | -2.25 Units on a scale | Standard Deviation 2.062 |
| MEDl7352 Low Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 18 | -2.50 Units on a scale | Standard Deviation 3.512 |
| MEDl7352 Meduim Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 4 | -0.85 Units on a scale | Standard Deviation 1.819 |
| MEDl7352 Meduim Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 8 | -0.92 Units on a scale | Standard Deviation 1.881 |
| MEDl7352 Meduim Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 10 | -1.67 Units on a scale | Standard Deviation 1.435 |
| MEDl7352 Meduim Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 2 | 0.00 Units on a scale | Standard Deviation 1.354 |
| MEDl7352 Meduim Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 18 | -2.17 Units on a scale | Standard Deviation 2.329 |
| MEDl7352 Meduim Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 12 | -2.17 Units on a scale | Standard Deviation 1.899 |
| MEDl7352 Meduim Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 6 | -1.00 Units on a scale | Standard Deviation 1.859 |
| MEDI7352 High Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Day 1 | 1.00 Units on a scale | — |
| MEDI7352 High Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 4 | -1.19 Units on a scale | Standard Deviation 1.891 |
| MEDI7352 High Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 6 | -1.85 Units on a scale | Standard Deviation 2.093 |
| MEDI7352 High Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 8 | -1.84 Units on a scale | Standard Deviation 2.665 |
| MEDI7352 High Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 2 | -0.94 Units on a scale | Standard Deviation 2.117 |
| MEDI7352 High Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 18 | -2.30 Units on a scale | Standard Deviation 3.053 |
| MEDI7352 High Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 12 | -2.53 Units on a scale | Standard Deviation 2.515 |
| MEDI7352 High Dose | Change From Baseline in Total Neuropathy Score-Nurse (TNSn) | Week 10 | -2.45 Units on a scale | Standard Deviation 3.042 |
Secondary
Change From Baseline in Weekly Average of Average Daily Pain Score
Change from baseline to Weeks 2, 4, 6, 8, 10, and 18 in weekly average of average daily pain score is reported. Participants assessed their perceived daily average neuropathic pain over the previous 24 hours using an 11-point NRS, with 0 representing no pain and 10 representing the worst pain imaginable. Participants were instructed to assess their average daily pain at approximately the same time every morning, and to record the response in a subject diary (ePRO).
Time frame: Baseline (Day -7 to Day -1, inclusive), Weeks 2, 4, 6, 8, 10, and 18
Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment. Here, number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 2 | -0.385 Units on a scale | Standard Deviation 0.6863 |
| Placebo | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 4 | -0.563 Units on a scale | Standard Deviation 1.0173 |
| Placebo | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 6 | -0.955 Units on a scale | Standard Deviation 1.3236 |
| Placebo | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 8 | -1.236 Units on a scale | Standard Deviation 1.6026 |
| Placebo | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 10 | -1.418 Units on a scale | Standard Deviation 1.6274 |
| Placebo | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 18 | -1.764 Units on a scale | Standard Deviation 1.8415 |
| MEDl7352 Low Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 18 | -2.607 Units on a scale | Standard Deviation 2.202 |
| MEDl7352 Low Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 8 | -2.393 Units on a scale | Standard Deviation 2.0249 |
| MEDl7352 Low Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 2 | -1.089 Units on a scale | Standard Deviation 1.0258 |
| MEDl7352 Low Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 6 | -2.458 Units on a scale | Standard Deviation 2.2156 |
| MEDl7352 Low Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 4 | -2.173 Units on a scale | Standard Deviation 1.4266 |
| MEDl7352 Low Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 10 | -2.595 Units on a scale | Standard Deviation 2.2003 |
| MEDl7352 Meduim Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 4 | -0.144 Units on a scale | Standard Deviation 0.9143 |
| MEDl7352 Meduim Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 6 | -0.578 Units on a scale | Standard Deviation 1.0715 |
| MEDl7352 Meduim Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 8 | -0.690 Units on a scale | Standard Deviation 1.2819 |
| MEDl7352 Meduim Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 18 | -0.550 Units on a scale | Standard Deviation 1.2333 |
| MEDl7352 Meduim Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 10 | -0.712 Units on a scale | Standard Deviation 1.2164 |
| MEDl7352 Meduim Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 2 | -0.311 Units on a scale | Standard Deviation 0.6285 |
| MEDI7352 High Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 10 | -2.629 Units on a scale | Standard Deviation 1.9943 |
| MEDI7352 High Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 18 | -2.559 Units on a scale | Standard Deviation 2.1241 |
| MEDI7352 High Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 4 | -1.508 Units on a scale | Standard Deviation 1.513 |
| MEDI7352 High Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 8 | -2.372 Units on a scale | Standard Deviation 2.0607 |
| MEDI7352 High Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 2 | -0.540 Units on a scale | Standard Deviation 1.2503 |
| MEDI7352 High Dose | Change From Baseline in Weekly Average of Average Daily Pain Score | Week 6 | -2.044 Units on a scale | Standard Deviation 1.7916 |
Secondary
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of hematology, clinical chemistry, coagulation, and urinalysis.
Time frame: Day 1 through 20.42 weeks (maximum observed duration)
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Urine analysis abnormal | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Bacterial test positive | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood bilirubin increased | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Protein urine present | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose increased | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose decreased | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypercholesterolaemia | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | C-reactive protein increased | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Coagulation test abnormal | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypoglycemia | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glomerular filtration rate decreased | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperglycaemia | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | White blood cells urine positive | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | White blood cells urine positive | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Urine analysis abnormal | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | C-reactive protein increased | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Bacterial test positive | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose decreased | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Protein urine present | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypoglycemia | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood bilirubin increased | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glomerular filtration rate decreased | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperglycaemia | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypercholesterolaemia | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Coagulation test abnormal | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose increased | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | White blood cells urine positive | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Alanine aminotransferase increased | 2 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose decreased | 1 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Aspartate aminotransferase increased | 1 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose increased | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | C-reactive protein increased | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Coagulation test abnormal | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glomerular filtration rate decreased | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Bacterial test positive | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood bilirubin increased | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Protein urine present | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Urine analysis abnormal | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypoglycemia | 1 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypercholesterolaemia | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperglycaemia | 1 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glomerular filtration rate decreased | 1 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose decreased | 1 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Urine analysis abnormal | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Coagulation test abnormal | 1 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | C-reactive protein increased | 1 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypoglycemia | 1 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose increased | 1 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperglycaemia | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood bilirubin increased | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Bacterial test positive | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypercholesterolaemia | 1 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Protein urine present | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | White blood cells urine positive | 1 Participants |
Secondary
Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle)
Number of participants with abnormal deep tendon reflex are reported. Deep tendon reflex (knee and ankle) strength is scored on 0-4 scale. The scale indicated 0 = normal, 1 = ankle reflex reduced, 2 = ankle reflex absent, 3 = ankle reflex absent and knee reflex reduced, and 4 = all reflexes (both ankle and knee) absent. Participants within a specific row are not included in any other row in the data table below.
Time frame: Day 1 through 20.42 weeks (maximum observed duration)
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were assessed for strength and deep tendon reflexes assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Ankle reflex reduced | 5 Participants |
| Placebo | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Ankle reflex absent | 4 Participants |
| Placebo | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Ankle reflex absent and knee reflex reduced | 11 Participants |
| Placebo | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | All reflexes absent | 15 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Ankle reflex absent | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Ankle reflex absent and knee reflex reduced | 1 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | All reflexes absent | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Ankle reflex reduced | 2 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Ankle reflex absent and knee reflex reduced | 3 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Ankle reflex absent | 1 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | All reflexes absent | 6 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Ankle reflex reduced | 2 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | All reflexes absent | 5 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Ankle reflex absent | 5 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Ankle reflex reduced | 3 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) | Ankle reflex absent and knee reflex reduced | 13 Participants |
Secondary
Number of Participants With Abnormal Dorsiflexion Strength
Number of participants with abnormal dorsiflexion strength is reported. Dorsiflexion strength is scored on 0-4 scale. The scale indicated 0 = normal power, 1 = mild weakness, 2 = moderate weakness, 3 = severe weakness, and 4 = paralysis.
Time frame: Day 1 through 20.42 weeks (maximum observed duration)
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were assessed for strength and deep tendon reflexes assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Dorsiflexion Strength | Mild Weakness | 9 Participants |
| Placebo | Number of Participants With Abnormal Dorsiflexion Strength | Moderate Weakness | 8 Participants |
| Placebo | Number of Participants With Abnormal Dorsiflexion Strength | Severe Weakness | 0 Participants |
| Placebo | Number of Participants With Abnormal Dorsiflexion Strength | Paralysis | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Dorsiflexion Strength | Moderate Weakness | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Dorsiflexion Strength | Severe Weakness | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Dorsiflexion Strength | Paralysis | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Dorsiflexion Strength | Mild Weakness | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Dorsiflexion Strength | Severe Weakness | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Dorsiflexion Strength | Moderate Weakness | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Dorsiflexion Strength | Paralysis | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Dorsiflexion Strength | Mild Weakness | 7 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Dorsiflexion Strength | Paralysis | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Dorsiflexion Strength | Moderate Weakness | 2 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Dorsiflexion Strength | Mild Weakness | 18 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Dorsiflexion Strength | Severe Weakness | 0 Participants |
Secondary
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, diastolic blood pressure, systolic blood pressure, heart \[pulse\] rate, and respiratory rate).
Time frame: Day 1 through 20.42 weeks (maximum observed duration)
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypertension | 1 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 0 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypotension | 3 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 1 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Blood pressure increased | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypertension | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypotension | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Blood pressure increased | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Blood pressure increased | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypertension | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypotension | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypertension | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 1 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Blood pressure increased | 1 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypotension | 0 Participants |
Secondary
Number of Participants With at Least One Concomitant Medication
Number of participants with at least one concomitant medication is reported. A concomitant medication is defined as any medication continuing or starting after first dose of study medication.
Time frame: Day 1 through 20.42 weeks (maximum observed duration)
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With at Least One Concomitant Medication | 54 Participants |
| MEDl7352 Low Dose | Number of Participants With at Least One Concomitant Medication | 4 Participants |
| MEDl7352 Meduim Dose | Number of Participants With at Least One Concomitant Medication | 14 Participants |
| MEDI7352 High Dose | Number of Participants With at Least One Concomitant Medication | 35 Participants |
Secondary
Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs)
Number of participants with clinically significant abnormal ECGs are reported.
Time frame: Day 1 through 20.42 weeks (maximum observed duration)
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Number of participants analyzed (N) denotes the number of participants who were evaluable for the specified outcome measure. Here, number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 8 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Day 1 | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 12 | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 4 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 18 (follow-up) | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 8 | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 4 | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 12 | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Day 1 | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 18 (follow-up) | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 18 (follow-up) | 1 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Day 1 | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 4 | 1 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 8 | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 12 | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 18 (follow-up) | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 12 | 1 Participants |
| MEDI7352 High Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 4 | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Day 1 | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 8 | 1 Participants |
Secondary
Number of Participants With Clinically Significant Findings in Neurological Examination
Number of participants with clinically significant findings in neurological examination is reported.
Time frame: Day 1 through 20.42 weeks (maximum observed duration)
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Findings in Neurological Examination | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Clinically Significant Findings in Neurological Examination | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Clinically Significant Findings in Neurological Examination | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Clinically Significant Findings in Neurological Examination | 0 Participants |
Secondary
Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs
Number of participants with clinically significant findings in physical examination reported as TEAE are reported. A complete physical examination (excluding the genitourinary examination, unless warranted) was performed.
Time frame: Day 1 through 20.42 weeks (maximum observed duration)
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs | 1 Participants |
| MEDl7352 Low Dose | Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs | 1 Participants |
Secondary
Number of Participants With Infusion Reaction
Number of participants with infusion reaction is reported.
Time frame: Day 1 through 20.42 weeks (maximum observed duration)
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Infusion Reaction | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Infusion Reaction | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Infusion Reaction | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Infusion Reaction | 2 Participants |
Secondary
Number of Participants With Injection Site Reaction
Number of participants with injection site reaction is reported.
Time frame: Day 1 through 20.42 weeks (maximum observed duration)
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Injection Site Reaction | 1 Participants |
| MEDl7352 Low Dose | Number of Participants With Injection Site Reaction | 1 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Injection Site Reaction | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Injection Site Reaction | 0 Participants |
Secondary
Number of Participants With Investigator Reported Significant Changes From Baseline in Motor and Sensory Nerve Conduction
Motor and sensory nerve conduction studies were performed in relevant lower and upper limb nerves (sural, peroneal, median/ulnar, fibular, and tibial nerves) wherein amplitude, peak latency, conduction velocity, and duration of nerve action potentials were recorded.
Time frame: Day 1 through 20.42 weeks (maximum observed duration)
Population: Safety population included all participants who received at least 1 dose of any study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Investigator Reported Significant Changes From Baseline in Motor and Sensory Nerve Conduction | 2 Participants |
| MEDl7352 Low Dose | Number of Participants With Investigator Reported Significant Changes From Baseline in Motor and Sensory Nerve Conduction | 0 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Investigator Reported Significant Changes From Baseline in Motor and Sensory Nerve Conduction | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Investigator Reported Significant Changes From Baseline in Motor and Sensory Nerve Conduction | 0 Participants |
Secondary
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352
Number of participants with positive ADA to MEDI7352 are reported. Treatment-induced ADA positive is defined as ADA negative at baseline and positive at least 1 post-baseline assessment. Treatment-boosted ADA positive is defined as ADA positive at baseline with pre-existing titre boosted by 4-fold or greater during the study period. Persistent positive is defined as ADA negative at baseline and positive at least 2 post-baseline assessments (with \>= 16 weeks between first and last positive) or ADA positive at last post-baseline assessment. Transiently positive is defined as ADA negative at baseline and at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.
Time frame: Pre-dose at baseline (Day -45 to -1) and Study Weeks 2, 4, 8, 10, 12, and 18 (follow-up)
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who had adequate ADA sample.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-induced ADA | 0 Participants |
| Placebo | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-boosted ADA | 0 Participants |
| Placebo | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Persistently positive ADA | 0 Participants |
| Placebo | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Transiently positive ADA | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-boosted ADA | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Persistently positive ADA | 3 Participants |
| MEDl7352 Low Dose | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Transiently positive ADA | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-induced ADA | 3 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Persistently positive ADA | 6 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-boosted ADA | 1 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Transiently positive ADA | 1 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-induced ADA | 7 Participants |
| MEDI7352 High Dose | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Transiently positive ADA | 2 Participants |
| MEDI7352 High Dose | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-boosted ADA | 1 Participants |
| MEDI7352 High Dose | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-induced ADA | 28 Participants |
| MEDI7352 High Dose | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Persistently positive ADA | 26 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time frame: Day 1 through 20.42 weeks (maximum observed duration)
Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 30 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 1 Participants |
| MEDl7352 Low Dose | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 0 Participants |
| MEDl7352 Low Dose | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 4 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 10 Participants |
| MEDl7352 Meduim Dose | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 0 Participants |
| MEDI7352 High Dose | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 23 Participants |
| MEDI7352 High Dose | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 0 Participants |
Secondary
Percentage of Participants Taking Any Rescue Medication
Percentage of participants taking any rescue medication are reported. Participants were asked to record all rescue medications they take for neuropathic pain in a paper diary.
Time frame: Baseline (Day -7 to Day -1, inclusive) through Week 12
Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Taking Any Rescue Medication | 13 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants Taking Any Rescue Medication | 0 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants Taking Any Rescue Medication | 14.3 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants Taking Any Rescue Medication | 8.6 Percentage of participants |
Secondary
Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score
Percentage of participants with \>= 30% and \>= 50% decrease in weekly average of average daily pain score from baseline is reported. Participants assessed their perceived daily average neuropathic pain over the previous 24 hours using an 11-point NRS, with 0 representing no pain and 10 representing the worst pain imaginable. Participants were instructed to assess their average daily pain at approximately the same time every morning, and to record the response in a subject diary (ePRO).
Time frame: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)
Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment. Here, number of participants analyzed (N) denotes those participants who were evaluable for the specified outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 8 | 28.3 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 12 | 32.6 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 8 | 13.0 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 18 | 15.0 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 4 | 1.9 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 18 | 35.0 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 12 | 11.6 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 4 | 3.7 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 12 | 50.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 4 | 0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 8 | 25.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 8 | 75.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 4 | 75.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 12 | 75.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 18 | 25.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 18 | 50.0 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 8 | 8.3 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 12 | 8.3 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 18 | 0 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 8 | 16.7 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 12 | 8.3 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 4 | 7.7 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 18 | 25.0 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 4 | 0 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 18 | 40.0 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 4 | 34.3 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 8 | 57.6 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 12 | 66.7 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=30%: Week 18 | 56.7 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 4 | 14.3 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 8 | 36.4 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score | >=50%: Week 12 | 42.4 Percentage of participants |
Secondary
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC)
Participants rated their overall improvement in health status using the PGIC. The PGIC consisted of a 7-point scale where 1 = very much improved and 7 = very much worse. The participants were asked the following question: How would you rate your overall improvement with treatment during the clinical study?, where the response options included the following: Very Much Improved, Much Improved, Minimally Improved, No Change, Minimally Worse, Much Worse, and Very Much Worse.
Time frame: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)
Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment. Number of participants analyzed (N) denotes the number of participants who were PGIC responders. Here, number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 12: Improved | 48.7 Percentage of participants |
| Placebo | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 8: Improved | 36.4 Percentage of participants |
| Placebo | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 18: Much Improved | 25.0 Percentage of participants |
| Placebo | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 8: Very Much Improved | 2.3 Percentage of participants |
| Placebo | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 8: Much Improved | 31.8 Percentage of participants |
| Placebo | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 4: Much Improved | 2.1 Percentage of participants |
| Placebo | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 4: Improved | 50.0 Percentage of participants |
| Placebo | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 18: Improved | 36.1 Percentage of participants |
| Placebo | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 12: Very Much Improved | 5.1 Percentage of participants |
| Placebo | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 4: Very Much Improved | 2.1 Percentage of participants |
| Placebo | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 18: Very Much Improved | 11.1 Percentage of participants |
| Placebo | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 12: Much Improved | 28.2 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 18: Very Much Improved | 25.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 4: Improved | 50.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 4: Much Improved | 25.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 4: Very Much Improved | 0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 8: Improved | 25.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 8: Much Improved | 50.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 8: Very Much Improved | 0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 12: Improved | 0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 12: Much Improved | 75.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 12: Very Much Improved | 25.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 18: Improved | 25.0 Percentage of participants |
| MEDl7352 Low Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 18: Much Improved | 50.0 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 12: Improved | 54.5 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 4: Much Improved | 27.3 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 18: Very Much Improved | 9.1 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 18: Improved | 27.3 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 12: Much Improved | 36.4 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 18: Much Improved | 54.5 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 4: Very Much Improved | 0 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 8: Much Improved | 41.7 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 4: Improved | 45.5 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 8: Improved | 58.3 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 12: Very Much Improved | 0 Percentage of participants |
| MEDl7352 Meduim Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 8: Very Much Improved | 0 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 12: Very Much Improved | 10.3 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 4: Very Much Improved | 6.5 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 12: Improved | 44.8 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 18: Much Improved | 41.4 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 12: Much Improved | 41.4 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 4: Much Improved | 29.0 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 8: Very Much Improved | 6.5 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 18: Improved | 31.0 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 8: Improved | 41.9 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 4: Improved | 41.9 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 8: Much Improved | 38.7 Percentage of participants |
| MEDI7352 High Dose | Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) | Week 18: Very Much Improved | 13.8 Percentage of participants |
Secondary
Serum Total Nerve Growth Factor (NGF) Concentrations
Serum concentrations of total NGF in ADA positive or negative participants are reported.
Time frame: Day 1 (pre-dose; baseline), Weeks 2, 4, 6, 8, 10 (Day 70; pre-dose, immediately before end of infusion, 8 hours and 24 hours post Day 70 infusion [Day 71]), 11, and 12 (approximately same time of day as Week 10 infusion)
Population: Safety population: participants received at least 1 dose of any double-blind study drug and were analyzed according to treatment actually received. Number of participants analyzed: participants evaluated for this outcome measure. Number analyzed (n): participants evaluable at specified time point. MEDl7352 low and medium dose group data is not reported due to change in assay during course of study and stability data not supporting re-analysis of early study samples with new in-house assay.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 2 | 62.613 pg/mL | Standard Deviation 15.1088 |
| Placebo | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 10 (before end of infusion) | 57.308 pg/mL | Standard Deviation 13.3588 |
| Placebo | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 6 | 64.661 pg/mL | Standard Deviation 18.6478 |
| Placebo | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 10 (8 hours post-dose) | 177.323 pg/mL | Standard Deviation 554.8131 |
| Placebo | Serum Total Nerve Growth Factor (NGF) Concentrations | Day 1 | 52.303 pg/mL | Standard Deviation 11.6178 |
| Placebo | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 10 (post 24 hours) | 222.980 pg/mL | Standard Deviation 772.9408 |
| Placebo | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 8 | 63.291 pg/mL | Standard Deviation 16.5332 |
| Placebo | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 11 | 59.441 pg/mL | Standard Deviation 13.6892 |
| Placebo | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 4 | 78.209 pg/mL | Standard Deviation 92.0122 |
| Placebo | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 12 | 63.416 pg/mL | Standard Deviation 18.4243 |
| Placebo | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 10 (pre-dose) | 173.383 pg/mL | Standard Deviation 563.8921 |
| MEDI7352 High Dose | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 12 | 1710.966 pg/mL | Standard Deviation 2838.0975 |
| MEDI7352 High Dose | Serum Total Nerve Growth Factor (NGF) Concentrations | Day 1 | 65.687 pg/mL | Standard Deviation 60.4036 |
| MEDI7352 High Dose | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 2 | 2384.760 pg/mL | Standard Deviation 1989.0309 |
| MEDI7352 High Dose | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 4 | 2213.699 pg/mL | Standard Deviation 2408.3112 |
| MEDI7352 High Dose | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 6 | 2361.855 pg/mL | Standard Deviation 2645.8141 |
| MEDI7352 High Dose | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 8 | 1992.129 pg/mL | Standard Deviation 2507.9826 |
| MEDI7352 High Dose | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 10 (pre-dose) | 1681.073 pg/mL | Standard Deviation 2455.0666 |
| MEDI7352 High Dose | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 10 (before end of infusion) | 1992.756 pg/mL | Standard Deviation 2968.1285 |
| MEDI7352 High Dose | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 10 (8 hours post-dose) | 2012.384 pg/mL | Standard Deviation 2795.8138 |
| MEDI7352 High Dose | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 10 (post 24 hours) | 1849.835 pg/mL | Standard Deviation 2671.9526 |
| MEDI7352 High Dose | Serum Total Nerve Growth Factor (NGF) Concentrations | Week 11 | 1743.100 pg/mL | Standard Deviation 2621.0687 |